ABSTRACT
Mutations in several subgenomic regions have been implicated in influencing response to interferon therapy; however, a comprehensive picture of Indian patients was lacking. Based on the viral load and clinical factors, 10 out of 15 patients were found to be complete responders, whereas 5 patients were nonresponders. The pretreatment viral RNA load of the patients was found to be between 5.20 and 6.13 log10 IU/ml, which eventually fell to 2.77 log10 IU/ml after 24 weeks of treatment, whereas in the case of nonresponders, the average was 5.38 log10 IU/ml. In order to study the influence of the hepatitis C virus genotype on the response to interferon therapy, the 5' untranslated region sequences of the samples were analyzed, which showed that genotype 3 patients responded better than genotype 1 patients. Additionally, the mutations in the interferon sensitivity-determining region (ISDR) of the NS5A protein and the double-stranded RNA-activated protein kinase-eukaryotic initiation factor 2 alpha phosphorylation homology domain (PePHD) of the E2 envelope protein, before and after treatment, were compared with nonresponder prototype J. Although, no clear correlation was found in the case of the mutated ISDR, some significant changes in residues were observed in the PePHD region, which could be helpful in understanding the molecular basis of resistance to therapy. Interestingly, analysis of the quasispecies variations showed a change in genotype in one sample during treatment, which might have contributed to the resistance. The results suggest that the mutations in different regions of the viral genome might have a concerted effect on the response to interferon therapy.
Subject(s)
Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C/virology , Interferons/pharmacology , 5' Untranslated Regions , Adult , Amino Acid Sequence , Drug Resistance, Viral/genetics , Female , Genes, Viral , Genotype , Hepacivirus/classification , Hepacivirus/isolation & purification , Humans , India , Male , Middle Aged , Molecular Sequence Data , Mutation , Phylogeny , Sequence Homology, Amino Acid , Viral Envelope Proteins/genetics , Viral Nonstructural Proteins/geneticsABSTRACT
The prevalence of hepatitis C virus (HCV) infection in the general population and in various high risk groups in south India was assessed. A total of 258 out of 3589 (7.1%) subjects (both general and risk groups) tested positive for HCV RNA by RT-PCR, while the third generation ELISA detected only 6.1% (221/3589). This suggests that a number of cases go unreported, as screening of blood and blood products is done primarily by ELISA. Among 124 chronic renal failure (CRF) patients with a history of renal transplant or haemodialysis, 37% were found to be positive for HCV RNA by RT-PCR. We also found a significantly higher rate of transmission of HCV among people exposed to tattooing (2.8%) and pilgrims (5.8%) (slashing a cultural practice in one sect of Muslims). In addition, our studies also reveal a high prevalence of HCV infection (44%) among patients with Lichen planus. The most prevalent genotype observed in our population was 1b (43.4%) followed by 3b (30.2%). The other genotype 1a was observed in 16.6% of patients followed by 3a observed in 3.4% of the patients. Our findings suggest that HCV may be the major cause of post-transplant hepatitis in Indian patients with CRF and indicate the necessity for stringent screening procedures for these viral infections.
