Hepatitis C Clearance by Direct-Acting Antivirals Impacts Glucose and Lipid Homeostasis.

Background: Chronic hepatitis C virus (HCV) infections are causally linked with metabolic comorbidities such as insulin resistance, hepatic steatosis, and dyslipidemia. However, the clinical impact of HCV eradication achieved by direct-acting antivirals (DAAs) on glucose and lipid homeostasis is still controversial. The study aimed to prospectively investigate whether antiviral therapy of HCV with DAAs alters glucose and lipid parameters.

Anemia and Systemic Inflammation Rather than Arterial Circulatory Dysfunction Predict Decompensation of Liver Cirrhosis.

Background: While systemic inflammation is recognized as playing a central role in the pathogenesis of organ failures in patients with liver cirrhosis, less is known about its relevance in the development of classical hepatic decompensation.

Aim: To characterize the relationship between systemic inflammation, hemodynamics, and anemia with decompensation of liver cirrhosis.

Methods: This is a post-hoc analysis of a cohort study of outpatients with advanced liver fibrosis or cirrhosis.

Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF.

Background & Aims: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze the blood metabolome in patients with cirrhosis, with and without ACLF.

Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials.

Background & Aims: Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non-adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non-adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non-adherence on sustained virological response at post-treatment week 12 (SVR12) rates in HCV genotype (GT) 1-6-infected patients.

Methods: Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit.

Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis.

Background & Aims: We performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP).

Methods: We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n = 61) or antibiotics alone (control group; n = 57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course.

Assessing Patient Preferences for Treatment Decisions for New Direct Acting Antiviral (DAA) Therapies for Chronic Hepatitis C Virus Infections.

Introduction: The new direct acting antiviral (DAA) therapies are able to effectively treat chronic hepatitis C (CHC). This study elicited the preferences of CHC patients for treatment attributes of new DAAs.

Methods: An online discrete choice experiment survey was designed to collect data from adult CHC patients in the USA, UK, France, Germany, Spain, and Italy.

miRNA-26b downregulation in peripheral blood mononuclear cells of patients with hepatitis C associated lymphomas is restored by successful interferon-free antiviral therapy.

Background: Patients with chronic HCV infection are at increased risk of developing B-cell non-Hodgkin lymphoma (B-NHL). Regression of HCV-associated B-NHL (HCV-NHL) can be achieved through HCV eradication using interferon (IFN). However, only about two-thirds of patients with sustained virological response (SVR) also had a consecutive lymphoma response.

Addressing Profiles of Systemic Inflammation Across the Different Clinical Phenotypes of Acutely Decompensated Cirrhosis.

Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up.

Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis.

Background & Aims: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections.

Methods: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study).

Treatment strategies for patients with decompensated liver cirrhosis due to hepatitis C virus infection eligible for liver transplantation: real-life data from five German transplant centers.

Background: Even with highly effective direct-acting antivirals (DAAs) treatment of patients with decompensated hepatitis C (HCV) cirrhosis remains challenging. Clinical deterioration and the need for liver transplantation (LT) may arise despite previous antiviral treatment. It is unclear whether in patients with high Model for End-Stage Liver Disease (MELD) antiviral treatment is too risky and should thus be deferred until after LT.

Orchestration of Tryptophan-Kynurenine Pathway, Acute Decompensation, and Acute-on-Chronic Liver Failure in Cirrhosis.

Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known.

Glecaprevir/Pibrentasvir in patients with chronic HCV genotype 3 infection: An integrated phase 2/3 analysis.

Glecaprevir coformulated with pibrentasvir (G/P) is approved to treat hepatitis C virus (HCV) infection and was highly efficacious in phase 2 and 3 studies. Treating HCV genotype (GT) 3 infection remains a priority, as these patients are harder to cure and at a greater risk for liver steatosis, fibrosis progression and hepatocellular carcinoma. Data were pooled from five phase 2 or 3 trials that evaluated 8-, 12- and 16-week G/P in patients with chronic HCV GT3 infection.

Vitamin D deficiency is associated with hepatic decompensation and inflammation in patients with liver cirrhosis: A prospective cohort study.

Background: Vitamin D is required to maintain the integrity of the intestinal barrier and inhibits inflammatory signaling pathways.

Objective: Vitamin D deficiency might be involved in cirrhosis-associated systemic inflammation and risk of hepatic decompensation in patients with liver cirrhosis.

Methods: Outpatients of the Hepatology Unit of the University Hospital Frankfurt with advanced liver fibrosis and cirrhosis were prospectively enrolled.

Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe.

Background & Aims: Antibiotic resistance has been increasingly reported in patients with decompensated cirrhosis in single-center studies. Prospective investigations reporting broad epidemiological data are scarce. We aimed to analyze epidemiological changes in bacterial infections in patients with decompensated cirrhosis.

Effectiveness and Safety of Direct-Acting Antiviral Combination Therapies for Treatment of Hepatitis C Virus in Elderly Patients: Results from the German Hepatitis C Registry.

Background: With the aging of the hepatitis C virus (HCV)-infected patient cohort and the availability of highly effective and tolerable treatment regimens, an increasing number of elderly patients are now eligible for HCV therapy. This study investigated clinical and epidemiologic characteristics of elderly HCV-infected patients as well as the effectiveness and safety of available therapies.

Methods: Patients were enrolled into the German Hepatitis C Registry (DHC-R), a prospective, multicenter, real-world cohort study.

Interferon-free treatment choice according to baseline RASs leads to high SVR rates in HCV genotype 1 infected patients.

Aim: Different combinations of direct antiviral agents (DAA) lead to high SVR rates in HCV genotype 1 infected patients. However, presence of baseline resistance-associated substitutions (RASs) represents a major risk factor for treatment failure. It is unknown whether choice of treatment based on RASs has the potential to decrease virologic failure rates.

Liver transplantation for chronic hepatitis C virus infection in the United States 2002-2014: An analysis of the UNOS/OPTN registry.

Chronic hepatitis C virus (HCV) infection is a leading cause for orthotopic liver transplantation (OLT) in the U.S. We investigated characteristics of HCV-infected patients registered for OLT, and explored factors associated with mortality.

Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis.

Unlabelled: Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival.

Patients: 407 patients with ACLF and 235 patients with acute decompensation (AD).

Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study.

Background & Aims: There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients.

Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously untreated patients with hepatitis C virus genotype 1b infection without cirrhosis (GARNET): a single-arm, open-label, phase 3b trial.

Background: Clinical studies have shown high rates of sustained virological response (hepatitis C virus [HCV] RNA <15 IU/mL) at post-treatment week 12 (SVR12) in patients with genotype 1b infection with and without cirrhosis who received coformulated ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin, for 12 weeks. In this study, we aimed to assess 8-week treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin in patients infected with HCV genotype 1b without cirrhosis.

Methods: We did a multicentre, open-label, single-arm, phase 3b study (GARNET) in 20 hospitals or clinics in Australia, Canada, France, Germany, Israel, Italy, Spain, and the UK, to assess the safety and efficacy of an 8-week treatment duration of once-daily oral ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, plus twice-daily oral dasabuvir 250 mg in previously untreated patients with chronic HCV genotype 1b infection without cirrhosis (as assessed by liver biopsy, transient elastography, or serum markers).

Global epidemiology of HCV subtypes and resistance-associated substitutions evaluated by sequencing-based subtype analyses.

Background & Aims: HCV genotype, subtype, and presence of resistance-associated substitutions (RASs) are key determinants for the selection of direct-acting antiviral (DAA) treatment regimens. However, current HCV genotyping assays have limitations in differentiating between HCV subtypes, and RAS prevalence is largely undefined. The aim of this study was to investigate HCV epidemiology in 12,615 patient samples from 28 different countries across five geographic regions.

Comparison of on-treatment HCV RNA during direct antiviral therapy using two different COBAS TaqMan HCV assays.

Background: Repeated measurements of hepatitis C virus (HCV) RNA levels during antiviral therapy are recommended to monitor treatment efficacy and adherence. Throughout most direct antiviral agent (DAA) approval studies, HCV RNA cutoffs and endpoints were established with the COBAS TaqMan assay for use with the High Pure System (HPS/CTM). Different assays used in clinical practice may yield different quantitative results and possibly impact treatment decisions.

Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response.

Background: Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e.

Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study.

Background: Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa is highly effective, but can be associated with frequent side-effects. We investigated the safety and efficacy of an interferon-free regimen for treatment of acute HCV infection.

Methods: In this prospective, open-label, multicentre, single-arm pilot study, we enrolled adults (≥18 years) with acute HCV genotype 1 monoinfection from ten centres in Germany.