Poster Presentations

Session Title: VIRAL HEPATITIS - g) HEPATITIS C – CLINICAL (THERAPY)
Presentation Date: Apr 24, 2009

THE ANTIFIBROTIC PENTOXYPHILLINE/A-TOCOPHEROL ASSOCIATION DOES NOT LIMIT LIVER FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C - ANRS HC 10

H. Fontaine^1,2, S. Fernandes^1,2, B. Nalpas^1,2, P. Bedossa³, J.-D. Grangé⁴, A. Tran⁵, J. Guéchot⁶, S. Candon⁷, F. Imbert-Bismut⁸, S. Pol^1,2
1Hepatology Unit, Hôpital Cochin - APHP, ²INSERM U567, Université Paris Descartes, Paris, ³Department of Pathology, Hôpital Beaujon, AP-HP and INSERM, U773, Centre de Recherche Biomédicale Bichat Beaujon , Université Paris 7-Denis-Diderot, Clichy, ⁴Hepatology Unit, Hôpital Tenon - APHP, Paris, ⁵Hepatology Unit, Hôpital de l'Archet, Nice, ⁶Service de Biochimie A, Hôpital Saint Antoine - APHP, ⁷Immunology, Hôpital Necker - APHP, ⁸Department of Biochemistry, Hôpital de la Pitié-Salpétrière - APHP, Paris, France

Background and aims: About 45 % of patients are non responders to the ribavirine-pegylated interferon combination and there is no therapy proven to be efficient in limiting liver fibrosis progression.
Aim: To analyse the efficacy and safety of the association of pentoxyphilline (anti-TNF activity) and a-tocopherol (antioxydant activity) in this population.
Methods: 91 patients, non responders or refusing the recommended combination (49 M and 38 F, mean age: 53 ± 10 years) were included in a prospective, randomised, placebo-controlled study. They were given pentoxyphilline 400 mg and tocopherol 500 mg (n = 46) or double placebo (n = 45), BID during one year. Baseline (BL) liver biopsies were performed less than 3 years before the inclusion and at the end of treatment. Criteria of judgement: 1. histopathology by morphometric analysis and Metavir scores; 2. variation of ALAT and non invasive tests (Fibrotest, hyaluronate, PIIIP, TNF-a) measured at the beginning, at 6 months and at the end of the treatment.
Results: There were no BL differences in the histopathological severity between both groups. By comparison between BL and at the end of therapy, there were no significant changes in fibrosis by morphometric analysis (treated 14.8 ± 6.8 vs 15.5 ± 6.7; placebo 13.1 ± 6.7 vs 14.1 ± 7.3) or Metavir score (treated 2.4 ± 0.5 vs 2.4 ± 0.9 ; placebo 2.3 ± 0.5 vs 2.3 ± 0.9). The Fibrotest decreased from 0.59 ± 0.25 to 0.57 ± 0.25 and increased non significantly from 0.56 ± 0.24 to 0.64 ± 0.20 in the treated and the placebo groups, respectively. There was no significant difference in hyaluronate, P IIIP, TNF-a and ALAT levels between the beginning and the end of the treatment in both groups. Treatment was safe: only 2 severe adverse effects unrelated to active therapy were recorded.
Conclusion: The association of a-tocopherol and pentoxyphilline during one year had no clear antifibrotic effect on liver fibrosis progression in patients with chronic hepatitis C.