Transjugular diagnostic procedures in hepatology: Indications, techniques and interpretation.

Measurement of the hepatic venous pressure gradient (HVPG) and transjugular liver biopsy have emerged as important tools in clinical hepatology. Measurement of HVPG is considered the gold standard for detecting clinically significant portal hypertension, with an HVPG of ≥10 mmHg being the key prognostic threshold in patients with compensated advanced chronic liver disease (cACLD; compensated cirrhosis). A transjugular liver biopsy can be obtained within the same procedure and may be preferred over percutaneous liver biopsy in patients with coagulopathy, ascites and/or significant obesity.

Detection of Hepatitis C Virus Infection from Patient Sera in Cell Culture Using Semi-Automated Image Analysis.

The study of hepatitis C virus (HCV) replication in cell culture is mainly based on cloned viral isolates requiring adaptation for efficient replication in Huh7 hepatoma cells. The analysis of wild-type (WT) isolates was enabled by the expression of SEC14L2 and by inhibitors targeting deleterious host factors. Here, we aimed to optimize cell culture models to allow infection with HCV from patient sera.

Acid Sphingomyelinase Activation and ROS Generation Potentiate Antiproliferative Effects of Mitomycin in HCC.

Sphingolipids play a major role in the regulation of hepatocellular apoptosis and proliferation. We have previously identified sphingolipid metabolites as biomarkers of chronic liver disease and hepatocellular carcinoma. Human hepatocellular carcinoma cell lines were transfected with a plasmid vector encoding for acid sphingomyelinase.

Sub-optimal therapy of patients with primary biliary cholangitis (PBC) in the real-life stetting of the German PBC cohort.

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.

[Hepatitis C: From diagnosis to global virus elimination].

Chronic infection with hepatitis C virus (HCV) is a common cause of complications such as liver cirrhosis and hepatocellular carcinoma (HCC). It is one of the most significant infectious diseases worldwide, posing a substantial health burden. Since the introduction of direct-acting antiviral agents (DAAs), the treatment landscape has undergone a revolution.

Impaired HBsAg release and antiproliferative/antioxidant cell regulation by HBeAg-negative patient isolates reflects an evolutionary process.

Background: The hepatitis B e antigen (HBeAg)-negative infection Phase 3 is characterized by no or minimal signs of hepatic inflammation and the absence of hepatic fibrosis. However, underlying molecular mechanisms leading to this benign phenotype are poorly understood.

Methods: Genotype A, B and D HBeAg-negative patient isolates with precore mutation G1896A from Phase 3 were analysed in comparison with respective HBeAg-positive rescue mutant and HBeAg-positive wild-type reference genomes regarding differences in viral replication, morphogenesis, infectivity and impact on NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE)-dependent gene expression and cellular kinome.

Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients.

Background And Aims: Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort.

Methods: A total of 129 patients with rare GT1-6 were included from the European resistance database.

[The status of national and global hepatitis C elimination].

Background: In 2016, the World Health Organization propagated the elimination of hepatitis C virus (HCV) by 2030 in order to address the public health threat posed by viral hepatitis. This article looks at the progress that has been made globally and in Germany since 2016.

Methods: A selective literature search was conducted, with particular focus on studies and reviews relating to the elimination of hepatitis C infection both globally and in Germany.

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure.

Background & Aims: Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts.

Methods: Consecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021.

[Intersectoral management of patients with abnormal liver enzymes and non-alcoholic fatty liver disease (NAFLD)].

The prevalence of fatty liver disease has increased significantly in Germany in recent years. With an estimated 18 million German citizens being affected, it is now among the most prevalent diseases. Furthermore, it is also considered a relevant and independent risk factor for other common cardiovascular diseases such as heart attack or stroke.

SARS-CoV-2 neutralizing antibody therapies: an early retrospective cohort study of 26 hospitalized patients treated with bamlanivimab or casirivimab/imdevimab.

Objectives: In this early retrospective cohort study, a total of 26 patients with SARS-CoV-2 were treated with bamlanivimab or casirivimab/imdevimab, and the reduction of the viral load associated with the developed clinical symptoms was analyzed.

Methods: Patients in the intervention groups received bamlanivimab or casirivimab/imdevimab. Patients without treatment served as control.

Association of Alpha-1 Antitrypsin Pi*Z Allele Frequency and Progressive Liver Fibrosis in Two Chronic Hepatitis C Cohorts.

(1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant 'Pi*Z' emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage ('Pi*MZ' genotype) as an additional risk factor in patients with chronic viral hepatitis C to develop progressive liver fibrosis. (2) Methods: Two prospectively recruited cohorts totaling 572 patients with therapy-naïve chronic viral hepatitis C (HCV) were analyzed.

The role of serum sphingolipids as potential biomarkers of non-response to direct acting antiviral therapy in chronic hepatitis C virus infection.

Elimination strategies of chronic hepatitis C virus (HCV) infection aim to optimize the high antiviral potency of direct-acting antivirals (DAAs). Sphingolipids (SLs) constitute bioactive lipid compounds with a remarkable second messenger potential. SL levels associate with responsiveness to interferon treatment in HCV-patients, thus prompting the question whether failure to DAAs can be predicted by the serologic sphingolipidomic profile.

Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure.

Background & Aims: Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).

Methods: We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database.

Elevated liver enzymes predict morbidity and mortality despite antiviral cure in patients with chronic hepatitis C: Data from the German Hepatitis C-Registry.

While direct-acting antivirals (DAAs) cure chronic hepatitis C virus (HCV) infection in almost all patients, some patients remain at risk of liver disease despite HCV cure. In order to identify risk factors indicating liver-related morbidity and death after viral cure, we included 6982 patients from the national multicenter real-world German Hepatitis C Registry with regular follow-up visits for up to 7 years after DAA therapy. Definitions for normal liver function tests (in women/men) were alanine aminotransferase (ALT; ≤35/≤50 U/L), ALT according to American Association for the Study of Liver Diseases (AASLD; ≤19/≤30 U/L), and gamma-glutamyltransferase (GGT; ≤40/≤60 U/L).

Safety and Effectiveness Using 8 Weeks of Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis: The CREST Study.

Introduction: In clinical trials with hepatitis C virus-infected treatment-naïve (TN) patients with compensated cirrhosis (CC), glecaprevir/pibrentasvir (G/P), a fixed-dose, once-daily, pangenotypic regimen, has demonstrated sustained virologic response at posttreatment Week 12 (SVR12) > 95%. We evaluated the real-world safety and effectiveness of 8-week G/P therapy in TN patients with CC, including certain subgroups of interest.

Methods: The CREST study is a real-world, noninterventional, multicenter study retrospectively assessing data from Canada, Germany, Israel, Italy, and Spain.

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals.

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure.

Efficacy and Safety of ELOM-080 as Add-On Therapy in COVID-19 Patients with Acute Respiratory Insufficiency: Exploratory Data from the Prospective Placebo-Controlled COVARI Trial.

Introduction: Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases.

Patients/methods: This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14 days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency.

Updated epidemiology of hepatitis C virus infections and implications for hepatitis C virus elimination in Germany.

In 2014, an analysis was conducted to evaluate the hepatitis C virus (HCV) epidemiology and disease burden in Germany. Since then, there have been considerable developments in HCV management such as the implementation of direct acting antivirals. The aim of this analysis was to assess the recent data available for Germany, establish an updated 2020 HCV prevalence and cascade of care and evaluate the impact of what-if scenarios on the future burden of disease using modelling analysis.

[Treatment of parenterally transmittable viral hepatitis].

The parenterally transmittable hepatitides B, D and C and their complications are a problem worldwide and also in Germany that should not be underestimated. Due to the estimated high gray area, a broad distribution, particularly by drug abuse, increasing prevalence due to immigration and a pandemic-related delay in the diagnostics, the identification of affected persons and therefore potentially infectious patients represents a great challenge for the healthcare system. Highly effective treatment concepts with practically no side effects and a tablet ingestion once daily are available for hepatitis B and also hepatitis C.