Autoimmune thyroid dysfunction induced by interferon-alpha treatment for chronic hepatitis C: screening and monitoring recommendations.

OBJECTIVE

To analyze the proposed mechanisms of action of recombinant interferon-alpha (IFN-a) in causing autoimmune thyroid dysfunction, to identify pretreatment risk factors, and to provide recommendations for screening and monitoring of thyroid dysfunction during IFN-a therapy for chronic hepatitis C.

METHODS

Selected publications were reviewed to analyze the proposed mechanisms of autoimmune thyroid disorders. In addition, we examined the interrelationship of the thyroid and the liver, the occurrence of thyroid dysfunction in patients with chronic hepatitis C before and after IFN-a therapy, and the presence or absence of antithyroid antibodies in association with thyroid disease. Case reports were selected to demonstrate various IFN-a-induced thyroid dysfunction.

RESULTS

IFN-a induces thyroid dysfunction in 3 to 14% of all treated patients with chronic hepatitis C, leading to hypothyroidism, hyperthyroidism, or thyroiditis. In a few patients, thyroid disease will develop in the absence of antithyroid antibodies, a scenario that suggests a nonimmune-mediated mechanism. More frequently, patients develop antithyroid antibodies, which may progress to overt thyroid dysfunction. Through its immunomodulatory properties, IFN-a seems to act through major histocompatibility complex class I antigens to produce antithyroid antibodies and thyroid disease.

CONCLUSION

In patients receiving IFN-a therapy for chronic hepatitis C infection, identifiable risk factors for developing autoimmune thyroid dysfunction are preexisting overt thyroid or autoimmune disease, subclinical thyroid or autoimmune thyroid disease, and female gender. Pretreatment screening is recommended for all patients in whom IFN-a therapy is being considered, and periodic monitoring should be performed during such therapy. Thyroid disease need not be a contraindication to IFN-a therapy; early detection of subclinical or overt thyroid disease may allow uninterrupted continuation of IFN-a treatment.