Angiopoietin 2 levels decrease after HCV-cure and reflect the evolution of portal hypertension.

Background: Portal hypertension (PH) does not resolve in a considerable proportion of patients who achieved HCV-cure.

Aims: To investigate (i)whether HCV-cure impacts cytokines that orchestrate angiogenesis (i.e.

Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR.

Genetic variants including and have been shown to influence progression to advanced chronic liver disease (ACLD) in patients with chronic hepatitis C (CHC). We aimed to investigate their impact on disease regression (i.e.

Noninvasive Risk Stratification After HCV Eradication in Patients With Advanced Chronic Liver Disease.

Background And Aims: Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of noninvasive surrogates of portal hypertension (liver stiffness measurement [LSM] by vibration-controlled transient elastography and von Willebrand factor/platelet count ratio [VITRO]) for development of hepatic decompensation and hepatocellular carcinoma in patients with pretreatment advanced chronic liver disease (ACLD) who achieved HCV cure.

Approach And Results: A total of 276 patients with pretreatment ACLD and information on pretreatment and posttreatment follow-up (FU)-LSM and FU-VITRO were followed for a median of 36.

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy.

Background And Aims: Sustained virologic response (SVR) to interferon (IFN)-free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN-free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH.

Follow-up of sustained virological responders with hepatitis C and advanced liver disease after interferon/ribavirin-free treatment.

Background: The introduction of direct-acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long-term durability of viral eradication after successful DAA therapy are scarce.

Aim: To evaluate the long-term success of viral eradication in patients with advanced fibrosis or cirrhosis treated with DAAs.

Efficacy of ledipasvir/sofosbuvir plus ribavirin for 12 weeks in patients with chronic hepatitis C genotype 3 and compensated liver disease.

Introduction: In the era of direct-acting antivirals, hepatitis C virus (HCV) genotype (GT) 3 remains as the most difficult-to-treat HCV-GT. Currently, data on the efficacy of ledipasvir/sofosbuvir plus ribavirin (SOF/LDV+RBV) in GT3-infected patients are limited. We investigated the efficacy of this regimen in a real-life cohort from Austria.

Ultra-high-field magnetic resonance spectroscopy in non-alcoholic fatty liver disease: Novel mechanistic and diagnostic insights of energy metabolism in non-alcoholic steatohepatitis and advanced fibrosis.

Background & Aims: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD.

Methods: MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22).

Long-term outcomes of patients with Wilson disease in a large Austrian cohort.

Background & Aims: Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease.

Methods: We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes.

Role of FDFT1 polymorphism for fibrosis progression in patients with chronic hepatitis C.

Background: In chronic hepatitis C (CHC), steatosis is associated with fibrosis and impaired response to antiviral therapy. Recently, a polymorphism of single nucleotide polymorphism SNP rs2645424 of farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified in NAFLD/NASH as a possible causal link to steatosis and fibrosis progression. SNP rs738409 in the adiponutrin gene (PNPLA3) is a well described factor for steatosis.

Effect of gender and ITPA polymorphisms on ribavirin-induced anemia in chronic hepatitis C patients.

Background & Aims: Single nucleotide polymorphisms (SNPs) in the inosine triphosphate pyrophosphatase (ITPA) gene protect patients from ribavirin induced anemia. To investigate other possible protective cofactors, gender differences were analyzed in patients with HCV genotype 1.

Methods: Hemoglobin levels at baseline (Hb0) and the decline after 4 weeks of treatment (HbΔ4) were analyzed in 308 chronic hepatitis C patients participating in 5 Austrian trials (n=308, age 43.

Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C.

Background & Aims: Insulin resistance, fibrosis and steatosis are established predictors of response to peg-interferon/ribavirin therapy in chronic hepatitis C (CHC). Several host genetic polymorphisms (IL28B, PNPLA3) modify treatment-outcome, the degree of steatosis or fibrosis. The aim of our study was to evaluate the role of these polymorphisms on insulin resistance (IR) in treatment-naïve patients with chronic hepatitis C.

Serum level of IP-10 increases predictive value of IL28B polymorphisms for spontaneous clearance of acute HCV infection.

Background & Aims: Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC).

Methods: We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls).

Intravenous silibinin as 'rescue treatment' for on-treatment non-responders to pegylated interferon/ribavirin combination therapy.

Background: Intravenous silibinin (ivSIL) is a potent antiviral agent against HCV. In vitro silibinin (SIL) inhibits viral replication, possibly by inhibiting HCV RNA polymerase. In this proof-of-concept study, ivSIL was tested in on-treatment non-responders to full-dose of pegylated interferon-α2a/ribavirin (standard of care [SOC]).

Impact of IL28B on treatment outcome in hepatitis C virus G1/4 patients receiving response-guided therapy with peginterferon alpha-2a (40KD)/ribavirin.

Unlabelled: The IL28B genotype is the most important pretreatment predictor of treatment outcome in patients with chronic hepatitis C. The impact of the rs12979860 genotype on relapse was retrospectively evaluated in genotype 1/4 patients who received response-guided therapy with peginterferon alpha-2a 180 μg/week plus ribavirin 1,000/1,200 mg/day in a large, randomized, multicenter study. Patients with a rapid virologic response (RVR: hepatitis C virus [HCV] RNA <50 IU/mL) at week 4 were treated for 24 weeks; those with a slow virologic response (no RVR but undetectable HCV RNA or ≥ 2-log(10) decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B).

Treatment of chronic hepatitis C genotype 1 patients at an academic center in Europe involved in prospective, controlled trials: is there a selection bias?

Unlabelled: Pegylated interferon-alpha2/ribavirin (peg-IFN/RBV) is the standard of care (SOC) for patients with chronic hepatitis C (CHC) infection. Currently, direct-acting antiviral agents (DAAs) are evaluated in clinical trials. The aim of this study was to compare baseline characteristics and sustained virologic response (SVR) rates in patients included in clinical trials to those receiving SOC.

Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin.

Background & Aims: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) are associated with high sustained virological response (SVR) rates in HCV genotype 1 patients. This study analyzes the impact of these IL28B polymorphisms on early treatment response (weeks 2 and 4) and SVR in HCV genotype 3 patients.

Methods: rs12979860 and rs8099917 were analyzed by the Step-OnePlus Real-time PCR system in 71 out of 72 Caucasian HCV genotype 3 patients participating, at our center, in a randomized study comparing 400mg with 800 mg ribavirin/day.

Comparison of alcohol-dependent patients at a gastroenterological and a psychiatric ward according to the Lesch alcoholism typology: implications for treatment.

Aims: To assess the clinical and biological status of alcohol-dependent patients admitted to a psychiatric or a gastroenterological ward, assessing and comparing dimensions important for prescribing treatment for withdrawal and relapse prevention.

Methods: Eighty patients, alcohol-dependent according to international classification of diseases tenth revision and diagnostic and statistical manual, text revised, version IV, admitted to the Vienna General Hospital between January 2005 and  November 2006, were examined, of whom 44 were admitted to the psychiatric ward and 36 to the gastroenterological ward. Dimensions of alcohol dependence were assessed using a computerized structured interview, the Lesch alcoholism typology (LAT).

Impact of IL28B genotype on the early and sustained virologic response in treatment-naïve patients with chronic hepatitis C.

Background & Aims: Single nucleotide polymorphisms (SNPs) in the gene that encodes interleukin (IL)-28B predict response of patients with chronic hepatitis C to antiviral therapy. We investigated the roles of polymorphisms rs12979860 and rs8099917 on the early virologic response of treatment-naïve patients.

Methods: SNPs were identified by real-time polymerase chain reaction analysis of samples from 682 patients (genotype [GT]1=372, GT2/3=208, GT4=102) who were treated with 180 μg pegylated interferon-α2a and 400 or 800 mg (GT2/3, depending on the protocol) or 1000-1200 mg (GT1/4) ribavirin/day.

Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 patients with slow virologic response.

Background & Aims: This randomized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000/1200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response (VR).

Methods: Patients with a rapid VR (RVR; undetectable hepatitis C virus [HCV]-RNA level (<50 IU/mL at week 4) were treated for 24 weeks, those with an early VR (EVR; no RVR but undetectable HCV-RNA level or >or=2-log(10) decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B; peginterferon alfa-2a was reduced to 135 microg/wk after week 48). Patients without an EVR continued treatment until week 72 if they had undetectable HCV-RNA levels at week 24.

Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by 1H magnetic resonance spectroscopy.

Background: Liver biopsy is the standard method for diagnosis of hepatic steatosis, but is invasive and carries some risk of morbidity.

Aims And Methods: Quantification of hepatocellular lipid content (HCL) with non-invasive single voxel (1)H magnetic resonance spectroscopy (MRS) at 3T was compared with histological grading and biochemical analysis of liver biopsies in 29 patients with chronic hepatitis C. Body mass index, indices of insulin resistance (homeostasis model assessment index, HOMA-IR), serum lipids and serum liver transaminases were also quantified.

Estimation of platelet function under high shear conditions to assist a rapid diagnosis of Heyde Syndrome.

Loss of high molecular weight von Willebrand factor (VWF) multimers in patients suffering from aortic valve stenosis and gastrointestinal (GI) bleeding has been regarded as the missing link between aortic stenosis and bleeding. Electrophoretic analysis of VWF multimers is laborious and time-consuming. Further, determination of overall haemostatic competence rather than evaluation of restricted portions thereof may be advantageous.

Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy.

Background & Aims: Oral Silibinin (SIL) is widely used for treatment of hepatitis C, but its efficacy is unclear. Substantially higher doses can be administered intravenously (IV).

Methods: Pedigreed nonresponders to full-dose pegylated (Peg)-interferon/ribavirin (PegIFN/RBV) were studied.

Peginterferon alfa-2a and ribavirin for 24 weeks in hepatitis C type 1 and 4 patients with rapid virological response.

Background & Aims: This analysis reports the rate of sustained virological response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 or 4 who were assigned to 24 weeks of treatment with pegylated interferon (peginterferon) alfa-2a 180 mug/wk plus ribavirin 1000/1200 mg/day after achieving a rapid virological response (RVR; HCV RNA level <50 IU/mL) at week 4 in a prospective trial investigating response-guided therapy.

Methods: Non-RVR patients with an early virological response were randomized to 48 or 72 weeks of therapy (this is a still-ongoing trial).

Results: A total of 150 of 516 patients (29%) had an RVR, 143 of whom completed 24 weeks of treatment.