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

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.

• Authors: Meng Wang, Jian-Sheng Li, Yu Ping, Zhi-Qin Li, Li-Ping Wang, Qian Guo, Zhen Zhang, Dong-Li Yue, Fei Wang, Teng-Fei Zhang, Mohammad Serajul Islam, Yi Zhang
• Journal: Archives of virology (Arch Virol) Vol. 160 Issue 4 Pg. 1043-54 (Apr 2015) ISSN: 1432-8798 [Electronic] Austria
• PMID: 25666200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• HLA-A Antigens
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2b
• peginterferon alfa-2a

Topics

• Adult
• Alleles
• Antiviral Agents (therapeutic use)
• Asian People (genetics)
• China
• Drug Therapy, Combination
• Female
• HLA-A Antigens (genetics)
• Hepacivirus (drug effects, genetics, physiology)
• Hepatitis C, Chronic (drug therapy, genetics)
• Humans
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Prospective Studies
• Recombinant Proteins (therapeutic use)
• Ribavirin (therapeutic use)
• Treatment Outcome