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…

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

2016

Background & 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…

Italian association for the study of the liver position statement on SARS-CoV2 vaccination.

2021

The vaccination campaign against Sars-CoV-2 commenced in Italy at the end of December 2020. The first ones to receive the immunization against the virus were the health workers and the residents of nursing homes, following which the vaccine would be available for the entire population, beginning with the most vulnerable individuals. SARS-CoV2 vaccines have been demonstrated to be safe for the general population, although no data for patients with liver diseases or those having undergone liver transplantation are available so far. The present position statement AISF is an attempt to suggest, based on the published data on the impact of Sars-Cov-2 infection in patients with chronic liver dise…

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…

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…

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…

Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

2019

AbstractNonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n = 181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000 G. Pathogenic variants were defined according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity. In NAFLD-HCC patients, we detected an enrichment in pathogenic (p = 0.024), and likely pathogenic variants (p = 1.9*10−6), particularly in APOB (p = 0.047). APOB variants were asso…

Is there an ‘ideal’ diet for patients with NAFLD?

2021

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic that encompasses three distinct clinical phenotypes: uncomplicated fatty liver, non-alcoholic steato-hepatitis (NASH) and NASH-related cirrhosis with its complications, including hepatocellular carcinoma. To date, no pharmacological treatments have been approved and lifestyle modifications including reduced caloric intake targeting a 7-10% weight loss from baseline assessment represent the standard approach. Mediterranean Diet has been recommended as the best dietary pattern since it is easy to follow and, independently of caloric intake its nutritional components have beneficial metabolic effects that not only improve steatosi…

Assessing the impact of COVID-19 on the management of patients with liver diseases: A national survey by the Italian association for the study of the…

2020

Abstract Background The COVID-19 pandemic had a huge impact on national and regional health systems. The impact of SARS-CoV-2 on the quality of care for patients with liver disease is still unknown. Aims The Italian Association for the Study of the Liver (AISF) conducted a survey to assess the impact of SARS-CoV-2 on hepatology units activities in Italy. Methods A prospective web-based survey was proposed to all AISF active members. The survey was available online from April 8 2020, to May 3 2020, (lockdown phase in Italy). Results 194 AISF members answered the questionnaire, most of whom were specialists in Gastroenterology (41%) or Internal Medicine (28%), and worked in Northern Italy (51…

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 …

Management of liver disease in Italy after one year of the SARS-CoV-2 pandemic: a web-based survey

2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)pandemic has severely limited the clinical activity of most hospitals around the world. A previous survey of the Italian Association for the Study of the Liver (AISF) has demonstrated a negative impact of the first pandemic wave on all inpatient and outpatient hepatologyactivities. Like other countries, Italy has subsequently experienced a second and third wave, which occurred in November 2020 and in March 2021 respectively. During the second and third wave many hospitals had already developed emergency management plans and improved knowledge on the management of mild-moderate COVID19 disease was available. However, it is unknown w…

Absolute targets for HCV elimination and national health policy paradigms: Foreseeing future requirements

2021

The World Health Organization (WHO) targets for eliminating HCV by 2030 may be overambitious for many high-income countries. Recent analyses (ie, data from 2017 to 2019) show that only 11 countries are on track for meeting WHO’s elimination targets. For a country to be truly on track, it is important that the majority of infected individuals be identified and treated. There is still a need for country and population-specific evaluations within the different HCV screening and treatment strategies available, in order to assess their cost-effectiveness and sustainability and support an evidence-based policy for HCV elimination. Any health policy model is affected by the diversity and quality o…

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

2017

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

Optimizing diagnostic algorithms to advance Hepatitis C elimination in Italy: A cost effectiveness evaluation

2021

Objectives: Optimized diagnostic algorithms to detect active infections are crucial to achieving HCV elimination. We evaluated the cost effectiveness and sustainability of different algorithms for HCV active infection diagnosis, in a context of a high endemic country for HCV infection. Methods: A Markov disease progression model, simulating six diagnostic algorithms in the birth cohort 1969‐1989 over a 10‐year horizon from a healthcare perspective was used. Conventionally diagnosis of active HCV infection is through detection of antibodies (HCV‐Ab) detection followed by HCV‐RNA or HCV core antigen (HCV‐Ag) confirmatory testing either on a second sample or by same sample reflex testing. The …

From current status to optimization of HCV treatment: Recommendations from an expert panel

2016

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-relat…

Impact of COVID-19 on global HCV elimination efforts.

2021

Background & Aims COVID-19 has placed significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in hepatitis C liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination program progress. Methods Previously developed models were adapted for 110 countries to include a status quo or “no delay” scenario and a “1-year delay” scenario assuming significant disruption in interventions (screening, diagnosis and …

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 …

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 < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both gro…

An a priori prediction model of response to peginterferon plus ribavirin dual therapy in naïve patients with genotype 1 chronic hepatitis C.

2014

none 29 no Background: Aim was to select naïve patients with genotype 1 chronic hepatitis C having a high probability of response to Peg-interferon. +. ribavirin therapy. Methods: In 1073 patients (derivation cohort), predictors of rapid and sustained virological response were identified by logistic analysis; regression coefficients were used to generate prediction models for sustained virological response. Probabilities at baseline and treatment week 4 were utilized to develop a decision rule to select patients with high likelihood of response. The model was then validated in 423 patients (validation cohort). Results: In the derivation cohort, 257 achieved rapid virological response and 8…

Optimizing systemic therapy for advanced hepatocellular carcinoma: the key role of liver function

2022

The number of effective systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC) is rapidly increasing, and the advent of immunotherapy has changed the treatment paradigm for these patients, leading to significantly improved survival outcomes. However, many patients with HCC will continue to receive tyrosine kinase inhibitors, partly because of contraindications to immune checkpoint inhibitors. Currently, the best sequential first- and second-line systemic treatment remains elusive. Maintenance of optimal liver function is crucial, it is likely to impinge on temporary or permanent treatment discontinuation, and should also be considered when defining the treatment seq…

The case for simplifying and using absolute targets for viral hepatitis elimination goals

2021

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes …

Therapy expectations and physical comorbidity affect quality of life in chronic hepatitis C virus infection.

2007

Summary.  Hepatitis C virus (HCV) infection is associated with a significant reduction of health related quality of life (QOL), the causes and mechanisms of which are still unknown. To explore whether treatment history could affect QOL, we examined patients with detectable HCV viraemia who had a different therapeutic background. Two hundred sixty-four consecutive subjects with chronic HCV infection and detectable viraemia were enrolled. Of these, 163 were untreated patients, 43 were relapsers, 58 were nonresponders (NR) to nonpegylated interferon (IFN) therapy. To assess QOL, three self-report instruments were employed: the Short Form-36 (SF-36), the Chronic Liver Disease Questionnaire (CLD…

Triple therapy with first-generation Protease Inhibitors for patients with genotype 1 chronic hepatitis C: Recommendations of the Italian Association…

2013

AbstractThe first-generation Protease Inhibitors Boceprevir and Telaprevir administered in triple therapy regimens with Peg-interferon alpha and Ribavirin have been proven effective in increasing the rate of Sustained Virological Response in both naive and treatment-experienced patients with chronic genotype-1 hepatitis C. However, at the individual level, the therapeutic advantage of triple therapy is highly variable and results from the combination of multiple factors related to the characteristics of patient, viral status and liver disease.The recommendations presented are promoted by the Italian Association for the Study of the Liver, with the aim to help the physician in the decision-m…

The economic cost and health burden of non-alcoholic steatohepatitis (NASH) in the EU5 countries

2020

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…

MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals

2017

AbstractNonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08–2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3’-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical fa…

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

2018

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed …

Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020

2022

Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published …

Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with…

2017

Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), …