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.

AIM:

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: M Mandorfer, K Kozbial, C Freissmuth, P Schwabl, A F Stättermayer, T Reiberger, S Beinhardt, R Schwarzer, M Trauner, A Ferlitsch, H Hofer, M Peck-Radosavljevic, P Ferenci
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 42 Issue 6 Pg. 707-18 (Sep 2015) ISSN: 1365-2036 [Electronic] England
• PMID: 26179884 (Publication Type: Journal Article)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Pyrrolidines
• Ribavirin
• Simeprevir
• Valine
• daclatasvir
• Sofosbuvir

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Carbamates
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Hypertension, Portal (etiology)
• Imidazoles (therapeutic use)
• Liver Cirrhosis (etiology)
• Male
• Middle Aged
• Portal Pressure (drug effects)
• Pyrrolidines
• Retrospective Studies
• Ribavirin (therapeutic use)
• Simeprevir (therapeutic use)
• Sofosbuvir (therapeutic use)
• Treatment Outcome
• Valine (analogs & derivatives)