Abstract

HCV infection is worldwide health problem. HCV has a high propensity for inducing lifelong persistent infections that can progress to significant liver diseases including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The sustained response rate among patients with different genotypes is variable and patients with higher initial HCV- RNA level had a lower response rate than those with lower level, independent of genotypes. The study was conducted to observe the treatment response and sustained response with combined antiviral therapy in relation to different genotypes in patients of chronic hepatitis C in interior of Sindh. Subjects and methods: A prospective cross-sectional, observational study carried out from August 2006 to December 2009 at Research Medical Center LUMHS Jamshoro, department of pathology, Peoples University of Medical and Health Sciences, Nawabshah and Biotechnology Department University of Karachi. A total of 344 HCV-PCR positive patients with different genotypes and histological evidence of chronic hepatitis with either fibrosis or inflammatory activity by biopsy were evaluated 239 men and 105 women with ages between 18–55 years of age years were included in the study. All the patients went for ELISA test for the presence of HCV antibodies by ELISA kit of Biokit Spain, a 10.0 ml sample of blood was collected in a tube with separating gel, to obtain serum, which was stored at -80^oC, the determination of HCV RNA and for HCV genotyping was performed by PCR on Anagen Kit. Than all the patients were given Interferon alpha 3 mu subcutaneously alternate days three times a week with Ribivirin 400mg three times a day as a combination therapy up to 6 to 12 months depending upon genotyping of HCV. In order to see the treatment response, the presence of HCV – RNA was checked after 6 months and 12 months, so that in this way result were tabulated Results: Out of 344 cases of chronic hepatitis-C patients 242 were of genotype 3a and 223 become HCV-PCR negative after completion of treatment and response rate of antiviral treatment was 92.14%, while 19 subjects were of 3b and response rate in these subjects was 84.21%. Out of 10 patients with genotype 1a, the response rate of combined antiviral therapy was 40% while 5 patients were of 1b and response rate in these patients was 20%. Only 4 patients were of genotype 2, and 3 subjects were of genotype 5, and response rate in these cases was 100%. Out of 9 subjects with mixed genotypes, the response rate was 22.22%. There were 52 patients who could not be genotyped and with these untypable genotypes the response rate of antiviral therapy was 46.15%. Out of 4 cases of genotype 1a with positive response to combined therapy only 1 case (25%) showed sustained response, while no case with genotype 1b showed sustained response. All the 4 cases of genotype 2 with positive response showed sustained response with combined antiviral therapy. Out of 223 cases of genotype 3a with positive response to combined therapy, 187(83.86%) cases showed sustained response, while 10(62.5%) out of 16 cases with positive response of genotype 3b showed sustained response. Out of 3 cases of genotype 5 with positive response 3 cases (66.66%) showed sustained response, while only 1 case (50%) from 2 cases with positive response of genotype mixed type showed sustained response. Out of 24 cases of genotype untypable with positive response to combined antiviral therapy, 10 cases (41.66%) showed sustained response. Conclusion: The data in the current study indicates that a person’s HCV genotype is the worldwide key-factor that influences their possible response and sustained response to antiviral therapy in relation to genotype 2,3 and 5 (p-value is statistically significant)