Hepatitis C virus chronic infection as a common cause of mixed cryoglobulinaemia and autoimmune liver disease.

Objectives: Mixed cryoglobulinaemia (MC) and autoimmune chronic hepatitis (AI-CH) are frequently associated with hepatitis C virus (HCV) chronic infection. Because HCV represents a possible common aetiological factor, the aim of the present study is to investigate the clinico-serological alterations of both MC and AI-CH and to verify a possible overlap between these disorders.

Setting: Patients from three tertiary referral centres.

Subjects: Two Italian series of 88 MC patients and 30 AI-CH type 1 were studied.

Results: MC and AI-CH share several clinico-serological features. The patients' mean age (MC vs. AI-CH: 60 +/- 9 vs. 57 +/- 13 years), disease duration (10.5 +/- 5 vs. 9.6 +/- 6 years), and female/male ratio (3.4 vs. 3.3) were very similar in the two series. Typical hallmarks of MC, i.e. purpura, arthralgias, and weakness, circulating mixed cryoglobulins with rheumatoid factor activity, and hypocomplementemia were also recorded in a significant number of AI-CH patients. Similarly, chronic active hepatitis was found in 68% of MC patients and its histological and serological alterations were comparable with those of AI-CH; moreover, amongst various autoantibodies, antinuclear antibodies and/or anti-smooth-muscle antibodies were detected in half of the cases of MC. Anti-HCV antibodies, detected by second-generation Chiron ELISA and RIBA, were present in a high percentage of both MC and AI-CH (94 vs. 80%), and frequently associated with HCV viraemia (86 vs. 77%). Finally, anti-GOR, the HCV-related autoantibodies, were found in half cases of MC and AI-CH.

Conclusions: On the whole, these data suggest that HCV in combination with other infectious and environmental and genetic factors can trigger a complex immunological disorder with different clinical patterns.