Decreased Frequency of the HLA-DRB1*11 Allele in Patients with Chronic Hepatitis C Virus Infection

Abstract

A genetically determined resistance or susceptibility to chronic hepatitis C virus (HCV) infection may make an important contribution to the course of liver disease and may be linked to the human major histocompatibility complex (MHC). The aim of this study was to investigate the HLA class II genotype profile in chronic hepatitis C and to determine the HLA-hepatitis C association. The experimental population was composed of 49 unrelated chronic HCV patients (31 females, 18 males; mean age, 54.4 ؎ 1.7 years; range, 34 to 73 years). The control population consisted of 43 ethnically matched healthy donors. HLA-DR and -DQ alleles were studied for patients and controls by a PCR-sequence-specific-primer low-resolution method. Anti-HCV was investigated with enzyme-linked immunosorbent assay II, and HCV RNA was investigated with reverse transcriptase nested PCR. The HLA class II allele, DRB1*11, was found at reduced frequency in 49 patients with chronic hepatitis C (anti-HCV and HCV RNA positive) compared to that for controls (22.4 versus 51.0%; P < 0.01, odds ratio ‫؍‬ 0.3, confidence interval ‫؍‬ 0.1 to 0.7). No further HLA associations with chronic HCV infection were observed, and there was no correlation between the stage of disease and HLA. DRB1*11 was also found at reduced frequency in all HCV antibody-positive patients compared to controls (corrected P ‫؍‬ not significant). DRB1*11 was associated with chronic HCV infection, and it is possible that HLA-DRB1*11 may have a protective feature in chronic HCV infection. In addition, DRB1*11 was associated with protection from HCV infection. These findings suggest that host HLA class II genotype is an important factor determining the outcome of infection with HCV.Hepatitis C virus (HCV) persists in the majority of infected individuals and is responsible for a wide spectrum of chronic liver lesions ranging from minimal inflammation to cirrhosis or hepatocellular carcinoma (8,18,19). The mechanisms whereby HCV establishes persistent infection and liver disease are still poorly understood. Both virus-related factors, such as viral heterogeneity and replicative activity (10,14), and the host's determinants, such as lack of efficient immune responses (13,15), are certainly involved in the pathogenesis of chronic hepatitis. Differences in the immunogenetic backgrounds of infected patients might in part account for the observed variation in the individual courses of disease. Indeed, polymorphisms of immune regulatory genes or HLA class I and II molecules are known to influence the host's ability to present or react to viral antigens (1, 7).Several studies have aimed to identify major histocompatibility complex class II alleles associated with different outcomes of HCV infection, but the results have not been consistent.In the present study, we have investigated the distribution of the HLA class II alleles in patients with chronic hepatitis C using the PCR-sequence-specific-primer low-resolution method. The aim of the present study was to investigate whether these alleles might...

Could Human Leukocyte Antigens (HLA) be Predictive Factors to Interferon Response among Chronic Hepatitis C Virus Hepatitis?

“…Observed that patients with the HLA-DRB1*11 allele cleared the virus more effectively, and this remained statistically significant even after correction for multiple testing. Similar results have been reported in various other studies [25,26]. It is worth mentioning that the HENCORE group did not see any significant association (after Bonferroni correction) between any MHC class II allele and the response of patients to IFN therapy [27].…”

Host genetic determinants in hepatitis C virus infection

“…54 Another allele that has been correlated with selflimiting HCV is DRB1*1101. 16,17,35,39,50 An Italian study found a protective role for the DR5 sero-group against HCV infection. 51 The molecularly-defined DRB1*1100 and DRB1*1200 groups of alleles are part of the serologically defined DR5 group.…”

Immunogenetics and infectious diseases: special reference to the mayor histocompatibility complex

“…The acute stage of the infection is generally asymptomatic, although it may evolve to chronic liver disease and hepatocellular carcinoma [105]. The manner in which the disease will develop depends on the characteristics of the host, mainly its immune response.…”