The rational use of albumin in patients with cirrhosis and ascites

2004

Abstract Background. Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients’ discharge from the hospital. Aims. Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites. Methods. The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts’ board and proposed to the 68 participating hepatology centres through two subsequent questionnair…

MBOAT7 locus rs641738 variant predisposes to hepatocellular carcinoma in nonalcoholic fatty liver

2016

HEPATITIS C AND DIABETES: THE INEVITABLE COINCIDENCE?

2009

Type 2 diabetes (T2D) and HCV infection are common conditions involving, respectively, at least 170 and 130 million people worldwide. However, the distribution of such cases does not overlap in the same age groups in different geographic areas. Following pioneering reports of increased prevalence of T2D in HCV-positive cirrhosis, interest concerning the relationship between HCV and T2D has escalated. HCV is able to induce insulin resistance (IR) directly and the role of specific viral genotypes responsible for such effect is disputed. IR has consistently been found to be closely linked to fibrosis in HCV infection, although also typically associated with T2D in prefibrotic stages. HCV infec…

Treatment options in HBV.

2005

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

Liver-related and extrahepatic events in patients with non-alcoholic fatty liver disease: a retrospective competing risks analysis.

2022

Background & Aim: Non-alcoholic fatty liver disease (NAFLD), and especially fibrotic non-alcoholic steatohepatitis, is associated with high risks of liver-related events (LRE) and extrahepatic events (EHE). We evaluated the competitive risk occurrence of LRE and EHE in a large cohort of biopsy-proven NAFLD stratified according to baseline severity of fibrosis. Methods: Two thousand one hundred thirty-five patients with biopsy-proven NAFLD were enrolled. Observed cumulative incidence functions (CIFs) were used to evaluate the risk of LRE and EHE; cause-specific Cox model and predicted CIFs were fitted to identify predictors of LRE and EHE. A replication cohort of NAFLD patients with live…

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

2019

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…

Expert opinion on managing chronic HCV in patients with cardiovascular disease

2018

International audience; Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment…

HCV genotype 5: an orphan virus

2013

HCV genotype 5 (HCV-5) is the least known HCV genotype. It is found mainly in South Africa and in restricted areas of Belgium, Spain, France, Syria and Greece. Sporadic cases are reported worldwide. The main modes of transmission are blood transfusion and iatrogenic causes. Little is known about its origin, but various studies have elucidated its spread worldwide. In endemic areas, patients infected with HCV-5 are on average older and have a higher viral load and more advanced fibrosis than those infected with non-HCV-5 genotypes. The current standard of care for HCV-5 chronic infection is 48 weeks of dual therapy with pegylated interferon plus ribavirin. ‘Favourable’ Il28B polymorphisms a…

Hepatitis Due to Non-A-E Viruses

2011

Early viral clearance and sustained response in chronic hepatitis C: a controlled trial of interferon and ribavirin after high-dose interferon induct…

2002

High-dose induction with alpha-interferon induces early viral clearance of hepatitis C and combined with ribavirin enhances sustained response. We assess whether adding ribavirin after viral clearance obtained by alpha-interferon induction increased the rate of viral eradication.Forty-one naïve patients with chronic hepatitis C were randomised to receive, after 4 weeks of 10 mU daily of alpha-interferon (induction), 3 mU daily for 22 weeks and 3 mU thrice weekly for 26 weeks of either interferon alone (monotherapy) or interferon plus 1000-1200 mg daily of ribavirin (combination therapy). At the end of the induction phase, 23 (56%) subjects had cleared HCV-RNA. During therapy, breakthrough w…

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

2017

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

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

2004

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

Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease: From a Clinical to a Molecular Association

2009

Hepatocellular carcinoma (HCC) is the most frequent primary neoplasm of the liver, and is the fourth most common malignancy worldwide. It is also the third leading cause of cancer-related deaths. Most cases of HCC develop on a pre-existing chronic liver disease, usually due to hepatitis C virus (HCV), hepatitis B virus (HBV), or alcohol. However, between 15% and 50% of HCC develops in the absence of a known etiology of liver disease, and different lines of evidence identify in non-alcoholic fatty liver disease (NAFLD) a possible relevant risk factor for occurrence of HCC. Insulin resistance (IR), steatosis, oxidative stress and imbalances in adipokine/cytokine interplay, the most important …

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

1996

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…

Does chemotherapy prevent HCV-related hepatocellular carcinoma? Cons.

2010

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

Early virologic response with pegylated interferons

2004

Abstract Recently, 12-week evaluation of viral response has been recommended as a means of reducing antiviral treatment morbidity and costs. The development of early stopping rules relies on an important assumption: rules must minimise discontinuation of treatment in patients who might ultimately respond after completion of the full course of therapy. Minimising loss of potential responders is the most important clinical goal in defining an early stopping rule because it provides the most sustained virological responders. This definition of the rule relies on maximising the negative predictive value. Conversely, rules that select patients based on optimising the positive predictive value pr…

Serum coding and non-coding RNAs as biomarkers of NAFLD and fibrosis severity

2019

Background & Aims: In patients with non-alcoholic fatty liver disease (NAFLD), liver biopsy is the gold standard to detect non-alcoholic steatohepatitis (NASH) and stage liver fibrosis. We aimed to identify differentially expressed mRNAs and non-coding RNAs in serum samples of biopsy-diagnosed mild and severe NAFLD patients with respect to controls and to each other. Methods: We first performed a whole transcriptome analysis through microarray (n = 12: four Control: CTRL; four mild NAFLD: NAS ≤ 4 F0; four severe NAFLD NAS ≥ 5 F3), followed by validation of selected transcripts through real-time PCRs in an independent internal cohort of 88 subjects (63 NAFLD, 25 CTRL) and in an external …

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

2017

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

Health policy model: long-term predictive results associated with the management of hepatitis C virus-induced diseases in Italy

2014

Francesco Saverio Mennini,1,2 Andrea Marcellusi,1,3 Massimo Andreoni,4 Antonio Gasbarrini,5 Salvatore Salomone,6 Antonio Craxì71Centre for Economic and International Studies (CEIS) – Economic Evaluation and HTA (EEHTA) Faculty of Economics, University of Rome Tor Vergata, Rome, Italy; 2Institute of Leadership and Management in Health, Kingston University, London, UK; 3Department of Demography, University of Rome La Sapienza, Rome, Italy; 4Department of Public Health and Cell Biology, School of Medicine, University of Rome Tor Vergata, Rome, Italy; 5Gastroenterology Division, Catholic University of the Sacred Heart of Rome, School of Medicine, Rome, Italy; 6Department of…

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

2011

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

Genetic susceptibility of increased intestinal permeability is associated with progressive liver disease and diabetes in patients with non-alcoholic …

2020

Abstract Background and aim Increased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods and results We recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 co…

Soluble complement receptor type 1 (sCR1) in chronic liver diseases: serum levels at different stages of liver diseases.

1998

SUMMARYComplement receptor type 1 (CR1) is an integral membrane protein of many haematopoietic cells and plays an important role in the clearance of complement-associated immune complexes, favouring their transport to liver and spleen macrophages. A small amount of soluble CR1 (sCR1) is also found in plasma and might originate directly from release of leucocytes and other circulating cells. In previous studies, an increase in serum sCR1 level has been observed in liver cirrhosis and end-stage renal failure. High levels have also been found in patients with some haematologic malignancies. sCR1 serum levels were measured using a specific double sandwich ELISA assay. The present study demonstr…

Real life experiences in HCV management in 2018

2019

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…

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

1991

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

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

2012

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.

2014

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…

Resistance test guided retreatment of HCV infected patients with a previous failure to a NS5A inhibitor-containing regimen: the Italian Vironet C rea…

2019

Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials &amp; methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/13…

Genotype 1 Relapsers and Non‐Responders

2011

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

2005

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…

Evaluating the association of serum ferritin and hepatic iron with disease severity in non‐alcoholic fatty liver disease

2019

Background & Aims Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non‐alcoholic fatty liver disease (NAFLD). However, it is unclear whether it reflects hepatic inflammation or true iron‐overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD. Methods We selected 468 patients with biopsy‐proven NAFLD from 2 European centres. Iron, hepatic and metabolic parameters were collected at the time of liver biopsy. Iron deposits in hepatocytes and reticuloendothelial c…

Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease.

2020

Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17…

Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation

2011

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

Modulation of epitope-specific anti-hepatitis C virus E2 (anti-HCV/E2) antibodies by antiviral treatment

2006

The dynamic features of three specific anti-hepatitis C virus (HCV) antibody subpopulations directed against different conformational epitopes of the viral E2 protein (HCV/E2) have been evaluated in patients with primary and persistent HCV infection; the three subpopulations are present in patients infected with different HCV genotypes and have shown a different activity using a pseudovirus neutralization assay (antibodies e301 and e137 exhibiting high neutralizing activity, while antibody e509 enhancement of HCV infectivity). In sequential samples from five patients with primary HCV infection and different virological outcome, all samples tested negative with the single exception of the e5…

Serology in adults with celiac disease: limited accuracy in patients with mild histological lesions.

2010

Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical patterns. It can occasionally be diagnosed in asymptomatic subjects. Our aim was to define the relationship among symptoms at diagnosis, serological markers [tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) anti-actin antibodies (AAA)] and degree of mucosal damage. A total of 68 consecutive adult patients with CD were enrolled. Intestinal biopsies were scored according to the Marsh classification modified by Oberhuber: I–II minimal lesions or absent villous atrophy; IIIA partial villous atrophy; IIIB–C total villous atrophy (TVA). HLA-typing was done for all patients. No asso…

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

2019

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 and recurrences after curative treatments of HCV-related early hepatocellular carcinoma. A meta-analysis of single arm studies

2017

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

2018

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

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

2015

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

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

2016

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

2002

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”…

The histological or ultrasonographic detection of steatosis affects the performance of LSM in patients with chronic HCV genotype 1 infection

2014

Transient elastography (TE) as a tool to evaluate acute liver damage: A prospective, multicentric cohort study

2008

Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions.

2013

Contains fulltext : 118153.pdf (Publisher’s version ) (Open Access) Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted dr…

The impact of antiviral therapy on the course of chronic HCV infection: A systematic review

2003

Aim. Chronic hepatitis C is a progressive disease that leads to liver cirrhosis and hepatocellular carcinoma in a period ranging from 10 to 30 y. Many factors have been related to disease progression and, among them, persistent HCV replication has been advocated as one of the major determinant of hepatic deterioration. With this respect any treatment of chronic hepatitis C is mainly aimed to reduce necro-inflammation by suppressing viral activity in the long-term. We evaluated the persistence of HCV clearance after interferon therapy during follow-up in patients considered as long-term responders. Secondly, we analyzed the rate of progression from hepatitis to cirrhosis and hepatocellular c…

PEG IFN alfa-2a vs. alfa-2b: And the winner is …?

2009

Abstract Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team. N Engl J Med 2009 Aug 6;361(6):580–93. Background Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. Methods At 118 sites, patients who had HCV genotype 1 infection and who had not …

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

2008

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…

PRIMARY BILIARY CIRRHOSIS AND CŒLIAC DISEASE

1978

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

2012

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

Cardiovascular diseases and HCV infection: a simple association or more?

2013

HCV infection, metabolic disorders and cardiovascular alterations, considered alone or in combination, are common conditions in a large proportion of the general population. Consequently, determining whether the association of HCV infection with cardiometabolic disorders is simply coincidental or, conversely, caused by pathogenetic mechanisms (in)directly linking chronic HCV infection to these disorders, would be of extreme relevance. Several clinical studies have shown that metabolic disorders—namely, type 2 diabetes,1 insulin resistance (IR)2 and hepatic steatosis3—are highly prevalent in patients with chronic hepatitis C (CHC) compared with non-infected patients. Experimental and clinica…

Assessment by Fibroscan of fibrosis in nonalcoholic fatty liver disease: XL versus M probe?

2012

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

2013

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…

Interferon for non-A, non-B chronic hepatitis

1991

Abstract We reviewed randomised clinical trials evaluating the effect of lymphoblastoid or recombinant α-interferon in non-A, non-B chronic hepatitis. The outcomes assessed were the rates of serum alanine aminotransferase normalization and relapse during and after stopping interferon. Data were pooled by meta-analysis and a 50% overall rate difference, favouring treated patients, was found. Results showed homogeneity in direction of treatment effect both after short-term (2–6 months, ≥ 2 mega-units thrice weekly) and long-term (9–18 months, variable dose) interferon course. Moreover, results did not change when type of publication (abstracts vs. full reports) and treatment duration or sched…

Characterization of Anti Liver Kidney Microsomal Antibody Associated with Chronic HDV Infection by Immunoblotting

1989

Cytoplasmic antibodies directed against antigen(s) present in the membranes of the endoplasmic reticulum have been reported in a proportion of patients with chronic HBV-HDV infection (Crivelli et al.,1981). While the immunofluorescence (IFL) pattern associated with LKMδ antibody is quite similar to that of the liver kidney microsomal antibody (LKM) described by Rizzetto et al. (1973) and associated with an autoimmune type of chronic active hepatitis (Thomas, 1980), the target antigen(s) was supposed to be different on the basis of blocking experiments. The target antigen of LKM antibody has been recently partially identified as a 50kD protein located in the membranes of the smooth endoplasm…

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

2017

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…

Management of hepatitis B virus infection in the underprivileged world

2011

Can we prevent and modify cardiometabolic disorders by controlling HCV infection?

2017

HCV infection has an estimated global prevalence of 1.0%, corresponding to roughly 71.1 million of infected individuals in 2015, with major geographical heterogeneity.1 Due to the large burden of infected individuals in the general population, the likelihood of co-occurrence of chronic HCV infection and common comorbidities is substantial regardless of causal linkages. Population-based studies show a higher overall mortality, both for liver-related and unrelated causes in HCV infected subjects compared with those uninfected, and cross-sectional and cohort studies identify HCV as an independent risk factor for extrahepatic manifestations.2 These issues are summarised in two meta-analyses rep…

Hepatitis C virus replication in ‘autoimmune’ chronic hepatitis

1991

Abstract Both high and low anti-hepatitis C virus antibody (anti-HCV) prevalence has been reported in autoimmune chronic active hepatitis. Therefore, we studied 15 consecutive HBsAg-negative, ELISA anti-HCV-positive, autoantibody-positive patients with biopsy proven chronic active hepatitis in order to confirm ELISA specificity by immunoblot test (RIBA-HCV), and to evaluate HCV replication by serum HCV-RNA. Nine patients were anti-nuclear, three type 1 anti-liver-kidney microsomal and three anti-smooth muscle antibody positive. None had associated autoimmune disease. All cases showed mild clinical disease and only moderate necroinflammatory activity. Response to prednisone was poor. RIBA-HC…

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy: a randomi…

2006

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)…

Hepatitis B virus reactivation and alemtuzumab therapy

2005

Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for heamatological malignancies occurs in 21–53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immmunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 epitopes on lymphocytes cells produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab. One of them developed full blown hepatitis with seroreversion from anti-HBs to HBsAg after four weeks of alemtuzumab the…

Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1)…

2014

Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus ribavirin has improved sustained virological response (SVR) in treatment-naive and treatment-experienced patients infected with hepatitis C virus (HCV) genotype 1, the regimens have a high pill burden and are associated with increased rates and severity of adverse events, such as anaemia and rash. The efficacy and safety of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in treatment-naive patients with HCV genotype 1 infection.In QUEST-1, a phase 3, randomise…

The course of oesophagogastric varices in patients with cirrhosis after DAA-induced HCV clearance

2018

Background and aims: Use of direct acting antivirals (DAAs) has allowed to clear HCV in almost all patients even in the presence of advanced cirrhosis. Although it has been suggested that cirrhotic portal hypertension may regress after SVR, the ultimate effect of HCV clearance on the development and progression of oesophagogastric varices (OV) is still unexplored. We assessed in a prospective cohort of patients with cirrhosis the evolution of endoscopic features of portal hypertension induced by SVR obtained with DAAs. Method: 321 consecutive patients (mean age: 65.1 ± 10.5, males: 58%) with HCV Child-Pugh A cirrhosis treated with DAAs were enrolled between January 2015 and May 2016. All pa…

Reply to: “Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients”

2014

Prof. Kitson’s comments give us the opportunity to clarify some issues that were not completely dealt with in our manuscript. In the study we reported a link between fructose intake and the severity of liver fibrosis in a cohort of Italian patients with genotype 1 chronic hepatitis C (CHC) [1], with an association found for industrial, but not for fruit fructose intake. Our results were in keeping with data already reported in patients with non-alcoholic fatty liver disease [2,3].

Predicting Early and Sustained Virological Responses in Prior Nonresponders to Pegylated Interferon alpha-2b Plus Ribavirin Retreated With Peginterfe…

2013

GOALS: To evaluate the predictive value of complete early virological response (cEVR) on sustained virological response (SVR) following retreatment with peginterferon alpha-2a (40 kDa) plus ribavirin in previous nonresponders to peginterferon alpha-2b (12 kDa). BACKGROUND: In the randomized multinational retreatment with Pegasys in patients not responding to PegIntron therapy study, a 72-week regimen of peginterferon alpha-2a (40 kDa) plus ribavirin improved SVR rates over a standard 48-week regimen in previous nonresponders to peginterferon alpha-2b (12 kDa). cEVR, defined as hepatitis C virus RNA <50 IU/mL at treatment week 12, was an important predictor of SVR. STUDY: We conducted an exp…

FNDC5 rs3480 A&gt;G polymorphism disentangles steatosis from fibrosis severity in patients with nonalcoholic fatty liver disease

2016

S. Petta1, L. Valenti2, R.M. Pipitone1, P. Dongiovanni2, C. Camma1, A.L. Fracanzani2, V. Di Marco1, M. Milano2, S. Grimaudo1, S. Fargion2, A. Craxi1 1 Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy 2 Department of Pathophysiology and Transplantation, Universita degli Studi, Internal Medicine, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Milano, Italy

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

2022

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…

Acute hepatitis C: in search of the optimal approach to cure.

2006

Abstract IFN monotherapy for acute hepatitis C can be supported, but a strategy taking into account both baseline (clinical presentation, genotype, HIV coinfection) and early (spontaneous viral decay) virologic response should be developed from carefully conducted, controlled prospective studies comparing a “wait and see strategy”, and different schedules of PEG IFN monotherapy to optimize adherence and costs and to reduce the number needed to treat. The price of the ultimate success of therapy for AVH due to HCV, i.e. a stable and definitive clearance of HCV with no residual liver disease in the long term, should not be paid by a high number of patients who are treated needlessly.

Luigi Pagliaro, 1931-2020.

2020

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial.

2012

BACKGROUND & AIMS: The Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% Child-Pugh A) were randomized to receive either sorafenib 400mg or matching placebo orally b.i.d. on a continuous basis. Because HCC is a heterogeneous disease, baseline patient characteristics may affect individual responses to treatment. In a comprehensive series of exploratory subgroup analyses, data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety o…

Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon-[alpha]2b: A Randomized Trial

2009

BACKGROUND Many patients with chronic hepatitis C have not responded to therapy with pegylated interferon plus ribavirin. OBJECTIVE To evaluate use of peginterferon-alpha2a plus ribavirin to re-treat nonresponders to peginterferon-alpha2b plus ribavirin. DESIGN Randomized, parallel-group trial conducted between September 2003 and February 2007. Patients and researchers were not blinded to intervention assignment. Random assignment was centralized, computer-generated, and stratified by geographic region, hepatitis C virus (HCV) genotype, and histologic diagnosis. SETTING 106 international centers. PATIENTS 950 nonresponders to 12 or more weeks of therapy with peginterferon-alpha2b plus ribav…

Duration of HCV infection as a predictor of nonresponse to interferon

1996

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…

Clinical Trial Results of Peginterferons in Combination with Ribavirin

2003

Of the large number of patients chronically infected with hepatitis C virus (HCV), only about one third have progressive liver disease, and will eventually develop cirrhosis and hepatocellular carcinoma. These are the patients for whom effective antiviral treatment is most needed. Therapy is currently recommended for patients with chronic hepatitis C who have abnormal alanine aminotransferase (ALT) levels, detectable hepatitis C virus ribonucleic acid (HCV RNA) in the blood, and significant necroinflammatory changes and/or fibrosis on liver biopsy. The current gold standard in terms of treatment efficacy is the combination of peginterferon (PEG-IFN) and ribavirin. The overall sustained viro…

Oesophagogastroduodenoscopy in patients with cirrhosis: Extending the range of detection beyond portal hypertension

2010

Background: Oesophagogastroduodenoscopy is currently recommended for the screening of varices in cirrhosis. In addition to the assessment of varices, oesophagogastroduodenoscopy can detect conditions that, while unrelated to portal hypertension, may require treatment. Aims: We evaluated in a large cohort of cirrhotic patients the prevalence of upper digestive findings other than oesophagogastric varices, the associations between upper gastrointestinal findings, portal hypertension and features of cirrhosis, and the incidence of new lesions in the course of a surveillance program. Methods: Analysis of the records of 611 consecutive cirrhotic patients undergoing oesophagogastroduodenoscopy fo…

Decrease in HDV endemicity in Italy.

1997

To evaluate a possible variation in hepatitis D virus endemicity in Italy, the data from a multicentre study concerning HBsAg chronic carriers first observed in 31 liver units during 1992 were compared with the corresponding figures from a similar study performed in 1987.In both studies the methodology for the recruitment of cases was the same. The overall anti-HD prevalence in 1992 was 14.4%, a significantly lower rate than that observed in 1987 (23.4%, p0.01). The decrease significantly (p0.01) affected both males and females; it occurred in all geographical areas, although to a greater extent in northern regions. It was evident in subjects below 50 years of age, but not in subjects older…

Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Ev…

2021

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…

PCSK9 rs11591147 R46L loss-of-function variant protects against liver damage in individuals with NAFLD

2020

Background and Aims: The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower low-density lipoprotein cholesterol (LDL-C) levels. In this study, we examined the impact of the PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models. Methods: We considered 1874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9, was genotyped by TaqMan assays. We also evaluated 1) PCSK9 mRNA…

Reducing treatment duration in patients infected with hepatitis C genotype 1: any need for further studies?

2009

The recommended treatment duration with pegylated interferon-α plus ribavirin for patients infected with hepatitis C virus (HCV) genotype 1 is 48 weeks. Interestingly, a subpopulation of genotype 1 patients experience rapid decreases in HCV RNA levels once treatment is initiated and attain rapid virological response, defined as undetectable HCV RNA at week 4 of therapy. Several studies have shown that these patients can be effectively treated for a 24-week period without any significant decreases in sustained virological response rates. The aim of this review was to consider the existing clinical evidence regarding the use of a 24-week treatment schedule among genotype 1 patients and to hi…

HCV CLEARANCE AFTER PEG IFN PLUS RBV IMPROVES THE COURSE OF HCV CIRRHOSIS REGARDLESS OF PORTAL HYPERTENSION

2009

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

2020

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…

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

2018

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter def…

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

2020

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.…

Clinical course and outcomes of drug-induced liver injury: Nimesulide as the first implicated medication

2010

Abstract Background and aims Drug-induced liver injury (DILI) is the most common cause of death from acute liver failure, and accounts for approximately 13% of cases of acute liver failure in the United States. The clinical presentation of DILI covers a wide spectrum, from asymptomatic liver test abnormalities to symptomatic acute liver disease, prolonged jaundice and disability, or overt acute or subacute liver failure. The aim of our study was to evaluate the number of DILI cases admitted to our Unit and to identify the drugs responsible. Thus, we reviewed all clinical records of patients with DILI admitted to our Unit from 1996 to 2006. Patients and methods A database was constructed, re…

Coeliac disease: Oral ulcer prevalence, assessment of risk and association with gluten-free diet in children.

2008

Aims. Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. Methods. A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. …

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

2022

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).

Endemic hepatitis C virus infection in a Sicilian town: Further evidence for iatrogenic transmission

2002

The prevalence of and risk factors for HCV and HBV infections in the general population and the predictive value of ALT screening in identifying anti-HCV positive subjects have been evaluated in a small Sicilian town. A random 1:4 sampling from the census of the general population was performed. Anti-HCV, HCV-RNA, HCV genotype, HBsAg, and anti-HBc were tested. The linkage between HCV infection and potential risk factors was evaluated by multiple logistic regression analysis. Among 721 subjects studied, 75 (10.4%) were anti-HCV positive. The HCV infection rate increased from 0.4% in subjects 10–29 years of age to 34% in those > 60 years of age. Among the 75 anti-HCV positive subjects, 66.7% …

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

2019

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. …

HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals

2017

Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low level…

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

2019

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…

630 SERUM BLYS/BAFF LEVELS IN ACUTE HEPATITIS C PREDICT CLINICAL OUTCOME

2008

Implication of Normal Liver Enzymes in Liver Disease

2009

Summary.  Chronic liver disease is usually asymptomatic until its late stages and also significant hepatic necroinflammation and fibrosis may be present in persistently normal ALT levels HBV, HCV carriers or similarly, in patients with nonalcoholic fatty liver disease. Given the large number of persons in the general population which may harbor a clinically significant liver disease behind the screen of normal alanine aminotransferase, more attention should be devoted to future research for alternative noninvasive markers of liver damage.

Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib

2015

Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression, liver decompensation, or adverse effects. While postprogression survival is clearly determined by the pattern of tumor progression, understanding the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included. Postsorafenib survival (PSS) was calculated from the last day of treatmen…

Usefulness of the index of NASH - ION for the diagnosis of steatohepatitis in patients with non-alcoholic fatty liver: An external validation study

2018

Background & Aims The non-invasive identification of steatohepatitis (NASH) in patients with Non-Alcoholic Fatty Liver Disease is an unmet need in clinical practice. Index of NASH (ION) is a new tool for the prediction of NASH. We aimed to externally validate ION and to compare it with CK-18. Since necroinflammation precedes fibrosis, we also tested ION in combination with non-invasive tools for fibrosis. Methods We analysed data from 292 Italian patients (169 Southern cohort, and 123 Northern cohort) with an histological diagnosis of NAFLD. The ION, FIB-4 and NFS scores were calculated according to published algorithms. Serum cytokeratin18-Aspartate396 levels and liver stiffness (LS) by Fi…

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

2018

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

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

2016

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

Is liver stiffness measurement unreliable in obese patients? authors’ reply

2011

150 LIVER RELATED EVENTS AND SURVIVAL IN PATIENTS WITH COMPENSATED HCV CIRRHOSIS: THE ROLE OF SUSTAINED VIROLOGICAL RESPONSE TO PEG-IFN BASED THERAPY…

2011

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

2021

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…

Add-On Peginterferon Alfa-2a Significantly Reduces HBsAg Levels in HBeAg-Negative, Genotype D Chronic Hepatitis B Patients Fully Suppressed on Nucleo…

2016

23 (36%) cases, respectively. Ribavirin (RBV) was used in 35% and 65% of the patients receiving SOF and DCV, respectively. Most of the patients were male (72%) and genotype 1b (81%). Median age was 59 years. Median baseline MELD and Child–Pugh (CPT) scores were 9 and 6, respectively. Among the patients with cirrhosis, 47% were CPT B/C. Tacrolimus was the immunosuppressant used in the majority of the patients (69%). At the beginning of therapy, 20 patients had ascites and 3 had hepatic encephalopathy (HE). Thirty-four patients completed the treatment course and 30 are still on therapy. End of treatment (EOT) response was 88% (30/34) and SVR12 was 83% (25/30). In patients receiving SMV+DCV±RB…

Hepatitis B- a Therapeutic Vaccine: Hope or Hype?

2010

Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease

2017

Abstract In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD‐HCC. In 40 patients with NAFLD‐HCC, 45 with NAFLD‐cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT‐PCR and hTERT coding regions and intron–exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD‐PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequ…

Extrahepatic Manifestations of Chronic HCV

2011

A number of extrahepatic manifestations have been reported in patients infected with HCV. The most prominent of theme are MC vasculitis, lymphoproliferative malignancies, renal disease, polyarthritis, thyroid and glucose disorders. Although these conditions might have a substantial impact on morbidity, patient management, and prognosis, for most of them the exact mechanisms underlying their development require further elucidation.

Forecasting liver disease burden

2018

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

2021

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.…

VALUTAZIONE DELLA CLEARANCE DI HCV-RNA SOTTO TRATTAMENTO ANTIVIRALE CON TRANSCRIPTION-MEDIATED AMPLIFICATION (TMA)

2005

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

1996

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 …

HBV recurrence after HCV clearance on DAAs: Sometimes they come back

2017

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

2010

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…

Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study

2018

BACKGROUND Cirrhosis is associated with morpho-functional cardiovascular alterations. AIMS To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs). METHODS Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain …

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

2011

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…

Immunoblotting as a confirmatory test for antimitochondrial antibodies in primary biliary cirrhosis.

1993

Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of whom were antimitochondrial antibody positive by immunofluorescence), 16 non-primary biliary cirrhosis patients (antimitochondrial antibody positive by immunofluorescence), 23 liver-kidney microsomal antib…

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

2017

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 …

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

2009

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

Survival of unresectable hepatocellular carcinoma: A meta-analysis of the control arms of 28 randomized trials

2009

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

2019

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 …

The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent

2016

Background &amp; Aims Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C&gt;T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD. Methods We genotyped rs641738 in DNA collected from 3854 participants from the Dallas Heart Study (a multi-ethnic…

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

2006

Prevalence and Risk Factors of Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Without Steatohepatitis

2019

In patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is a risk factor for the development of fibrosis. However, fibrosis has been observed in livers of patients without NASH. We aimed to estimate the prevalence of fibrosis in patients without NASH and risk factors for fibrosis.We analyzed data from 1738 subjects (44.9% with severe obesity) in a cross-sectional liver biopsy cohort enrolled at referral centers in Italy and Finland. Biopsy specimens were analyzed histologically by a blinded pathologist at each center, and a diagnosis of NASH was made based on steatosis (≥5% of hepatocytes), hepatocellular ballooning, and lobular inflammation. We also c…

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

2011

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

Fluoroquinolone-induced liver injury: three new cases and a review of the literature.

2012

PURPOSE: Fluoroquinolones are popular and widely used in primary care and hospital settings. Premarketing studies showed a favourable side-effect profile. However, significant morbidity and the need for liver transplantation for acute liver failure have been reported. We reviewed the available data on liver damage linked to fluoroquinolones. METHODS: A systematic search of case reports on the MEDLINE database encompassing the years 2000-2011 was carried out. Additional references were found by a manual search of the retrieved paper. We also describe three new cases of hepatotoxicity attributable to fluoroquinolones seen at our Unit. RESULTS: Thirty-five cases were retrieved from MEDLINE (51…

Will the COVID-19 pandemic affect HCV disease burden?

2020

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

2009

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…

Reply to: "Hepatic benefits of HCV cure: Don't forget coagulation!"

2020

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

2019

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.

Clinical course and prognostic factors of hepatorenal syndrome: A retrospective single-center cohort study

2013

AIM: To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short and long-term survival evaluating potential predictors of early mortality. METHODS: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients (53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and albumin, and three with albumin alone. No patients…

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

2001

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

A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding

2014

Abstract Background Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding. Aims To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality. Methods In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score. Results Overall, 602 patients underwent early upper endoscopy, and…

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

2009

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…

Multiple voltage‐gradient gel electrophoresis system

2001

A new device, based on the principle of voltage-gradient gel electrophoresis, was developed in order to enhance differentiation of the distance across the range of molecular masses in the electrophoretic fractionation of nucleic acids in an agarose matrix. The apparatus has a series of modular parallel plates, placed slantwise to allow reiteration of the voltage gradient effect along the gel. This subjects DNA fragments of variable length to differential runnings according to their original position in the gel. Both the number of slantwise plates and the distance between them can be changed to modify operating performance. Our system allows better fractionations as compared to conventional …

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

2011

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

Fecal Calprotectin in Clinical Practice

2012

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

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

2009

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

2019

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:…

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

2023

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

P1013 : Chronic intermittent hypoxia is associated with liver damage and atherosclerosis in patients with non-alcoholic fatty liver disease

2015

all the steatosis grades, except S2 vs S3. The diagnostic performances of CAP in quantifying each steatosis grade was: for S ≥1 AUC=0.813 (cutoff 260dB/m, Se = 64.84%, Sp =87.27%, PPV=80.8%, NPV=75%, +LR =5.09, −LR =0.40, DA=76.11%); for S ≥2 AUC=0.822 (cutoff 285dB/m, Se = 69.70%, Sp =85.12%, PPV=47.9%, NPV=93.5%, +LR =4.68, −LR =0.36, DA=82.08%); for S ≥3 AUC=0.838 (cutoff 294dB/m, Se =83.33%, Sp =82.54%, PPV=23.3%, NPV=98.7%, +LR =4.77, −LR =0.20, DA=81.59%). AUCs calculated between two steatosis grades only were: 0.772 (for S0 vs S1), 0.874 (S0 vs S2), 0.904 (S0 vs S3), 0.659 (S1 vs S2), 0.777 (S1 vs S3), and 0.665 (S2 vs S3) respectively. Conclusions: Maximal diagnostic accuracy could …

RUOLO DELL’INFEZIONE OCCULTA DA HBV NEL PAZIENTE IMMUNOCOMPROMESSO

2005

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The long-term course of chronic hepatitis B

1999

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

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

2009

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

Daclatasvir-based regimens in HCV cirrhosis: experience from the Italian early access program

2019

AbstractWe reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n = 221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n = 54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustai…

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

2017

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

Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection.

2003

Background & Aims: Occult hepatitis B virus (HBV) infection is characterized by persistence of HBV DNA into the tissue of hepatitis B surface antigen-negative individuals. The clinical relevance of this peculiar infection is still under debate. In particular, the impact of occult HBV infection in cases of hepatocellular carcinoma (HCC) is uncertain. We investigated the prevalence and molecular status of occult HBV in patients with HCC. Methods: We tested tumor tissues from 107 patients with HCC and the corresponding nontumor liver tissue from 72 of these patients for HBV DNA. We also examined liver specimens from 192 patients with chronic hepatitis. All cases were hepatitis B surface antige…

FibroScan Identifies Patients With Nonalcoholic Fatty Liver Disease and Cardiovascular Damage

2020

BACKGROUND &amp; AIMS: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely associated, and liver fibrosis has been related to macrovascular complications. We examined whether liver fibrosis, diagnosed by FibroScan® , correlates with chronic vascular complications in a cohort of T2DM. METHODS: We recruited 394 outpatients with T2DM attending five Italian diabetes centres who underwent liver ultrasonography (US), FibroScan® and extensive evaluation of macrovascular and microvascular diabetic complications. RESULTS: Steatosis by US was present in 89%. Almost all patients (96%) were on hypoglycaemic drugs, 58% had at least one chronic vascular complication,…

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

2013

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…

Occult HBV infection and suppression of HCV replication in the early phase of combination therapy for chronic hepatitis C

2003

Occult HBV infection in subjects with chronic hepatitis C is related to more severe disease outcome. It has been suggested that it might reduce sensitivity to antiviral treatment.To assess in HBsAg negative subjects with chronic hepatitis C any effect of the presence of HBV genomes in the liver on the early kinetics of HCV-RNA under PEG-IFN plus ribavirin.Twenty-two anti-HCV and HCV-RNA positive subjects, with biopsy-proven chronic hepatitis C (M/F 15/7; 50 +/- 8.6 years, 16 genotype 1b) were given PEG-IFN alpha 2b 1.0 microg qw plus ribavirin (800 to 1,200 mg daily according to body weight) for an intended 52 week period. Early virological response was assessed over the first 4 weeks of th…

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

2000

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…

Steatohepatitis and type 2 diabetes mellitus are influenced by genetic susceptibility to increased intestinal permeability in patients with non-alcoh…

2017

Reply.

2016

Serum antibodies to thymus epithelial cells in non-A, non-B and cryptogenic chronic liver disease

2008

Antibodies against thymus epithelial cells (anti-TEC) and the basal cell layer (BCLA) of squamous epithelia have been described in association with HDV-related chronic liver disease (CLD). Data are lacking on their presence during nAnB virus infection. Sera from 51 patients with nAnB post-transfusion hepatitis, including acute and chronic cases diagnosed during a prospective study on candidates for cardiac surgery, and 167 with various forms of CLD were tested for the presence of anti-TEC and BCLA using indirect immunofluorescence on human thymus and rat forestomach sections. Both antibodies mainly occurred in nAnB, HDV and cryptogenic CLD (anti-TEC: 51%, 47% and 42%; BCLA: 29%, 38% and 31%…

Hepatocellular carcinoma and direct-acting antivirals: A never ending story?

2017

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

2013

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

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

2021

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 …

The rs2294918 E434K variant modulates patatin-like phospholipase domain-containing 3 expression and liver damage

2016

The patatin-like phosholipase domain-containing 3 (PNPLA3) rs738409 polymorphism (I148M) is a major determinant of hepatic fat and predisposes to the full spectrum of liver damage in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate whether additional PNPLA3 coding variants contribute to NAFLD susceptibility, first in individuals with contrasting phenotypes (with early-onset NAFLD vs. very low aminotransferases) and then in a large validation cohort. Rare PNPLA3 variants were not detected by sequencing coding regions and intron-exon boundaries either in 142 patients with early-onset NAFLD nor in 100 healthy individuals with alanine aminotransferase22/20 IU/mL. …

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

2011

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

From viral pathobiology to the treatment of hepatitis B virus infection EASL Monothematic Conference (Istanbul, Turkey, October 6-8, 2005).

2006

Hepatitis B virus infection, which was for over a decade put aside by the rising star of hepatitis C, has seen over the last years a resurgence of interest. This stemmed from a better knowledge of the virus itself, from the availability of new drugs and combinations, and from the realization that far from being eradicated by mass immunization programs HBV is still on a worldwide basis the major cause of cirrhosis and hepatocellular carcinoma, alone or in combinations with other viruses, alcohol andmetabolic cofactors. This prompted the EASL Scientific Committee to organize a Monothematic Conference on HBV. Experts from Europe, USA, Canada, Australia, the Far East and other parts of the worl…

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

2008

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. …

Effectiveness of beta-blocker in primary prevention of variceal bleeding in patients with cirrhosis: A prospective evaluation by hepatic venous press…

2014

Optimizing the treatment of chronic hepatitis due to hepatitis C virus genotypes 2 and 3: a review

2009

Recently several randomized trials involving exclusively HCV 2 and 3 patients have explored the possibility of reducing the duration of therapy with PEG IFNs and ribavirin to 12–16 weeks. Among these, the largest studies (ACCELERATE, NORTH-C and NORDynamIC) have failed to demonstrate, by intention-to-treat analysis, that short treatment is non-inferior to the standard duration of 24 weeks originated by phase 3 trials. Even though obtaining univocal conclusions from these studies are difficult to obtain due to some critical differences (trial design, genotypes 2/3 ratio, rate of cirrhosis at baseline, ribavirin dose, assays to detect HCV-RNA etc), all have proved that a rapid virological res…

Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis

2002

Abstract Background. Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. Aim. To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. Results. The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to …

Reply: Fibrosis in liver as a predictive marker for hepatitis C virus therapy

2010

Laboratory Tests in Crohn’s Disease

2015

Laboratory tests are useful for diagnosing Crohn’s disease, assessing disease activity, identifying complications, and monitoring response to therapy. Their role has been considered limited in the past due to lack of specificity. The introduction of biological therapies in inflammatory bowel disease (IBD) has renewed interest in inflammatory markers, especially C-reactive protein (CRP), given their potential to select responders to these treatments. There are several reasons why laboratory markers have been studied in IBD in the past decades: firstly, to gain an objective measurement of disease activity as symptoms are often subjective; secondly, to avoid invasive (endoscopic) procedures wh…

The dilemma for patients with chronic hepatitis C: treat now or warehouse?

2013

Dual therapy with peginterferon and ribavirin, the only treatent for chronic hepatitis C available In Italy and in many other ountries worldwide up to 2013, obtains satisfactory response ates in infections with hepatitis C virus (HCV) genotype 2, but far rom optimal for other genotypes [1,2]. Eradication requires 6–12 onths of therapy, with significant inconvenience for patients: dverse reactions force premature termination in about 20% of atients and reduced the quality of life for almost all who persist n treatment. In view of the important and prolonged side effects, nterferon-based treatment is perceived as a nightmare by many symptomatic,well-being, socially activepatients (the largema…

Third-generation hepatitis C virus tests in asymptomatic anti-HCV-positive blood donors

1994

This study evaluated the performance of third-generation anti-HCV assays in blood donors who were positive by second-generation anti-HCV, and assessed any possible relationship between antibody patterns, HCV replication and liver damage. Fifty-two second-generation enzyme immunoassay-positive asymptomatic Italian blood donors were retested for anti-HCV by third-generation enzyme immunoassay and recombinant immunoblot assay (Ortho third-generation enzyme immunoassay, third-generation recombinant immunoblot assay), utilising recombinant C33c and NS5 and synthetic peptide C100 and C22 antigens, and for HCV-RNA by "nested" polymerase chain reaction with 5' region primers. Alanine aminotransfera…

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort

2023

Background and aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. Methods: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. Results: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% a…

Hepatitis B Virus Reactivation and Alemtuzumab Therapy.

2004

Abstract Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for haematological malignancies occurs in 21–53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 on lymphoid cells, produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab. One of them developed a full blown hepatitis with seroreversion from anti-HBs to HBsAg after four weeks of alemtuzumab. Lam…

Transient elastography vs. platelets or APRI score to assess fibrosis in chronic hepatitis C

2008

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

2006

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

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

2009

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

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

2010

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 …

A patient with acute hepatitis C and possible IFN toxicity

2003

Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy

2021

Background & Aims There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. Methods Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. Results Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis …

Regression of fibrosis after HBV antiviral therapy. Is cirrhosis reversible?

2014

Long-lasting HBV-DNA suppression is considered to be the best surrogate end-point of antiviral therapy in patients with hepatitis B virus (HBV) related chronic hepatitis or cirrhosis, and it is a prerequisite to prevent liver-related complications and improve survival. Treatment with oral antiviral drugs in patients with HBV cirrhosis is effective in restoring liver function and improving survival even in those with decompensated cirrhosis. These agents are generally well-tolerated for long-term treatment, and several evidences have demonstrated that they are able to reverse liver fibrosis and prevent the occurrence of HCC.

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

2020

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. Approach and Results: We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor (FGF) 19 levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain containing 3 (PNPLA3), and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and nonlean NAFLD were investigated in a cohort of Caucasian patients with biopsy-proven NAFLD (n …

Are hepatitis G virus and TT virus involved in cryptogenic chronic liver disease?

2002

Abstract Background . Hepatitis G virus can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. Little is known about the relation of another newly discovered agent, the TT virus, with chronic liver disease. Aim . To investigate the rate of infection with hepatitis G virus and TT virus in patients with cryptogenic chronic liver disease. Patients . A total of 23 subjects with chronically raised alanine transaminase and a liver biopsy in whom all known causes of liver disease had been excluded, and 4D subjects with hepatitis C virus-related chronic liver disease. Methods . Evaluation of anti-hepatitis G virus by enzyme immunoassay. Hepatiti…

Hepatocellular cancer: optimal strategies for screening and surveillance.

2009

Hepatocellular carcinoma (HCC) is a challenging malignancy of global importance and is associated with a high rate of mortality. Individuals with chronic viral hepatitis and other forms of liver disease are at risk for developing HCC. The stage of cancer dictates the therapeutic choice, making early detection a primary objective. Many observational studies have reported that HCC is diagnosed at an earlier stage in patients who received surveillance. The guidelines of the American Association for the Study of Liver Diseases suggest that surveillance should be performed using ultrasonography at an interval of every 6–12 months. This interval is based upon mainly observational data and the exp…

Occult hepatitis B virus infection

2000

Many studies have shown that hepatitis B virus infection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virus infection may contribute to chronic liver damage, considering that it is usually associated…

Characteristics of hepatocellular carcinoma in Italy.

1998

This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values.A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included.We found that 71.1% of cases were positive for hepatitis C virus antibodies but negati…

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

2013

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…

FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin…

2011

Background & Aims EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon–alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Methods Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV)…

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

2007

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…

Occult hepatitis B virus infection and hepatocellular carcinoma development in patients with chronic hepatitis C

2011

Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study

2018

PubMed: 29599078

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

2013

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?

2009

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…

A mathematical model by route of transmission and fibrosis progression to estimate undiagnosed individuals with HCV in different Italian regions.

2022

Abstract Background Although an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown. Methods A probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0–F3 (i.e. patients without liver cirr…

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

2011

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

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

2010

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

2015

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…

Immunological alterations in hepatitis C virus infection

2013

A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjogren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will out…

Needle track seeding following percutaneous procedures for hepatocellular carcinoma.

2009

Neoplastic seeding may arise after diagnostic or therapeutic percutaneous procedures for hepatocellular carcinoma. The true incidence of seeding with hepatocellular carcinoma is difficult to assess precisely, but a significant risk of seeding exists and is greater when performing diagnostic biopsy as compared to therapeutic percutaneous procedures [radiofrequency ablation, radiofrequency ablation (RFA); percutaneous ethanol injection, Percutaneous ethanol injection (PEI)]. Whenever liver transplantation is feasible, diagnostic needle biopsies should be avoided, but RFA and PEI are often needed as “bridge” treatments. The role of adjuvant treatments in reducing the incidence of seeding follo…

Statin use and non-alcoholic steatohepatitis in at risk individuals.

2015

Background &amp; Aims Excess hepatic free cholesterol contributes to the pathogenesis of non-alcoholic steatohepatitis, and statins reduce cholesterol synthesis. Aim of this study was to assess whether statin use is associated with histological liver damage related to steatohepatitis. Methods The relationship between statin use, genetic risk factors, and liver damage was assessed in a multi-center cohort of 1201 European individuals, who underwent liver biopsy for suspected non-alcoholic steatohepatitis. Results Statin use was recorded in 107 subjects, and was associated with protection from steatosis, NASH, and fibrosis stage F2-F4, in a dose-dependent manner (adjusted p &lt;0.05 for all).…

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

2018

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 …

OC.03.2 THE PRESENCE OF WHITE MATTER LESIONS IS ASSOCIATED WITH THE HISTOLOGICAL SEVERITY OF NON-ALCOHOLIC FATTY LIVER DISEASE

2016

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

2014

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