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Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis

A Majumdar1,2, M T Kitson1, S K Roberts1

  • 1Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.

Alimentary Pharmacology & Therapeutics
|April 19, 2016
PubMed

Insights

Direct-acting antiviral therapies offer effective treatment for hepatitis C virus (HCV) cirrhosis, achieving high sustained virological response rates. Challenges remain for difficult-to-cure patient groups, necessitating combination therapies.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacology

Background:

  • Hepatitis C virus (HCV) cirrhosis presents a significant and growing global health burden.
  • Traditional interferon-based therapies are often poorly tolerated in patients with HCV cirrhosis.
  • Direct-acting antiviral (DAA) therapies have emerged as a highly effective treatment option for this population.

Purpose of the Study:

  • To systematically review the efficacy and safety of DAA therapies in patients with HCV cirrhosis.
  • To identify and discuss the persistent challenges associated with DAA treatment in this patient group.

Main Methods:

  • A comprehensive literature search of Medline was performed to identify relevant phase II and III clinical trials.
  • Cross-referencing of review articles and manual review of conference abstracts from major hepatology meetings (EASL, AASLD) were conducted.
  • Keywords included hepatitis C, cirrhosis, and specific DAA agents (e.g., sofosbuvir, velpatasvir).

Main Results:

  • DAA regimens can achieve sustained virological response (SVR) rates of 90-95% in patients with HCV cirrhosis, including those with decompensated liver disease.
  • Excellent treatment success is observed in genotype 1 (GT1) cirrhosis, while genotype 3 (GT3) cirrhosis remains more challenging to cure.
  • The pangenotypic combination of sofosbuvir and velpatasvir shows promise for GT3 cirrhosis, with reported SVR rates around 90%.

Conclusions:

  • DAA therapies offer safe and effective treatment options for patients with HCV cirrhosis, including those previously ineligible for treatment.
  • Combination therapy with multiple DAA classes is crucial for maximizing efficacy and preventing viral resistance.
  • Key challenges include treating difficult-to-cure GT3 cirrhosis, managing DAA treatment failures, and addressing potential drug-drug interactions.
Abstract

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