Investigation of the relative infectivity and pathogenicity of different hepatitis C virus genotypes in hemophiliacs

To assess the relative infectivity and pathogenicity of variants of hepatitis C virus (HCV) genotypes, the distribution of genotypes in hemophilic patients who had been treated with nonvirally inactivated factor concentrates or cryoprecipitates prepared from local blood donors was compared with those found in the respective blood donor populations. Genotype frequencies differed markedly in the four countries investigated (Scotland, Hungary, South Africa, and Thailand) but in each, the HCV genotype distributions in hemophiliacs and blood donors were similar. In addition, HCV genotypes in recipients of commercially manufactured concentrates were similar to those found in the US general population. These findings provide no evidence that HCV genotypes differ significantly from each other in replication rate, transmissibility, or infectivity.

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The distribution of hepatitis C virus genotypes in patients with hepatocellular carcinoma

Asian Journal of Medical Sciences ◽

10.3126/ajms.v10i6.25720 ◽

2019 ◽

Vol 10 (6) ◽

pp. 28-32

Author(s):

Ayfer Bakır ◽

Nuran Karabulut ◽

Sema Alaçam ◽

Barış Bakır ◽

Ali Ağaçfidan

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatic Cirrhosis ◽

Genotype 1 ◽

High Association ◽

Hcv Genotypes ◽

Genotype 1B ◽

Virus Genotypes ◽

Hepatitis C Virus Genotypes ◽

Chronic Hcv

Background: Hepatic cirrhosis develops within 20-30 years in approximately 20% of individuals chronically infected with hepatitis C virus (HCV). Aims and Objective: This study aimed to determine the distribution of HCV genotypes in patients with HCV-associated HCC in our region and thus to contribute to the epidemiology of HCV. Materials and Methods: HCC patients referred to the virology laboratory for HCV genotype identification between January 2013 and April 2018 were included in this study. Genotyping of HCV was performed by a commercial reverse hybridization line probe-based assay. Results: Seventeen patients who were diagnosed with HCC and whose HCV genotypes were analyzed were included in this study. Genotype 1 was detected in all 17 patients with HCC. When evaluating subtypes of genotype 1, genotype 1b was detected in 16 (94%) of the patients. The HCV subtyping in one patient (6%) could not be performed. Conclusion: As a result, genotype 1b, one of the major risk factors for HCC, was detected in 94% of the patients included in this study. This study, consistent with the literature, shows a high association between the development of HCC and genotype 1b in patients with chronic HCV.

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Comparison of Daclatasvir Resistance Barriers on NS5A from Hepatitis C Virus Genotypes 1 to 6: Implications for Cross-Genotype Activity

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02788-14 ◽

2014 ◽

Vol 58 (9) ◽

pp. 5155-5163 ◽

Cited By ~ 50

Author(s):

Chunfu Wang ◽

Lingling Jia ◽

Donald R. O'Boyle ◽

Jin-Hua Sun ◽

Karen Rigat ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Activity ◽

Rank Order ◽

Replicon Cell ◽

Hcv Genotypes ◽

Resistance Selection ◽

Virus Genotypes ◽

Hepatitis C Virus Genotypes

ABSTRACTA comparison of the daclatasvir (DCV [BMS-790052]) resistance barrier on authentic or hybrid replicons containing NS5A from hepatitis C virus (HCV) genotypes 1 to 6 (GT-1 to -6) was completed using a replicon elimination assay. The data indicated that genotype 1b (GT-1b) has the highest relative resistance barrier and genotype 2a (GT-2a M31) has the lowest. The rank order of resistance barriers to DCV was 1b > 4a ≥ 5a > 6a ≅ 1a > 2a JFH > 3a > 2a M31. Importantly, DCV in combination with a protease inhibitor (PI) eliminated GT-2a M31 replicon RNA at a clinically relevant concentration. Previously, we reported the antiviral activity and resistance profiles of DCV on HCV genotypes 1 to 4 evaluated in the replicon system. Here, we report the antiviral activity and resistance profiles of DCV against hybrid replicons with NS5A sequences derived from HCV GT-5a and GT-6a clinical isolates. DCV was effective against both GT-5a and -6a hybrid replicon cell lines (50% effective concentrations [EC50s] ranging from 3 to 7 pM for GT-5a, and 74 pM for GT-6a). Resistance selection identified amino acid substitutions in the N-terminal domain of NS5A. For GT-5a, L31F and L31V, alone or in combination with K56R, were the major resistance variants (EC50s ranging from 2 to 40 nM). In GT-6a, Q24H, L31M, P32L/S, and T58A/S were identified as resistance variants (EC50s ranging from 2 to 250 nM). Thein vitrodata suggest that DCV has the potential to be an effective agent for HCV genotypes 1 to 6 when used in combination therapy.

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