HLA association with hepatitis C virus infection

Abstract

Hepatitis is one of the most important infectious diseases in Thailand. The knowledge of host factors that influence the course of the disease is still limited. In this study, the HLA class I and class II phenotypes were analyzed in the 2 groups of HCV-infected Thai populations. The first group included 43 individuals with transient HCV infection (HCV antibody positive, HCV RNA PCR negative), and the second included 57 individuals with persistent chronic HCV infection (HCV antibody positive, PCR positive). HLA class I typing was performed by 2-stage microlymphocytotoxicity test, and HLA class II typing, by PCR-SSO. No significant difference in the frequencies of HLA-A and -B antigens was observed between the 2 groups of HCV-infected individuals. The frequency of DRB1∗0301 and DQB1∗0201 was significantly higher in the persistent-infection group than in the transient-infection group (Pc = 0.03, Pc = 0.04, respectively). In addition, DRB1∗0701 and DQA1∗0201 were significantly decreased in all the HCV-infected patients compared with levels in the normal controls (Pc = 0.003, Pc = 0.001, respectively). This study demonstrated that DRB1∗0301 and DQB1∗0201 are associated with persistent HCV infection, whereas DRB1∗0701 and DQA∗0201 are associated with protection against HCV infection.

Introduction

Hepatitis C virus (HCV) is a major causative agent of posttransfusion hepatitis. Viral hepatitis caused by this virus is one of the most important infectious diseases found in Thailand, with a prevalence of around 1.5–5% in the general population 1, 2. The most significant consequence of HCV infection is that more than 50% of HCV-infected patients develop chronic hepatitis [3]. Furthermore, there is a strong correlation between chronic hepatitis C infection and hepatocellular carcinoma. Patients with chronic hepatitis C infection stand a greater chance of developing liver cancer than do those chronically infected with hepatitis B virus. In Thailand, the evidence of HCV infection was detected in about 15% of hepatocellular carcinoma cases [4].

HCV-infected individuals may have outcomes varying in spectrum from persistent hepatitis with HCV viremia, to very mild liver injury, to good health with clearing of the virus 5, 6. Many factors are thought to influence the outcome of HCV infection, such as the virus strain, the mode of transmission, and host factors.[7] The human leukocyte antigen (HLA)-linked genetic factors play important roles in determining the outcome against viral agents. The association between HLA antigen and clinical outcome of viral infection has been reported in hepatitis B virus and HIV infection [8]. A number of studies on the association of HLA antigens and the clinical outcome of HCV infection were reported, but the results were debatable 9, 10, 11, 12, 13. In Caucasian populations, a British and a French group reported the association of DRB1∗1101 and DQB1∗0301 with hepatitis C virus clearance, and there was no association of HLA antigens with the persistent HCV infection 10, 11. In contrast, a German study showed an association of DRB1∗0301 with chronic HCV [12]. In addition, a Japanese group reported the association of DRB1∗0405 and DQB1∗0401 with chronic liver disease from HCV, and association of DRB1∗1101, DRB1∗1302, and DQB1∗0604 with the HCV carriers has been reported [13]. In this study, we investigated the frequencies of HLA class I and class II in an HCV-infected Thai population and compared the frequencies of the persistent–HCV infection group and the transient–HCV infection group.