Association with 5'-untranslated region and response to interferon in chronic hepatitis C

The 5'-untranslated region (5'UTR) of hepatitis C virus (HCV) is a useful region for determinations of genotype and viral load. 5'UTR can be used for simultaneous analysis of HCV genotype and viral load, therefore several assays have been described. A method which used direct sequencing of the 5'UTR can also be used to identify mutations in this region. The objective of the present study was to evaluate possible associations of 5'UTR mutations with responsiveness to interferon (IFN) therapy in chronic hepatitis C patients.

Seventy patients with chronic hepatitis C were included in this study. The relations between responsiveness to IFN therapy and HCV genotype, viral load, and 5'UTR mutations before IFN treatment were evaluated.

We detected HCV genotype 1a (n = 5), 1b (n = 32), 2a (n = 15), 2b (n = 12), and 3a (n = 6). Forty-eight patients were non-sustained responders (NR). Seven of 37 (18.9%) patients with the 1a or 1b genotype were sustained responders (SR), and 14 of 27 (51.9%) patients with genotype 2a or 2b were SR. Responses of patients with genotype 1 were poorer than those of patients with genotype 2. HCV viral loads of all SR patients infected with genotype la or 1b were less than 100 KIU/mL, but more than 50% of SR patients infected with genotype 2a or 2b had viral loads over 100 KIU/mL. Thus, viral load in patients with genotype 1 is strongly associated with IFN sensitivity. 5'UTR were well conserved, and there were no differences in the distribution of genotypes between SR and NR.

The 5'UTR is a suitable region for determining HCV genotype and viral load, which are predictors of responsiveness to IFN therapy, but specific mutations of the 5'UTR do not appear to be associated with responsiveness to IFN.