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<%AbstractTime%> S16.
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Treatment of Hepatitis C
R. T. Chung
Massachusetts Gen. Hosp., Harvard Med. Sch., Boston
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Background: Significant strides have been made in the management of chronic hepatitis C, which remains one of the few chronic infections that can be successfully eradicated. Interferon-?-based regimens remain the mainstay of treatment of established infection. However, it was not until the addition of ribavirin that these regimens produced substantial improvements in virologic response rates. Until recently, combination interferon and ribavirin resulted in sustained virologic response rates (loss of HCV RNA 6 months after cessation of therapy) near 40%, with significant disparities between the more prevalent genotype 1 (28%) and the less common genotypes 2/3 (65%). The picture has improved further with modifications of interferon that impair its clearance, permitting less frequent dosing. Pivotal clinical trials of the combination of these pegylated interferons with ribavirin in mono-infection have reported sustained virologic responses of 54-56%, with genotype 1 SVRs increased to 42-45%, and genotype 2/3 SVRs to 75-80%. Thus, pegylated interferon and ribavirin have become standard of care in chronic HCV. However, the other edge of this promise is a significant frequency of dose-limiting side effects and toxicities, which are even more problematic in the co-infected host. These include myelosuppression, hemolysis, neuropsychiatric effects, and potential interactions with antiretroviral regimens. Indeed, early combination treatment trials in HIV/HCV co-infection reveal high permanent discontinuation rates, and consequently diminished HCV SVR rates in these patients. Current treatment trials are examining the efficacy and safety of pegylated interferon with ribavirin in co-infection.
Conclusions: Because of the more rapid fibrosis progression and its consequences for morbidity and mortality in the co-infected population, the merits of maintenance therapy and other liver disease-modifying strategies warrant consideration. In addition, the role of early treatment of HCV in permitting successful initiation of ART in co-infected persons with or without a history of ART hepatotoxicity should be examined, especially with the raising of thresholds for initiation of ART. Whether control of HCV will have an independent beneficial effect on HIV disease progression, as has been suggested in some studies, awaits longer-term follow-up. Finally, the coming development of compounds that interrupt key viral enzymatic or lifecycle functions will be an essential addition to the arsenal against HCV, especially in the co-infected host.
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