The relation of HLA genotype to hepatitis C viral load and markers of liver fibrosis in HIV-infected and HIV-uninfected women

Mark H. Kuniholm, Xiaojiang Gao, Xiaonan (Nan) Xue, Andrea Kovacs, Darlene Marti, Chloe L. Thio, Marion G. Peters, Ruth M. Greenblatt, James J. Goedert, Mardge H. Cohen, Howard Minkoff, Stephen J. Gange, Kathryn Anastos, Melissa Fazzari, Mary A. Young, Howard Strickler, Mary Carrington

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1807-1814
Number of pages8
JournalJournal of Infectious Diseases
Volume203
Issue number12
DOIs
StatePublished - Jun 15 2011

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Hepatitis C
HLA Antigens
Viral Load
Hepacivirus
Liver Cirrhosis
Biomarkers
Genotype
HIV
Virus Diseases
Blood Platelets
Transaminases
Confidence Intervals
Liver Diseases
Fibrosis
Odds Ratio
Alleles
Aspartate Aminotransferases

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

The relation of HLA genotype to hepatitis C viral load and markers of liver fibrosis in HIV-infected and HIV-uninfected women. / Kuniholm, Mark H.; Gao, Xiaojiang; Xue, Xiaonan (Nan); Kovacs, Andrea; Marti, Darlene; Thio, Chloe L.; Peters, Marion G.; Greenblatt, Ruth M.; Goedert, James J.; Cohen, Mardge H.; Minkoff, Howard; Gange, Stephen J.; Anastos, Kathryn; Fazzari, Melissa; Young, Mary A.; Strickler, Howard; Carrington, Mary.

In: Journal of Infectious Diseases, Vol. 203, No. 12, 15.06.2011, p. 1807-1814.

Research output: Contribution to journalArticle

Kuniholm, MH, Gao, X, Xue, XN, Kovacs, A, Marti, D, Thio, CL, Peters, MG, Greenblatt, RM, Goedert, JJ, Cohen, MH, Minkoff, H, Gange, SJ, Anastos, K, Fazzari, M, Young, MA, Strickler, H & Carrington, M 2011, 'The relation of HLA genotype to hepatitis C viral load and markers of liver fibrosis in HIV-infected and HIV-uninfected women', Journal of Infectious Diseases, vol. 203, no. 12, pp. 1807-1814. https://doi.org/10.1093/infdis/jir192
Kuniholm, Mark H. ; Gao, Xiaojiang ; Xue, Xiaonan (Nan) ; Kovacs, Andrea ; Marti, Darlene ; Thio, Chloe L. ; Peters, Marion G. ; Greenblatt, Ruth M. ; Goedert, James J. ; Cohen, Mardge H. ; Minkoff, Howard ; Gange, Stephen J. ; Anastos, Kathryn ; Fazzari, Melissa ; Young, Mary A. ; Strickler, Howard ; Carrington, Mary. / The relation of HLA genotype to hepatitis C viral load and markers of liver fibrosis in HIV-infected and HIV-uninfected women. In: Journal of Infectious Diseases. 2011 ; Vol. 203, No. 12. pp. 1807-1814.
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abstract = "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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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 (Nan)

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

AU - Carrington, Mary

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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DO - 10.1093/infdis/jir192

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