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Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients

par Brouwer, Johannes;Nevens, Frederik;Kleter, Bernhard;Elewaut, Andre;Alder, Michael;Brenard, Réginald;Chamuleau, Robert Afm;Michielsen, Peter;Pirotte, Jean;Hautekeete, Marc Leopold;Weber, Joseph;Bourgeois, Nadine ;Hansen, Bettina;Bronkhorst, Carolien C.M.;Ten Kate, Fibo J W;Heijtink, Rudolf R.A.;Fevery, Johan;Schalm, Solko Walle
Référence Journal of hepatology, 28, 6, page (951-959)
Publication Publié, 1998-06

Article révisé par les pairs

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Résumé :

Background/Aims: In an attempt to improve the limited efficacy of treatment of chronic hepatitis C with interferon-alpha 3 MU tiw, we studied the effects of double-dose therapy followed by downward titration, and analyzed the pre- and pretreatment factors associated with response or non- response. Methods: Three hundred and fifty-four consecutive patients in 19 centers were randomized to interferon-alpha 3 MU tiw for 6 months or 6 MU tiw for 8 weeks followed by down-titration (3,1 MU tiw) till alanine aminotransferase remained normal and plasma HCV RNA was repeatedly undetectable. The primary outcome measure was sustained alanine aminotransferase and HCV RNA response 6 months after treatment. Results: Three hundred and thirty-six patients received treatment. The sustained response rate for patients receiving 3 MU tiw for 6 months was 14% (9-21%) and for patients receiving double dose tiw for 8 weeks and thereafter titrated therapy 15% (10-21%) (p=0.8). Pretreatment factors associated with a sustained alanine aminotransferase plus HCV RNA response were the absence of cirrhosis, presence of genotype 2 or 3, a low viral load and, in addition, a low alanine aminotransferase/aspartate aminotransferase ratio; a model was developed to allow estimation of the chance of response for the individual patient. The most powerful predictor of sustained response, however, was plasma HCV RNA at week 4; a positive test virtually precluded a sustained response (1.7%, 0.4-5.0%). If week 4 HCV RNA was not detectable, the chance of a sustained response was 21% (12-34%) for genotype 1 versus 40% (28-54%) for the others (p=0.02). Six MU tiw led to a significantly higher week 4 HCV RNA response (47% not detectable) than 3 MU (37%) (p=0.02). During down- titration this difference in viral on-treatment response was lost. Conclusions: In the treatment of hepatitis C, an early HCV RNA response is a prerequisite for long-term efficacy. Doubling the initial interferon dose increases this early response, but subsequent downward titration negates this effect, especially in genotype 1.