Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-alpha therapy.
OBJECTIVE
Hepatitis C virus is involved in the induction of autoimmunity and interferon can also induce hepatic and non-hepatic autoimmune reactions. This study assessed the prevalence of thyroid autoantibodies and autoimmune thyroid disorders in patients with chronic hepatitis C before and during interferon therapy.


METHODS
We studied prospectively 207 patients positive for anti-HCV and viral RNA. One hundred and forty-four of them received a therapeutic trial of one year with interferon-alpha. Free thyroxine, TSH and autoantibodies to thyroglobulin and thyroid microsomes were systematically tested at entry and at weeks 12 and 24 in both untreated and treated patients.


RESULTS
Sixteen of the 207 patients (7.7%) had thyroid dysfunction, including positive antithyroid antibodies in 14 (6.7%) and hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during pretreatment evaluation one patient developed clinical hyperthyroidism after transient subclinical hypothyroidism and another had subclinical hyperthyroidism. Prevalences of positive antithyroid antibodies and hypothyroidism were significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P < 0.01) and were directly associated with increasing age (P < 0.01). The incidence of thyroid dysfunction was also significantly higher in patients with other autoantibodies such as anti-nuclear (ANA) (P < 0.01). A trial with interferon was initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid abnormalities developed thyroid dysfunction, including positive antithyroid antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P < 0.01) and also directly related to increasing age (P < 0.01). An association was found between the development of thyroid dysfunction during interferon therapy and the presence of other autoantibodies, including ANA, anti-DNA and anti-Sjögren's antibodies (P < 0.01), as well as with the induction of autoimmune hepatitis and Sjögren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid abnormalities were reversed in all patients when interferon therapy was discontinued.


CONCLUSIONS
No significant association was found between chronic hepatitis C and the presence of thyroid autoimmunity in female patients. On the contrary, interferon therapy induced antithyroid autoantibodies and thyroid dysfunction de novo in patients with chronic hepatitis C without pre-existing thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible after discontinuation of therapy.
Marazuela
M
M
Endocrinology Service, Hospital de la Princesa, Universidad Autónoma, Madrid, Spain.
García-Buey
L
L
González-Fernández
B
B
García-Monzón
C
C
Arranz
A
A
Borque
M J
MJ
Moreno-Otero
R
R
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000150:complications* / Q000628:therapy; D006521:Hepatitis, Chronic / Q000097:blood / Q000150:complications* / Q000628:therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008861:Microsomes / Q000276:immunology; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000150:complications*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D001323:Autoantibodies; D016898:Interferon-alpha; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine