Chronic hepatitis C infection and sicca syndrome: a clear association with HLA DQB1*02.

BACKGROUND: Hepatitis C virus infection is a major cause of nonA, nonB hepatitis worldwide. A high prevalence of immunological abnormalities has been shown to occur in patients with chronic hepatitis C virus infection. AIM: The aim of this study was to assess the development of sicca syndrome in a cohort of patients infected with a single strain of hepatitis C virus, namely genotype 1b, and correlate this with viral persistence and human leukocyte antigen type of the patients. METHODS: Ninety-five patients infected with the single strain hepatitis C virus were used in this study, 32 of whom were polymerase chain reaction-negative and 63 polymerase chain reaction-positive. Patient details were reviewed for symptoms consistent with sicca syndrome. Human leukocyte antigen class I (A, B and C) and class II (DRB and DQB1) typing was performed on all patients. Auto-antibodies were also measured. RESULTS: DQB1*02 was highly significantly associated with viral persistence (P<0.0001). Nineteen of 21 patients with sicca syndrome were hepatitis C virus-polymerase chain reaction-positive demonstrating a strong association with viral persistence and the development of the syndrome. Human leukocyte antigen DQB1*02 was significantly associated with the development of sicca syndrome, P=0.02. CONCLUSION: The development of autoimmune disease in patients with chronic hepatitis C virus infection depends on the interaction of multiple factors. This study suggests that important factors in this process are viral persistence and human leukocyte antigen type of the patients.

Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source.

The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included chi(2) testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < or = .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. 19.8%; P =.002). In combination with previously reported class II allele associations, over 75% that successfully eliminate HCV carry either A*03, DRB1*0101, or *0401, compared with only 37% of those with chronic infection (P <.0001). The haplotypes A*03-B*07-DRB1*15-DQB1*0602 and A*02-B*27-Cw*01-DRB1*0101-DQB1*0501 are associated with viral clearance (P =.004 and.01, respectively). By multiple logistic regression analysis, the alleles A*03, B*27, DRB1*0101, *0401, and *15 are associated with viral clearance, and B*27 has the strongest association (odds ratio [OR] 7.99). The haplotype A*01-B*08-Cw*07-DRB1*03011-DQB1*0201 is associated with chronic infection (P =.002), being independent for DQB1*0201 (OR 0.27). In conclusion, certain class I alleles are associated with outcome in this homogeneous cohort. More significantly, either HLA-A*03, -DRB1*0101, or -*0401 are carried by an overwhelming majority of those subjects who successfully clear HCV.