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All-trans retinoic acid for treatment of chronic hepatitis C

Wulf O Böcher1, Christian Wallasch, Thomas Höhler

  • 1I Department of Internal Medicine, Johannes Gutenberg University Hospital, Mainz, Germany. boecher@mail.uni-mainz.de

Liver International : Official Journal of the International Association for the Study of the Liver
|February 23, 2008
PubMed
Abstract

Insights

All-trans retinoic acid (ATRA) showed antiviral activity against hepatitis C virus (HCV) in vitro. In vivo, ATRA monotherapy or combination therapy with PegIFN-alpha2a demonstrated viral load reduction in treatment-experienced patients.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacology

Background:

  • In vitro studies identified all-trans retinoic acid (ATRA) as a potential therapeutic agent against hepatitis C virus (HCV).
  • The subgenomic HCV replicon system demonstrated ATRA's antiviral properties.
  • Further in vivo assessment of ATRA's therapeutic potential was warranted.

Purpose of the Study:

  • To evaluate the in vivo antiviral efficacy of all-trans retinoic acid (ATRA) in patients with chronic hepatitis C.
  • To compare ATRA monotherapy with a combination of ATRA and pegylated interferon-alpha2a (PegIFN-alpha2a).

Main Methods:

  • Twenty treatment-experienced patients with serotype 1 HCV non-responsive to standard therapy were enrolled.
  • Patients received either 12 weeks of ATRA monotherapy (Group A) or ATRA plus PegIFN-alpha2a (Group B).
  • Hepatitis C virus RNA levels were quantified using bDNA assay and sensitive polymerase chain reaction.

Main Results:

  • ATRA monotherapy resulted in a >1 log drop in viremia in 50% of patients.
  • Combination therapy led to a >2 log drop in viremia in 50% of patients by week 8, with 30% achieving undetectable HCV RNA.
  • Viral load reduction was transient, with relapse observed after treatment cessation. ATRA was generally well-tolerated.

Conclusions:

  • ATRA exhibits transient antiviral activity against HCV in vivo, supporting its potential therapeutic role.
  • The combination of ATRA and PegIFN-alpha2a showed a significant additive or synergistic effect in non-responders.
  • Further controlled trials are recommended to fully assess the therapeutic potential of ATRA for hepatitis C treatment.

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