Current and forthcoming perspectives in linkage to care of hepatitis C virus infection: Assessment of an Italian focus group

Abstract Hepatitis C virus (HCV) remains a significant public health problem and is one of the major causes of chronic liver disease worldwide. In recent years many new tools to facilitate widespread HCV screening and new therapeutic options with excellent efficacy and tolerability profiles and cost lowering policies have become available. To fully utilise these new tools, the link between local and specialist centres for the management of HCV infection must be reinforced. In order to GAIN further insight into these aspects, with a particular focus on the Italian scenario, a group of experts met to discuss relevant aspects and open issues on chronic HCV. As a summary of that meeting, the fo…

The effect of antiviral therapy on clinical outcome of HCV cirrhosis with portal hypertension: a prospective cohort study.

HCV viraemia is more important than genotype as a predictor of response to interferon in sicily (Southern Italy)

Abstract Background/Aims: To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. Methods: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of t…

IMPACT OF NON-ALCOHOLIC FATTY LIVER DISEASE ON CARDIOVASCULAR RISK IN A GENERAL POPULATION

Background: Background:Nonalcoholic fatty liver (NAFL) is a major cause of liver disease worldwide leading also to a higher risk of cardiovascular events. We aimed to evaluate the impact of fatty liver and fibrosis on cardiovascular risk factors in a general population. Methods: 604 subjects included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study were recruited. Steatosis (CAP >288 dB/m) and fibrosis (> 8.7 KPa by M and > 7.2 KPa by XL probe) were assessed with FibroScan Cardiovascular risk was evaluated by the Atherosclerotic Cardiovascular Disease (ASCVD) risk estimator and de ned low if <5%, borderline if 5%-7 4%, intermediate if 7-9% a…

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)…

Infezione occulta da HBV in pazienti con malattie oncoematologiche

EVALUATING THE RISK OF HEPATITIS B REACTIVATION IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES: IS THE SERUM HEPATITIS B PROFILE RELIABLE?

Background/Aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. Results: Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (a…

Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation

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 n = 24, C n = 16) treated with TACE were enrolled. …

Evidence for Three Distinct Classes of Phenotype Severity in Beta-Thalassaemia

Background: Classification of phenotype severity in patients with beta-thalassaemia has so far relied mainly on expert opinion using parameters of genotype, clinical features at diagnosis, and transfusion requirement. The aim of this study was to use a large dataset of patients with beta-thalassaemia and evaluate a classification system based on onset variables agreed on by an international expert group, including age at diagnosis, at first transfusion, and at first iron chelation. Methods: A retrospective dataset of 7910 patients with homozygous or compound heterozygous beta-thalassaemia was used and subjected to cluster and classification analysis starting with the onset variables. Result…

Real life experiences in HCV management in 2018

Introduction: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Treatment of chronic hepatitis C has considerably improved in the last few years thanks to the introduction of direct-acting antivirals able to achieve sustained virological response in more than 95% of patients. Successful anti-HCV treatment can halt liver disease progression and solve the HCV-related extra-hepatic manifestations, eventually reducing liver-related and overall mortality. Areas covered: With the aim to respond to unmet needs in patient’s identification, universal access to antiviral therapy and treatment optimiza…

IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection.

Background. Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection. Design and Methods. We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 Thalassemia Major patients with Hepatitis C Virus infection. Results. Ninety-eight patients (40%) had a spontaneous viral clearance, while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; p=0.008) or C/C genotype of rs12979860 p…

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…

HBV-DNA suppression and disease course in HBV cirrhosis patients on long-term lamivudine therapy

In hepatitis B virus (HBV) cirrhosis patients on long-term lamivudine (LAM), the relationships between HBV suppression, development of viral resistance and disease outcome are unclear. We analysed the dynamic of serum HBV-DNA and its relationship with the clinical course of 59 patients (52 males, mean age 51.4 ±8.4 years, 12 HBeAg positive and 47 HBeAg negative, and 57 genotype D and two genotype A) with cirrhosis (45 in Child-Turcotte-Pugh class A) and high levels of serum HBV-DNA (median 14.7x107 genomes/ml) treated with LAM [median (range): 44 (15–78) months]. A total of 50 patients (84.7%) achieved a virological response (serum HBV-DNA negative by PCR) during the first 6 months of ther…

Point‐of‐care HCV RNA testing in the setting of DAA therapy: HCV‐FiS (HEpatitis C Virus Fingerstick Study)

HCV-RNA assessment during therapy with Direct-Acting Antiviral (DAA) regimens still relies on assays requiring blood collection and transport to a specialised laboratory, which may compromise linkage to care. GeneXpert-HCV Viral Load (GXHVL) (Cepheid) is a plasma-based assay used at point of care (POC) with a sensitivity of ≤10 IU/mL, and, results available within 2 hours. Fifty-nine consecutive HCV-patients ready for DAAs treatment were enrolled. HCV-RNA was simultaneously tested using Roche TaqMan RT-PCR (venous blood sample) and GXHVL (capillary blood collected by fingerstick), at baseline (BL), week 4 (W4) of therapy, end of therapy (EOT) and week 12 of follow-up (W12FU). Both assays de…

Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population.

Background &amp; Aims: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. Methods: The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age- and se…

Virological profiles in patients with chronic hepatitis C and overt or occult HBV infection

Abstract OBJECTIVES: The virological profiles of hepatitis B and C viruses (HBV and HCV) and their interplay in cases of coinfection are undefined. A suppressed and occult HBV infection may occur in hepatitis B surface antigen (HBsAg) negative patients with chronic hepatitis C. The HCV core protein is able to inhibit HBV “in vitro,” and serines at positions 99 and 116 are essential for such inhibition. We aimed to assess the HBV and HCV virological profiles in cases of coinfection and to evaluate the relationship between HCV core gene variability and HBV activity. METHODS: Eighty-two anti-HCV positive patients were examined: 35 cases were HBsAg positive, 24 were HBsAg negative with “occult”…

An Outbreak of Hepatitis C Virus Infection Among Transfused Thalassemia Patients: Root Cause Analysis, Phylogenetic Epidemiology and Antiviral Therapy

Background: Occurrence of HCV infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. We report an outbreak of 11 patients with HCV acute hepatitis (seven new infections and four re-infections) among 128 thalassemia patients followed at a Hospital in Sicily. Methods All patients with acute hepatitis and known chronic infection were tested for HCV-RNA, HCV genotyping, and NS3, NS5A and NS5B HCV-genomic regions sequencing.  To identify transmission clusters we built phylogenetic trees for each gene employing Bayesian methods.  Findings All patients with acute hepatitis were infected with HCV genotype 1b…

Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C.

Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liv…

La termoablazione nel trattamento delle neoplasie epatiche primitive e secondarie

Radiofrequency thermoablation is a locoregional procedure based on the use of electromagnetic waves that induce movement and consequently the production of heat. This is the basis for the coagulative necrosis produced in the tissues. The method, experimented with and developed in the '90s, is today extensively used in the treatment of focal hepatic lesions, both primary and secondary. The factors that condition the procedure are related essentially to the characteristics of the tumours and to the possibility of obtaining a predictable area of necrosis that guarantees the radicality of the treatment. As regards primary neoplasms, it should be stressed that the treatment for hepatocellular ca…

A rs4374383 Single Nucleotide Polymorphisms of MERTK gene is linked to a higher likelihood of hepatocellular carcinoma in patients with HCV cirrhosis

Halitosis and HCV-related liver disease:true association

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…

Improved survival of patients with hepatocellular carcinoma and compensated hepatitis C virus-related cirrhosis who attained sustained virological response.

Background Few studies examined the outcome of patients with hepatitis C virus (HCV)-related cirrhosis who developed hepatocellular carcinoma (HCC). The relative weight as determinant of death for cancer vs end-stage liver disease (ESLD) and the benefit of HCV eradication remain undefined. This multicentre, retrospective analysis evaluates overall survival (OS), rate of decompensation and tumour recurrence in compensated HCC patients treated with interferon (IFN) according to HCV status since HCC diagnosis. Methods Two groups of patients with HCV-related cirrhosis and HCC were followed since HCC diagnosis: (i) compensated cirrhotics with prior sustained virological response (SVR) on IFN-bas…

Fibrosis evaluation by transient elastography in patients with long-term sustained HCV clearance.

Background: Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy. Objectives: Measuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting. Patients and Methods: We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4). Results: TE was not…

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy: a randomized controlled trial.

AIM: To assess the efficacy of different schedules of consensus interferon (CIFN) plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy. METHODS: Forty-five patients (34 males and 11 females) with chronic hepatitis due to hepatitis C virus (HCV) genotype 1 who relapsed after a previous course of rIFN monotherapy were randomized to receive 9 μg CIFN three times per week for 52 wk (group A, n = 22) or 18 μg CIFN three times per week for 52 wk (group B, n = 23) in combination with ribavirin 800 to 1200 mg daily for 52 wk (according to body weight). Virological response was evaluated at week 24 (EVR), at the end of treatment (ETR)…

Patologie da sovraccarico di ferro:recenti acquisizioni

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…

Hepatitis E virus infection as a cause of acute hepatitis in Southern Italy

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…

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

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 and metaboli…

Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Evaluation by the controlled attenuation parameter (CAP).

Background: Chronic hepatitis C (CHC) is associated with hepatic steatosis, related to both a direct viral action and metabolic features. Vice-versa data on hepatic steatosis after viral eradication by direct-acting antiviral agents (DAA) are undefined although the presence of metabolic alterations could strongly influence the occurrence of steatosis as in NAFLD. The controlled attenuation parameter (CAP) (FibroscanⓇ) allows the qualitative and quantitative evaluation of fatty liver. Aim: to evaluate in patients with CHC whether hepatic steatosis diagnosed by CAP modifies after DAAs-induced sustained virologic response (SVR). Methods: Data were collected the day of DAAs therapy starting and…

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 thirty-six 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 high-density lipoprotein cholesterol. All biopsies were scored by on…

The impact of sustained virological response on clinical outcomes in compensated HCV cirrhosis: a prospective cohort study

Hepatitis C virus eradication by direct antiviral agents abates oxidative stress in patients with advanced liver fibrosis

Background and aims: HCV eradication improves non-hepatic outcomes such as cardiovascular diseases, although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction in systemic oxidative stress after viral clearance. Methods: We studied a retrospective cohort of 105 patients (age 62.4 ± 11.2 years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow-up. Levels of 8-iso-prostaglandin F2α (F2-isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative str…

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…

Seeding after radiofrequency thermal ablation of hepatocellular carcinoma in cirrhosis: a prospective study

Suggestive caratteristiche istomorfologiche della mucosa orale sana in pazienti affetti da morbo celiaco vs pazienti non celiaci:studio caso-controllo.

&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.…

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).

A multicenter Italian Study of rescue adefovir dipivoxil tehrapy in lamivudine resistant patients: a 2-year anlysis of 604 patients.

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. …

Optimizing patient referral and center capacity in the management of chronic hepatitis C: Lessons from the Italian experience

Abstract Aims In 2017 the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) revised the criteria for access to therapy for patients with chronic hepatitis C as part of a three-year plan to eradicate HCV. We conducted a Delphi study to determine strategies to identify and treat patients with HCV and to develop through a shared pathway, a model to manage patient referral and optimize prescription center capacity with the overall aim of increasing access to therapy. Methods The process took place in two phases – Phase I (January 2017), before the criteria for treatment of HCV were revised and Phase II (May 2017) when AIFA developed a framework for the eradication of HCV infection in Ita…

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…

Perception of the Role of Food and Dietary Modifications in Patients with Inflammatory Bowel Disease: Impact on Lifestyle

Background: Diet has a relevant role in triggering symptoms in inflammatory bowel disease (IBD) from the patients’ perspective, but there is gap the between patients’ and doctors’ perceptions. Few studies have addressed this topic. The aim of this study was to evaluate food habits and nutrition knowledge in a homogeneous cohort of patients with IBD from southern Italy. Methods: 167 consecutive patients with IBD were recruited. The survey was based on the administration of a semi-structured questionnaire assessing demographics, disease features, dietary behavior, and food intolerance. Results: The majority of patients did not consider food a cause of their disease. However more than 80% chan…

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…

Treatment of hepatitis C virus infection with direct-acting antiviral drugs is safe and effective in patients with hemoglobinopathies

Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chron…

Emocromatosi

Factors Enhancing Treatment of Hepatitis C Virus-Infected Italian People Who Use Drugs: The CLEO-GRECAS Experience.

INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed.…

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 …

A complication risk score to evaluate clinical severity of thalassaemia syndromes

The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complications. Nine independent variables were included in the investigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non-transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminas…

Liver stiffness measurement by transient elastography predicts early recovery from acute hepatitis

We read with interest the lead article by Castera and Pinzani,1 particularly the comment regarding the role of transient elastography (TE) in the context of acute hepatitis (AH). The assumption that liver stiffness is determined exclusively by hepatic fibrosis has been challenged by evidence that patients with AH can have high values of liver stiffness measurement (LSM) by TE.2 AH is a suitable model for studying the kinetics of LSM, since inflammation and necrosis increase rapidly and sometimes massively, but may revert with equal speed. We evaluated 92 consecutive patients (mean age 41.8±16.3 years, 71.7% males) with symptomatic AH to assess how LSM was influenced by aetiology, and whethe…

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…

Current and future challenges in HCV: insights from an Italian experts panel

Background: The recent availability of direct acting antiviral drugs (DAAs) has drastically changed hepatitis C virus (HCV) treatment scenarios, due to the exceedingly high rates of sustained virological response (SVR) and excellent tolerability allowing for treatment at all disease stages. Methods: A panel of Italian experts was convened twice, in November 2016 and January 2017, to provide further support on some open issues and provide guidance for personalized HCV care, also in light of forthcoming regimens. Results and conclusions: Treatment recommendations issued by international and national liver societies to guide clinicians in the management of HCV infection are constantly updated …

Virus-related insulin resistance in HCV genotype 1 chronic hepatitis C : a major disease modifier

Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach

Background & aims Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Non-invasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis at disease presentation in PBC. Approach & results We collected data from 167 consecutive treatment-naive PBC patients who underwent liver biopsy(LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to Ludwig sy…

Development of a Severity Score System for Thalassemia Syndromes

Introduction Thalassemia Syndromes (TS) are a group of inherited haemoglobin disorders characterized by different phenotype severity falling among heterozygote state, no transfusion dependent thalassemia (NTDT) and transfusion dependent Thalassemia (TDT) (Graffeo et al, 2018; Taher &amp; Saliba, 2017). Several factors, independently by genotype and globin chain unbalance, modulate the severity of ineffective erythropoiesis (Rivella et al, 2015). Considering the complexity of this pathophysiology, one tool to evaluate patients on an individual basis is needed. The aim of this study was to develop a severity scoring system with a view to initiate timely interventions that would prevent any fu…

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 …

Efficacy and Safety of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Virus Infection and Inherited Blood Disorders: Final Data from the C-Edge Ibld Study

Abstract Background: Complications from chronic hepatitis C virus (HCV) infection are a major cause of morbidity and mortality among individuals with inherited blood disorders (IBLD). Inability to tolerate ribavirin and frequent comorbidities have limited HCV treatment options in these patients. The aim of the C-EDGE IBLD study was to evaluate the efficacy and safety of a once-daily, fixed-dose combination of elbasvir 50 mg (EBR, an NS5A inhibitor) and grazoprevir 100 mg (GZR, an NS3/4A protease inhibitor) in patients with HCV infection and IBLD, including those with hemoglobinopathies. Methods: C-EDGE-IBLD was a randomized, double-blind, placebo-controlled study of treatment-naïve and trea…

Serum BLyS/BAFF predicts the outcome of acute hepatitis C virus infection.

Summary.  B-lymphocyte stimulator/B activating factor (BLyS/BAFF) is a tumour necrosis factor-family cytokine that plays a key role in generating and maintaining the mature B-cell pool. BLyS/BAFF expression by macrophages is stimulated by interferon-γ and interleukin-10, and its serum levels are increased in chronic hepatitis C (CHC). The aim of this study was to assess serum levels of BLyS/BAFF in patients with acute hepatitis C (AHC) and correlate them with disease outcome. We studied 28 patients with AHC (14 males, mean age 59.3 ± 15 years), followed for at least 7 months since onset, comparing them with 86 CHC patients and 25 healthy blood donors (HBD). BLyS/BAFF levels were assessed at…

Update of the statements on biology and clinical impact of occult hepatitis B virus infection

In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.

Liver stiffness quantification in biopsy-proven nonalcoholic fatty liver disease patients using shear wave elastography in comparison with transient elastography

Purpose: This study prospectively assessed the performance of liver stiffness measurements using point shear-wave elastography (p-SWE) in comparison with transient elastography (TE) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). Methods: Fifty-six consecutive adult patients with a histological diagnosis of NAFLD prospectively underwent TE and p-SWE on the same day. The median of 10 measurements (SWE-10), the first five (SWE-5), and the first three (SWE-3) measurements were analyzed for p-SWE. Liver biopsy was considered as the reference standard for liver fibrosis grade. Receiver operating characteristic (ROC) curves and areas under the ROC curves (AUROCs) were cal…

Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.

The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-beta-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0.70; P > 0.001) independently of liver iron concentration (r = 0.01; P = 0.932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0.997 (95% confidence interval [CI]: 0.925-1.000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69.0-100.0) and 95% specificity (95% CI: 84.2-99.3). Transient elastography is a reliable non-invasive too…

Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of chronic HCV-infected and non-alcoholic steatohepatitis patients.

To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty-four chronic untreated HCV-infected subjects and seven patients with non-alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded accordin…

Changing aetiological factors of hepatocellular carcinoma and their potential impact on the effectiveness of surveillance

BACKGROUND: The aetiological factors of hepatocellular carcinoma may vary over time. AIMS: The study assessed the potential impact of the aetiological factors on the effectiveness of surveillance in real-world patients. METHODS: Multicentre, cross-sectional study enrolling consecutive hepatocellular carcinoma cases during a six month period. RESULTS: 1733 cases (1311 prevalent and 422 incident) were recruited (mean age 68.6 years; 46.1% cases over 70 years; 73.9% males; 95.3% with cirrhosis); 63.0% were hepatitis C virus positive and 23.7% were virus negative. Amongst incident HCCs, 34.5% were single ≤3cm and 54.4% met the Milan criteria; 61.6% were diagnosed during surveillance; virus nega…

Variability of reverse transcriptase and overlapping S gene in hepatitis B virus isolates from untreated and lamivudine-resistant chronic hepatitis B patients

Background The high degree of diversity of the hepatitis B virus (HBV) quasispecies in chronically infected individuals raises the possibility that HBV genetic variants favouring resistance to nucleoside/nucleotide analogues (NAs) might pre-exist to treatment. The aim of this study was to investigate the genetic variability of the entire HBV reverse transcriptase (RT) domain and of the overlapping S gene in a large series of untreated hepatitis B surface antigen carriers and in lamivudine (3TC)-resistant patients. Methods Sequencing analysis of the entire HBV RT domain of isolates from 100 untreated (treatment- naive group) and 59 3TC-resistant (3TC-resistant group) consecutive patients wit…

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:…

VARIABILITY OF THE HBV POL GENE REVERSE-TRANSCRIPTASE DOMAIN IN VIRAL ISOLATES FROM UNTREATED AND LAMIVUDINE-RESISTANT CHRONIC HEPATITIS B PATIENTS

SAFE biopsy: A validated method for large-scale staging of liver fibrosis in chronic hepatitis C

The staging of liver fibrosis is pivotal for defining the prognosis and indications for therapy in hepatitis C. Although liver biopsy remains the gold standard, several noninvasive methods are under evaluation for clinical use. The aim of this study was to validate the recently described sequential algorithm for fibrosis evaluation (SAFE) biopsy, which detects significant fibrosis (≥F2 by METAVIR) and cirrhosis (F4) by combining the AST-to-platelet ratio index and Fibrotest-Fibrosure, thereby limiting liver biopsy to cases not adequately classifiable by noninvasive markers. Hepatitis C virus (HCV) patients (2035) were enrolled in nine locations in Europe and the United States. The diagnosti…

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.…

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

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 …

Management of HCV-Related Liver Disease in Hemophilia and Thalassemia

AbstractChronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that howev…

Hepatic expression of cycloxygenase-2 in non-alcoholic fatty liver disease

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…

Chronic hepatitis C in children is a mild and curable liver disease

Hepatitis C virus (HCV) infection is a major health problem orldwide, but children constitute only a small portion of infected atients. HCV transmission can occur through blood transfusion, nd the incidence of HCV infection was very high in children transused before 1990 for treatment of chronic haematological diseases 1] or other diseases that required blood transfusion [2]. Since he introduction of screening for HCV infection, blood transfusions ave become safe in developed countries, and the residual risk is oday very limited. In developed countries, maternal–fetal transmission has ecome themajor risk factor for HCV in children,with an estimated isk of infection ranging from 2% to 6% [3]…

Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.

The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-b-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0Æ70; P > 0Æ001) independently of liver iron concentration (r = 0Æ01; P = 0Æ932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0Æ997 (95% confidence interval [CI]: 0Æ925–1Æ000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69Æ0–100Æ0) and 95% specificity (95% CI: 84Æ2–99Æ3). Transient elastography is a reliable non-invasive tool f…

Combined treatment of relapse of chronic hepatitis C with high-dose α2b interferon plus ribavirin for 6 or 12 months

Abstract Background/Aims: Retreatment of relapses of chronic hepatitis C with a standard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b . We aimed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness, and also to evaluate the tolerability, and to identify the determinants of sustained response. Methods: Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of α-interferon monotherapy were randomised to receive α 2 b interferon (6 MU tiw) plus ribavirin (1000–1200 mg daily) for 6 or 12 months. ALT nor…

Effectiveness of a screening program for HBV, HCV, and HIV infections in African migrants to Sicily

BACKGROUND Migrants from Africa are vulnerable to viral infections during their journey. METHODS Migrants who arrived in western Sicily were offered early screening for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection. A questionnaire was administered to evaluate risk factors, and antiviral therapy was offered to subjects with active infection. A multiple regression analysis and adjusted odds ratio were obtained to evaluate risk factors. RESULTS Overall, 2,639 of 2,751 (95.9%) migrants who arrived between 2015 and 2017 accepted screening and 1,911 (72.4%) completed the questionnaire. HBsAg was positive in 257 (9.7%) migrants, 24 (0.9%) were …

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. …

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…

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

Impact of direct-acting antivirals (DAAs) on cardiovascular diseases in patients with chronic hepatitis C

INTRODUCTION: In the last years the Hepatitis C virus (HCV) infection was a relevant public health problem due to the large number of affected people worldwide and the impact on hepatic and extrahepatic complications. The availability of direct-acting antivirals (DAAs) and the very high rate of sustained virological response (SVR) after treatment has radically changed the course of HCV chronic infection. EVIDENCE ACQUISITION: We searched PubMed for articles published between January 1, 1995, through December 31, 2020, in English language. EVIDENCE SYNTHESIS: Robust evidence showed a close link between HCV infection and development of cardiovascular disease (CVD), as result of the atherogeni…

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…

Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension:a randomized controlled trial

Abstract BACKGROUND/AIMS: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertension are poorly known. METHODS: We performed a randomized controlled trial in 102 HCV patients with compensated cirrhosis and portal hypertension: 51 received 1 microg/kg/week of Pegylated-interferon alpha-2b and 51 Pegylated-interferon plus 800 mg/day of ribavirin up to 52 weeks. RESULTS: By intention-to-treat analysis, five patients on monotherapy and eleven on combination therapy achieved a sustained virological response (9.8% vs. 21.6%, p=0.06). The response was more frequent for genotypes 2 or 3 than genotype 1 (66.6% vs. 11.3%, p=0.001). Genotype 1, who had low viral load at start of…

HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years

Background & Aims In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. Methods One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5years were included. Biochemical and virological tests were assessed every 3months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequen…

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

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 significant fibrosi…

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. …

Evaluating the risk of hepatitis B reactivation in patients with haematological malignancies: is the serum hepatitis B virus profile reliable?

Background/Aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. Results: Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (a…

INSULIN RESISTANCE AND SEVERITY OF FIBROSIS IN HCV GENOTYPE 1 CHRONIC HEPATITIS.

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel.

AbstractChelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus– or hepatitis C virus–related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical manage…

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…

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 …

Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders.

HCV elimination; Mental health disorders; Sofosbuvir/velpatasvir Eliminación del VHC; Trastornos de salud mental; Sofosbuvir/velpatasvir Eliminació del VHC; Trastorns de salut mental; Sofosbuvir/velpatasvir Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 w…

Cinetica della risposta virologica e della comparsa di mutanti virali in pazienti con malattia cronica di fegato HBV-correlatain terapia con adefovir

Primary HBB gene mutation severity and long-term outcomes in a global cohort of β-thalassaemia

In β-thalassaemia, the severity of inherited β-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 β-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as β0 /β0 , β0 /β+ , β+ /β+ , β0 /β++ , β+ /β++ , and β++ /β++ . Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, β0 and β+ mu…

Treatment of Hepatitis C virus infection in Italy: A consensus report from an expert panel

Abstract Hepatitis C virus (HCV) infection remains one of the main causes of chronic liver disease worldwide. The advent of direct-acting antivirals (DAAs) has significantly improved the course of patients with chronic HCV infection (CHC), due to the ability of these drugs to achieve high rates of sustained virological response (SVR). These exceedingly high rates of SVR and the excellent safety data have been confirmed in real life practice. Evolving guidelines have been issued by national and international scientific societies in accordance with the progression of clinical knowledge and the availability of new DAAs. These recommendations, however, may not be applied universally because of …

Dual therapy with peg-interferon and ribavirin in thalassemia major patients with chronic HCV infection: Is there still an indication?

Background: Iron overload and hepatitis C virus (HCV) infection together can lead to chronic liver damage in thalassemia major (TM) patients. Aims: We investigated viral, genetic, and disease factors influencing sustained virological response (SVR) after peg-interferon and ribavirin therapy in TM patients with HCV infection. Methods: We analyzed 230 TM patients with HCV infection (mean age 36.0 ± 6.3 years; 59.1% genotype 1; 32.2% genotype 2; 3.4% genotype 3; and 5.3% genotype 4; 28.7% carried CC allele of rs12979860 in IL28B locus; 79.6% had chronic hepatitis and 20.4% cirrhosis; 63.5% naive and 36.5% previously treated with interferon alone) treated in 14 Italian centers. Results: By mul…

Mer Tyrosine Kinase (MERTK) modulates liver fibrosis progression and hepatocellular carcinoma development.

BackgroundMerTK is a tyrosine kinase receptor that belongs to the TAM (Tyro3/Axl/Mer) receptor family. It is involved in different processes including cellular proliferation/survival, cellular adhesion/migration, and release of the inflammatory/anti-inflammatory cytokines. Although it is reported that MERTK polymorphisms affect the severity of viral and metabolic liver diseases, being able to influence fibrosis progression and hepatocellular carcinoma development, the mechanisms remain unknown. Methods: using a microarray approach, we evaluated the liver expression of genes involved in fibrogenesis and hepatocarcinogenesis in patient with chronic hepatitis C (CHC), stratified for MERTK geno…

Histomorphological features of health oral mucosa in celiac patients:unexspected association with spongiosis.

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…

PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION 8 RFTA) OF SMALL HEPATOCELLUALR CARCINOMA: A PROSPECTIVE STUDY

PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION 8 RFTA) OF SMALL HEPATOCELLUALR CARCINOMA: A PROSPECTIVE STUDY Data: 2004 Dettaglio tipologia d'Ateneo: 3a - Articoli su riviste ISI (anche on line)

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…

Percutaneous radiofrequency therma ablation of small hepatocellular carcinoma: a prospective study

A muticenter Italian Study od rescue adefovir dipivoxil therapy in lamivudine resistant patients: a 2 years analysis of 650 pATIENTS.

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…

Adefovir and Lamivudine combination therapy is superior to adefovir monotherapy for lamivudine-resistant patients with HBeAg-negative chronic hepatitis B

PEG-INTERFERON PLUS RIBAVIRIN IN COMPENSATED HCV CIRRHOSIS WITH PORTAL HYPERTENSION: THE ROLE OF RAPID AND EARLY VIROLOGICAL RESPONSE IN PREDICTING THE SUSTAINED VIROLOGICAL RESPONSE

Paraduodenal hernia: an uncommon cause of recurrent abdominal pain.

Internal abdominal hernias are a rare entity and may cause unexplained abdominal pain. This report concerns a 46 year old male patient, with a four year history of episodic colicky peristaltic abdominal pains, in whom a left paraduodenal hernia was found at surgical exploration after a negative diagnostic screening by ultrasound, CT and small bowel enema. Upon laparotomy the Authors found a left-sided paraduodenal hernia with an empty herniated sack. Repair of the hernial defect resulted in the complete and stable resolution of abdominal symptoms. The importance of considering paraduodenal hernias in the differential diagnosis of unexplained intermittent abdominal pain is discussed.

Safety and Efficacy of Direct-Acting Antiviral Drugs in Patients with Haemoglobinophaties and Chronic Hepatitis C Infection

Abstract Background and Aim: Direct-acting antiviral drugs (DAAs) have a very high efficacy in patients with hepatitis C virus (HCV) infection, but they have not been extensively used in patients with haemoglobinophaties. To evaluate the safety and efficacy of DAA regimens in this subset we used the ITHACA-SITE dataset, which includes patients with haemoglobinophaties and chronic HCV liver disease treated in Italy. Patients and methods: Between March 2015 and June 2016, 121 patients included in the ITHACA-SITE dataset started DAA regimens. Cirrhosis was defined by FibroScan®showing≥12 kPa performed within 6 months before the treatment. Regimen choice and use of ribavirin were based on viral…

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…

Phylogenetic Analysis of isolates from new cases of HBV infection in Southern Italy.

The level of endemicity of hepatitis B virus (HBV) infections in Italy is low and genotype D infections predominant. New HBV strains may however be introduced as a result of movements of people from regions of high endemicity. The aim of the present study was to determine whether strains from new cases of acute hepatitis B detected in southern Italy were due to endemic or new HBV strains. We studied 34 isolates from patients with acute hepatitis B infection, and 35 from chronic hepatitis B patients. A phylogenetic analysis of preS/S region was done by comparing the sequences from the acute and chronic cases with references sequences. The study showed that 44% of strain from acute hepatitis …

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…

Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication

Background &amp; Aims: The risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients. Methods: Data from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death. Results: Included were 1…

Smouldering hepatitis B virus replication in patients with chronic liver disease and hepatitis delta virus superinfection

Hepatitis B virus deoxyribonucleic acid (HBV-DNA) was studied by Southern blot analysis in liver biopsy specimens from 75 HBsAg-positive patients with chronic liver disease living in southern Italy. Twenty-seven of the patients were hepatitis delta virus (HDV) superinfected. Intrahepatic HBV-DNA was detected in 54 (72%) patients, 32 (59%) of them with replicative forms. The presence of replicative forms was directly related to liver HBcAg and inversely related to liver HDAg, as shown by multivariate analysis. However, 14 patients with intrahepatic HBV-DNA non-replicative pattern and about half of HDV-infected patients were liver HBcAg and/or serum HBV-DNA positive, mostly in low amounts. Hi…

Anti-tissue transglutaminase antibodies in patients with abnormal liver tests: is it always coeliac disease?

Coeliac disease (CD) is found in 5-10% of patients with chronically abnormal liver tests and no obvious cause of liver disease. In this population the efficacy of screening for CD by anti-tissue transglutaminase (anti-tTG) may be impaired by the high rate of positive anti-tTG found in chronic liver disease.To evaluate the prevalence of coeliac disease and the role of anti-tTG in patients with non-viral, non-autoimmune chronic and no obvious cause of liver damage.Out of 2,512 consecutive patients with abnormal liver tests, 168 (118 men, 50 women; mean age 40.7 +/- 12.6 years) were defined, on the basis of clinical data and liver biopsy, as NAFLD or cryptogenic chronic hepatitis. All were tes…

Efficacy of 8 weeks elbasvir/grazoprevir regimen for naïve-genotype 1b, HCV infected patients with or without glucose abnormalities: Results of the EGG18 study.

Background and aim: Direct Acting Antivirals(DAAs) achieve the highest rate of sustained viral re- sponse(SVR) in patients with genotype-1b(G1b) Hepatitis C virus(HCV) infection. Reducing treatment du- ration can simplify the management and improve adherence of therapy. Patients and methods: The study evaluates the efficacy of 8 weeks of elbasvir/grazoprevir regimen in 75 treatment-naïve(TN), G1b patients with mild-moderate fibrosis(Liver Stiffness by Fibroscan®&lt; 9.0 kPa). Viral load(VL) has been evaluated by Roche TaqMan RT-PCR(LLOQ &lt; 15 IU/ml). Results: Mean age was 61.0 ±14.2 years, 44% were male, mean LS by Fibroscan®was 6.1 ±1.8 kPa. Twenty-eight patients(37.3%) had an HOMA &gt; …

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

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). Aims We aimed to assess the potential association between uric acid serum levels and histological liver damage in a homogeneous cohort of biopsy-proven NAFLD patients. Methods Consecutive NAFLD patients (n = 166), assessed by liver biopsy (Kleiner score), anthropometric, biochemical and metabolic features, were included. Enzymatic colorimetric test was used for serum uric acid assays (Roche Diagnostics GmbH, Mannheim, Germany). Hyperuricemia was diagnosed when…

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…

Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop

Abstract The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as “possible”, “optional” or “mandatory” according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the…

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…

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. …

Hepatitis C Viremia in Chronic Liver Disease: Relationship to Interferon-α or Corticosteroid Treatment

We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody–positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (× 103 genome equivalents/ml ± S.D.), as assessed with the branched-DNA test, was 5,700 ± 7,618 in the 48 patients wi…

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…

Targeted Therapies in Hepatocellular Carcinoma

Abstract: The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients a…

Prevalence and severity of nonalcoholic fatty liver disease by transient elastography: Genetic and metabolic risk factors in a general population.

BACKGROUND & AIMS The worldwide spread of obesity is leading to a dramatic increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) and its complications. We aimed to evaluate both prevalence and factors associated with NAFLD in a general population in a Mediterranean area. METHODS We considered 890 consecutive individuals included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340). Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were measured with FibroScan. Participants were genotyped for PNPLA3 rs738409 and TM6SF2 rs58542926 variants. RESULTS The prevalence of NAFLD in the cohort was 48%. NAFL…

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…

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…

Oral Mucosa of celiac patients produces anti-endomysial and anti-transglutaminase antibodies. Diagnostic usefulness of an in vitro culture system.

Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients

Purpose: We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. Methods: This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) &lt; 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics …

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…

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…

Hepatitis E virus infection as a cause of acute hepatitis in Southern Italy

Abstract Background Hepatitis E virus (HEV) is a major cause of acute hepatitis in developing countries, whereas it is not considered a major health problem in Western World. Aims To investigate the spread of HEV and its possible role in causing acute hepatitis in Southern Italy. Methods Four hundred and thirty patients observed from April to December 2009 were studied and grouped as follows: 55 individuals with acute hepatitis (AH), 33 of whom cryptogenic; 321 individuals with chronic liver diseases (CLD), (278 Italians and 43 immigrants); 54 individuals without liver disease (control-group). Serum samples from all cases were tested for IgG anti-HEV antibodies and those positive to this te…

Impact of HBV genotypes A and D genetic variability on infection evolution

HBV is characterized by a high genetic variability, which is the basis of its classification into eight genotypes (A-H). HBV infection is associated with different outcomes, from self-limiting acute hepatitis to active chronic hepatitis, asymptomatic carriage, and occult infection. The aim of this study was to analyze the genetic variability of HBV genotypes A and D isolates from 79 cases of self-limiting acute hepatitis and chronic hepatitis, in order to identify HBV variants associated with resolution or chronicity of acute HBV infection. The entire preS-S sequence and a fragment of 346 bp of the preC-C region, containing Enhancer II and Basal Core Promoter sequences, were analyzed. A phy…

Congenital Hepatic Fibrosis

The disease presentation of autosomal recessive polycystic kidney disease (OMIM #263200, ARPKD) is highly variable and includes polycystic kidneys, pulmonary hypoplasia, and congenital hepatic fibrosis. The authors report an unusual case of ARPKD presenting with hepatosplenomegaly and cytopenia mimicking acute leukemia.

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 …

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

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.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.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.One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among…

Survival and causes of death in 2,033 patients with non-transfusion-dependent β-thalassemia

Transmembrane 6 Superfamily Member 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis From Cardiovascular Disease

Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed …

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…

PEG_interferon plus Ribavirin in compensated HCV cirrhosis with portal hypertension: the role of rapid and early virological response in predicting the sustained virological response

AISF position paper on HCV in immunocompromised patients.

Abstract This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.

Caratterizzazione biochimica e molecolare di ceppi di Mannheimia isolati da ovini siciliani.

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…

Parvovirus B19 and ‘cryptogenic’ chronic hepatitis

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

Background Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly…

Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals

Background: Despite the dramatic improvement in viral eradication rates that has been reached with direct antiviral agents (DAAs),the real benefit of viral eradication after DAAs on hepatocellular carcinoma (HCC) development is still controversial. Aim: To prospectively assess the risk of HCC occurrence and early recurrence in a large cohort of DAAtreated HCV-cirrhotic patients and to identify potential predictors of HCC development. Methods: We analyzed data prospectively collected from 1927 consecutive HCV-infected cirrhotic patients treated with DAA from January to December 2015 in 10 tertiary liver centers in Italy and followed-up for one year after therapy. 161 patients had a previous …

Interplay between non-alcoholic fatty liver disease and cardiovascular risk in an asymptomatic general population

BACKGROUND AND AIMS Non-alcoholic fatty liver (NAFLD) is a major cause of liver disease worldwide leading also to a higher risk of cardiovascular events. We aimed to evaluate the impact of fatty liver and fibrosis on cardiovascular risk in a general population. METHODS Five hundred and forty-two subjects included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study were recruited. Steatosis (controlled attenuation parameter > 288 dB/m) and severe fibrosis (low risk, liver stiffness measurement [LSM] < 7.9 KPa with M probe and < 5.7 KPa with XL probe; intermediate risk, LSM 7.9-9.5 KPa with M probe and 5.7-9.2 KPa with XL probe; high risk, LSM ≥ 9.6 KPa with…

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.

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

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 patients un…

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…

Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study

Background and aims: HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events. Methods: In a prospective multicentre study, 2204 HCV patients (F0–F2:29.5%, F3–F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59–74) years and BMI 25.9 (23.1–28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels &gt;200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24–39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral st…

HBsAg quantification in HBeAg negative cirrhosis on nucleoside/nucleotide analogue (NA) and risk of development of HCC

The impact of sustained virological response on clinical outcome in compensated HCV cirrhosis: a prospective cohort study

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…

Current epidemiological trends and outcome in a large cohort of acute hepatitis C patients.

Interferon-α for chronic hepatitis C: An analysis of pretreatment clinical predictors of response

To identify predictors of short-term and sustained ALT normalization after interferon treatment in adult patients with chronic hepatitis C, we performed a metanalysis of individual patients'data, with construction and cross-validation of a prediction rule, in 361 patients from two randomized trials. In one trial, 116 subjects with transfusion-related chronic hepatitis C were treated with lymphoblastoid interferon (5 MU/m 2 three times a week for 2 mo, then 3 MU/m 2 three times a week for 4 or 10 mo)

INFEZIONE OCCULTA DA HBV NEL PAZIENTE IMMUNOCOMPROMESSO: STUDIO DELLA ETEROGENEITA’ VIRALE

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…

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

Histomorphology of healthy oral mucosa in untreated celiac patients: unexpected association with spongiosis.

BACKGROUND: The jejunal mucosa is the major site involved in celiac disease, but modifications have also been found in the gastric, rectal and esophageal mucosa. Few studies have focused on the histomorphological features of the oral mucosa in celiac disease patients. Our objectives were: (i) to assess the presence, quality and intensity of lymphocytic infiltrate in clinically healthy oral mucosa and its relation to celiac disease severity (villous height to crypt depth ratio); and (ii) to detect any other histological features connected to celiac disease. METHODS: Twenty-one untreated celiac disease patients (age range 13-68 years) with clinically healthy oral mucosa were enrolled and comp…

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…

Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis.

Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson’s trichrome (MT), Sirius Red (SR), and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC) with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA) by Digital Image Analysis (DIA)) and correlate them with transient elastography (TE).Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein.Results. MT, SR, and orcein staining showed concord…

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…

Caratterizzazione molecolare di ceppi di Mannheimia isolati da ovini siciliani

Oral Mucosa of celiac disease patients produces anti-endomysial and anti-transglutaminase antibodes. Diagnostic usefulness of an in vitro culture system

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…

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…

Histomorphological features of healthy oral mucosa in coeliac patients: unexpected association with spongiosis”.

The presence of White Matter Lesions is not associated with Non-alcoholic Fatty Liver Disease but with its histological severity

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…

Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition.

Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients na&iuml

ISDR pattern and evolution in patients with chronic hepatitis C treated with standard or Peg-IFN plus ribavirin

The aim of the study was to characterize the interferon sensitivity determining region (ISDR) mutation pattern and its changes at 4 weeks of treatment in a population of patients infected with hepatitis C virus (HCV) genotype 1b receiving standard or PEG-IFN plus ribavirin (RBV), to find possible early correlates of therapy outcome.Forty-five patients with chronic hepatitis due to HCV 1b were treated by PEG-IFN-α2b (n=23) or IFN-α2b (n=22) plus RBV 1000–1200 mg/day. They were classified 24 weeks after stopping therapy as sustained responders (SR), relapsers (REL) or non-responders (NR). Sixteen patients were SR, 12 REL and 17 NR. ISDR mutations were evaluated by direct sequencing at baselin…

Risk of mortality from anemia and iron overload in nontransfusion-dependent β-thalassemia

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…

NS5A gene analysis by next generation sequencing in HCV nosocomial transmission clusters of HCV genotype 1b infected patients

Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with &beta

Metformina e pioglitazone in soggetti affetti da diabete mellito tipo 2 con steatosi epatica

STAGING OF FIBROSIS BY LIVER STIFFNESS MEASUREMENT IN THALASSEMICS WITH IRON OVERLOAD

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…

Schistosomiasis and antiviral treatment of chronic hepatitis C

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…

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…

Who is more likely to respond to dual treatment with pegylated-interferon and ribavirin for chronic hepatitis C? A gender-oriented analysis.

Summary We assessed, in real-life practice, viral, demographic, genetic and metabolic factors influencing the sustained virologic response (SVR), with a gender-oriented analysis, in patients with chronic hepatitis C virus (HCV) treated with pegylated interferon and ribavirin. Six hundred and seventy naive patients were treated with dual therapy and evaluated by gender and HCV genotype. Associations between baseline variables and SVR were assessed by multivariate logistic regression analysis. Among 362 genotype 1 patients, SVR was achieved in 158 patients (44%), and SVR was independently associated with age less than 50 years (OR 2.12; 95% CI 1.09–4.30; P = 0.039) and C/C genotype rs12979860…

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…

On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites

Background &amp; Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regres…

Impact of direct acting antivirals (DAAs) on cardiovascular events in HCV cohort with pre-diabetes

Background and aims: Beyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort. Methods and results: In this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We…

PATTERNS DI RECIDIVA EPATICA CON MDCT DOPO TERMOABLAZIONE A RADIOFRAQUENZA

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C.

Aims To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. Methods Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in ‘naı¨ve’ patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. Results Forty-eightpatientswereincluded(M/F28/20;meanage50.0 12.6years; 62.5% genotype-1). Body mass index was 26.4 4.0 kg/m2 , and visceral obesity was present in 24…

Valutazione della clearance di HCV-RNA sotto trattamentio antivirale con Transcription-Mediated Amplification (TMA)

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 …

Reduced incidence of type 2 diabetes in patients with chronic hepatitis C virus infection cleared by direct-acting antiviral therapy: A prospective study

Aim HCV infection increases the risk of type 2 diabetes mellitus (T2DM). However, it remains still unclear whether HCV clearance by direct-acting antivirals (DAA) reduces T2DM. Therefore, the effect of HCV eradication on T2DM incidence was assessed. Methods A prospective multicenter case-control study was performed, which included 2,426 HCV patients, 42% of which with liver fibrosis F0-F2 and 58% F3-F4. Study population consisted of a control group including 1099 untreated patients and 1327 cases treated with DAA. T2DM incidence was assessed during a follow-up median period of 30 [IQR: 28-42] months. Risk factors of T2DM were assessed by Cox regression model (Relative risk (RR), Hazard risk…

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…

Infezione occulta da HBV nel paziente immunocompromesso.studio dell'eterogeneità virale

Halitosis: could it be more than mere bad breath?

Halitosis is a generic term used to describe unpleasant odor emanating from the mouth air and breath, independent of the source where the odor substances originate. It affects between 50 and 65% of the population, but despite its frequency, this problem is often unaccepted and declared as taboo. Ninety percent of patients suffering from halitosis have oral causes: a small, but important percentage, of oral malodor cases have an extra-oral etiology, very often falling into the category of "blood-borne halitosis". Several systemic diseases have been found to provoke malodor or to be a cofactor; bad breath may be an early sign of a serious local or systemic condition. A psychogenic halitosis a…

The aetiological pattern of hepatocellular carcinoma ( HCC) in Italy is changing

The aetiological pattern of hepatocellular carcinoma ( HCC) in Italy is changing.

Comparison of three algorithms of non-invasive markers of fibrosis in chronic hepatitis C

High rate of spontaneous viral clearance in patients with iatrogenic acute hepatitis C

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…

Three Distinct Groups of Phenotype Severity in Beta-Thalassemia

Background Thalassemia Syndromes (TS) are commonly classified as transfusion-dependent-thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) at diagnosis on the basis of requirement for lifelong regular transfusion therapy for survival. However, data from observational studies and expert opinion suggest that these categories may reflect a wide spectrum rather than a dichotomy, and may actually be interchangeable at many parts of the disease journey. Thus, an evaluation of alternate clusters to classify TS patients remains of merit. Aims The aim of this study was to cluster TS patients on the basis of possible clinical indicators of phenotype severity (IPhS) using suitable algori…

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…

Caratterizzazione molecolare di ceppi di Mannheimia isolati da ovini siciliani