Heterogeneity of hepatitis C-virus in genotype 1 patients treated with the combination therapy of pegylated interferon and ribavirin
Hepatitis C is a global health problem. Hepatitis C virus is the etiological agent. After the acute phase of infection, which is asymptomatic in most patients, at least 80% of patients develop chronic hepatitis C. 20%-40% of infected people may develop cirrhosis, and 2%-4% of them may ultimately develop liver cancer. At present, HCV-related end-stage liver disease is the leading reason for liver transplantation. Hepatitis C has been first described in 1989. Over the past 15 years treatment has been constantly improved. Today a combination therapy with pegylated interferon a (PEG-IFN) and ribavirin is recommended. The sustained virological response rate six months after stop of treatment (SVR) is about > 55% in treatment naive patients. Because the treatment with PEG-IFN plus ribavirin is 6 to 12 months with a large number of adverse events and costly, it is mandatory to find factors to predict the effect of therapy. As a typical RNA virus, HCV has a high mutation rate, which is especially pronounced in the HVR1 of the N-amino terminal region of E2. Genotypes, subtypes and quasispecies can be distinguished. Quasispecies refer to the genetic diversity of a virus population that can be observed in a single infected individual with individual viral genomes differing 1%-5% in nucleotide sequence. Single stand conformation polymorphism (SSCP) is an accurate and reproducible method to study the complexity of HCV quasispecies. This study investigated the degree of complexity of HCV by f-SSCP. The data suggest that f-SSCP reflects the complexity of HCV quasispecies. Complexity – identified by the number of f SSCP peaks, is an important factor for the response to treatment with PEG-IFN plus ribavirin. A low number of SSCP peaks indicate a low degree of HCV quasispecies complexity, which corresponds with a higher response rate to therapy. Low HCV quasispecies in genotype 1 patient might be an additional predictor to response to therapy. On the other hand it could be shown that treatment with PEG-IFN plus ribavirin affects the quasispecies complexity of HCV. The data indicate that quasispecies may be an additional factor which may be important for the response of the chronic HCV infection to PEG-IFN and Ribavirin.
Genotyp 1, pegyliertem Interferon, Ribavirin, genotype 1, pegylated interferon
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