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 & 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…

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…

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…

Forecasting liver disease burden

2018

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

2019

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

Current epidemiology of HCV in Sicily: the RESIST-HCV model

2019

Background: Real-world data to guide hepatitis C virus (HCV)- related public health initiatives and linkage to care of patients are lacking in our region. Aims: To describe the epidemiological features of a large cohort of patients with chronic HCV infection from Sicily included in a regional network aimed at DAA treatment (RESIST-HCV). Methods: Demographic and clinical data were recorded on a web-based platform before starting treatment with DAAs. Gender, year of birth, HCV genotype, co-infections, stages of liver disease and co-morbidities were analyzed. Chi-square with Yates correc- tion was appliedto assess the differences between cohorts. Results: Overall, 15,270 patients were register…

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

2018

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

Treatment of elderly HCV patients with severe fibrosis: safety and efficacy data from RESIST-HCV, a large regional database

2016

Corrigendum to “Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV” [J Hepatol 68 (2018) 33–41](S01688278173…

2018

It has come to our attention that the PITER framework investigator, Alessandro Federico, was incorrectly listed as F. Alessandro in the original manuscript. Please note that the correct name of this author is Alessandro Federico (2nd University of Naples). The correct list of PITER investigators is in the footnote below.

The HCV Sicily Network: A web-based model for the management of HCV chronic liver diseases

2016

Epidemiological studies report that in Sicily reside about 30,000 citizens with a diagnosis of chronic hepatitis due to HCV. The availability of direct antiviral action (DAA) is a real therapeutic breakthrough, but the high cost of the therapeutic regimes limits their use and forced the National Health System to establish clinical priority for the treatment.The HCV Sicily Network is a web-based model of best medical practice, which was designed to improve the management and the treatment of HCV chronic hepatitis and cirrhosis. The network includes 41 centers and 84 gastroenterologists or infectivologists connected by a web platform that recorder the diagnosis and the clinic priority for the…

Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: A multicentre independent study supported by the Italian Drug Agency

2014

a b s t r a c t Background: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in “real world” chronic hepatitis C patients in Italy. Methods: Independent observational multicentre study including consecutive patients receiving Peginterferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. Results: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sust…

Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen-negative chronic hepatitis B genot…

2019

Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D-infected patients. We conducted an open-label study of peginterferon alfa-2a 180 μg/week added to ongoing NA therapy in hepatitis B e antigen (HBeAg)-negative, genotype D-infected patients with HBV DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48-week add-on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per-protocol population) was 67.4% (29/43) at…

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

2011

Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C

2021

Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SO…

Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV

2017

Background &amp; Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER)…

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…

Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicen…

2017

SummaryBackground Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. Aim To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. Methods We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the…

The changing scenario of hepatocellular carcinoma in Italy: an update

2021

Background and aims: Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, management and prognosis of HCC in Italy during the last 15 years. Methods: Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004-2008, 2009-2013 and 2014-2018). Results: The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non-viral cases and, particularly, of ‘metabolic’ and ‘metabolic + alc…

Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data

2019

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulativ…

Pattern of macrovascular invasion in hepatocellular carcinoma

2021

Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed …

Supplementary Material for: Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Tra…

2021

Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) …