Francesco Negro

University of Geneva | UNIGE · Division of Gastroenterology and Hepatology

Simple Summary The introduction of direct-acting antivirals (DAAs) has significantly improved the treatment of Hepatitis C, achieving high success rates and reducing complications and deaths. Despite their success, there are concerns about the potential risk of developing liver tumors after DAA treatment. This study analyzed data from the Swiss Hep...

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C. We analysed the use of different generations of DAAs over time in Switzerland and investigated factors predictive of treatment failure. METHODS: This retrospective study was conducted within the framework of the Swiss Association for the S...

BACKGROUND AND AIMS: Chronic hepatitis B infection (defined as sustained detection of hepatitis B virus [HBV] surface antigen [HBsAg] protein in serum) is a leading cause of cirrhosis, hepatocellular carcinoma and liver-related deaths. A situation analysis carried out by the Swiss Federal Office of Public Health estimated the HBsAg prevalence in Sw...

Hepatitis D virus (HDV) is a defective virus requiring the hepatitis B virus (HBV) to complete its life cycle and cause liver damage in humans. HDV is responsible for rare acute and chronic liver diseases and is considered the most aggressive hepatitis virus. Acute infection may associate with acute liver failure, while persistent infection is most...

Chronic hepatitis C (CHC) is associated with the development of metabolic disorders, including both hepatic and extra-hepatic insulin resistance (IR). Here, we aimed at identifying liver-derived factor(s) potentially inducing peripheral IR and uncovering the mechanisms whereby HCV can regulate the action of these factors. We found ANGPTL4 (Angiopoi...

Background & Aims Chronic hepatitis delta is the most severe form of chronic viral hepatitis associated with a faster progression towards cirrhosis, liver decompensation, and hepatocellular carcinoma. Its tight dependency on the hepatitis B virus (HBV) and the host cell machinery for its life cycle limits the development of directly acting antivira...

Chronic hepatitis C (CHC) is associated with the development of metabolic disorders, including both hepatic and extra-hepatic insulin resistance (IR). Here, we aimed at identifying liver-derived factor(s) potentially inducing peripheral IR and uncovering the mechanisms whereby HCV can regulate the action of these factors. We found ANGPTL4 (Angiopoi...

Advances in diagnostics and therapeutics have brought the elimination of chronic viral hepatitis into focus. The World Health Organization has defined the targets for elimination, but it is unclear how these can be achieved and how they should be measured. The goal of this special conference was to examine current efforts and metrics to assess prog...

Background & Aims The World Health Organization (WHO) HBV and HCV elimination targets, set in 2016 and based on projections to 2030, were unable to consider the impact of intervening factors. To evaluate the impact of the COVID-19 pandemic on viral hepatitis elimination programs, the European Association for the Study of the Liver (EASL) conducted...

Résumé L’hépatite virale est une problématique de santé publique majeure contre laquelle l’organisation mondiale de la santé (OMS) a proposé de nombreuses stratégies pour son élimination. Malgré de nombreuses avancées thérapeutiques, il reste des freins pour atteindre les objectifs ambitieux proposés par l’OMS. Concernant le virus de l’hépatite B (...

Background Switzerland has made strides towards hepatitis C virus elimination, but as of 2019, elimination was not guaranteed. However, political interest in viral hepatitis has been increasing. We sought to develop a better understanding of Switzerland’s progress toward HCV elimination and the profile of remaining HCV-RNA positive patients. Metho...

The microRNA 21 (miR-21) is upregulated in almost all known human cancers and is considered a highly potent oncogene and potential therapeutic target for cancer treatment. In the liver, miR-21 was reported to promote hepatic steatosis and inflammation, but whether miR-21 also drives hepatocarcinogenesis remains poorly investigated in vivo. Here we...

Background The cost and complexity of the polymerase chain reaction (PCR) test are barriers to diagnosis and treatment of hepatitis C virus (HCV) infection. We investigated the cost-effectiveness of testing strategies using antigen instead of PCR testing. Methods We developed a mathematical model for HCV to estimate the number of diagnoses and cas...

Treatment of hepatitis C has known major progress thanks to direct-acting antivirals resulting in the healing, defined by a viral clearance (sustained virological response [SVR]), in the vast majority of patients. However, there is a residual risk of progressive liver damage in a minority of patients, potentially leading to complications such as li...

IntroductionGlecaprevir/pibrentasvir is approved for treating chronic hepatitis C virus (HCV) genotypes (GT) 1–6. We evaluated real-world effectiveness, safety, and patient-reported outcomes of glecaprevir/pibrentasvir in underserved patient populations, focusing on persons who use drugs infected with HCV.Methods Data were pooled from nine countrie...

Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the standard taxonomy norms for viruses. Being a satellite virus of hepatitis B virus (HBV), HDV requires HBV envelope glycoproteins for its infection cycle and its transmission. HDV pat...

Background: The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to driv...

Background & Aims People hospitalised due to mental illness often have risk factors for contracting hepatitis C virus (HCV). Scaling-up HCV screening for all psychiatric inpatients as a case-detection strategy for viral elimination is under-explored. This study aimed to evaluate the cost-effectiveness of scaling-up HCV screening and treatment for p...

Aim of the study: In the era of pangenotypic treatment regimens against hepatitis C virus (HCV) infection, data from postmarketing observational studies are crucial to better understand the treatment patterns used in specific countries and treatment outcomes under real-life conditions. We report data from Switzerland from an ongoing, multinational...

Background and Aims There is conflicting data regarding the epidemiology of hepatocellular carcinoma (HCC) arising in the context of non-alcoholic and metabolic associated fatty liver disease (NAFLD and MAFLD). We aimed to examine the changing contribution of NAFLD and MAFLD, stratified by sex, in a well-defined geographical area and highly charact...

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. T...

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of hepatic pathology ranging from non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH) occasionally complicated with hepatic fibrosis or even cirrhosis. In order to propose a diagnosis with positive criteria, a panel of experts recently proposed the use of an alternative nomen...

Hepatitis D virus causes chronic hepatitis D. The virus is defective, meaning it requires simultaneous presence of hepatitis B virus within the hepatocytes to complete its viral cycle. Globally, 15 to 20 millions people are estimated to be chronically co-infected by hepatitis B and D viruses. Current therapy remains limited to pegylated interferon...

Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of...

Background With direct-acting antiviral agents (DAA), mortality rates and causes of death among persons with hepatitis C virus (HCV) infection may change over time. However, the emergence of such trends may be delayed by the slow progression of chronic hepatitis C. To date, detailed analyses of cause-specific mortality among HCV-infected persons ov...

The coronavirus disease (COVID‐19) pandemic has had a substantial impact on the lives of most of the worlds’ population. We are aware that for liver disease patients this has been especially concerning. The editorial from Sun and colleagues [1] provides an overview of the major challenges facing liver specialists as they strive to deliver essential...

Background & Aims Chronic hepatitis D (CHD) is the most severe form of chronic viral hepatitis but its role in the development of hepatocellular carcinoma (HCC) remains debated. We conducted a systematic review and meta-analysis of epidemiological studies to examine whether CHD is associated with an increased risk of HCC. Methods We searched Pubme...

Background & aims: Our understanding of non-alcoholic fatty liver disease (NAFLD) pathogenesis is improving, but there is still limited data on the function of resident liver macrophages in this context, especially when considering their contribution in dampening liver inflammation. Methods: Liver macrophages were studied in mouse models of prol...

Background & Aims With the introduction of direct-acting antiviral agents (DAA), mortality rates and causes of death among persons with hepatitis C virus (HCV) infection are likely to change over time. However, the emergence of such trends may be delayed by the relatively slow progression of chronic hepatitis C. To date, detailed analyses of cause-...

As a result of epidemic levels of obesity and diabetes mellitus, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) will contribute to increases in the liver-related disease burden in Switzerland. A Markov model was built to quantify fibrosis progression among the NAFLD and NASH populations, and predict disease burden...

Background The cost and complexity of polymerase chain reaction (PCR) testing is a significant barrier for the diagnosis and treatment of patients infected with hepatitis C virus (HCV). We investigated the cost-effectiveness of various testing strategies using antigen as an alternative to PCR. Methods We developed a mathematical model for HCV to e...

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as ma...

Purpose of Review Chronic hepatitis D is the most severe form of viral hepatitis. Currently, no drug has been approved for its treatment and pegylated interferon alpha remains the only recommended therapy, with dismal efficiency and important side effects. This review summarizes the recent advances in drug development for chronic hepatitis D. Rece...

Background: Hepatitis C virus (HCV) among people living in detention (PLD) is typically high in many countries including Switzerland, where it is estimated that the HCV prevalence rate is between 5.7% and 6.2%. In Switzerland, the existing screening strategy involves routine screening of PLD who indicate they are from HCV high-risk populations bas...

Die Schweizer Hepatitis-Strategie hat – wie die Weltgesundheitsorganisation WHO – zum Ziel, Hepatitis B und C bis 2030 zu eliminieren. Damit ist gemeint, die Raten von Neuansteckungen und Folgeerkrankungen gegen null zu bringen. Alle Instrumente für die Elimination, sprich Präventionsmassnahmen, Therapien und Impfungen, sind vorhanden. Nun gilt es,...

Late diagnosis and treatment may increase morbidity and mortality among persons with hepatitis C virus (HCV) infection. We included all participants of the Swiss Hepatitis C Cohort Study (SCCS). We used unadjusted and adjusted logistic and Cox regressions to determine the association between the geographic origin of the participants and the followi...

Background and aims Hepatitis C virus (HCV) infection is associated with insulin resistance, which may lead to type 2 diabetes and its complications. Although HCV infects mainly hepatocytes, it may impair insulin sensitivity at the level of uninfected extrahepatic tissues (muscles and adipose tissue). The aim of this study was to assess whether an...

Background: Hepatitis C virus (HCV) antigen testing is less expensive than quantitative RT-PCR but has lower sensitivity for very low viral loads (VLVL; HCV RNA ≤3,000 IU/ml). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce. Methods: We assessed prevalence...

Background & Aims miR‐21‐5p is a potent oncogenic microRNA targeting many key tumor suppressors including PTEN. We recently identified PTEN as a key factor modulated by HCV to promote virion egress. In hepatocytes, expression of HCV‐3a core protein was sufficient to downregulate PTEN and to trigger lipid droplet accumulation. Here, we investigated...

Hepatitis delta virus (HDV) is a defective virus that requires the hepatitis B virus (HBV) to complete its life cycle in human hepatocytes. HDV virions contain an envelope incorporating HBV surface antigen protein and a ribonucleoprotein containing the viral circular single-stranded RNA genome associated with both forms of hepatitis delta antigen,...

BACKGROUND AND AIMS: A previous analysis of hepatitis C virus (HCV)-related healthcare costs in Switzerland found that the annual healthcare costs of untreated HCV infection (excluding antiviral treatment) could increase by more than 25 million Swiss francs (CHF) between 2013 and 2030. Since that publication, highly efficacious direct-acting antivi...

Background: Interleukin-1 (IL-1)β and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1β signaling with IL-1Ra impacts on liver fibrosis. Methods: We assessed the effects of IL-1β on human hepatic stellate cells (HSC) and in mouse models of...

BACKGROUND AND AIMS: Direct-acting antiviral agents have revolutionised hepatitis C treatment. In 2014, the Swiss Hepatitis Strategy was developed to eliminate hepatitis C virus (HCV) infection and the associated liver-related morbidity and mortality by 2030. Though numerous national studies and assessments have identified a relatively low prevalen...

Catalyzed by the concerns over the growing public health and economic burden of Hepatitis C virus (HCV) in Switzerland, a diverse group of experts and patient representatives came together in 2014 to develop the Swiss Hepatitis Strategy, setting targets for the elimination of viral hepatitis in Switzerland by 2030. Previous studies have reported th...

HCV disease burden model, forecasting viremic prevalence. (DOCX)

Comparison of the goals of the Swiss Hepatitis Strategy (SHS) and the Global Health Sector Strategy (GHSS). (DOCX)

Outcomes of the sensitivity and uncertainty analyses. (DOCX)

Background Hepatitis B virus (HBV) is a major health concern in prison, but data are scarce in European prisons. This study aims to measure the prevalence of HBV infection, risk factors, awareness about infection, and HBV knowledge among inmates in Switzerland’s largest pre-trial prison. Methods Serological blood tests (HBsAg, anti-HBs, and anti-H...

In Swiss prisons, more than 70% of detained people are foreigners and over one-third originate from sub-Saharan Africa or Latin America. These two regions are endemic for various tropical diseases and viral infections, which persist after migration to nonendemic countries. Parasitic infections (schistosomiasis; strongyloidiasis) and cooccurrent vir...

People who inject drugs (PWID) are a key high‐risk group for HCV infection due to the sharing of needles and drug‐preparation equipment. However, only approximately 50% of PWID are currently screened for HCV in Switzerland. At present, screening of PWID occurs in general practice via venepuncture. Compared to venepuncture, screening via rapid antib...

Here we summarize new European recommendations for the management of hepatocellular carcinoma (HCC), the main form of cancer affecting the liver, usually occurring in the context of underlying liver disease. Screening for HCC by bi-annual ultrasound is indicated in most cirrhotic and non-cirrhotic patients. The detection of a new hepatic lesion sho...

The activating natural cytotoxicity receptor NKp30 is critical for natural killer (NK) cell function and tumor immune surveillance. The natural cytotoxicity receptor-3 (NCR3) gene is transcribed into several splice variants whose physiological relevance is still incompletely understood. In this study, we investigated the role of NKp30 and its major...

Hepatitis C is a potentially fatal viral infection that mainly affects vulnerable patient groups. Given the high efficacy of the new direct-acting antivirals (DAAs), the World Health Organization (WHO) aims to eliminate viral hepatitis as a global health threat by 2030. However, due to the high cost of DAAs, this recommendation has put significant...

Background: Nonalcoholic fatty liver disease (NAFLD) with resulting nonalcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma (HCC) globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model...

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi‐center cohort of HBV‐HCV subjects, and by performing a systematic review a...

Infection with hepatitis E virus (HEV) is a significant cause of morbidity and mortality, representing an important global health problem. Our understanding of HEV has changed completely over the past decade. Previously, HEV was thought to be limited to certain developing countries. We now know that HEV is endemic in most high-income countries and...