https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840210243

Variability of hepatitis C virus

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840220406

Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.510250637

The molecular virology of hepatitis C

Variation in the 5′ non-coding region (5′NCR) of hepatitis C virus (HCV) was investigated in detail by comparing 314 5′NCR sequences of viruses of genotypes 1 to 6. Evidence was obtained for the existence of associations between particular 5′NCR sequence motifs and virus types and subtypes. No recombination was observed between the 5′NCR and coding regions of different genotypes, implying that the sequence of subgenomic regions such as the 5′NCR can be used to deduce virus genotype. The distribution of polymorphic sites within the 5′NCR is used to propose improved oligonucleotide primers for virus detection and quantification that would be equally efficient in detecting RNA of different virus genotypes. The accuracy of two different genotyping methods (RFLP and the line probe assay) based on analysis of sequence polymorphisms in the 5′NCR is predicted from the sequences surveyed to be 97% and 83% respectively for types 1 to 6, with higher accuracies for distinguishing between subtypes 1a/1b, 2a/2b or 3a/3b. Several sites of genotype-specific polymorphism were covariant and maintained the base pairings required for a secondary structure model of the 5′NCR. Other sites of variation suggest minor modifications to this model and have implications for the probable functions of the 5′NCR

Variation of the hepatitis C virus 5′ non-coding region: implications for secondary structure, virus detection and typing

The hepatitis C virus (HCV), a single-stranded RNA virus, is the major cause of posttransfusion hepatitis. HCV isolates differ in nucleotide and amino acid sequences. Nucleotide changes are concentrated in hypervariable regions and may be related to immune selection. In most immunocompetent persons, HCV infection is diagnosed serologically, using antigens from conserved regions. Amplification of RNA may be necessary to detect infection in immunosuppressed patients. Transmission by known parenteral routes is frequent; other means of spread are less common and may represent inapparent, percutaneous dissemination. Infection can lead to classical acute hepatitis, but most infected persons have no history of acute disease. Once infected, most individuals apparently remain carriers of the virus, with varying degrees of hepatocyte damage and fibrosis ensuing. Chronic hepatitis may lead to cirrhosis and hepatocellular carcinoma. However, disease progression varies widely, from less than 2 years to cirrhosis in some patients to more than 30 years with only chronic hepatitis in others. Determinants important in deciding outcome are unknown. Alpha interferon, which results in sustained remission in selected patients, is the only available therapy. Long-term benefits from such therapy have not been demonstrated. Prevention of HCV infection by vaccination is likely to be challenging if ongoing viral mutation results in escape from neutralization and clearance.

Hepatitis C: progress and problems.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840180606

M D Yoshinao Kobayashi

Papers

Quantitation and typing of serum hepatitis C virus RNA in patients with chronic hepatitis C treated with interferon-β