PubMed ID:
18852273
Public Release Type:
Journal
Publication Year: 2009
Affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA. YeeL@edc.pitt.edu
DOI:
https://doi.org/10.1128/AAC.00947-08
Authors:
Hoofnagle JH,
Fontana RJ,
Wang D,
Kleiner DE,
Terrault N,
Seeff LB,
Zacks S,
Afdhal N,
Agudelo E,
Baker SM,
Belle SH,
Bilonick RA,
Bisceglie AD,
Block G,
Brown RS Jr,
Brown S,
Bugawan T,
Burton JR,
Callison K,
Cannon N,
Cline J,
Conjeevaram HS,
Davis P,
DeMedina M,
Donlin M,
Doo E,
Dougherty K,
Dove L,
Erlich H,
Everhart J,
Ferris M,
Fried MW,
Geahigan T,
Haritos M,
Harsh D,
Hermitt C,
Hinds M,
Howell CD,
Im K,
Im K,
Jeffers LJ,
Kelley S,
Kelsey S,
Klarquist J,
Koozer L,
Lawlor S,
Liang TJ,
Liang TJ,
Li J,
Rhodes SL,
Robuck P,
Rosen HR,
Rosen HR,
Sanda C,
Schaley J,
Shrestha R,
Smith SR,
Stovel S,
Straley S,
Tang G,
Tavis JE,
Taylor MW,
Theodore D,
Thomas SB,
Virahep-C Study,
Wahed A,
Wahed AS,
Wang P,
Wei Y,
Weston S,
Wiley TE,
Williams M,
Yang H,
Yang H,
Yao E,
Yee LJ,
Yee LJ
Studies:
Viral Resistance to Antiviral Therapy of Chronic Hepatitis C
The dynamics of the viral decline immediately after the start of therapy for chronic hepatitis C virus (HCV) infection may have prognostic potential for ultimate sustained virologic response. Considerable interindividual variability in the decline has been reported, including differences by race. The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in the immune response to viral infections. We examined whether carriage of specific human MHC alleles are associated with the rate of the early viral decline. Longitudinal viral level data (baseline and days 1, 2, 7, 14, and 28 of treatment), medium resolution MHC genotyping, and random coefficients models were used to examine associations between MHC class I and class II allele carriage and the dynamics of the viral decline in 180 African-Americans (AAs) and 194 Caucasian Americans (CAs) with genotype-1 HCV infection over the first 28 days of treatment with peginterferon alpha2a plus ribavirin. Baseline viral levels were similar by race, irrespective of allele carriage. However, the rate of change in the viral decline was associated with both allele and race. Among the four subgroups defined by race and specific allele, the fastest rates of decline were observed (in terms of estimated mean viral declines log(10) IU/ml during the first four weeks) in CA noncarriers for A*03 (2.75; P = 0.018), in CA carriers for Cw*03 (2.99; P = 0.046), and in CA noncarriers for DQA1*04 (2.66; P = 0.018) or DQB1*0402 (2.65; P = 0.018). MHC alleles are associated with the viral decline during the first 28 days of peginterferon therapy.