Prognostic impact of steatosis in the clinical course of chronic HCV infection-Results from the German Hepatitis C-Registry.

Background: Liver steatosis is often observed in chronic HCV infection and associated to genotype or comorbidities. NAFLD is an important risk factor for end-stage liver disease. We aimed to analyse the course of NAFLD as a concomitant disease in a cohort of HCV patients.

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).

Weight Gain after Interferon-Free Treatment of Chronic Hepatitis C-Results from the German Hepatitis C-Registry (DHC-R).

Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C.

[Evolution of hepatitis C virus genotype 1a vs. 1b distribution in Germany between 2004 and 2018 - An analysis of 17093 patients from different real world registries].

Background:  Hepatitis C virus (HCV) genotype (GT) 1 is the most common HCV GT in Western and Central Europe. The main focus of this present work is to analyze the change of baseline characteristics of 17 093 HCV-patients with genotype 1a/1b with antiviral therapy in Germany between 2004 and 2018. We analyzed five periods: (i) 2004-2007, (ii) 2008-2010, (iii) 2010-2013, (iv) 2014-2016, (v) 2017-2018.

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy - data from the German hepatitis C registry (DHC-R).

Background:  Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis.

Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register).

Background: Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting.

Baseline risk factors determine lack of biochemical response after SVR in chronic hepatitis C patients treated with DAAs.

Background And Aims: Liver function tests (alanine aminotransferase, ALT; gamma-glutamyltransferase, GGT) not always normalize after elimination of hepatitis C virus (HCV) by direct acting antivirals (DAAs), possibly indicating concomitant non-viral liver diseases. We analysed factors determining the biochemical response (normalized ALT/GGT) of DAA therapy in a large real-world cohort.

Method: The German Hepatitis C-Registry is a national multicenter registry study.

Outcomes and costs of treating hepatitis C patients with second-generation direct-acting antivirals: results from the German Hepatitis C-Registry.

Objective: Chronic hepatitis C virus infection is associated with a significant health burden. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of direct-acting antivirals (DAA) has led to an increase in sustained virologic response rates (SVR), but is accompanied by higher treatment costs.

Clinical significance of detectable and quantifiable HCV RNA at the end of treatment with ledipasvir/sofosbuvir in GT1 patients.

Background & Aims: AASLD/IDSA treatment guidelines for hepatitis C virus (HCV) infection state that testing for quantitative HCV RNA can be considered at the end of antiviral treatment (EOT) with interferon-free regimens. However, it remains unclear how to respond to a detectable or even quantifiable HCV RNA result. The aim of this study was to analyse the frequency and predictive value of detectable and quantifiable HCV RNA results at the EOT in patients with HCV genotype 1 infection treated with ledipasvir (LDV) and sofosbuvir (SOF) ± ribavirin (RBV) in a large real-world cohort.

Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis.

Objective: Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis.

Design And Method: Circulating RBP4 levels were measured in 19 patients with liver cirrhosis at different clinical stages of the disease and in 20 age-, sex- and body mass index (BMI)-matched controls.

Cytokine gene polymorphisms and the susceptibility to liver cirrhosis in patients with chronic hepatitis C.

Background: The speed of fibrosis progression varies considerably between patients with chronic hepatitis C. This study analyzed whether cytokine gene polymorphisms are associated with a progressive course of the disease.

Methods: Leukocyte DNA from 101 patients with chronic hepatitis C, 52 patients with hepatitis C virus (HCV)-induced cirrhosis and 200 Caucasian blood donors was prepared.

Expression and coordinated regulation of matrix metalloproteinases in chronic hepatitis C and hepatitis C virus-induced liver cirrhosis.

Matrix metalloproteinases (MMPs) are central to tissue remodelling; however, little is known about the temporal pattern and differential regulation of hepatic MMP expression in the course of chronic human liver disease. Using quantitative reverse transcription-PCR ELISA assays, we studied hepatic mRNA expression of MMP-1, -2, -3, -7, -9, -10, -11, -13 and -14 in patients with chronic hepatitis C and hepatitis C virus-induced end-stage liver cirrhosis and controls. Results were compared with histology, hepatic expression of tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -3, procollagen types I and IV, laminin, and with circulating protein levels of hyaluronate, TIMP-1 and -2 and MMP proenzymes, as measured by ELISA.

Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumors.

Background: Patients suffering from hepatic metastases of neuroendocrine tumors (NET) are potential candidates for orthotopic liver transplantation. Because recurrence rates are high and outcome is variable, prognostic indicators are required. The aim of our study was to identify predictors of long-term survival with a focus on the impact of tumor biology.

Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C.

Background: Circulating levels of tissue inhibitor of metalloproteinase (TIMP)-1 and matrix metalloproteinase (MMP)-2 are investigated as parameters for the diagnosis of fibrosis in chronic liver disease. We evaluated their diagnostic potential in comparison to hepatic histology, serum hyaluronate and standard liver function tests.

Methods: Commercially available ELISA assays were used to study circulating values of TIMP-1 and MMP-2 (Bindazyme, Biotrak, Quantikine) in patients with chronic hepatitis C (CAH; n=59), hepatitis C virus-induced cirrhosis (n=19) and 30 healthy controls.