Viral sequence evolution in Chinese genotype 1b chronic hepatitis C patients experiencing unsuccessful interferon treatment

The efficiencies of IFN-α based therapy in chronic genotype 1b HCV patients are still unsatisfied to date. The mechanisms underlining treatment failure remain unclear and controversial. To investigate HCV sequence evolution in unsuccessfully treated genotype 1b patients before, during and after the therapy, full-length open-reading-frame of HCV genomes at week 0, week 48 and year 5 in one breakthrough and one nonresponse patients were amplified by reverse transcription (RT)-nested-PCR and sequenced. Mutations were scored and analyzed according to their locations in the HCV genome. HCV sequences in the breakthrough patient displayed significantly more mutations during the one-year therapy than that in the nonresponse patient, with p7 and NS2 encoding regions having the highest mutation rates. Most of the mutations selected during the therapy phase in the breakthrough patient were maintained and few new mutations arose in the four-year post-therapy phase, suggesting these mutations might not compromise viral fitness. Altogether our data suggest that mutations occurred during the therapy phase in the breakthrough patient are likely driven by the action of interferon and ribavirin, and these mutations may have important effects on the responses to interferon based therapy in genotype 1b HCV patients.

Research highlights▶ Longitudinal sequencing analysis of HCV genomes in unsuccessfully treated patients. ▶ HCV genome mutation rate in the breakthrough patient was high during the therapy. ▶ HCV genome mutation rate in the nonresponse patient was low during the therapy. ▶ Most HCV mutations in the breakthrough patient were kept in the post-therapy phase. ▶ Viral mutations may account for interferon resistance in HCV breakthrough patients.