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Contribution of genome-wide HCV genetic differences to outcome of interferon-based therapy in Caucasian American and African American patients

Donlin, MJ and Cannon, NA and Aurora, R and Li, J and Wahed, AS and Di Bisceglie, AM and Tavis, JE (2010) Contribution of genome-wide HCV genetic differences to outcome of interferon-based therapy in Caucasian American and African American patients. PLoS ONE, 5 (2).

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Abstract

Background: Hepatitis C virus (HCV) has six major genotypes, and patients infected with genotype 1 respond less well to interferon-based therapy than other genotypes. African American patients respond to interferon α-based therapy at about half the rate of Caucasian Americans. The effect of HCV's genetic variation on treatment outcome in both racial groups is poorly understood. Methodology:We determined the near full-length pre-therapy consensus sequences from 94 patients infected with HCV genotype 1a or 1b undergoing treatment with peginterferon α-2a and ribavirin through the Virahep-C study. The sequences were stratified by genotype, race and treatment outcome to identify HCV genetic differences associated with treatment efficacy. Principal Findings:HCV sequences from patients who achieved sustained viral response were more diverse than sequences from non-responders. These inter-patient diversity differences were found primarily in the NS5A gene in genotype 1a and in core and NS2 in genotype 1b. These differences could not be explained by host selection pressures. Genotype 1b but not 1a African American patients had viral genetic differences that correlated with treatment outcome. Conclusions & Significance: Higher inter-patient viral genetic diversity correlated with successful treatment, implying that there are HCV genotype 1 strains with intrinsic differences in sensitivity to therapy. Core, NS3 and NS5A have interferonsuppressive activities detectable through in vitro assays, and hence these activities also appear to function in human patients. Both preferential infection with relatively resistant HCV variants and host-specific factors appear to contribute to the unusually poor response to therapy in African American patients. © 2010 Donlin et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Donlin, MJ
Cannon, NA
Aurora, R
Li, J
Wahed, ASWahedA@edc.pitt.eduWAHED
Di Bisceglie, AM
Tavis, JE
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorOtt, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 3 February 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0009032
Schools and Programs: Graduate School of Public Health > Biostatistics
Refereed: Yes
MeSH Headings: Adult; African Americans--statistics & numerical data; Antiviral Agents--therapeutic use; Drug Therapy, Combination; European Continental Ancestry Group--statistics & numerical data; Female; Gene Frequency; Genetic Variation; Genome, Viral; Genotype; Hepacivirus--classification; Hepacivirus--genetics; Hepatitis C--drug therapy; Hepatitis C--ethnology; Hepatitis C--genetics; Humans; Interferon-alpha--therapeutic use; Male; MicroRNAs--genetics; Middle Aged; Outcome Assessment (Health Care); Phylogeny; Polyethylene Glycols--therapeutic use; Recombinant Proteins; Ribavirin--therapeutic use; Viral Core Proteins--genetics; Viral Nonstructural Proteins--genetics
Other ID: NLM PMC2815788
PubMed Central ID: PMC2815788
PubMed ID: 20140258
Date Deposited: 03 Aug 2012 18:43
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/13315

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