Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis…

2019

Wong, Grace LH/0000-0002-2863-9389; Wong, Vincent WS/0000-0003-2215-9410; Mangia, A/0000-0002-2600-3555; Brahmania, Mayur/0000-0002-4671-1479; Chan, Henry Lik-Yuen/0000-0002-7790-1611; Brouwer, Willem Pieter/0000-0001-8713-1481; Feld, Jordan/0000-0003-2640-2211; Tanwandee, Tawesak/0000-0001-7634-0843; Jaroszewicz, Jerzy/0000-0003-0139-4753; Chuaypen, Natthaya/0000-0002-5415-510X

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…

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…

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…

RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE St…

2022

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

Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

2019

Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; media…

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…

Forecasting liver disease burden

2018

High efficacy of direct-acting anti-viral agents in hepatitis C virus-infected cirrhotic patients with successfully treated hepatocellular carcinoma

2018

Background: The efficacy of direct-acting anti-viral (DAA) therapy in patients with a history of hepatocellular carcinoma (HCC) is unknown. Aim: We prospectively evaluated whether previously treated HCC affects DAA efficacy in a large real-life cohort of cirrhotic patients. Methods: From January to December 2015 all consecutive HCV mono-infected patients with cirrhosis and/or history of HCC attending 10 Italian tertiary liver centres were enrolled. Baseline characteristics and response to therapy were recorded. 1927 patients were enrolled (mean age: 62.1 10.9 years; 1.205 males). Genotype 1 was the most frequent (67.9%) followed by genotypes 3 (12.4%), 2 (11.2%) and 4 (8.6%). 88.4% and 10.9…

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.

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…

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 …

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

2012

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

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 tria…

2019

© 2019 Elsevier Ltd. All rights reserved.

Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy

2021

Valentina Burgio,1 Massimo Iavarone,2 Giovanni Giuseppe Di Costanzo,3 Fabio Marra,4 Sara Lonardi,5,6 Emiliano Tamburini,7 Fabio Piscaglia,8 Gianluca Masi,9,10 Ciro Celsa,11 Francesco Giuseppe Foschi,12 Marianna Silletta,13 Daniela Caterina Amoruso,14 Margherita Rimini,15 Mariangela Bruccoleri,2 Raffaella Tortora,3 Claudia Campani,4 Caterina Soldà,6 Massimo Giuseppe Viola,16 Antonella Forgione,8 Fabio Conti,12 Francesca Salani,9,10 Silvia Catanese,9,10 Carmelo Marco Giacchetto,17 Claudia Fulgenzi,13 Carmine Coppola,14 Pietro Lampertico,18 Antonio Pellino,6,19 Gabriele Rancatore,17 Giuseppe Cabibbo,17 Francesca Ratti,20 Federica Pedica,21 Angelo Della Corte,22 Massimo Colombo,18 Francesco De…

Clinical evaluation and applications of the Amplicor HBV Monitor™ test, a quantitative HBV DNA PCR assay

1998

Viral load has emerged recently as a reliable marker of disease progression and therapeutic efficacy in chronic infections, including AIDS and hepatitis C. The clinical management of type B hepatitis could also be improved by monitoring viremia levels in patients with chronic liver disease undergoing anti-viral treatment. To address this question we evaluated the performance of a newly developed, quantitative PCR assay (Amplicor HBV Monitor test, Roche Diagnostic Systems) in the assessment of viremia changes over time in a group of 45 patients with chronic active hepatitis (CAH) who received interferon treatment. Of the 45 patients, 14 were HBsAg and anti-HBeAg positive and 31 HBsAg, HBeAg …

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

2011

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

Dual proteotoxic stress accelerates liver injury via activation of p62‐Nrf2

2021

Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and H…

Add-on Peginterferon Alfa-2a significantly reduces HBsAg levels in chronic hepatitis B, HBeAg-negative, genotype D patients fully suppressed on nucle…

2015

AISF position paper on HCV in immunocompromised patients.

2018

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

Regorafenib Efficacy After Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation:A Retrospective Study

2021

Background and aim Safety of regorafenib in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been recently demonstrated. We aimed to assess the survival benefit of regorafenib compared to best supportive care (BSC) in LT-patients after sorafenib discontinuation. Methods This observational multicenter retrospective study included LT-patients with HCC-recurrence who discontinued first-line sorafenib. Group-1 was constituted by regorafenib-treated patients, while control group was selected among patients treated with best supportive care (BSC) due to unavailability of second-line options at the time of sorafenib discontinuation and who were sorafenib-tolerant prog…

A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B

2018

Background Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. Aims To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this e…

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

2018

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

A multicenter randomized controlled trial of recombinant interferon-α2b in patients with acute transfusion-associated hepatitis C

1994

To assess whether interferon-α might prevent non-A, non-B hepatitis from becoming chronic, 45 consecutive patients with transfusion-associated hepatitis were enrolled in a randomized clinical trial. Thirty-eight patients had hepatitis C virus infection, and 7 had non-A, non-B, non-C hepatitis. Twenty-six patients (22 with HCV) were given 3 MU of recombinant interferon-α2b three times a week for 12 wk, whereas 19 (16 with HCV) were not. Biochemical and virological parameters were monitored at regular intervals during an 18-mo follow-up. At the end of the 3-mo therapy, 16 (73) patients with hepatitis C had normal serum ALT activity, compared with 7 (44) who were not treated (NS). Fifty-three …

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

2021

Background &amp; aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P &lt; 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER …

2021

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p &lt; 0.001), females 56.5% vs. 45.3%, (p &lt; 0.001), HBsAg positivity 3.8% vs. 1.4%, (p &lt; 0.05). Genotype 1b was prevalent in both gro…

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

2021

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 77…

Effectiveness and safety of switching to entecavir hepatitis B patients developing kidney dysfunction during tenofovir

2019

Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. Methods: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (e…

Serological Tests Do Not Predict Residual Fibrosis in Hepatitis C Cirrhotics with a Sustained Virological Response to Interferon

2016

BACKGROUND AND AIM: Liver biopsy (LB) has lost popularity to stage liver fibrosis in the era of highly effective anti-hepatitis C virus (HCV) therapy, yet diagnosis of persistent cirrhosis may have important implications following HCV eradication. As performance of serological non-invasive tests (NITs) to predict residual fibrosis in non-viremic HCV patients is unknown, we investigated accuracy of NITs to predict residual fibrosis in cirrhotics after a sustained virological response (SVR) to interferon (IFN). METHODS: Thirty-eight patients with a pre-treatment histological diagnosis of cirrhosis and a 48–104 months post-SVR LB were tested with APRI, CDS, FIB-4, FibroQ, Forns Score, GUCI Ind…