TY - JOUR
T1 - The relation of HLA genotype to hepatitis C viral load and markers of liver fibrosis in HIV-infected and HIV-uninfected women
AU - Kuniholm, Mark H.
AU - Gao, Xiaojiang
AU - Xue, Xiaonan
AU - Kovacs, Andrea
AU - Marti, Darlene
AU - Thio, Chloe L.
AU - Peters, Marion G.
AU - Greenblatt, Ruth M.
AU - Goedert, James J.
AU - Cohen, Mardge H.
AU - Minkoff, Howard
AU - Gange, Stephen J.
AU - Anastos, Kathryn
AU - Fazzari, Melissa
AU - Young, Mary A.
AU - Strickler, Howard D.
AU - Carrington, Mary
N1 - Funding Information:
Data for this study were collected by the WIHS Collaborative Study Group with centers (principal investigators) at New York City/Bronx Consortium (K. A.); Brooklyn, NY (H. M.); Washington DC, Metropolitan Consortium (M.A.Y.); the Connie Wofsy Study Consortium of Northern California (R. G.); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (M. H. C.); and the Data Coordinating Center (S. J. G.). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study was also funded by the National Cancer Institute (NCI) (contract HHSN261200800001E), the National Institute on Drug Abuse, the National Institute on Deafness and Other Communication Disorders, the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131), and the National Institute of Allergy and Infectious Diseases (5R01AI057006 to H. D. S. and R01A1052065 to A. K.); and the Intramural Research Program of the NIH, NCI, Center for Cancer Research. This work was supported in part by the Einstein-Montefiore CFAR (NIH AI-51519).
PY - 2011/6/15
Y1 - 2011/6/15
N2 - Background. Human leukocyte antigen (HLA) class I and II genotype is associated with clearance of hepatitis C virus (HCV) infection, but little is known regarding its relation with HCV viral load or risk of liver disease in patients with persistent HCV infection. Methods. High-resolution HLA class I and II genotyping was conducted in a prospective cohort of 519 human immunodeficiency virus (HIV) - seropositive and 100 HIV-seronegative women with persistent HCV infection. The end points were baseline HCV viral load and 2 noninvasive indexes of liver disease, fibrosis-4 (FIB-4), and the aspartate aminotransferase to platelet ratio index (APRI), measured at baseline and prospectively. Results. DQB1*0301 was associated with low baseline HCV load (β = -.4; 95% confidence interval [CI], -.6 to -.3; P < .00001), as well as with low odds of FIB-4 - defined (odds ratio [OR], .5; 95% CI, .2-.9; P = .02) and APRI-defined liver fibrosis (OR, .5; 95% CI, .3-1.0; P = .06) at baseline and/or during follow-up. Most additional associations with HCV viral load also involved HLA class II alleles. Additional associations with FIB-4 and APRI primarily involved class I alleles, for example, the relation of B*1503 with APRI-defined fibrosis had an OR of 2.0 (95% CI, 1.0-3.7; P = .04). Conclusions. HLA genotype may influence HCV viral load and risk of liver disease, including DQB1*0301, which was associated with HCV clearance in prior studies.
AB - Background. Human leukocyte antigen (HLA) class I and II genotype is associated with clearance of hepatitis C virus (HCV) infection, but little is known regarding its relation with HCV viral load or risk of liver disease in patients with persistent HCV infection. Methods. High-resolution HLA class I and II genotyping was conducted in a prospective cohort of 519 human immunodeficiency virus (HIV) - seropositive and 100 HIV-seronegative women with persistent HCV infection. The end points were baseline HCV viral load and 2 noninvasive indexes of liver disease, fibrosis-4 (FIB-4), and the aspartate aminotransferase to platelet ratio index (APRI), measured at baseline and prospectively. Results. DQB1*0301 was associated with low baseline HCV load (β = -.4; 95% confidence interval [CI], -.6 to -.3; P < .00001), as well as with low odds of FIB-4 - defined (odds ratio [OR], .5; 95% CI, .2-.9; P = .02) and APRI-defined liver fibrosis (OR, .5; 95% CI, .3-1.0; P = .06) at baseline and/or during follow-up. Most additional associations with HCV viral load also involved HLA class II alleles. Additional associations with FIB-4 and APRI primarily involved class I alleles, for example, the relation of B*1503 with APRI-defined fibrosis had an OR of 2.0 (95% CI, 1.0-3.7; P = .04). Conclusions. HLA genotype may influence HCV viral load and risk of liver disease, including DQB1*0301, which was associated with HCV clearance in prior studies.
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U2 - 10.1093/infdis/jir192
DO - 10.1093/infdis/jir192
M3 - Article
C2 - 21606539
AN - SCOPUS:79957482719
SN - 0022-1899
VL - 203
SP - 1807
EP - 1814
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -