Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: Incidence, associated factors and prognosis.

BACKGROUND AND AIMS: Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long-term reversibility of thyroid dysfunction. METHODS: In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN-alpha-2b, 3 or 5 million units thrice weekly, or pegylated (PEG)-IFN-alpha-2b 80 or 100 microg weekly combined with ribavirin 1-1.2 g daily for 24-48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed. RESULTS: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6-5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG-IFN-treated patients (49/391 vs 9/70; P = 1.00). Under a nested case-control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age- (+/- 5 years) and sex-matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2-27.9). Ten patients ( approximately 2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function. CONCLUSIONS: Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long-term thyroid dysfunction may persist in a small group of patients ( approximately 2%).