Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy.
OBJECTIVE
Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha) may induce thyroid disorders. We evaluated whether this risk is related to the dosage of IFN-alpha or the virological treatment response. Other possible risk factors as well as the evolution of the thyroid abnormalities were also studied.


METHODS
In this prospective trial (n=254), thyroid-stimulating hormone (TSH), free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before, during and after treatment for hepatitis C virus (HCV). The patients were randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for 4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU 3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or 1200 mg) daily. Sustained virological response was defined as loss of detectable HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2-4.5 MIU L-1).


RESULTS
Biochemical thyroid dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5 MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients. Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment was discontinued because of thyroid dysfunction in three of these patients. Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who completed all 6 months of HCV treatment, a sustained virological response was obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without (P=0.24). By multivariate analysis female gender and Asian origin were independent predictors of developing biochemical thyroid dysfunction (P < 0.01).


CONCLUSIONS
Thyroid dysfunction occurred in 11.8% of patients treated for chronic hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the virological response to treatment were related to the incidence of thyroid dysfunction.
Dalgard
O
O
Department of Medicine, Unit of Hepatology, Aker University Hospital, Oslo, Norway. olav.dalgard@ioks.uio.no
Bjøro
K
K
Hellum
K
K
Myrvang
B
B
Bjøro
T
T
Haug
E
E
Bell
H
H
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013959:Thyroid Diseases / Q000139:chemically induced*; D013960:Thyroid Function Tests
D001323:Autoantibodies; D016898:Interferon-alpha; D007453:Iodide Peroxidase