Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C

Background. A high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis duri ng interferon-alpha therapy. Aim. To evaluate whether thyroid autoimmunity and dysfunction, induced by i nterferon-alpha therapy, could be viewed as predictors for treatment respon se and as valid prognostic markers of liver disease progression. Patients. A total of 136 subjects (96 males/40 females; median age 48 years ; range 23-64) affected by biopsy-proven chronic hepatitis C (33.1% with co mpensated liver cirrhosis). Methods. All subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12-108). Routine laboratory tests, virological assessment, l iver ultrasound, thyroid function tests (serum free-triiodothyronine, free- thyroxine, serum thyrotropin), and autoimmunity were performed for all subj ects. Results. Percentage of thyroid autoimmunity and thyroid dysfunction in long -term responders was not significantly different compared to that in non-re sponders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant) . The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9-115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover: the occurrence of thyroid autoimmunity du ring interferon therapy was similar both in patients with or without worsen ing of liver disease (33.3% and 39.8%, respectively; p = not significant). No subject with on-going liver disease developed thyroid dysfunction during treatment, as opposed to the 10/118 (8.4%) with a better course of liver d isease; however: this difference was not statistically significant. The mul tivariate model showed that age was the only covariate significantly associ ated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% conf idence interval: 2.3-151.9, for those over 48 years vs younger patients). Conclusions. There is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulatin g the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However: our study confirmed that liver dis ease seems to progress more slowly in younger subjects.