title: Interferon-free regimens for chronic hepatitis C overcome the effects of portal hypertension on virological responses.
abstract: BACKGROUND
  Portal hypertension is the strongest predictor of virological response to pegylated interferon (IFN)/ribavirin in patients with chronic hepatitis C (CHC)-related cirrhosis.
  
  
  OBJECTIVE
  To investigate the effects of portal pressure assessed by hepatic venous pressure gradient (HVPG) measurement on virological responses in patients treated with IFN-free regimens outside of clinical trials.
  
  
  METHODS
  Fifty-six patients with CHC and cirrhosis who underwent HVPG measurement before starting an IFN-free therapy were retrospectively studied. Patients were treated with sofosbuvir in combination with daclatasvir (n = 32), ribavirin (n = 12) or simeprevir (n = 11), or the combination of simeprevir/daclatasvir (n = 1), for 12-24 weeks.
  
  
  RESULTS
  Hepatic venous pressure gradient values ≥10 mmHg and ≥16 mmHg were observed in 41 (73%) and 31 (55%) patients respectively. The distributions of treatment regimens and durations were comparable between patients with or without portal hypertension. Patients with portal hypertension had lower platelet counts and albumin levels, while bilirubin levels, INR, MELD and Child-Pugh scores were higher than in patients without portal hypertension. Importantly, rates of on-treatment virological response and viral kinetics, as well as the rates of sustained virological response 12 weeks after the end of therapy [96% (54/56)] were not affected by portal hypertension. Anti-viral therapy improved liver stiffness, platelet count, serum albumin and bilirubin levels, as well as prothrombin time.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that IFN-free regimens overcome the negative effect of portal hypertension on virological responses and viral kinetics. Improvements in liver stiffness and platelet count might reflect an anti-portal hypertensive effect of IFN-free treatments.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Mandorfer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Kozbial
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Freissmuth
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Schwabl
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: A F
authors.initials: AF
authors.lastname: Stättermayer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Reiberger
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Beinhardt
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Schwarzer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Trauner
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Ferlitsch
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Hofer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Ferenci
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology*; D007093:Imidazoles / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D017082:Portal Pressure / Q000187:drug effects*; D011759:Pyrrolidines; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir