Sequence analysis of the hepatitis C virus non-structural 5A region [NS5A] in patients with hepatocellular carcinoma

ABSTRACT

The current study was aimed to analyze the sequence of hepatitis C virus non-structural 5A region [NS5A] from patients with hepatocellular carcinoma [HCC] on top of hepatitis C virus and compare these sequences with those of hepatitis C virus non-structural 5A region [NS5A] from patients with chronic active hepatitis C virus to characterize the similarity and/or differences between the two groups. This study included 20 male Egyptian patients, their age ranged from 43 to 74, with hepatitis C virus _ related hepatocellular carcinoma [HCV-related HCC] and no evidence of extrahepatic metastasis. All were negative for hepatitis B surface antigen [HBsAg]. All patients were HCV genotype-4a. Ten Egyptian patients with chronic active hepatitis C virus with matched age and sex were also included as reference group. Serum samples were collected for HCVRNA extraction, amplification and sequencing. Sequence analysis revealed that 11 patients out of 20 [55%] of the HCV-related HCC group harbored a wild-type strain sequence of NS5A region [Accession # NP patient [45%] harbored mutations ranged from 4-6 with an average of 5 mutations / case with a mean sequence identity of 96.0%. A significant increase of the mean number of mutations in the IFN-sensitivity-determining region [ISDR] in the reference group [P < 0.001] compared to the patient group with 84% change. Mutation in PKR-bd region in the reference group was [P < 0.001] compared to the patient group with 73.5% change. The wild type NS5A region was significantly higher in HCV-related HCC patients and the amino acid substitutions in ISDR/PKR domains could be significant factor associated with the development of HCC in long standing patients with chronic active hepatitis