HLA-DRS ANTIGEN - A GENETIC-FACTOR INFLUENCING THE OUTCOME OF HEPATITIS-C VIRUS-INFECTION

Background: Prognosis may be quite different among individuals infecte d with hepatitis C virus (HCV): a chronic liver disease is believed to occur in half the patients while in the other half there are no signs of histologic progression of liver damage. The host immune response m ight play an important role in such different outcomes. A relationship has been shown between HLA. genes and immune response to viral hepati tis B, but to our knowledge, no evidence of an association with HCV ha s been reported so far. We investigated whether HLA class II alleles m ight influence the outcome of HCV infection. Methods: Eighty-seven ind ividuals, positive for anti-HCV by second-generation enzyme-linked imm unosorbent assay and recombinant immunoblot assay tests, enrolled from May 1, 1991, to June 31, 1992, were evaluated. Thirty-six were sympto m-free subjects found to have HCV antibodies when screened for blood d onation: they all had normal results of liver function tests; normal r esults Of physical examination, and normal hepatobiliary ultrasonograp hy. Fifty-one were patients diagnosed as having a chronic liver diseas e by percutaneous liver-biopsy specimen; histologic assessment was chr onic persistent hepatitis in 15, chronic active hepatitis in 28, and l iver cirrhosis in eight. A group of 231 donors of platelets and bone m arrow, negative for anti-HCV, was used as a control population. All pa rticipants were typed for HLA class II antigens (DR and DQ) using Nati onal Institutes of Health recommended microlymphocytotoxicity test and were followed up by means of alanine aminotransferase and HCV testing for at least 1 year. Results: Frequency of HLA-DRS antigen was higher in symptom-free anti-HCV-positive individuals (52.8%) than among HCV- related patients with chronic liver disease (13.7%). The difference wa s statistically significant (corrected P value=.005; 95% confidence in terval, 19.6% to 58.6%); between DR5 and long-term evolution of hepati tis C, there was a negative association (relative risk=0.142). Moreove r, frequency of HLA-DR5-positive subjects appeared to be inversely pro portional to severity of liver disease (52.8% in symptom-free patients , 26.6% in patients with chronic persistent hepatitis, 10.7% in patien ts with chronic active hepatitis, and 0% in patients with liver cirrho sis, P<.001). Conclusions: Our results point to a strict relationship between HLA haplotype and ability of immune response to influence the outcome of HCV infection. Presence of HLA-DRS antigen appears as a pro tective factor against a severe outcome of chronic infection, being co rrelated with a benign evolution of the infection, often asymptomatic, or a less severe chronic liver disease.