[show abstract][hide abstract] ABSTRACT: Hepatitis C virus (HCV) shows considerable variation in its genomic structure, allowing classification into six main genotypes. Epidemiological studies have shown marked differences in genotype distribution by geographical region, and between patient groups. Improved understanding of the rate of nucleotide sequence mutation in HCV has allowed the approximate time of divergence of major genotypes to be estimated, and the origin and spread of the present epidemic of hepatitis C to be better defined. Improved methods of genotype definition over the last few years have enabled the importance of genotype in the progression of HCV-related disease and response to anti-viral therapy to be studied. Present data strongly indicates that HCV genotype is an important determinant of response to treatment, but the effect of genotype on disease progression has been harder to clarify. This is largely due to the absence of model systems of HCV infection, the epidemiological differences in patient groups infected with the different genotypes, and the lack of good prospective longitudinal clinical data. As a result of advances in methodology, and recent results of large clinical trials of combination therapy, a knowledge of HCV genotype is now central to the clinician in the management of patients with chronic hepatitis C.
Baillière' s Best Practice and Research in Clinical Gastroenterology 05/2000; 14(2):229-40. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The most consistently identified predictive factors for a response to both IFN-alpha monotherapy and IFN-alpha in combination with ribavirin are a low HCV RNA level, the absence of fibrosis, infection with HCV genotype 2 and 3, and a prolonged duration of treatment. In addition, an early response to IFN-alpha predicts response to IFN-alpha monotherapy but not necessarily to combination therapy. There does not appear to be any major gain in treating IFN-naive patients with HCV genotype 2 or 3 infection with a combination of IFN-alpha and ribavirin for longer than 6 months. The identification of these predictive factors has allowed improvement in study design and assessment and may provide a patient with an idea of the likelihood of response, making possible a more informed decision regarding treatment. At present, none of these factors, either alone or in combination, completely predicts response to IFN-alpha. Thus, individual patients should not be denied treatment on the basis of these factors.
Clinics in Liver Disease 12/1999; 3(4):775-91. · 2.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: The major objective of treatment of chronic hepatitis C virus (HCV) infection is to prevent progression to cirrhosis, and thereby prevent complications of end-stage liver disease. The established treatment of chronic HCV is with alpha interferon. Recent results with ribavirin and alpha interferon together suggest that combination antiviral therapy will become the benchmark treatment. For both naive and relapsed patients, however, it has become important to assess the long-term outcome of treatment, in order to gauge whether treatment has indeed modified the natural history of chronic hepatitis C virus infection. It seems likely that most sustained responders (85-90%) treated with combination ribavirin and alpha interferon will continue to have a long-term biochemical and virological response, as has been demonstrated with alpha interferon alone, but further long-term follow-up of patients treated with combination therapy is required.