Treatment options in HBV.

The available evidence on interferon-alpha (IFN) treatment for chronic hepatitis B is sufficient to conclude that in patients with HBeAg positive chronic hepatitis, standard IFN therapy significantly improves clearance of HBeAg (number needed to treat [NNT] = 4), loss of HBV-DNA (NNT = 4) and clearance of HBsAg (NNT = 18). HBeAg positive patients with normal or slightly raised ALT should be treated only if there is histological evidence of progressive disease. In patients with HBeAg negative chronic hepatitis, less than 20% of subjects who have achieved an end-of-treatment virological response after a course of standard IFN maintain a sustained virological response in the long-term. IFN tre…

The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints

Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt prop…

Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD

SummaryBackground The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited. Aim To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients. Methods We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan. Results LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM ha…

Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis

Background: The benefit of neoadjuvant chemoradiotherapy in oesophageal cancer has been extensively studied but data on survival are still equivocal. Objective: To assess the effectiveness of chemoradiotherapy followed by surgery in the reduction of mortality in patients with resectable oesophageal cancer. Methods: Computerised bibliographic searches of MEDLINE and CANCERLIT (1970–2002) were supplemented with hand searches of reference lists. Study selection: Studies were included if they were randomised controlled trials (RCTs) comparing preoperative chemoradiotherapy plus surgery with surgery alone, and if they included patients with resectable histologically proven oesophageal cancer wit…

Does chemotherapy prevent HCV-related hepatocellular carcinoma? Cons.

The accuracy and the reliability of well-recognized clinical, virologic, histologic, and molecular risk factors for hepatocellular carcinoma (HCC) are still insufficient. Thus, accurate risk prediction of cancer development in individual patients with the aim of selecting high risk cohorts of patients for HCC chemoprevention programs remains an elusive goal. Future directions in chemoprevention of HCC will be in the development of molecular risk models and of new chemopreventive agents. Studies examining multiple genes and proteins (genomics and proteomics) in the same HCCs will be required to evaluate this possibility thoroughly. A strategy aiming at preventing chronic liver disease of any…

Telemedicine Is an Effective Tool to Monitor Disease Activity in IBD Patients in the COVID-19 Era: A Single Centre Experience Based on Objective Data

Background: The COVID-19 outbreak has led IBD clinics to adopt a remote monitoring approach in order to guarantee an adequate follow-up of patients with inflammatory bowel disease (IBD) and ensure the rules of social distancing. Aim: The aim of the study was to perform a survey on IBD patients who underwent remote monitoring in our tertiary referral center, to assess adherence, patients’ perceptions and satisfaction, and finally their opinions for future monitoring. Furthermore, we evaluated changes in disease activity and Quality of Life (QoL) using validated questionnaires. Methods: Consecutive patients with IBD scheduled for follow-up visits were switched to remote monitoring throu…

Role of LI-RADS Indeterminate Observations in the Risk of Hepatocellular Carcinoma after HCV Eradication with Direct-Acting Antivirals.

Purpose: To assess whether HCC (LR-5) occurrence may be associated with the presence of Liver Imaging Reporting and Data System (LI-RADS) indeterminate observations in patients with hepatitis C virus infection treated with direct acting antiviral (DAA) therapy. Materials and methods: This retrospective study included patients with HCV-related cirrhosis who achieved sustained virologic response (SVR) after DAA therapy between 2015 and 2019 and submitted to CT/MRI follow-ups with a minimum interval time of six months before and after DAA. Two blinded readers reviewed CT/MRI to categorize observations according to LI-RADS version 2018. Differences in rate of LI-RADS 5 observations (i.e., LR-5)…

Metabolic syndrome and severity of fibrosis in nonalcoholic fatty liver disease: An age-dependent risk profiling study

Background & Aims: Metabolic syndrome (MS) and its individual components are associated with the severity and progression of nonalcoholic fatty liver disease (NAFLD). We sought to evaluate the relationship between MS components and the risk of severe hepatic fibrosis in NAFLD patients discriminated by age. Methods: We considered 863 consecutive patients with biopsy-proven NAFLD, who had been fully evaluated for components of MS. Results: Multivariate logistic regression analysis showed that F3-F4 was associated with visceral obesity, IFG/diabetes, and low high-density lipoprotein (HDL) cholesterol, but not triglycerides >150 or arterial hypertension. A significant interaction was found betw…

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2012; 35: 238–247 Summary Background  Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Aims  To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. Methods  One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and H…

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection

Background: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. Methods: 124 HCC patients, who underwent a primary hepatic …

Transmission of hepatitis B and hepatitis delta viruses in the households of chronic hepatitis B surface antigen carriers: A regression analysis of indicators of risk

Abstract To evaluate whether clinical and laboratory features of a hepatitis B surface antigen (HBsAg) carrier can predict risks of infection, its chronicity, and the development of liver disease among close contacts, the authors studied a cohort of 994 first degree relatives or cohabitants (household contacts) of 226 non-drug-addicted chronic HBsAg carriers (index cases), of whom 77% had liver disease and 26% were superinfected by hepatitis D virus (HDV). A logistic form of regression analysis was used to assess the role of each feature in the index case as predictor of hepatitis B virus (HBV)- and HDV-related outcomes among household contacts. Six models of risk, expressed as odds ratios,…

Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1 chronic hepatitis C.

Background & Aims: In Chronic Hepatitis C (CHC), the influence of steatosis on liver stiffness measurement (LSM) is still debated. We assessed the impact of steatosis and its ultrasonographical sign – bright liver echo pattern (BLEP) – on LSM values and on transient elastography (TE) accuracy for the diagnosis of liver fibrosis, in a cohort of consecutive patients with Genotype 1 (G1) CHC. Methods: Patients (n = 618) were assessed by clinical, ultrasonographic and histological (Scheuer score) features. TE was performed using the M probe. Results: Male gender (p = 0.04), steatosis as continuous variable (p <0.001), severity of necroinflammation (p = 0.02) and stage of fibrosis (p <0.001) wer…

Insulin resistance in HCV mono-infected and in HIV/HCV co-infected patients: Looking to the future

Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation

Aliment Pharmacol Ther 2011; 34: 196–204 Summary Background  Transarterial chemoembolisation (TACE) is first-line treatment in unresectable hepatocellular carcinoma (HCC) and rescue treatment after failure of radical treatments in early stage HCC. Prognostic tools for HCC using time-fixed Cox models may be unreliable in patients treated with TACE because time-varying predictors interact. Aim  To explore time-dependent variables as survival predictors in patients with HCC receiving TACE as first-line or second-line treatment. Methods  Eighty four consecutive patients with HCC (mean age 68; male gender 62%; Child-Pugh class: A n = 73, B n = 11; Barcelona Clinic Liver Cancer class: A n = 44, B…

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in post-operative Crohn's disease

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease. Renna S, Cammà C, Modesto I, Cabibbo G, Scimeca D, Civitavecchia G, Mocciaro F, Orlando A, Enea M, Cottone M. Dipartimento di Medicina, Pneumologia e Fisiologia della Nutrizione Umana, Università di Palermo, Palermo, Italy. BACKGROUNDS &#38; AIMS: The benefit of therapy for prevention of postoperative recurrence of Crohn's disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurr…

Diagnostic performance of endoscopic ultrasound through‐the‐needle microforceps biopsy of pancreatic cystic lesions: Systematic review with meta‐analysis

Objectives Endoscopic ultrasound through-the-needle biopsy (EUS-TTNB) is a useful tool for differential diagnosis among pancreatic cystic lesions (PCLs). Cystic fluid cytology (CFC) is recommended by guidelines, but its diagnostic accuracy is about 50%. The aim of this meta-analysis is to assess the clinical impact of EUS-TTNB in terms of technical success (TS), histological accuracy (HA) and diagnostic yield (DY). Methods Original studies in English language on EUS-TTNB were searched in MEDLINE and EMBASE until October 2019. Diagnostic accuracy of EUS-TTNB for identification of mucinous PCLs was calculated using individual diagnostic data of patients who underwent CFC and surgery. Results …

Intermediate and advanced hepatocellular carcinoma management in four Italian centers: patterns of treatment and costs

Should we cure hepatitis C virus in patients with hepatocellular carcinoma while treating cancer?

Direct acting antivirals stabilize or improve liver function in the majority of patients with hepatitis C virus cirrhosis. Hepatic decompensation is the main driver of death of patients with early, successfully treated hepatocellular carcinoma superimposed to cirrhosis. Treatment with direct acting antivirals could improve the prognosis of these subjects, independently from the subsequent course of hepatocellular carcinoma, if the efficacy in obtaining viral clearance is as high as in patients without a history of hepatocellular carcinoma, and if the risk of hepatocellular carcinoma recurrence is unaffected. When dealing with hepatocellular carcinoma patients, direct acting antivirals can b…

Cost-effectiveness of sofosbuvir plus ribavirin with or without pegylated interferon for the treatment of chronic hepatitis C in Italy.

Objective:Across Italy up to 7.3% of the population is infected with hepatitis C virus (HCV), with long-term complications resulting in high medical costs and significant morbidity and mortality. Current treatment options have limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological response (SVR) rates, especially for the most severe patients). Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir, administered with ribavirin (RBV) and with or without pegylated interferon (PEG-INF), resulted in &gt;90% SVR across treatment-naïve (TN) genotype (GT) 1-6 patients. It is also t…

Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma

Background: Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing. Aim: To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium. Methods: Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival. Results: Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6 …

How important is the role of iterative liver direct surgery in patients with hepatocellular carcinoma for a transplant center located in an area with a low rate of deceased donation?

IntroductionHepatocellular carcinoma (HCC) accounts for nearly 90% of primary liver cancers, with estimates of over 1 million people affected by 2025. We aimed to explore the impacting role of an iterative surgical treatment approach in a cohort of HCC patients within the Milan criteria, associated with clinical risk factors for tumor recurrence (RHCC) after liver transplant (LT) and loco-regional therapies (LRT), as well as liver resection (LR) and/or microwave thermal ablation (MWTA).MethodsWe retrospectively analyzed our experience performed during an 8-year period between January 2013 and December 2021 in patients treated for HCC, focusing on describing the impact on preoperative end-st…

Assessment of treatment response in hepatocellular carcinoma: a review of the literature

Hepatocellular carcinoma (HCC) has a high incidence all over the world. Even if the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and could have a key role in clinical management. Since 1950 several radiological response criteria have been applied; however, it was not until 2000 that specific criteria for HCC were introduced by the European Association for the Study of the Liver (EASL), and these were then standardized in 2010 with the development of the modified Response Evaluation Criteria for Solid Tumors (mRECIST) for HCC. The purpose of this brief review is to compare data in literature regarding the application an…

Chronic hepatitis C and interferon alpha: conventional and cumulative meta-analyses of randomized controlled trials.

The purpose of this study was to evaluate the clinical usefulness of surrogate markers of the interferon effect (i.e., alanine aminotransferase levels and serum HCV-RNA status) as predictors of long term response, and to identify the optimal schedule of treatment for patients with chronic hepatitis C by means of meta-analysis.Pertinent randomized clinical trials and prospective studies were selected using MEDLINE (1986-1996), a reference list from published articles or reviews. Twenty-six prospective studies reporting data on surrogate markers of interferon response were selected. Thirty-nine trials comparing interferon alpha to no treatment and 25 trials comparing different schedules of in…

IL28B and PNPLA3 Polymorphisms Affect Histological Liver Damage in Patients with Non-alcoholic Fatty Liver Disease.

Background & Aims: Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients. Methods: One hundred sixty consecutive NAFLD patients were assessed by liver biopsy (Kleiner score); anthropometric, and biochemical and metabolic features were included. IL28B rs12979860 C>T, IL28B rs8099917 G>C, and PNPLA3 rs738409 C>G single nucleotide polymorphisms were tested. Results: Seventy-four (46.2%) patients had IL28B rs12979860 CC polymorph…

Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients.

Background and aims: Lower 25-Hydroxyvitamin D (25[OH]D) serum lev- els have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reduc- tase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Material and methods: Two hundred sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels wer…

Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling

Simple Summary Intrahepatic cholangiocarcinoma is a rare disease with increasing incidence and mortality still characterized by an insufficient clinical outcome. Growing attention has recently surrounded this disease, and liver transplantation has emerged as a novel curative treatment for cholangiocarcinoma, along with a better understanding of genetic alterations potentially capable of driving tumorigenesis. The aim of this paper is to present a clinical description of our case series of patients affected by intrahepatic cholangiocarcinoma and by mixed forms of hepatocellular and cholangiocellular carcinoma, together with a genomic profiling of mutations occurring in a panel of genes relev…

A Genetic and Metabolic Staging System for Predicting the Outcome of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver-related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis-4 (FIB-4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinom…

Sorafenib for Hepatocellular Carcinoma: From Randomized Controlled Trials to Clinical Practice.

Hepatocellular carcinoma is a challenging malignancy of global importance. It is the sixth most common solid malignancy and the third leading cause of cancer-related death, worldwide. Curative treatments at early stages include liver transplantation, resection and percutaneous ablation, while transarterial chemoembolization can improve survival in patients with intermediate tumor stage. Patients with mild, related symptoms and/or macrovascular invasion or extrahepatic spread are classified under the advanced stage. The standard of care in this group is sorafenib, an inhibitor of Raf kinase and vascular endothelial growth factor receptor, whose effectiveness has been proven by 2 recent rando…

Duration of HCV infection as a predictor of nonresponse to interferon

Duration of hepatitis C virus (HCV) infection is a key feature in determining responsiveness to interferon (IFN). Studies assessing its value as a predictive factor in chronic HCV infection show that a long duration of infection reduces the likelihood of a sustained response to IFN (defined as ALT normalization and clearance of serum HCV-RNA). The effect of HCV infection duration is independent of the presence of cirrhosis and level of HCV viremia. Meta-analysis of IFN trials in acute HCV infection shows an obvious effect of the drug on long-term ALT normalization and HCV-RNA clearance. Treatment of HCV infection during the acute or early chronic phase could therefore maximize therapeutic e…

Percutaneous and surgical treatment of pyogenic liver abscesses: Observation over a 21-year period in 148 patients

Percutaneous drainage of pyogenic liver abscess has become first-line treatment. In the past surgical drainage was preferred in some centres.The aim of this retrospective study was to assess the effectiveness of percutaneous treatments and surgical drainage, in terms of treatment success, hospital stay and costs.Data of 148 patients (90 males; 58 females; mean age, 61 yrs; range, 30-86 yrs) were retrospectively analysed.Patients' outcomes, including the length of hospital stay, procedure-related complications, treatment failure and death, were recorded. Multiple logistic regression model was used for statistical analysis.One hundred and four patients (83 with solitary and 21 with multiple a…

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

Background: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D). Methods: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by dec…

Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy

A multicenter randomized controlled trial established sorafenib as a standard of care for patients with advanced hepatocellular carcinoma (HCC). Because the study was prematurely interrupted due to survival benefits in the sorafenib arm, we conducted an observational study to adequately assess risks and benefits of this regimen in field practice. Starting in 2008, all clinically compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy, for tolerability as well as radiologic and survival response to 800-mg/d sorafenib therapy. Treatment was down-dosed or inter…

Predicting in-hospital mortality from Coronavirus Disease 2019: A simple validated app for clinical use

Backgrounds Validated tools for predicting individual in-hospital mortality of COVID-19 are lacking. We aimed to develop and to validate a simple clinical prediction rule for early identification of in-hospital mortality of patients with COVID-19. Methods and findings We enrolled 2191 consecutive hospitalized patients with COVID-19 from three Italian dedicated units (derivation cohort: 1810 consecutive patients from Bergamo and Pavia units; validation cohort: 381 consecutive patients from Rome unit). The outcome was in-hospital mortality. Fine and Gray competing risks multivariate model (with discharge as a competing event) was used to develop a prediction rule for in-hospital mortality. D…

&lt;i&gt;NR1H4&lt;/i&gt; rs35724 G&amp;gt;C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease

Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 variant, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms was genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n=124). Results: The NR1H4 rs35724 variant was protective against severity of steatosis (OR 0.89, 95% C.I.…

Unsatisfactory quality of hepatological information on the internet

A cholestatic pattern predicts major liver-related outcomes in patients with non-alcoholic fatty liver disease

NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO).

PNPLA3 Rs738409 C&amp;gt;G Variant Predicts Liver-Related Outcomes in Patients with Non-Alcoholic Fatty Liver Disease

Background: Patients with NAFLD are at higher risk of developing liver-related complications -liver decompensation(LD) and hepatocellular carcinoma (HCC), including death-. A single nucleotide polymorphism in PNPLA3 gene is associated with a higher prevalence of liver damage and HCC, but prospective date are not available. We aimed to assess whether the common rs738409 variant in PNPLA3 gene can predict the occurrence of liver-related events and death in a large cohort of NAFLD patients.   Methods: We considered 471 consecutive Italian individuals with histological diagnosis of NAFLD or clinical diagnosis of compensated NAFLD-related cirrhosis, prospectively followed for at least 6 months. …

The obesity paradox: Analysis from the SMAtteo COvid-19 REgistry (SMACORE) cohort

Summary Background and aims Obesity has been suggested as a possible risk factor for a more severe course of COVID-19; however, conclusive evidence is lacking and few studies have investigated the role of BMI as a risk factor for admission to intensive care unit (ICU) and mortality. We retrospectively analysed a COVID-19 cohort recruited during the first 40 days of the epidemic in Italy. We examined the association between obesity and 30-day mortality, admission to ICU, mortality and length of hospital stay in patients with COVID-19. Methods and results Demographic, clinical and outcome data were retrospectively analyzed in 331 patients with COVID-19 admitted to hospital between 21 February…

RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study: SIMPLE: Scoring Index to Monitor Progression of Low-risk Esophageal varices.

Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria).All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-H…

Recurrence of hepatocellular carcinoma after liver transplantation: an update.

Liver transplantation is the only curative alternative for selected patients with hepatocellular carcinoma (HCC) who are not eligible for resection and/or with decompensated cirrhosis. According to Milan criteria the 5-year survival rate is 70–85%, with a recurrence-free survival of 75%. However, HCC recurrence rate after liver transplantation remains a significant problem in the clinical practice. The prognosis in patients with HCC recurrence is poor. The treatment of choice for HCC recurrence is surgery, but it seems that a systemic treatment based on combination of an mTOR inhibitor with sorafenib can be used. Data on safety and efficacy are limited, clinical monitoring is necessary. Th…

Disease outcomes after DAA-induced SVR: Data from the resist-HCV cohort

Background and aims: Large scale, real life data on the long term course of liver disease after HCV clearance obtained with DAAs are still scanty, and the separate effects on hepatic and non-hepatic causes of death still unclear. Method: We evaluated 4147 patients (mean age: 65.7 ± 11.5 years, 57.6% males) included in the prospective RESIST-HCV cohort who started DAAs treatment in 22 centres between March 2015 and April 2017. All patients were follow after SVR to register liver-related and unrelated outcomes. The primary endpoint was the evaluation of survival since starting DAAs. Cox regression analysis was used to assess the predictors of liver-related and unrelated death. Results: Patien…

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease.

Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients.We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45years old (median age 31.6±8.1years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed b…

How the Pricing Strategy of 2nd Generation HCV Direct Antiviral Agents Can Affect the Number of Treated Patients in Italy and the National Drug Budget

A Cholestatic Pattern Predicts Liver-Related Events in Patients with Nonalcoholic Fatty Liver Disease

Background & Aims: Liver test alteration patterns can be categorized as: predominantly hepatocellular(H), with an ALT/ALP ratio>5; predominantly cholestatic pattern(C) with a ratio 55 years(HR2.55,95%C.I.1.17-5.54;p=0.01), platelets<150,000/mmc(HR0.14,95%C.I.0.06-0.32;p<0.001), albumin<4g/L(HR0.62,95%C.I.0.35-1.08;p=0.09), C vs M pattern(HR7.86,95%C.I.1.03-60.1;p=0.04), C vs H pattern(HR12.1,95% C.I.1.61-90.9;p=0.01) and fibrosis F3-F4(HR35.8,95%C.I.4.65-275.2;p<0.001) were independent risk factors for LRE occurrence. C vs M pattern(HR14.3,95%C.I.1.90-105.6;p=0.008) and C vs H pattern(HR15.6,95%C.I. 2.10-115.1;p=0.0068) were confirmed independently associated with LRE occurrence in the vali…

Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study

Objective The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC.Design Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V-0 and V-1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of su…

Ethical assessment of hepatitis C virus treatment: The lesson from first generation protease inhibitors

Abstract Since chronic hepatitis C has mostly become curable, issues concerning choice and allocation of treatment are of major concern. We assessed the foremost ethical issues in hepatitis C virus therapy with 1st generation protease inhibitors using the personalist ethical framework within the health technology assessment methodology. Our aim was to identify values at stake/in conflict and to support both the physicians’ choices in hepatitis C therapy and social (macro-) allocation decision-making. The ethical assessment indicates that: (1) safety/effectiveness profile of treatment is guaranteed if its use is restricted to the patients subgroups who may benefit from it; (2) patients shoul…

P178 Remote monitoring as an effective management strategy in inflammatory bowel disease: the lesson from COVID-19 pandemic

Abstract Background During the COVID-19 outbreaks many IBD clinics in Italy adopted a remote monitoring approach both to ensure an adequate follow-up of patients with inflammatory bowel disease (IBD) and respect the rules of social distancing, while access to hospital was restricted. Aim of the study was to perform a survey on IBD patients submitted to remote monitoring in our tertiary referral center in order to assess adherence and patients’ perceptions and satisfaction as well as their opinions for future monitoring. Changes in disease activity and Quality of Life were also evaluated. Methods Consecutive patients with IBD scheduled for follow-up visits were switched to remote monitoring …

Mesalamine and relapse prevention in Crohn's disease

Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study

AbstractBinge drinking (BD) is a common pattern of alcohol consumption among adolescents. At present few data are available on the possible relationship between BD and alcohol use disorders (AUD) in adolescents. The aim of this study was to assess the prevalence of BD and relationship between BD behavior and AUD among adolescents. A total of 2704 students attending 10 purposively selected high schools from three Italian provinces were surveyed. Questionnaires regarding socio-demographic data, pattern and amount of alcohol intake, smoking habits, use of illicit drugs, and physical activity were administered. AUD and affective disorders were also evaluated. Alcohol intake was reported by 2126…

Letter: liver dysfunction and survival in hepatocellular carcinoma treated by transarterial chemoembolisation - authors’ reply

Transfusion-associated chronic hepatitis C: alpha-n1 interferon for 6 vs. 12 months.

Abstract Aims: To compare the long-term effects of brief and prolonged therapy with alpha-n 1 interferon for transfusion-associated chronic hepatitis C. Methods: One hundred and sixteen subjects (male/female 4868, mean age 46.9 years) were studied. Sixty patients were randomised to brief treatment (group 1: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 4 months), and 56 to prolonged treatment (group 2: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 10 months). All were followed for 12 months after stopping interferon. Results: The early response rate was 47.4% (Group 1 [45%], Group 2 [50%]). No "breakthrough" reactivations were observed. The early …

High liver RBP4 protein content is associated with histological features in patients with genotype 1 chronic hepatitis C and with nonalcoholic steatohepatitis.

Abstract Background and aim To investigate the hepatic expression of retinol-binding protein-4 (RBP4) in chronic hepatitis C (CHC) and nonalcoholic steatohepatitis (NASH) patients, and its association with biochemical and histological patterns of liver damage. Materials and methods Sixty-six genotype 1 CHC and 32 NASH patients were tested for hepatic RBP4 expression. Liver expression at immunostaining was scored as 0 (slight), 1 (mild), 2 (moderate), and 3 (intense). In addition, the mRNA and the quantitative protein expressions of RBP4 were tested by PCR and by western blot, respectively, in 12 NASH and 28 CHC patients. Twelve subjects undergoing elective cholecystectomy served as controls…

Staging systems of hepatocellular carcinoma: A review of literature

Hepatocellular carcinoma (HCC) is a major health problem with a high incidence and mortality all over the world. Natural history of HCC is severe and extremely variable, and prognostic factors influencing outcomes are incompletely defined. Over time, many staging and scoring systems have been proposed for the classification and prognosis of patients with HCC. Currently, the non-ideal predictive performance of existing prognostic systems is secondary to their inherent limitations, as well as to a non-universal reproducibility and transportability of the results in different populations. New serological and histological markers are still under evaluation with promising results, but they requi…

Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitis.

BACKGROUND: In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM. AIMS: To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis. METHODS: Nondiabetic patients with genotype 1 CHC (n = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemi…

Diagnostic and therapeutical role of vitamin D in chronic hepatitis C virus infection

Although initially identified as a calcium homeostatic hormone, vitamin D is now known to have pleiotropic functions, dealing with both innate and adaptative immunity. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is expressed not only by intestine, bone and kidney but also on cell membranes of T lymphocytes, B lymphocytes, dendritic cells and macrophages. Vitamin D plays a role on the degree of liver damage in patients with chronic hepatitis C (CHC): low vitamin D levels have been associated with high hepatic necroinflammatory activity and progression of liver fibrosis. Vitamin D, in CHC patients, could also affect the response to antiviral th…

Aminopyrine breath test predicts liver-related events and death in HCV-related cirrhosis on SVR after DAA therapy

Background &amp; Aims: In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. Methods: Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation – defined as Child A6 (N = 22, 44%) or previous decompensation …

Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19

Key Points Three-day change in angiopoietin-2 levels predicts COVID-19 in-hospital mortality, whereas the 10-day trend is associated with chronic lung disability. Angiopoietin-2 may play an important pathogenic role in patients with COVID-19, and it could be a target for new treatments.

Treating patients with HCV genotype 1 and low viraemia: More than meets the eye

TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

Summary.  The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate–severe if ≥30%. Anthropometric an…

Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years

Background & aims: Increased morbidity and mortality from liver disease have been reported in chronic hepatitis B surface antigen (HBsAg) carriers, but data on survival are equivocal. To assess the impact of hepatitis B virus (HBV) infection on survival and liver-related complications, we re-evaluated, after a mean follow-up of 30 years, a cohort of 296 blood donors excluded from donation 30 years ago when HBsAg screening became mandatory. Methods: Clinical and ultrasound examination and biochemical and virologic tests were performed. The cause of death was recorded and survival was compared with a control population of 157 HBV-negative blood donors selected at baseline. Results: Thirty-two…

Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach.

Abstract Background/Aims : To evaluate by meta-analysis of available literature whether interferon (IFN) reduces the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV)-related Child A cirrhosis. Methods : Three randomized controlled trials and 15 nonrandomized controlled trials, including 4614 patients and comparing IFN to no treatment, were selected. Data on the incidence of HCC in IFN treated and untreated patients were extracted from each study. Meta-analysis by the DerSimonian and Laird risk difference (RD) method was used to pool observations. Results : A different incidence of HCC between treated and untreated cirrhotic pati…

Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease

SUMMARY Background Hyperuricemia has been associated with metabolic disorders. In this line recent studies observed an independent link between higher uric acid serum levels and clinical diagnosis of non-alcoholic fatty liver disease (NAFLD). Mean uric acid serum level was 5.75 mg ⁄ dL, and about 20% of patients had hyperuricemia, that was independently associated with younger age (OR 0.951, 95% CI 0.918-0.984, P = 0.004), lobular inflammation (OR 2.144, 95% CI 1.055-4.357, P = 0.03) and steatosis grade (OR 1.859, 95% CI 1.078-3.205, P = 0.02), by multivariate logistic regression analysis. Female gender (OR 2.656, 95% CI 1.190-5.928, P = 0.01), higher HOMA index (OR 1.219, 95% CI 1.043- 1.4…

Fecal Calprotectin in Clinical Practice

Background: Surrogate markers of colorectal inflammation are increasingly being recognized as important in differentiating organic from functional intestinal disorders. Fecal calprotectin (FC) can be easily measured in the stool, being released by leukocytes in inflammatory conditions. Aim: We evaluated FC as an index of inflammation in consecutive outpatients referred for colonoscopy for chronic, nonbloody diarrhea. Methods: Stool specimens of 346 outpatients with chronic, nonbloody diarrhea, referred for colonoscopy, were measured for FC levels. The proportion of patients correctly diagnosed with the test and the relationship with endoscopic and histologic findings were measured. Results:…

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS:…

Mortality after transjugular intrahepatic portosystemic shunt in older adult patients with cirrhosis: A validated prediction model

Background and Aims Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in patients with cirrhosis with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (greater than or equal to 70 years) is debated, and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults. Approach and Results We prospectively enrolled 411 consecutive patients observed at four referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of va…

Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease

Background and aims: Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G&gt;C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholi…

Causes of and prevention strategies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a challenging malignancy of global importance. It is associated with a high rate of mortality and its prevalence in the United States and in Western Europe is increasing. Cirrhosis is the strongest and the most common known risk factor for HCC, usually due to hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. However, different lines of evidence identify in non-alcoholic fatty liver disease (NAFLD) a possible relevant risk factor for occurrence of HCC. Given the continuing increase in the prevalence of obesity and diabetes, the incidence of non-alcoholic steatohepatitis-related HCC may also be expected to increase, and a potential role of behav…

Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon

none 48 no Background: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infec…

The long-term course of chronic hepatitis B

The aim of this study was to assess the long-term outcome in hepatitis B virus (HBV)-infected patients according to HBV, hepatitis C virus (HCV), and hepatitis D virus (HDV) replication, focusing on survival, liver failure, and hepatocellular carcinoma (HCC). A cohort of 302 hepatitis B surface antigen (HBsAg)-positive subjects (mean age, 34 +/- 15.3 years; male/female 214/88; 39 subjects under 14 years) with biopsy-proven chronic hepatitis (86 with cirrhosis) was prospectively assessed, with a median follow-up of 94 +/- 37.6 months. One hundred nine patients received interferon alfa (IFN). At baseline, 86 subjects (28.5%) were hepatitis B e antigen (HBeAg)-positive (wild-type HBV), 80 (26.…

Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites.

Summary Background  In patients with cirrhosis, ascites is defined as refractory when it cannot be mobilized or recurs early in standard diuretic therapy. Aim  To compare the safety and efficacy of intravenous high-dose furosemide + hypertonic saline solutions (HSS) with repeated paracentesis in patients with cirrhosis and refractory ascites. Patients and methods  Eighty-four subjects (59/25 M/F) with cirrhosis, mostly of viral aetiology, admitted for refractory ascites, were randomly assigned to receive furosemide (250–1000 mg/bid i.v.) plus HSS (150 mL H2O with NaCl 1.4–4.6% or 239–187 mEq/L) (60 patients, Group A) or to repeated paracentesis and a standard diuretic schedule (24 patients,…

Adult to Adult Living Donor Liver Transplantation in Recipients with Low MELD: A Strategy Intended to Overcome Donor Shortage

Recent series have demonstrated advantages of living donor over deceased donor liver transplantation, with particular benefit for those with low model for end-stage liver disease score. The logic underlying the transplantation of patients before they become too sick is intuitive. It reduces mortality and drop outs from the waiting list and makes transplant surgery less demanding. Those principles have to be balanced with donor safety and transplant benefit for the recipient avoiding early, futile transplantation. The authors report a case of adult to adult right lobe living donor liver transplantation performed for a recipient affected by primary biliary cirrhosis with MELD score of 15, in …

Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

Giorgio Lorenzo Colombo,1 Calogero Camm&amp;agrave;,2 Adolfo Francesco Attili,3 Roberto Ganga,4 Giovanni Battista Gaeta,5 Giuseppina Brancaccio,5 Jean Marie Franzini,6 Marco Volpe,6 Giuseppe Turchetti7 1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy; 3Department of Clinical Medicine, University of Rome (La Sapienza) Rome, Italy; 4Clinical Medicine Division, Ospedale Brotzu, Cagliari, Italy; 5Viral Hepatitis Unit, Second University, Naples, Italy; 6Business Integration Partners S.p.A., Milan, Italy; 7Scuola Superiore Sant&amp;rsquo;Anna, Pisa, Italy Background: Hepatocellular carcinoma (HCC) is…

Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease

Background: Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Aim: To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. Methods: We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass…

Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial

Summary Background : The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response. Aim : To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease. Methods : The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without i…

Young gastrointestinal angle: E-learning in gastroenterology: Future is now

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Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data

Summary Background There is clear evidence from two systematic reviews that radiotherapy (RT) reduces the risk of local recurrence in patients with resectable rectal cancer, though the data on survival are still equivocal. Objective To assess the effects of chemotherapy combined concomitantly with radiotherapy (CRT) on the increase of overall survival, and on the prevention of local recurrence and distant metastases. Data sources Computerized bibliographic searches of MEDLINE and CANCERLIT (1970–2008) were supplemented with hand searches of reference lists. Study selection Studies were included if they were randomized controlled trials (RCTs) comparing preoperative or postoperative CRT to p…

PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

Background and Aim To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. Methods We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results we…

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Survival of patients treated with sorafenib for hepatocellular carcinoma recurrence after liver transplantation: A systematic review and meta-analysis

Background: Data on survival and safety of sorafenib for hepatocellular carcinoma recurrence after liver transplant are still equivocal. Aim: We performed a meta-analysis of published studies, with the aim of estimating the 1-year rates of survival, analysing the variability in survival rates and, finally, identifying the factors associated with a longer survival. Methods: Data from 8 of the 17 selected studies were pooled, while the other 9 were excluded because survival rates were missing. All included studies were retrospective. Results: Overall, the 1-year survival ranged from 18% to 90%. Tumour progression was the main cause of death. The second cause was bleeding, reported only in pat…

Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy.

Background: The key end point for treatment efficacy in chronic hepatitis C is absence of detectable virus at six months after treatment. However, the incidence of clinical events during long term follow up of patients with sustained virological response is still poorly documented and may differ between the Eastern and Western world. Aims: To assess clinical end points during long term follow up of European patients with a sustained virological response to interferon monotherapy. Methods: Meta-analysis of individual patient data from eight European protocolled follow up studies of interferon treatment for chronic hepatitis C. Results: A total of 286 sustained virological responders and 50 b…

Effects of IL28B rs12979860 CC Genotype on Metabolic Profile and Sustained Virologic Response in Patients With Genotype 1 Chronic Hepatitis C

Patients with genotype 1 chronic hepatitis C (G1 CHC) frequently develop steatosis and insulin resistance (IR), caused by metabolic and viral factors. These accelerate the progression of liver disease and reduce the response to therapy. A sustained virologic response (SVR) to therapy in patients with G1 CHC is associated strongly with polymorphisms near the interleukin-28B (IL28B) gene, but the interaction between IL28B genotype and IR, and their combined effects on SVR, have not been defined. We tested the association between the IL28B rs12979860 single-nucleotide polymorphism and metabolic features, including IR, and evaluated their effects on SVR.We performed genotype analysis of IL28B r…

Intermediate and Advanced Hepatocellular Carcinoma Management in four Italian Centers: Patterns of Treatment and Costs.

Early Treatment in HCV: Is it a Cost-Effective Option from the Italian Perspective?

Background: The aim of this study is to perform an economic analysis to estimate the cost-utility of the early innovative therapy in Italy for managing HCV-infected patients.Methods: The incremental cost-utility analysis was carried out to quantify the benefits of the early treatment approach in HCV subjects. A Markov simulation model including direct and indirect costs and health outcomes was developed from Italian National Healthcare Service and societal perspective. 5,000 Monte Carlo simulations were performed on two distinct scenarios: Standard of Care (SoC) which includes 14.000 Genotype 1 patients in Italy treated with innovative interferon-free in the Fibrosis stage 3 and 4 (F3-F4) v…

Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C

Summary.  Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All p…

Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis C virus genotype 1.

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild &lt;30%, or moderate-severe &gt; or =30%. Thirty nondiabetic, nonobese blood donors served as controls. …

Prognostic scores for hepatocellular carcinoma: none is the winner

Cancer classification and indication of treatment are critical steps in the management of patients with hepatocellular carcinoma (HCC). The prediction of outcome is relevant to provide adequate information to patients and relatives, both at the time of treatment selection and after the application of therapy. Tumour staging describes the extent of an individual's tumour burden in the original primary organ and spread throughout the body, and other cofactors such as age or histological grade are only seldom considered. This is common to all malignancies and diseases. However, whereas for most neoplasms prognosis and treatment are largely dictated by tumour stage at the time of diagnosis, the…

Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites: A Meta-analysis of Individual Patient Data

Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shunt (TIPS) with large-volume paracentesis in cirrhotic patients with refractory ascites. Although all agree that TIPS reduces the recurrence rate of ascites, survival is controversial. The aim of this study was to compare the effects of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites by means of meta-analysis of individual patient data from 4 randomized controlled trials.The study population consisted of 305 patients: 149 allocated to TIPS and 156 to paracentesis. Cumulative probabilities of transplant-free survival and of hepatic encephalopathy (HE) were estimated…

Portal Hypertension and Ascites: Patient-and Population-centered Clinical Practice Guidelines by the Italian Association for the Study of the Liver (AISF)

Abstract Portal hypertension and ascites are two crucial events in the natural history of liver cirrhosis, whose appearance marks a downward shift in the prognosis of the disease. Over the years, several international and national societies have issued clinical practice guidelines for the diagnosis and management of portal hypertension and ascites. The present document addresses the needs of an updated guidance on the clinical management of these conditions. Accordingly, the AISF Governing Board appointed a multi-disciplinary committee of experts for drafting an update of the most recent EASL Clinical Practice Guidelines. The aim of this work was to adapt the EASL recommendations to nationa…

Oxidative stress inhibits IFN-α-induced antiviral gene expression by blocking the JAK–STAT pathway

Abstract BACKGROUND/AIMS: Unresponsiveness to IFN-alpha is common in chronic hepatitis C. Since conditions associated with an increased oxidative stress (advanced age, steatosis, fibrosis, iron overload, and alcohol consumption) reduce the likelihood of response, we hypothesized that oxidative stress may affect the antiviral actions of IFN-alpha. METHODS: We examined in a human hepatocellular carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a generator of oxidative stress, on the IFN-alpha signaling pathway. RESULTS: Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. Th…

Fibrosis staging in chronic hepatitis C: Analysis of discordance between transient elastography and liver biopsy

Summary.  In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir ≥ F2) is variable. Constitutional and liver disease-related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)-RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy-six of 286 (26.6%) had stage ≥F2 and TE < 7.1 kPa (false negat…

Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1.

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirtysix consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and highdensity lipoprotein cholesterol. All biopsies were scored by one …

Body Mass Index and Liver Stiffness Affect Accuracy of Ultrasonography in Detecting Steatosis in Patients With Chronic Hepatitis C Virus Genotype 1 Infection

Background & Aims: Few studies have evaluated the accuracy of ultrasonography in detecting steatosis in patients with chronic hepatitis C. We assessed its accuracy in detecting steatosis and factors that affect its diagnostic performance in consecutive patients with chronic hepatitis C virus genotype 1infection. Methods: We analyzed data from 515 patients with chronic hepatitis C, confirmed by liver biopsy, assessing anthropometric, biochemical, metabolic, virologic, and ultrasonography features. Transient elastography was performed to measure liver stiffness. Steatosis was identified with ultrasonography based on detection of a bright liver echo pattern. Results: Ultrasonography identified…

Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women

AIM: To investigate the safety/efficacy of Boceprevirbased triple therapy in hepatitis C virus (HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure (7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEGIFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNA-positive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virolo…

Author Correction: Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study

Binge drinking (BD) is a common pattern of alcohol consumption among adolescents. At present few data are available on the possible relationship between BD and alcohol use disorders (AUD) in adolescents. The aim of this study was to assess the prevalence of BD and relationship between BD behavior and AUD among adolescents. A total of 2704 students attending 10 purposively selected high schools from three Italian provinces were surveyed. Questionnaires regarding socio-demographic data, pattern and amount of alcohol intake, smoking habits, use of illicit drugs, and physical activity were administered. AUD and affective disorders were also evaluated. Alcohol intake was reported by 2126 partici…

Inflammation and Aortic Stiffness: An Individual Participant Data Meta‐Analysis in Patients With Inflammatory Bowel Disease

Background The recent finding that aortic pulse wave velocity ( aPWV ) is increased in patients with inflammatory bowel disease may explain why the cardiovascular risk is increased despite the low prevalence of traditional cardiovascular risk factors. We aimed to test whether inflammation is associated with aortic stiffening in this setting after adjustment for major confounders and to perform subgroup analyses. Methods and Results A systematic literature search for aPWV in inflammatory bowel disease was performed using PubMed, Scopus, Web of Science, and Google Scholar databases (last accessed May 7, 2017). Inclusion criterion was peer‐reviewed publications on clinical studies reporting o…

Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients.

Background & Aims: Unhealthy food intake, specifically fructose, has been associated with metabolic alterations and with the severity of liver fibrosis in patients with non-alcoholic fatty liver disease. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of fructose intake with the severity of liver histology. Methods: Anthropometric and metabolic factors, including waist circumference (WC), waist-to-hip ratio (WHR), dorso-cervical lipohypertrophy and HOMA were assessed in 147 consecutive biopsy-proven G1 CHC patients. Food intake, namely industrial and fruit fructose, was investigated by a three-day structured interview and a computed database. …

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Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C .

Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients.One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI.TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating ch…

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

Background/Aims We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Methods Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defi…

The evolutionary scenario of hepatocellular carcinoma in Italy: an update

Background and aims Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of etiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Methods Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centers from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). Results The main results were: 1) progressive patient aging; 2) progressive expansion of non-viral cases and, namely, of “metabolic” hepatocellular carcinoma…

Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis.

Background & Aims: Baveno VI and expanded Baveno VI criteria can avoid the need for esophagogastroduodenoscopy (EGD) to screen for varices needing treatment (VNT) in a substantial proportion of compensated patients with viral and/or alcoholic cirrhosis. This multicenter, cross-sectional study aims to validate these criteria in patients with compensated cirrhosis due to non-alcoholic fatty liver disease (NAFLD), accounting for possible differences in liver stiffness measurement (LSM) values between M and XL probes. Methods: We assessed 790 patients with NAFLD-related compensated cirrhosis who had EGD within six months of a reliable LSM, measured by FibroScan® using M and/or XL probe. Baveno …

Personalized cost-effectiveness of boceprevir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C

Abstract Background We assessed the cost-effectiveness of boceprevir-based triple therapy compared to peginterferon alpha and ribavirin dual therapy in untreated patients with genotype 1 chronic hepatitis C; patients were discriminated according to the combination of baseline plus on-treatment predictors of boceprevir-based triple therapy. Methods Cost-effectiveness analysis performed according to data from the available published literature. The target population was composed of untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C, and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian Nati…

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Second line systemic therapies for hepatocellular carcinoma: Reasons for the failure

Hepatocellular carcinoma (HCC) is the main cause of death in patients with cirrhosis, with an increasing incidence worldwide. Sorafenib is the choice therapy for advanced HCC. Over time several randomized phase III trials have been performed testing sunitinib, brivanib, linifanib and other molecules in head-to-head comparison with Sorafenib as first-line treatment for advanced-stage HCC, but none of these has so far been registered in this setting. Moreover, another feared vacuum arises from the absence of molecules registered as second-line therapy for patients who have failed Sorafenib, representing an urgent unmet medical need. To date all molecules tested as second-line therapies for ad…

Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data.

Background and aims: Retreatment with a combination of α interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies. Methods: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000–1200 mg/daily depending on body weight) was given for 24–60 (mean 39.5) weeks. Results: Biochemical …

A performance evaluation of the expert system 'Jaundice' in comparison with that of three hepatologists.

The diagnostic performance of an Expert System (Jaundice) designed to discriminate between different causes of jaundice was evaluated in a test sample of 200 consecutive in-patients with serum bilirubin greater than or equal to 51 mumol/l. The average probability assigned to true diagnosis, the non-error rate and the overall accuracy were, respectively, 55%, 77% and 70%. The Expert System's discriminatory ability in probabilistic prediction, assessed by a method based on continuous functions of the diagnostic probabilities (Brier score) was good. We also compared the ability of our Expert System to that of three experienced hepatologists, who were required to give a diagnosis in 20 cases fo…

Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE).

AbstractAn accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality…

Hepatitis C Virus Infection Is Associated With Increased Cardiovascular Mortality: A Meta-Analysis of Observational Studies

There have been many studies of the effects of hepatitis C virus (HCV) infection on cardiovascular risk, but these have produced ambiguous results. We performed a meta-analysis of these studies to systematically assess the risk of HCV infection on cardiovascular disease (CVD)-related morbidity and mortality.We searched PubMed Central, Medline, Embase, and Cochrane Library, as well as reference lists of articles, for studies published through July 2015 that compared the occurrence of CVD between HCV-infected and HCV-uninfected subjects, or assessed the prevalence of HCV infection among subjects with CVDs. In total, 22 studies were analyzed. Data on the patient populations and outcomes were e…

Risk of pancreatic malignancy and mortality in branch-duct IPMNs undergoing surveillance: A systematic review and meta-analysis

Abstract Background Safety of non-operative management for low-risk branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. Aim To perform a systematic review/meta-analysis to determine their risk of developing pancreatic malignancy and of pancreatic malignancy-related deaths. Methods A MEDLINE search was performed and methodology was based on PRISMA statement. Incidence rates of overall pancreatic malignancy, malignant BD-IPMN, IPMN-distinct PDAC, and of pancreatic malignancy-related death rates were calculated by dividing the total number of events by the total number of person-years (pyrs) of follow-up. Heterogeneity was determined by I2 statistic. Results 20 studies …

Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis

Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, ca…

Treatment of hepatocellular carcinoma: present and future

Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesi…

The impact of antiviral treatments on the course of chronic hepatitis C: an evidence-based approach.

Hepatitis C virus chronic infection is currently the most common cause of end-stage liver disease. The benefit of antiviral therapy on liver histology and its impact on the long-term course of the disease has been extensively studied. However, the results are still equivocal and the overall assessment of treatment effect remains difficult to evaluate. Although the conclusions of the last National Institute of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues still remain unanswered. We review the available data by an evidence-based approach and conclude that: 1) peginterferon alfa is more effective than conventional interferon in …

Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C

UNLABELLED 25-Hydroxyvitamin D (25[OH]D) can potentially interfere with inflammatory response and fibrogenesis. Its role in disease progression in chronic hepatitis C (CHC) and its relation with histological and sustained virological response (SVR) to therapy are unknown. One hundred ninety-seven patients with biopsy-proven genotype 1 (G1) CHC and 49 healthy subjects matched by age and sex were consecutively evaluated. One hundred sixty-seven patients underwent antiviral therapy with pegylated interferon plus ribavirin. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. Tissue expression of cytochrome (CY) P27A1 and CYP2R1, liver 25-hydroxylating enzymes, were as…

First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Seque…

Cardiac involvement in patients with cirrhosis: a focus on clinical features and diagnosis

Cirrhotic heart has been traditionally considered protected from cardiovascular disease, even if a large amount of literature has recently shown that patients affected by chronic liver disease are exposed to cardiovascular events, as well. Since the first recognition of cardiac involvement in cirrhosis, all published studies explain that decompensated cirrhotic patients suffer from haemodynamic changes, currently known as hyperdynamic syndrome, which finally lead to cirrhotic cardiomyopathy. This is defined by the presence of a subclinical systolic dysfunction unmasked under stress conditions, impaired diastolic function and electrophysiological abnormalities, in the absence of any known ca…

Effects of Eradicating Hepatitis C Virus Infection in Patients With Cirrhosis Differ With Stage of Portal Hypertension.

Clearance of hepatitis C virus (HCV) via antiviral treatment changes the course of liver disease. We evaluated the benefit of sustained virologic response (SVR) in patients with HCV and cirrhosis without (stage 1) and with (stage 2) esophageal varices (EV).We performed a prospective cohort study of 444 patients with HCV and compensated cirrhosis (218 with stage 1 and 226 with stage 2 disease) treated with peg-interferon and ribavirin from June 2001 through December 2009 at the University of Palermo, Italy and followed for a median of 7.6 years (range, 1-12.6 years). We used Cox regression analysis to identify variables associated with appearance or progression of EVs, development of hepatoc…

Impact of Obesity and Alanine Aminotransferase Levels on the Diagnostic Accuracy for Advanced Liver Fibrosis of Noninvasive Tools in Patients with Nonalcoholic Fatty Liver Disease

Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels.METHODS:We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease. FIB-4, NFS, and LSM by FibroScan were measured.RESULTS:LSM was better than both FIB-4 and NFS for staging F3-F4 fibr…

Epicardial Fat, Cardiac Geometry and Cardiac Function in Patients with Nonalcoholic Fatty Liver Disease: Association with the Severity of Liver Disease

Background & Aims Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk, including coronary artery disease and cardiac dysfunction. In addition, recent evidence highlighted the possible role of epicardial fat as a new cardiometabolic risk factor. We tested the correlation between epicardial fat, alterations in cardiac geometry and function, and severity of liver damage, in patients with biopsy-proven NAFLD. Methods The anthropometric, biochemical and metabolic features were recorded in 147 consecutive biopsy-proven NAFLD cases (Kleiner score). Epicardial fat thickness was measured by echocardiography. Results Epicardial fat was higher in patients w…

The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease

In nonalcoholic fatty liver disease, the influence of severity of steatosis on liver stiffness measurement (LSM) is poorly studied and still debated. We assessed the impact of steatosis severity and its ultrasonographic (US) sign, severe bright liver echo pattern, on LSM values and on transient elastography accuracy for the diagnosis of liver fibrosis in a cohort of consecutive patients with nonalcoholic fatty liver disease. Patients (n = 253) were assessed by clinical, US, and histological (Kleiner score) features. Transient elastography was performed using the M probe. Among patients with low amounts of fibrosis (F0-F1 and F0-F2), median LSM values, expressed in kilopascals, were signific…

Response-adjusted α-interferon therapy for chronic hepatitis C in HIV-infected patients

Abstract In patients with chronic hepatitis C and HIV infection, responsiveness to the standard schedule of α-interferon (IFN) is unsatisfactory. To quantify the effectiveness of tailoring IFN dosage according to HCV viral load under treatment, we enrolled 41 patients (M/F 32/9) chronically coinfected by HCV and HIV with chronic liver disease. All were former i.v. drug addicts, with a mean age of 32±4 years, and had clinical and histological evidence of chronic hepatitis (10% with cirrhosis). The CDC stage was A1 in five, A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty four patients were on triple therapy with protease inhibitors, 11 were on two-drug anti-HIV regimen…

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C

Summary Background The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). Aim To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. Methods Four hundred and thirty-four consecutively biopsied Caucasian G1-CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of s…

When and how to treat acute hepatitis C?

Background: Appropriate treatment of acute hepatitis C is still a matter of controversy due to the lack of large controlled trials. Aim: To assess the effectiveness of interferon as treatment for acute hepatitis C by meta-analysis. Methods: MEDLINE search (1985-2002) was supplemented with manual searches of reference lists. Studies were included if they were controlled trials comparing interferon to no treatment and if they included patients with either post-transfusion or sporadic acute hepatitis C. Twelve trials were analyzed (414 patients). The outcome assessed was the sustained virological response (SVR) rate (undetectable hepatitis C virus RNA in serum at least 6 months after cessation…

Early Treatment in HCV: Is it a Cost-Utility Option from the Italian Perspective?

In Italy, the Italian Pharmaceutical Agency (AIFA) criteria used F3–F4 fibrosis stages as the threshold to prioritise the treatment with interferon (IFN)-free regimens, while in genotype 1 chronic hepatitis C (G1 CHC) patients with fibrosis of liver stage 2, an approach with pegylated interferon (PEG-IFN)-based triple therapy with simeprevir was suggested. The key clinical question is whether, in an era of financial constraints, the application of a universal IFN-free strategy in naive G1 CHC patients is feasible within a short time horizon. The aim of this study is to perform an economic analysis to estimate the cost-utility of the early innovative therapy in Italy for managing hepatitis C…

Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter.

Background &amp; Aims Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. Methods CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n = 340; validation cohort, n = 414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52 ± 14; body mass index 27.2 ± 5.3 kg/m2). The primary outco…

The complex interplay between vitamin D deficiency and diabetes

It has been recently highlighted the link between vitamin D and metabolic and immunological pro- cesses, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and through the activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and other immunological functions. In this setting, vita- min D has also been reported to influence glucose regulation via effects on insulin secretion and action. Vitamin D deficiency is strongly associated with obesity mostly due to the storage of vitamin D in adipose tissue because of its lipophilic properties. The dec…

AGILE 3+ Score for the Diagnosis of Advanced Fibrosis and for Predicting Liver-related Events in NAFLD.

Background &amp; aims: We aimed to assess the diagnostic accuracy of AGILE 3+, a recently developed score based on the combination of aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, age, and liver stiffness measurement (LSM) by transient elastography, when compared with Fibrosis-4 (FIB-4) and LSM, for the diagnosis of advanced fibrosis and for the prediction of liver-related events (LREs) occurrence in patients with NAFLD. Methods: A total of 614 consecutive patients with biopsy-proven NAFLD or clinical diagnosis of NAFLD-related compensated cirrhosis were enrolled. LREs were recorded during follow-up. FIB-4, LSM by transient elastography (Fi…

Hepatotoxicity of systemic therapies for unresectable hepatocellular carcinoma

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data

Multicenter randomized trials have shown that once-weekly pegylated interferon (peginterferon) alfa-2a is more efficacious than conventional interferon alfa-2a (IFN) in patients with chronic hepatitis C. We performed a meta-analysis of 1,013 previously untreated patients (from 3 randomized trials) with pretreatment and post-treatment liver biopsies to assess the differences between peginterferon alfa-2a and IFN in terms of their effects on liver histology. Reported values were standardized mean differences (SMD) between patients receiving peginterferon alfa-2a and those receiving IFN (post-treatment value minus baseline value for each group). We used a random-effects model to quantify the a…

Fibronectin Type III Domain–Containing Protein 5 rs3480 A&gt;G Polymorphism, Irisin, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Context Contrasting data have been reported on the role of irisin, a novel myokine encoded by the fibronectin type III domain-containing protein 5 (FNDC5) gene, in nonalcoholic fatty liver disease (NAFLD) pathogenesis. We tested in patients with suspected nonalcoholic steatohepatitis (NASH) the association of FNDC5 variants, hepatic expression, and circulating irisin with liver damage (F2 to F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models. Methods We considered 593 consecutive patients who underwent liver biopsy for suspected NASH and 192 patients with normal liver enzymes and wit…

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems

Summary Background  A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. Aim  To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. Methods  We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. Results  One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated p…

Long-term course of interferon-treated chronic hepatitis C

Abstract Background/Aims: To evaluate whether sustained response to α-interferon improves clinical outcome in patients with chronic hepatitis C. Methods: A cohort of 410 consecutive patients (65% with chronic hepatitis, 35% with cirrhosis) were treated with α-interferon in two trials (mean follow-up 62.1 months, range 7–109 months). All were serum HCV RNA positive before therapy and received first 10 then 5 million units of α-2b or α-n1 interferon three times weekly for 6 to 12 months. Sustained response was defined as normal aminotransferases 12 months after stopping interferon. Results: Sixty-two patients (15.1%: 54 with chronic hepatitis, eight with cirrhosis) were sustained responders. …

Treatment of small hepatocellular carcinoma with percutaneous ethanol injection: a validated prognostic model.

OBJECTIVE: Percutaneous ethanol injection may prolong the survival of patients with small hepatocellular carcinoma associated with cirrhosis. The aim was to identify prognostic factors of survival and of local recurrence, as well as separate new lesions. METHODS: We performed Cox regression analysis in 115 consecutive patients with hepatocellular carcinoma (81 Child-Pugh class A, 34 Child-Pugh class B) treated by percutaneous ethanol injection. The validity of the model was tested by comparing predicted and observed survival in 105 independent patients from an external series. RESULTS: Overall survival rates were 89%, 63%, and 43% at 1, 2, and 3 yr, respectively. The 1-, 2-, and 3-yr surviv…

Serial combination of noninvasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with nonalcoholic fatty liver disease

NR1H4 rs35724 G>C variant modulates liver damage in nonalcoholic fatty liver disease

Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G&gt;C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G&gt;C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n = 124). Results: The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic conf…

Carotid atherosclerosis and chronic hepatitis C: A prospective study of risk associations

BACKGROUND AND AIMS: There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. MATERIALS AND METHODS: One hundred seventy-four consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements. One hundred seventy-four patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of > 1.3 mm a…

Interferon-α for HBeAg-positive chronic hepatitis B

Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents.

Background &amp; Aims: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. Methods: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurren…

Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.

Background and Aims: Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis. Methods: 843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and…

Time-course of insulin resistance during antiviral therapy in non-diabetic non-cirrhotic patients with genotype 1 HCV infection

Retinol-binding protein 4 (RBP4): A new marker of G1 HCV-induced steatosis

Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C.

Conflicting data exist regarding the relationship between hepatitis C virus genotype 1 and hepatic steatosis as well as the latter's role in the progression of fibrosis and treatment response. We assessed factors associated with hepatic steatosis in genotype 1 chronic hepatitis C and the impact of hepatic fat on fibrosis development and interferon responsiveness. Two hundred ninety-one non-diabetic patients with genotype 1 chronic hepatitis C were examined for the presence of steatosis and its correlation with clinical, virological, and biochemical data, including insulin resistance (IR), evaluated by the homeostasis model assessment (HOMA) score. Steatosis was graded as mild (1%-20% of hep…

CT enterography as a powerful tool for the evaluation of inflammatory activity in Crohn’s disease: relationship of CT findings with CDAI and acute-phase reactants

Few studies have correlated computed tomography enterography (CTE) findings with Crohn’s disease (CD) clinical and biochemical activity. The aim of this study was to evaluate correlations between CTE findings with CD activity. The CTE datasets from 62 patients were retrospectively reviewed for different parameters: bowel wall thickening and hyperenhancement, mesenteric alterations, abdominal free fluid and complications related to the disease (fistulas, strictures, abscesses). Activity was assessed using the Crohn’s Disease Activity Index (CDAI) and some biochemical markers (C-reactive protein, erythrocyte sedimentation rate, alpha 2-globulins, fibrinogen, platelets, haemoglobin). Correlati…

Insulin resistance is a risk factor for esophageal varices in hepatitis C virus cirrhosis

Indirect methods to predict the presence of esophageal varices (EV) in patients with cirrhosis are not sensitive enough to be used as a surrogate for endoscopy. We tested the effectiveness of liver stiffness measurement (LSM) by transient elastography and the presence of insulin resistance (IR), a marker associated with fibrosis progression, in the noninvasive prediction of portal hypertension. One hundred four consecutive patients with newly diagnosed Child A hepatitis C virus (HCV) cirrhosis underwent upper gastrointestinal endoscopy to search for EV. Clinical, anthropometric, biochemical, ultrasonographic, and metabolic features, including IR by the homeostasis model assessment (HOMA), a…

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: An individual patient data meta-analysis

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk fac…

A randomized controlled trial of high-dose maintenance interferon therapy in chronic hepatitis C

In chronic hepatitis C virus (HCV) infection, the rate of sustained response to interferon is low. We evaluated, in patients responding to a 26-week course of interferon, the effect of high-dose maintenance therapy in preventing relapse. Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis, 80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8 weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%) normalized aminotransferases, and were allocated randomly either to continue on 5 MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop interferon (brief therapy group: 64 patients). Fifty-two w…

The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease.

Background & Aims The accuracy of noninvasive tools for the diagnosis of severe fibrosis in patients with nonalcoholic fatty liver disease(NAFLD) in clinical practice is still limited. We aimed at assessing the diagnostic performance of combined noninvasive tools in two independent cohorts of Italian NAFLD patients. Methods We analysed data from 321 Italian patients(179 Sicilian-training cohort, and 142 northern Italy-validation cohort) with an histological diagnosis of NAFLD. Severe fibrosis was defined as fibrosis ≥ F3 according to Kleiner classification. The APRI, AST/ALT, BARD, FIB-4, and NFS scores were calculated according to published algorithms. Liver stiffness measurement(LSM) was …

Consequences of Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Methicillin-Resistant Staphylococcus aureus Carriage in Awaiting Liver Transplant Patients.

Infections in patients with cirrhosis are associated with liver-related complications (LRCs), especially in patients awaiting liver transplantation (LT). The aim of this study was to evaluate the impact of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase colonization on infections and LRCs for patients on the wait list and on infections after LT. We retrospectively included 250 of 483 patients with cirrhosis who were placed on the wait list for LT from December 2015 to January 2018. These patients were screened for MRSA or extended spectrum beta-lactamase–producing Enterobacteriaceae (ESBLE) at the time of wait-list placement and after LT. Of the patie…

Early menopause is associated with lack of response to antiviral therapy in women with chronic hepatitis C.

Background & Aims Chronic hepatitis C (CHC) and liver fibrosis progress more rapidly in men and menopausal women than in women of reproductive age. We investigated the associations among menopause, sustained virologic response (SVR), and liver damage in patients with CHC. Methods We performed a prospective study of 1000 consecutive, treatment-naive patients 18 years of age and older with compensated liver disease from CHC. Liver biopsy samples were analyzed (for fibrosis, inflammation, and steatosis) before patients received standard antiviral therapy. From women (n = 442), we collected data on the presence, type, and timing of menopause; associated hormone and metabolic features; serum lev…

Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C

We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…

Outcomes of hepatocellular carcinoma patients treated with sorafenib: a meta-analysis of Phase III trials

Aim: To benchmark overall survival (OS) and time to radiological progression (TTP) of patients enrolled in randomized controlled trials (RCTs) assessing sorafenib in advanced hepatocellular carcinoma using individual participant survival data, and to meta-analyze prognostic factors for OS and TTP. Methods: RCTs were identified through literature search until December 2018. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: Ten RCTs were included. Median OS was 10.0 months (95% CI: 9.6–10.5), and median TTP was 4.1 months (95% CI: 3.8–4.3). Multivariable analyses showed HCV positivity, absence of macrovascular invasion and extra-…

Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C.

Background Genotype 1 (G1) chronic hepatitis C (CHC) patients achieving a rapid virological response (RVR) on pegylated interferon (PEG-IFN) plus ribavirin have a high chance of sustained virological response (SVR), influenced by IL28B status, viral load, fibrosis and insulin resistance. We assessed whether 25-hydroxyvitamin D (25[OH]D) serum levels are linked to RVR and can be used together with IL28B to construct a pretreatment model to predict RVR. Methods A total of 117 consecutive patients with G1 CHC were evaluated by biopsy and anthropometric and metabolic measurements. 25(OH)D serum levels were measured by HPLC. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated. All p…

Treatment of hepatitis C: critical appraisal of the evidence

Chronic hepatitis C virus infection is currently the most common cause of end stage liver disease worldwide. Although the conclusions of the last National Institutes of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues remain unanswered. This paper reviews the available data using an evidence-based approach. Current evidence is sufficient to recommend IFN treatment for all patients with acute hepatitis. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during month 1 is the best treatment option. The current gold standard of efficacy for treatment-naive patients with ch…

Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients with Non-alcoholic Fatty Liver Disease

Background & Aims Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk for liver-related complications, such as decompensation, hepatocellular carcinoma (HCC), and death; the severity of liver fibrosis and metabolic comorbidities are the main risk factors. A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3 (PNPLA3) gene is associated with higher prevalence of liver damage and HCC, but there are no data from prospective studies of outcomes of patients with this polymorphism. We investigated whether the common rs738409 variant in PNPLA3 gene associates with the occurrence of liver-related events and death in a large cohort of patients w…

Direct antiviral agents and risk for HCC early recurrence: Much ado about nothing

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Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C.

BACKGROUND AND AIMS: Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assess the cost-effectiveness of TT compared to DT in the treatment of untreated patients with G1 CHC. METHODS: We created a Markov Decision Model to evaluate, in an untreated Caucasian patients aged 50 years, weight 70 kg, with G1 CHC and Metavir F2 liver fibrosis score, for a time horizon of twenty years, the cost-effectiveness of the following 5 competing strategie…

High sCD36 plasma level is associated with steatosis and its severity in patients with genotype 1 chronic hepatitis C

Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate-severe i…

Genetic predisposition to thrombophilia in inflammatory bowel disease

BACKGROUND Inflammatory bowel disease (IBD) is linked to a definite risk of thromboembolic events (TE), but data on the role of prothrombotic genetic mutations are conflicting. STUDY Fourteen genetic factors involved in TE pathogenesis were investigated in a homogeneous cohort of Sicilian patients with IBD with and without history of TE and in healthy controls. Forty IBD patients (21 CD, 19 UC) and 20 healthy individuals were enrolled. Genetic testing was based on the reverse hybridization principle by a commercial assay that analyzes 14 polymorphisms involved in thrombophilia and cholesterol metabolism. The rate of genetic polymorphisms and mutations was compared between IBD patients and h…

HCV: the best cure possible or the best possible cure?

Progress in medicine goes along with an exponential growth of the cost of drugs and devices. While any person has the right to obtain the best possible benefit from medical care, a state needs to strike a balance between granting the optimal personal benefit to each individual and the needs of the society as a whole. Health systems in all countries therefore are facing a huge problem of distributive justice, as while they should guarantee individual rights, among which the right to health in its broader sense, including physical, psychological and social well-being (therefore not limited to healing, but extending to compliance and quality of life), they must also grant equal access to the h…

Are radiological endpoints surrogate outcomes of overall survival in hepatocellular carcinoma treated with transarterial chemoembolization?

Background&amp; Aims: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. Methods: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS …

The impact of radiotherapy on survival in resectable gastric carcinoma: A meta-analysis of literature data.

Summary Background The benefit of external radiotherapy for gastric carcinoma has been extensively studied, but data on survival are still equivocal. Objective To assess the effectiveness of surgery combined with preoperative radiotherapy or postoperative chemoradiotherapy in the reduction of all-cause mortality in patients with resectable gastric carcinoma. Methods Computerised bibliographic searches of MEDLINE and CANCERLIT (1970–2006) were supplemented with hand searches of reference lists. Study selection Studies were included if they were randomised controlled trials (RCTs) comparing mortality of surgery combined with preoperative radiotherapy or postoperative chemoradiotherapy to surg…

Survival of patients with hepatocellular carcinoma (HCC) treated by percutaneous radio-frequency ablation (RFA) is affected by complete radiological response.

Background: Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments. Aim: To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis. Methods: A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA. A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients. Results: The overall survival rates …

Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis

Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis.MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourteen trials were included in t…

Prevention of Hepatocellular Carcinoma

The accuracy and the reliability of well-recognized clinical, virologic, histologic, and molecular risk factors for HCC are still insufficient; thus, accurate risk prediction of developing cancer in individual patients remains an elusive goal. Future directions in chemprevention of HCC will be on the development of molecular risk models and of new chemopreventive agents. The design of targeted molecular therapies may need to be tailored to the specific molecular phenotype of a specific HCC. Studies examining multiple genes and proteins (genomics and proteomics) in the same HCCs will be required to evaluate this possibility thoroughly. In the setting of primary prevention, the epidemiologic …

Correlation between FIB4, liver stiffness and metabolic parameters in patients with HIV and hepatitis C virus co-infection.

Assessment of liver fibrosis is crucial in HIV/HCV coinfected patients, in whom metabolic disturbances are frequent. Aims of this study were to analyse the association of two non-invasive liver fibrosis evaluation methods, liver stiffness measurement and FIB4, and their correlation with metabolic parameters.This was a single centre cross-sectional study. All patients underwent biochemical and virological assessment, FIB4 score, HOMA and transient elastography.Seventy-five patients were evaluated. Liver stiffness values positively correlated with FIB4 (R = 0.62; p0.0001). By ROC curve analysis the optimal cut-off for liver stiffness to identify high FIB4 was calculated as 10.1 kPa. The area …

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

[Background & Aims] Patients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events.

Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma

The purpose was to assess the cost-effectiveness of sorafenib in the treatment of hepatocellular carcinoma (HCC) patients incorporating current prices and the results of the recent published field practice SOraFenib Italian Assessment (SOFIA) study. We created a Markov Decision Model to evaluate, in a hypothetical cohort of Caucasian male patients, aged 67 years with Barcelona Clinic Liver Cancer (BCLC) C HCC, or BCLC B HCC who were unfit or failed to respond to locoregional therapies, well compensated cirrhosis, and with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG), the cost-effectiveness of the following strategies: (1) full or dose-adjusted sorafenib for …

Long-term evolution of LI-RADS observations in HCV-related cirrhosis treated with direct-acting antivirals.

Background &amp; Aims The risk of progression of indeterminate observations to hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA) is still undetermined. To assess whether DAA therapy changes the risk of progression of observations with low (LR-2), intermediate (LR-3) and high (LR-4) probability for HCC in cirrhotic patients and to identify predictors of progression. Methods This retrospective study included cirrhotic patients treated with DAA who achieved sustained virological response between 2015 and 2019. A total of 68 patients had pre-DAA indeterminate observations and at least six months CT/MRI follow-up before and after DAA. Two radiologists reviewed CT/MRI studies to…

751 RETINOL-BINDING PROTEIN 4 (RBP4): A NEW MARKER OF G1 HCV-INDUCED STEATOSIS

Reproductive status is associated with the severity of fibrosis in women with hepatitis C.

Introduction Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men. Materials and Methods A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contrib…

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors

Background: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, be-coming the standard of care of systemic therapy.Aim: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors.Methods: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients.Results: 422 (…

Efficacy of lumen-apposing metal stents or self-expandable metal stents for endoscopic ultrasound-guided choledochoduodenostomy: a systematic review and meta-analysis

Abstract Background Endoscopic ultrasound (EUS)-guided biliary drainage is becoming an option for palliation of malignant biliary obstruction. Lumen-apposing metal stents (LAMS) are replacing self-expandable metal stents (SEMS). The aim of this meta-analysis was to evaluate the efficacy and safety of LAMS and SEMS for EUS-guided choledochoduodenostomy (EUS-CDS). Methods A meta-analysis was performed using PRISMA protocols. Electronic databases were searched for studies on EUS-CDS. The primary outcome was clinical success. Secondary outcomes were technical success, reintervention, and adverse events. We used the random effects model with the DerSimonian–Laird estimation, and the results were…

Time course of insulin resistance during antiviral therapy in non-diabetic, non-cirrhotic patients with genotype 1 HCV infection

Background Genotype 1 (G1) hepatitis C virus (HCV) is associated with insulin resistance (IR) and its clearance seems to improve insulin sensitivity. We aimed to evaluate the time course of IR in response to antiviral therapy in non-diabetic, non-cirrhotic G1 HCV patients and to assess the effect of metabolic factors on sustained virological response (SVR). Methods A total of 83 consecutive treatment-naive G1 chronic hepatitis C (CHC) patients were evaluated by anthropometric and metabolic measurements, including IR using the homeostasis model assessment (HOMA). Patients were considered to have IR if HOMA was &gt;2.7. All cases had a liver biopsy scored for staging, grading and steatosis. A…

Lactitol in treatment of chronic hepatic encephalopathy. A meta-analysis.

The efficacy and side effects of lactitol in the treatment of chronic hepatic encephalopathy was compared to that of other disaccharides in a meta-analysis of published randomized clinical trials (RCTs). The outcomes assessed were: (1) the rate of patients free from episodes of clinically detectable encephalopathy, and (2) the rate of patients free from one or more side effects in the different treatment groups. Four RCTs were eligible for analysis; in three lactitol was compared to lactulose, in one the alternative treatment was lactose in lactase-deficient patients. The methodological quality of these studies was high. Meta-analysis showed that lactitol was as effective as other disacchar…

Radiomics Analysis on Gadoxetate Disodium-Enhanced MRI Predicts Response to Transarterial Embolization in Patients with HCC

Objectives: To explore the potential of radiomics on gadoxetate disodium-enhanced MRI for predicting hepatocellular carcinoma (HCC) response after transarterial embolization (TAE). Methods: This retrospective study included cirrhotic patients treated with TAE for unifocal HCC naïve to treatments. Each patient underwent gadoxetate disodium-enhanced MRI. Radiomics analysis was performed by segmenting the lesions on portal venous (PVP), 3-min transitional, and 20-min hepatobiliary (HBP) phases. Clinical data, laboratory variables, and qualitative features based on LI-RADSv2018 were assessed. Reference standard was based on mRECIST response criteria. Two different radiomics models were construc…

The Presence of White Matter Lesions Is Associated With the Fibrosis Severity of Nonalcoholic Fatty Liver Disease

Abstract We tested whether nonalcoholic fatty liver disease (NAFLD) and/or its histological severity are associated with vascular white matter lesions (WML) in patients with biopsy-proven NAFLD and in non-NAFLD controls. Data were recorded in 79 consecutive biopsy-proven NAFLD, and in 82 controls with normal ALT and no history of chronic liver diseases, without ultrasonographic evidence of steatosis and liver stiffness value  45 years (OR 3.09, 95% CI: 1.06–9.06, P = 0.03; and OR 11.1, 95% CI: 1.14–108.7, P = 0.03), and F2–F4 fibrosis (OR 3.36, 95% CI: 1.29–8.73, P = 0.01; and OR 5.34, 95% CI: 1.40–20.3, P = 0.01) were independently associated with WML (mostly of mild grade) by multivariate…

Natural history of untreatable hepatocellular carcinoma: A retrospective cohort study

Abstract AIM: To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality. METHODS: From January 1999 to December 2010, 320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected…

Peginterferon alfa-2b plus ribavirin for naïve patients with genotype 1 chronic hepatitis C: a randomized controlled trial

We assessed the effectiveness and safety of an induction dose of peginterferon alfa-2b (PEG-IFN) plus ribavirin for initial treatment of patients with genotype 1 chronic HCV infection in a randomized, controlled, multicenter trial.Three hundred and eleven naïve patients infected with genotype 1 and chronic hepatitis were randomly assigned to 48-week treatment with PEG-IFN once weekly (80-100 micrograms depending on body weight for 8 weeks, followed by 50 micrograms for the next 40 weeks), or standard interferon alfa-2b (IFN) 6 million units on alternate days, both in combination with ribavirin (1000-1200 mg/day).PEG-IFN plus ribavirin significantly increased sustained virological response (…

Management of chronic hepatitis C in childhood: The impact of therapy in the clinical practice during the first 2 decades

Background and aim: Treatment of chronic hepatitis C in children is controversial and its role in the clinical practice is unknown. We retrospectively investigated the impact of treatment in a large cohort of children with chronic hepatitis C over the past 20years. Methods: 376 hepatitis C virus RNApositive children were recruited consecutively in five Italian centres since 1990and followed for1–17years. Results: 86 (23%)subjects were treated: 73 with recombinant interferon alone and 13 with pegylated-interferon and ribavirin. Sustained clearance of hepatitis C virus RNA was observed in 25%of the former, in 92%of the latter and in 9% of untreated cases(p &lt; 0.001). Loss of viraemia was re…

Mortality in patients with hepatocellular carcinoma predicted by six scoring systems: None is the winner

Hyperuricaemia: another metabolic feature affecting the severity of chronic hepatitis because of HCV infection.

Background Several works observed a link between uric acid serum levels and clinical and histological features of nonalcoholic fatty liver disease. An association between chronic hepatitis C (CHC) and uric acid levels has been poorly investigated. Aims To assess the potential association between uric acid serum levels and both histological features of liver damage and sustained virological response (SVR) in a homogeneous cohort of CHC patients. Methods Consecutive biopsy-proven CHC patients were included. Hyperuricaemia was diagnosed with uric acid serum levels >7 mg/dl in men, and >6 mg/dl in women. Patients underwent therapy with pegylated interferon plus ribavirin. Results Hyperuricaemia…

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study

BACKGROUND: No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (R…

Refining sorafenib therapy: lessons from clinical practice

ABSTRACT  Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symp…

Effect of pharmacological interventions and placebo on liver Histology in nonalcoholic steatohepatitis: A network meta-analysis

Background: The aims of this study were to quantify the histological improvement and its risk factors in patients with NASH enrolled in the placebo arms of randomized controlled trials (RCTs), and to indirectly compare the effect of several investigational drugs for NASH on validated histological outcomes.Data synthesis: A comprehensive search was conducted to detect phase 2 and 3 RCTs comparing pharmacological interventions in patients with NASH. According to Food and Drug Administra-tion (FDA) recommendations, primary outcomes included: 1) NASH resolution without wors-ening of fibrosis; 2) At least 1-point reduction in fibrosis without worsening of NASH. Meta -analysis and meta-regression…

Years of life that could be saved from prevention of hepatocellular carcinoma

Summary Background Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. Aim To assess how many years of life are lost after HCC diagnosis. Methods Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Results Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18–61 y…

Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis

ABSTRACT Contrasting data exist on the effect of gender and menopause on the susceptibility, development and liver damage progression in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether menopause is associated with the severity of liver fibrosis in individuals with NAFLD and to explore the issue of ovarian senescence in experimental liver steatosis in zebrafish. In 244 females and age-matched males with biopsy-proven NAFLD, we assessed anthropometric, biochemical and metabolic features, including menopausal status (self-reported); liver biopsy was scored according to ‘The Pathology Committee of the NASH Clinical Research Network’. Young and old male and female zebraf…

Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study.

Objective To determine whether chronic hepatitis C virus (HCV) infection is an independent risk factor for hepatocellular carcinoma and whether it increases the cirrhosis-related risk for hepatocellular carcinoma. Design Two pair-matched case-control studies. Setting A referral-based hospital. Patients In study I, 212 patients with hepatocellular carcinoma (197 of whom had known underlying cirrhosis) were compared with controls who had chronic nonhepatic diseases. In study II, the 197 patients with hepatocellular carcinoma and cirrhosis were compared with 197 pair-matched controls who had cirrhosis but not hepatocellular carcinoma. Measurements Levels of antibody to HCV (anti-HCV), hepatiti…

Liver eosinophilic infiltrate is a significant finding in patients with chronic hepatitis C.

Eosinophilic infiltrate of liver tissue is described in primary cholestatic diseases, hepatic allograft rejection and drug-induced liver injury, but its significance and its implications in chronic hepatitis C are unknown. The aim of this study was to investigate the clinical significance of eosinophilic liver infiltrate in patients with chronic hepatitis C. We retrospectively evaluated 147 patients with chronic hepatitis C. The presence of eosinophilic infiltrate was investigated in liver biopsies, and a numeric count of eosinophilic leucocytes in every portal tract was assessed. An eosinophilic infiltrate of liver tissue (> or =3 cells evaluated in the portal / periportal spaces) was obse…

Modeling sequential systemic therapy for unresectable hepatocellular carcinoma in the era of immunotherapy: What comes next?

324 Background: Atezolizumab plus Bevacizumab represents the new best performing first-line approach for unresectable hepatocellular carcinoma (u-HCC). However, the best sequential strategy after every first-line failure (for progression or intolerance) remains elusive, and options for retreating patients failing Atezolizumab plus Bevacizumab with multi-kinase inhibitors (MKI) or immune checkpoint inhibitor (ICI) are yet undefined. Methods: We developed a Markov model to analyze simulated-Overall Survival (s-OS) of second-line ICIs or MKIs after first-line Atezolizumab plus Bevacizumab over a lifetime horizon. For first-line therapy, PFS of Atezolizumab plus Bevacizumab was extracted from …

The presence of white matter lesions is not associated with non-alcoholic fatty liver disease but with its histological severity

Interferon lambda 4 rs368234815 TT&gt;δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease

Background and Aims: The IFNL3/4 locus influencing innate immunity regulation has been associated with the severity of hepatitis and fibrosis progression during chronic hepatitis C infection, while contrasting results were reported in NAFLD. In this study, we examined whether rs12979860 and the linked causal rs368234815 variant encoding for the alternative IFNL4 protein variant are associated with liver fibrosis and damage in a large multicenter cohort of patients at risk of NASH. To clarify the mechanism, we also evaluated the impact on interferon-stimulated gene (ISG) hepatic expression in a subset of patients. Methods: We considered 946 consecutive Italian individuals at risk of NASH wit…

Hepatitis B: Prognosis and Treatment

Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C

We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…

Increased incidence or recurrence of hepatocellular carcinoma in hepatitis C virus cirrhotic patients treated with direct-acting antivirals: myth or fact?

Recalibrating survival prediction among patients receiving trans‐arterial chemoembolization for hepatocellular carcinoma

Background &amp; Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient …

The effect of interferon on the liver in chronic hepatitis C: a quantitative evaluation of histology by meta-analysis.

Several randomized clinical trials of interferon in chronic hepatitis C have examined the histological changes in paired biopsy specimens. We have attempted a quantitative evaluation by meta-analysis.Randomized Clinical Trials found by MEDLINE search were included if: a) they compared different IFN regimens with non-active treatment or with each other, b) they obtained biopsies before starting and at the time of stopping IFN in a sizable proportion of the treated and control patients, and c) they assessed the biopsy-specimens semi-quantitatively according to Scheuer's numerical scoring system or Knodell's Histological Activity Index, with quantitation of fibrosis and of lobular, portal and …

Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values

Background and aims: Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis In Nonalcoholic Fatty Liver Disease (NAFLD). Controlled Attenuation Parameter (CAP) is a new parameter provided by the same machine used for LSM, and associated with both steatosis and BMI, the two factors mostly affecting LSM peformance in NAFLD. We aimed to determine wheter prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Methods: Patients (n=324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower from 132 to 298, middle from 299 to 338, highe…

Hyperferritinemia is a risk factor for steatosis in chronic liver disease.

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty l…

TM6SF2 rs58542926 is not associated with steatosis and fibrosis in largecohort of patients with genotype 1 chronic hepatitis C

Background & Aims We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. Methods A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5–29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Results Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosi…

PNPLA3 rs738409 C>G Variant Predicts Fibrosis Progression by Noninvasive Tools in Nonalcoholic Fatty Liver Disease

Liver fibrosis is the main predictor of events in patients with nonalcoholic fatty liver disease (NAFLD),1 and its evolution is characterized by a nonlinear trend2,3 mostly affected by metabolic risk factors, severity of liver inflammation and steatosis, and weight loss.3 The rs738409 C&gt;G common variant in PNPLA3 gene has been associated with severity of fibrosis and risk of liver-related events in NAFLD.4,5 Noninvasive tests as Fibrosis-4 (FIB-4) and liver stiffness measurement (LSM) are useful to rule-out advanced fibrosis and they could be reliable to predict fibrosis progression.2,6 We aimed to evaluate in patients with NAFLD whether PNPLA3 rs738409 C&gt;G variant impacts on fibrosis…

GEMS, a GEnetic and Metabolic Staging predicting the outcome of non-alcoholic fatty liver disease

Background and Aim: Non-alcoholic fatty liver disease(NAFLD) is an emergent cause of liver-related events(LRE). We have assessed the ability of a composite score based on clinical features, metabolic comorbidities and genetic background, to predict LRE. Methods: 546 consecutive patients with NAFLD were recruited and stratified according to FIB-4(low risk <1.3;intermedium-high risk ≥1.3). LRE were defined as occurrence of HCC or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LRE. Results: Over a median follow-up of 73.8 months, 58 patients experienced LRE(only 1 in the cohort of patients with FIB-4 65 years(HR 17.96), plat…

Direct antiviral agents and risk of HCC: Waiting for Godot.

Glucokinase Regulatory Protein Gene Polymorphism Affects Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

BACKGROUND AND AIMS: Variant in glucokinase regulatory protein (GCKR), associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C-->T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype. METHODS: In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy), we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed. RESULTS: At multivariate logistic regression an…

Monofocal hepatocellular carcinoma: How much does size matter?

Background &amp; Aims: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (&gt;5 cm) monofocal (HCC). Methods: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (&gt;5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). Results: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P…

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

Abstract Aim This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results In more deprived regions, HCC was more frequently diagnosed during surveillan…

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background &amp; Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAA…

Endothelial angiopoietin-2 overexpression in explanted livers identifies subjects at higher risk of recurrence of hepatocellular carcinoma after liver transplantation

BackgroundThough the precise criteria for accessing LT are consistently being applied, HCC recurrence (HCC-R_LT) still affects more than 15% of the patients. We analyzed the clinical, histopathological, and biological features of patients with HCC to identify the predictive factors associated with cancer recurrence and survival after LT.MethodsWe retrospectively analyzed 441 patients with HCC who underwent LT in our center. Overall, 70 (15.8%) of them developed HCC-R_LT. We matched them by age at transplant and etiology with 70 non-recurrent patients. A comparable cohort from the Liver Transplant Centre of Bologna served as validation. The clinical and biochemical characteristics and pre-LT…

Enoxaparin Prevents Portal Vein Thrombosis and Liver Decompensation in Patients With Advanced Cirrhosis

BACKGROUND & AIMS: We performed a randomized controlled trial to evaluate the safety and efficacy of enoxaparin, a low-molecular-weight heparin, in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis. METHODS: In a nonblinded, single-center study, 70 outpatients with cirrhosis (Child-Pugh classes B7-C10) with demonstrated patent portal veins and without hepatocellular carcinoma were assigned randomly to groups that were given enoxaparin (4000 IU/day, subcutaneously for 48 weeks; n = 34) or no treatment (controls, n = 36). Ultrasonography (every 3 months) and computed tomography (every 6 months) were performed to check the portal vein axis. The primary outcome was pre…

Impact of virus eradication in patients with compensated hepatitis C virus-related cirrhosis: competing risks and multistate model

BACKGROUND & AIMS No published study to date has provided a careful analysis of the effects of a sustained viral response (SVR) on the outcomes of patients with compensated hepatitis C virus (HCV)-related cirrhosis in relation to the degree of portal hypertension. Therefore, we estimated the impact of achieving SVR on disease progression, hepatocellular carcinoma (HCC) development and mortality in a large cohort of HCV patients with cirrhosis with or without oesophageal varices (OVs) at the start of antiviral therapy. METHODS A total of 535 Caucasian patients were prospectively recruited to this study. All patients had a clinical or histological diagnosis of compensated HCV-related cirrhosi…

Surveillance for hepatocellular carcinoma with a 3-months interval in “extremely high-risk” patients does not further improve survival

Abstract Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveil…

Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16–152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver a…

Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity.

Background & Aims Lean nonalcoholic fatty liver disease (NAFLD) is defined as NAFLD that develops in patients with a body mass index (BMI) less than 25 kg/m2. We investigated the differences between lean NAFLD and NAFLD in overweight and obese persons, factors associated with the severity of liver and cardiovascular disease, and the effects of visceral obesity. Methods We performed a retrospective cohort study of 669 consecutive patients with biopsy-proven NAFLD seen at 3 liver centers in Italy. We collected anthropometric, clinical, and biochemical data, as well as information on carotid atherosclerosis (artery intima-media thickness and plaque), liver histology (nonalcoholic steatohepatit…

Prognostic ability of BCLC-B subclassification in patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Background and aims. A subclassification system for intermediate hepatocellular carcinoma (HCC) was recently proposed to optimize treatment allocation. The aim of this study was to assess the prognostic ability of that substaging proposal. Patients and methods This is a retrospective multicenter cohort study including patients with intermediate HCC treated with transarterial chemoembolization (TACE). Predictors of survival were identified using the Cox proportional regression model. Results 289 Barcelona Clinic Liver Cancer (BCLC) B patients were included. Medi…

Chronic hepatitis C: Interferon retreatment of relapsers. A meta-analysis of individual patient data

Relapse after interferon (IFN) therapy for chronic hepatitis C virus (HCV) infection occurs in 50% of patients after the initial response. The benefit of retreatment with IFN alone has not been assessed in large controlled studies. To assess the effectiveness and the tolerability of IFN retreatment and to identify the optimal second course regimen, we performed a meta-analysis of individual patient's data on a set of 549 patients (mean age 43.8 years; 12.2 SD, men: 65%) who had an end-of-treatment biochemical response to a first IFN course and then relapsed. Retreatment was started within 24 months after the end of the first course. Biochemical end-of-treatment responses (ETR) and sustained…

Clinical aspects of bleeding complications in cirrhotic patients

Liver disease is a frequent cause of haemostatic abnormalities, which may lead to overt or occult bleeding. Clinical manifestations of hepatic coagulopathy include upper and lower gastrointestinal haemorrhage, easy bruising and bleeding from gums, nose or the female genital tract. The most significant bleeding problem among patients with chronic liver disease is blood loss due to portal hypertension. About 30% of subjects with oesophageal or gastric varices resulting from cirrhosis have an episode of gastrointestinal bleeding in their lifetime. Risk factors for the first episode of variceal bleeding include the severity of liver dysfunction, large varices, and the presence of endoscopic red…

Cost effectiveness of boceprevir or telaprevir for previously treated patients with genotype 1 chronic hepatitis C.

Background & Aims Randomised controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype 1 (G1) chronic hepatitis C (CHC) patients with previous relapse (RR), partial response (PAR), and null-response (NR). We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC. Methods The available published literature provided the data source. The target population was made up of previously treated Caucasian patients with G1 CHC and these were evaluated over a lifetime horizo…

The ocular manifestations in IBD screening (OMIS) questionnaire: pilot study on detection of ocular involvement in inflammatory bowel diseases.

Purpose: To assess the usefulness of a dedicated questionnaire for patients with inflammatory bowel diseases (IBD) treated with biological drugs for the detection of ocular extraintestinal manifestations (EIMs). IBD can cause extraintestinal symptoms including ocular complaints which are frequently ignored and may be associated with significant morbidity, including blindness. Methods: We developed a questionnaire, named Ocular Manifestations in IBD Screening (OMIS) questionnaire, after agreement between gastroenterologists and ophthalmologists. The questionnaire was administered by a non-ophthalmologist physician to 96 IBD patients treated with biological drugs. Results: 35 patients (36.5%)…

Is the efficacy of sorafenib treatment in patients with hepatocellular carcinoma affected by age?

Cancer is a prevalent disease in the elderly population and hepatocellular carcinoma (HCC) is a major health problem among all tumors. Curative treatments for early-stage include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib, classified as non-curative treatments, can improve survival for patients with intermediate and advanced tumors, respectively. Even if the incidence of HCC progressively increases with advanced age in all populations, reaching a peak at 70 years, few reports concerning correct management of HCC in elderly patients exist. Moreover, data from large randomized controlled trials (RCT) poorly reflect the elde…

MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease

Background & Aim Homozygosity for a common non-coding rs4374383 G>A polymorphism in MERTK (myeloid-epithelial-reproductive tyrosine kinase) has been associated with the protection against fibrosis progression in chronic hepatitis C. The main study objective was to assess whether MERTK AA genotype influences liver fibrosis, and secondarily MERTK expression in patients with non-alcoholic fatty liver disease (NAFLD). We also investigated whether MERTK is expressed in human hepatic stellate cells (HSC) and in murine models of fibrogenesis. Methods We considered 533 consecutive patients who underwent liver biopsy for suspected non-alcoholic steatohepatitis (NASH) without severe obesity from two …

A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma.

Knowing the spontaneous outcome of hepatocellular carcinoma (HCC) is important for designing randomized controlled trials (RCTs) of new therapeutic approaches; however, survival of patients in the absence of treatment is highly variable, and prognostic factors influencing outcomes are incompletely defined. The aims of this meta-analysis were to estimate the 1-year and 2-year survival rates of untreated HCC patients enrolled in RCTs of palliative treatments, and to identify prognostic factors. RCTs evaluating therapies for HCC with placebo or no-treatment arms were identified on MEDLINE through April 2009. Data were combined in a random effect model. Primary outcomes were 1-year and 2-year s…

Systematic review by meta-analyses on the possible role of TNF-alpha polymorphisms in association with Alzheimer's disease.

It has been hypothesized that polymorphisms of Tumor Necrosis Factor (TNF)-alpha gene affect the risk of developing Alzheimer's disease (AD). However, results of different studies are often inconsistent. Our aim was to investigate by meta-analysis the association of the common polymorphisms comprehensively defining the genetic variability of the TNF-alpha gene with AD risk. Hence, the results being stated are of a meta-analysis across studies, and that this meta-analysis does not invalidate the results of the individual studies previously performed. Seventeen studies that investigated the association between 5 TNF-alpha polymorphisms (-850, -308, -863, -238, and -1031) and AD were retrieved…

Definition of response to antiviral therapy in chronic hepatitis C

Sicily Network for Liver Cancer: A Multidisciplinary Network Model for the Management of Primary Liver Tumors

Background: The management of primary liver tumors requires the involvement of multiple specialist skills and the best possible treatment in terms of cost, risk, and benefit that could be provided by hepatobiliary or transplant surgeon, interventional radiologist, hepatologist, radiotherapist, or oncologist is needed to be chosen for each patient. This is particularly relevant for hepatocellular carcinoma (HCC), that is the most common primary liver tumor, and it occurs in more than 90% of cases in the setting of cirrhosis. Methods: To address the increasing complexity of cancer care, multidisciplinary tumor boards (MDTBs) have evolved to offer patients appropriate and tailored cancer treat…

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection

Background and aims: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. Material and methods: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was def…

Hepatitis C Virus Eradication by Direct Antiviral Agents Improves Carotid Atherosclerosis in patients with Severe Liver Fibrosis.

Abstract BACKGROUND AND AIM: Recent studies suggest an association between HCV infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive HCV patients with advanced fibrosis or compensated cirrhosis were evaluated by virological, anthropometric and metabolic measurements. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickne…

Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO).

Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made follow…

Direct-acting antiviral agents and risk of Hepatocellular carcinoma: Critical appraisal of the evidence

Direct-acting antivirals (DAAs) revolutionized the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), even in advanced cirrhosis, with modest contraindications and a low rate of adverse events. However, the risk of hepatocellular carcinoma (HCC) persists due to the underlying chronic liver disease, both in patients with and without history of HCC. Although some initial studies reported a presumptive high risk of HCC development after DAA therapy, more recent observational studies denied this hypothesis. The residual risk for HCC occurrence after HCV eradication seems being progressively reduced with time after SVR. Data on recurrence of HC…

NT pro BNP plasma level and atrial volume are linked to the severity of liver cirrhosis.

BACKGROUND AND AIMS: Plasma levels of NT-pro-BNP, a natriuretic peptide precursor, are raised in the presence of fluid retention of cardiac origin and can be used as markers of cardiac dysfunction. Recent studies showed high levels of NT pro BNP in patients with cirrhosis. We assessed NT pro-BNP and other parameters of cardiac dysfunction in patients with cirrhosis, with or without ascites, in order to determine whether the behaviour of NT pro BNP is linked to the stage of liver disease or to secondary cardiac dysfunction. METHODS: Fifty eight consecutive hospitalized patients mostly with viral or NAFLD-related cirrhosis were studied. All underwent abdominal ultrasound and upper GI endoscop…

Progression-Free Survival Early Assessment Is a Robust Surrogate Endpoint of Overall Survival in Immunotherapy Trials of Hepatocellular Carcinoma

Background: Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods. Methods: A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan&nd…

Clinical implications of the hyperdynamic syndrome in cirrhosis.

Abstract The hyperdynamic syndrome is a late consequence of portal hypertension in cirrhosis. The principal hemodynamic manifestations of the hyperdynamic syndrome are high cardiac output, and increased heart rate and total blood volume, accompanied by reduced total systemic vascular resistance. Pathophysiology involves a complex of humoral and neural mechanisms that can determine hemodynamic changes, and lead to hyperdynamic circulation. In this review we focus our attention on the manifestations of the hyperdynamic syndrome. Some of these are well described and directly related to portal hypertension (varices, ascites, hepatic encephalopathy, and hepatorenal syndrome), while others, such …

Reliability of liver stiffness measurement in non-alcoholic fatty liver disease: the effects of body mass index

Summary Background  Liver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its performance in patients with non-alcoholic fatty liver disease (NAFLD) are incompletely understood. Aim  To assess LSM. Methods  Consecutive NAFLD patients (n = 169), assessed by liver biopsy (Kleiner score), anthropometrical, biochemical and metabolic features, underwent LSM using TE with standard M probe. Results  Liver stiffness measurement was not reliable in 23 patients (14%) due to obesity. Among patients with a reliable TE, a LSM value >7.25 kPa was the best cut-off for predicting signifi…

Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta-analysis

Background &amp; Aims: Risk for relapse after induction of remission with steroid therapy has been studied extensively in patients with autoimmune pancreatitis (AIP), but findings have been equivocal. We performed a systematic review and meta-analysis to estimate the relapse rate of AIP after initial remission after steroid treatment and to identify factors associated with relapse. Methods: Three reviewers searched MEDLINE, SCOPUS, and EMBASE until July 2018 to identify studies on rate of relapse of AIP after induction of remission with steroid therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random-effects model. This study was conducted in accordance …