All-trans retinoic acid for treatment of chronic hepatitis C.
OBJECTIVE
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-alpha (Peg-/IFN-alpha) and ribavirin were randomly assigned to 12 weeks of monotherapy with ATRA (group A) or a combination of ATRA and PegIFN-alpha2a (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-alpha2a treatment demonstrates a strong additive or synergistic ATRA effect and calls for a controlled trial to assess the therapeutic potential of this drug.
Böcher
Wulf O
WO
I Department of Internal Medicine, Johannes Gutenberg University Hospital, Mainz, Germany. boecher@mail.uni-mainz.de
Wallasch
Christian
C
Höhler
Thomas
T
Galle
Peter R
PR
D000328:Adult; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012367:RNA, Viral / Q000378:metabolism*; D013997:Time Factors; D014212:Tretinoin / Q000627:therapeutic use*
D012367:RNA, Viral; D014212:Tretinoin