Liver International 28 (3) , 347–354 doi:10.1111/ j.1478-3231. 2007.01666. x


Abstract
CLINICAL STUDIES
All-trans retinoic acid for treatment of chronic hepatitis C

Wulf O. Böcher11 I Department of Internal Medicine, Johannes Gutenberg
University Hospital, Mainz, Germany, Christian Wallasch22 GPC Biotech (former
AXXIMA Biotech), München, Germany, Thomas Höhler33 Department of Internal
Medicine, Prosper Hospital, Recklinghausen, Germany and Peter R. Galle11 I
Department of Internal Medicine, Johannes Gutenberg University Hospital, Mainz,
Germany1 I Department of Internal Medicine, Johannes Gutenberg University
Hospital, Mainz, Germany
2 GPC Biotech (former AXXIMA Biotech), München, Germany
3 Department of Internal Medicine, Prosper Hospital, Recklinghausen, Germany
Correspondence
Wulf O. Böcher, MD, I Department of Internal Medicine, Johannes Gutenberg
University Hospital, Langenbeckstrasse 1, 55131 Mainz, Germany
Tel: +49 6131 172666
Fax: +49 6131 176621
e-mail: boecher@mail. uni-mainz. de

Abbreviations
ATRA, all-trans retinoic acid; EVR, early virological response; GI-GPx,
gastrointestinal glutathione peroxidase; PegIFN-α, pegylated interferon-alpha;
SVR, sustained virological response.

Abstract

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.

http://www.blackwel l-synergy. com/doi/abs/ 10.1111/j. 1478-3231. 2007.01666. x


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