Human leukocyte antigen phenotypes and hepatitis C viral load.

BACKGROUND: After hepatitis C virus (HCV) infection, 55% to 85% of patients become chronic carriers. HCV-RNA could be detected in the sera of these patients though the viral load varies. Various factors may be involved in determining the viral load. OBJECTIVES: In this study, we want to investigate the relationship between human leukocyte antigen phenotypes and hepatitis C viral load. STUDY DESIGN: One hundred and sixty HCV-RNA positive subjects were investigated in this study. RESULTS: We have analyzed 160 HCV-RNA positive subjects and found that lower HCV viral load is significantly associated with HBsAg-positivity (P = 0.017) but not age, gender, or mixed infection (infection with different HCV genotypes). One hundred and fifty-four HBsAg-negative subjects were further analyzed to explore the relationship between human leukocyte antigen (HLA) phenotypes and HCV viral load. Subjects with certain HLA alleles (A*34, B*56, DRB1*1502) have significantly lower viral load than those without these alleles (P = 0.0074, 0.0039 and 0.016, respectively) while those with HLA-B*4001 have significantly higher viral load (P = 0.0026). Furthermore, lower viral load was significantly associated with HLA-DRB1 heterozygosity in subjects with HLA-B heterozygosity (P = 0.048). CONCLUSIONS: Our data suggests a role for host immunogenetic factors in determining viral load during HCV infection.

HLA phenotypes and outcomes of hepatitis B virus infection in Taiwan.

The relationship of HLA phenotype and outcome of hepatitis B virus (HBV) infection was studied in two ethnic groups of Taiwan: Han Chinese and Taiwanese Aborigines. In Han Chinese, the study groups consisted of 98 persons who tested both hepatitis B surface antigen (HBsAg) and anti-HBs negative (Uninfected Group), 324 persons who tested HBsAg negative and both anti-HBs and anti-HBc positive (Recovered Group), and 98 patients who tested HBsAg positive for at least 6 months (Chronically Infected Group). In Taiwanese Aborigines, the study groups consisted of 34 persons in Uninfected Group, 229 persons in the Recovered Group, and 138 patients in the Chronically Infected Group. All subjects were tested for HLA (A, B, DRB1) phenotypes by sequence-specific oligonucleotide probe hybridization (SSOPH). HLA-DR*0406 was significantly more frequent in the Recovered Group, compared with the Chronically Infected Group (P < 0.001) in Han Chinese. There was a significant excess of HLA-B*4001 (P = 0.045) in the Recovered Group, compared with the Chronically Infected Group in Taiwanese Aborigines. The observation that different HLA phenotypes associated with recovery from HBV infection in different racial groups implies that various HLA molecules could present different HBV epitopes to induce effective immune responses.

Combined effects of chronic hepatitis virus infections and substance-use habits on chronic liver diseases in Taiwanese aborigines.

BACKGROUND AND PURPOSE: Chronic liver disease (CLD) is a major cause of death in Taiwanese aborigines. The roles of substance-use habits and hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in the development of CLD are not well understood in this indigenous population. METHODS: A hospital-based, case-control study of 79 consecutive CLD patients and 107 non-CLD controls was performed. Serostatus of hepatitis B surface antigen (HBsAg) and antibodies against hepatitis C virus (anti-HCV) were determined in all subjects. Each subject completed an epidemiologic questionnaire about the risk factors of CLD. RESULTS: Atayal ethnicity, alcohol drinking, cigarette smoking, betel quid chewing, seropositivity of HBsAg and anti-HCV antibodies were associated with a significantly elevated CLD risk. In the combinatory analyses of HBsAg serostatus and substance-use habits, HBsAg-positive substance users had the highest CLD risk, followed by HBsAg-positive non-users, HBsAg-negative users, and HBsAg-negative non-users. Similarly, anti-HCV-positive alcohol drinkers and betel quid chewers had greater CLD risks than other groups. The multivariate-adjusted odds ratios (ORs) for males, Atayal ethnicity and seropositivity of HBsAg and anti-HCV were significantly elevated. There was a biologic gradient in the risk of developing CLD associated with the number of substance-use habits. The multivariate-adjusted ORs were 4.7 (95% confidence interval [CI], 1.3-16.8) and 7.9 (95% CI, 2.1-30.4) for subjects with 1-2 and 3 habits, respectively, compared to subjects with no habit. CONCLUSION: Our data suggest that chronic HBV and HCV infections, alcohol drinking, cigarette smoking, and betel quid chewing play important roles in the development of CLD in Taiwanese aborigines.