Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: incidence, associated factors and prognosis.
OBJECTIVE
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%).
Kee
Kwong-Ming
KM
Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Lee
Chuan-Mo
CM
Wang
Jing-Houng
JH
Tung
Hung-Da
HD
Changchien
Chi-Sin
CS
Lu
Sheng-Nan
SN
Wang
Pei-Wen
PW
D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001323:Autoantibodies / Q000096:biosynthesis; D016022:Case-Control Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011379:Prognosis; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D012307:Risk Factors; D013959:Thyroid Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D000998:Antiviral Agents; D001323:Autoantibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C056626:thyroid microsomal antibodies; D011092:Polyethylene Glycols; D012254:Ribavirin; D013972:Thyrotropin; C417083:peginterferon alfa-2b; D013974:Thyroxine