All-trans retinoic acid for treatment of chronic hepatitis C
Article first published online: 15 FEB 2008
© 2008 The Authors
Volume 28, Issue 3, pages 347–354, March 2008
How to Cite
Böcher, W. O., Wallasch, C., Höhler, T. and Galle, P. R. (2008), All-trans retinoic acid for treatment of chronic hepatitis C. Liver International, 28: 347–354. doi: 10.1111/j.1478-3231.2007.01666.x
- Issue published online: 15 FEB 2008
- Article first published online: 15 FEB 2008
- Received 25 June 2007Accepted 20 November 2007
- all-trans retinoic acid;
- chronic hepatitis;
- glutathione peroxidase;
Background/Aims: In vitro studies in the subgenomic hepatitis C virus (HCV) replicon system have identified all-trans retinoic acid (ATRA) as a potential therapeutic against hepatitis C. Thus, the antiviral potential of this drug should be assessed in vivo.
Methods: Twenty highly treatment experienced serotype 1 patients with non-response to conventional or pegylated interferon-α (Peg-/IFN-α) and ribavirin were randomly assigned to 12 weeks of monotherapy with ATRA (group A) or a combination of ATRA and PegIFN-α2a (group B). HCV RNA was assessed by bDNA assay and if negative by highly sensitive polymerase chain reaction.
Results: During treatment, five of 10 patients in group A had a drop of viraemia >1log, while in group B after 8 weeks five of 10 dropped >2log, and three of 10 cleared HCV RNA from serum. Viraemia relapsed after treatment cessation. ATRA was rather well tolerated, with transient headache, dry skin and mucosa representing the most common side effects.
Conclusions: The viral load reduction under ATRA monotherapy, although limited and transient, supports the antiviral activity of ATRA. However, the rapid loss of HCV RNA in three of 10 previous non-responders under ATRA and PegIFN-α2a treatment demonstrates a strong additive or synergistic ATRA effect and calls for a controlled trial to assess the therapeutic potential of this drug.