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The host HLA-A*02 allele is associated with the response to pegylated interferon and ribavirin in patients with chronic hepatitis C virus infection

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Abstract

Human leukocyte antigen (HLA) alleles are associated with both the progression of chronic hepatitis C (CHC) and the sustained virological response (SVR) to antiviral therapy. HLA-A*02 is the most common HLA allele in people of European/Caucasian descent and the Chinese and Japanese population. Therefore, we investigated whether HLA-A*02 expression is associated with disease outcome in Chinese CHC patients. Three hundred thirty-one treatment-naïve CHC patients were recruited in this study. The expression of HLA-A*02 was tested by FACS and LABType SSO assays. All patients were treated weekly with pegylated interferon plus ribavirin (PEG-IFN/RBV) according to a standard protocol. Virological response was assessed by TaqMan assay at the 4th, 12th, 24th, and 48th week of therapy, and again at the 24th week post-therapy. By the end of the study, 293 CHC patients, including 144 HLA-A*02-positive patients and 149 HLA-A*02-negative patients, were evaluable for analysis. There were no statistical differences in clinicopathological parameters between HLA-A*02-positive and negative patients before antiviral therapy (P > 0.05). The HLA-A*02-positive patients had a higher rapid virological response (RVR, 74.3 % versus 62.4 %, P = 0.03) and SVR (78.5 % versus 64.4 %, P = 0.01) and a lower relapse rate (4.2 % versus 11.9 %, P = 0.03) than HLA-A*02-negative patients. Multivariable logistic regression analysis showed that HLA-A*02 expression, liver fibrosis stages <S3, HCV genotype 2a, IL-28B rs8099917 TT, and RVR were independent predictive factors of SVR (P < 0.05). Host HLA-A*02 allele expression is associated with SVR, highlighting the importance of considering HLA-A*02 as a predictor of the response to PEG-IFN/RBV treatment in the Chinese population with CHC.

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Acknowledgments

We thank all the clinical staff in the Biotherapy Center for their assistance in experiments. In addition, we thank the staff in the Department of Infectious Disease and the Department of Gastroenterology for their assiduous collection of blood samples and data of patients. Finally, we are grateful to all of the participants and their families for generously agreeing to take part in this study. The work was supported by grants from the National Natural Science Foundation of China (Grant no. 81271815), Research Grant from the Ministry of Public Health (Grant no. 20110110001), the Basic and Advanced Technology Research Foundation from Science and Technology Department of Henan Province (Grant nos. 112300410153 and 122300410155), Funds for Creative Research Team of Henan Province, Creative Research Team of Higher Education of Henan Province and the Innovation Team of the First Affiliated Hospital of Zhengzhou University, Henan, China.

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Meng Wang, Jian-sheng Li & Mohammad Serajul Islam

  2. The Biotherapy Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Meng Wang, Zhen Zhang, Dong-li Yue, Fei Wang, Teng-fei Zhang & Yi Zhang

  3. School of Life Sciences, Zhengzhou University, Zhengzhou, China

    Yu Ping & Yi Zhang

  4. Department of Infections, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Zhi-qin Li & Qian Guo

  5. Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Li-ping Wang & Yi Zhang

  6. Key Laboratory of Clinical-Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Yi Zhang

Authors
  1. Meng Wang
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  2. Jian-sheng Li
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  3. Yu Ping
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  4. Zhi-qin Li
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  5. Li-ping Wang
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  6. Qian Guo
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  7. Zhen Zhang
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  8. Dong-li Yue
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  9. Fei Wang
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  10. Teng-fei Zhang
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  11. Mohammad Serajul Islam
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  12. Yi Zhang
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Corresponding author

Correspondence to Yi Zhang.

Electronic supplementary material

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705_2015_2361_MOESM1_ESM.tif

HLA-A*02 expression in CHC patients. (A) The HLA-A*02 of CD3+ CD8+ T cells was tested by FACS Cano II. (B) The HLA-A*02 expression in five CHC patients was tested by SSO LABType. The products were electrophoresed in a 1 % agarose gel and visualized by ethidium bromide staining. The outer pair of primers produced a 511-bp PCR product, and the inner pair of primers produced a 236-bp PCR product (TIFF 296 kb)

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Wang, M., Li, Js., Ping, Y. et al. The host HLA-A*02 allele is associated with the response to pegylated interferon and ribavirin in patients with chronic hepatitis C virus infection. Arch Virol 160, 1043–1054 (2015). https://doi.org/10.1007/s00705-015-2361-y

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  • DOI: https://doi.org/10.1007/s00705-015-2361-y

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