Traitement de l’hépatite C

Treatment of hepatitis C

Service d’Hépatologie, Centre de recherche Claude Bernard sur les hépatites virales, Inserm U.481, Hôpital Beaujon, 100, boulevard du Général Leclerc 92110 Clichy, France

Résumé

Depuis la découverte du virus de l’hépatite C en 1989, le traitement de l’hépatite C a considérablement progressé. Avec l’interféron α en monothérapie, le taux de réponses virologiques prolongées est inférieur à 20 %. Par la suite, l’utilisation d’une bithérapie associant l’interfé-ron α et la ribavirine a permis d’obtenir 40 % de réponses prolongées. Plus récemment, il a été démontré que les interférons pégylés sont globalement deux fois plus efficaces que l’interféron standard. La bithérapie associant les interférons pégylés et la ribavirine donne environ 55 % de réponse virologique prolongée. Avec le recul, il apparaît que la réponse virologique prolongée est associée à un bénéfice histologique et probablement à une diminution du risque de cirrhose et de carcinome hépatocellulaire. Afin d’améliorer l’efficacité du traitement, plusieurs stratégies thérapeutiques sont envisagées  : tri-thérapie (interféron pégylé + ribavirine + aman-tadine), cytokines, inhibiteurs enzymatiques, oligonucléotides anti-sens, ribozymes ou vaccin thérapeutique.

Abstract

Since the discovering of the hepatitis C virus in 1989, the treatment of hepatitis C has considerably improved. Initially, with interferon alpha used as a single drug, the sustained virological response rate was below 20%. Then, with the use of combination therapy of interferon alpha with ribavirin, the response rate increased to 41%. More recently, pegylated interferons were shown to be twice more effective than standard interferons. The combination of pegylated interferons with ribavirin give a response rate of about 55%. The long-term follow-up studies showed that sustained virological response is generally associated with clinical and histological improvement and probably with a decreased risk of development of cirrhosis and hepatocellular carcinoma. The indication of therapy is mainly based on the results of the liver biopsy which is the best way to assess the prognosis of the liver disease. Therefore, treatment is indicated in patients with moderate or severe necroinflammation or fibrosis. The tolerability of combination therapy is relatively poor with a frequent flulike syndrom and an impaired quality of life. The most frequent adverse events are depression, thyroid dysfunction, neutropenia and anemia which need reduction of dosage in about 40% and interruption of treatment in about 10% of treated patients. The chances to obtain a sustained virological response depends essentially on the viral genotype and the viral load. To further improve the efficacy of therapy, different new drugs are under investigation (amantadine, cytokines). These drugs may be candidates for new combinations. In addition, intensive research is currently done for the development of inhibitors of viral enzymes (helicase, proteases or polymerase) and anti-sense oligonucleotides, ribozymes and therapeutic vaccine.