Antiviral therapy with pegylated interferon combined with ribavirin is currently recognized as an effective standard of care for hepatitis C. However, thyroid disease is complicated by the application of interferon therapy in about 40% of patients, which seriously affects the antiviral treatment. In turn, thyroid function status before antiviral therapy is closely related to the development of thyroid disease after treatment. Thus, the Guidelines for the Prevention and Treatment of Hepatitis C include thyroid disease as a relative contraindication to antiviral therapy. Yi Jianhua, Department of Infection, Wuhan Union Hospital I. Abnormal thyroid function associated with hepatitis C. The liver is the main organ for the metabolic conversion and excretion of thyroid hormones and the site of synthesis of thyroid binding globulin (TBG). On the one hand, the deiodination of thyroid hormone is catalyzed by 5′-deiodinase enzyme synthesized in the liver, and T4 is converted to T3 by the action of 5′-deiodinase enzyme, and the conversion of T4 to T3 in peripheral tissues is reduced in patients with liver disease due to massive damage to hepatocytes, and thus low On the other hand, plasma TBG concentrations are altered in liver lesions and there may be inhibitors of T4 binding to TBG, causing an imbalance in the ratio of bound to free thyroxine in the blood, which in turn may affect thyroid hormone levels by feedback regulation. Antonelli et al. tested thyroid hormone levels in 630 patients with hepatitis C not treated with interferon and found that 13% were hypothyroid; moreover, the rate of positive thyroglobulin antibodies (TGAb) was 17% and thyroid peroxidase antibodies (TPOAb) was 21%. Therefore, it is believed that HCV infection is associated with the development of autoimmune thyroid disease (AITD). The study in China also showed that about 12% of hepatitis C patients develop thyroid disease, mostly hypothyroidism and subthyroidism (5.3% and 4.5%, respectively), but also hyperthyroidism (about 2.3%) and low T3 syndrome. TPO, a key enzyme in thyroid hormone synthesis, is an important autoantigen causing AITD and can stimulate the body to produce anti-TPOAb, which activates the complement, the TGAb is an antibody produced by TBG in the thyroid follicle after entering the blood, which can catalyze the hydrolysis of TBG to reduce TBG in the blood and thyroid gland, resulting in a decrease in T3 and T4 synthesis. It has been found that TGAb and TPOAb are significantly higher in patients with hepatitis C than in the normal population. On the one hand, this may be due to thyroid dysfunction caused by liver injury, resulting in elevated TGAb and TPOAb; on the other hand, it has been reported in the literature that hepatitis C predisposes to a variety of immune-related diseases, including AITD, resulting in significant changes in TGAb and TPOAb. The incidence of thyroid disease in patients with chronic hepatitis C is significantly higher than that in the general population, and its clinical type is diverse, which can be manifested as hypothyroidism, subhypothyroidism or hyperthyroidism, the first two being more common. The effect of interferon therapy on thyroid function The effect of interferon on thyroid function has been reported more frequently. The incidence of interferon-induced thyroid disease during antiviral therapy for hepatitis C is about 2%-20%. Interferon enhances MHC-Ⅰ expression in thyroid cells, and high-dose lymphokine treatment can exacerbate pre-existing thyroiditis. It was found that HLA-A2, B46 and Cw7 were increased in patients with AITD induced by interferon in hepatitis C treatment; the effect of interferon treatment on thyroid function was also associated with cytokine activation. In addition, immune cells produce cytokines such as interferon that mimic both the effects of adrenocorticotropic hormone to promote steroid hormone production in the adrenal cortex and thyroid-stimulating factors to promote iodine uptake by thyroid cells, thereby directly inhibiting thyroid hormone synthesis and release. AITD is one of the most common adverse effects during interferon therapy. The mechanism is not well understood and may be related to the induction of autoimmunity by interferon and the production of thyroid autoantibodies. The autoantibodies before treatment are closely related to the occurrence and development of TGAb and TPOAb positivity and thyroid function abnormalities. The mechanism may be that interferon increases the expression of MHC-Ⅰ on the cell surface, which lifts the immune tolerance state and leads to the formation of destructive antibodies such as TGAb and TPOAb. Interferon stimulates B-cell and macrophage hyperfunction, which is also a cause of abnormal thyroid function. Although the Guidelines for the Prevention and Treatment of Hepatitis C lists thyroid disease as a relative contraindication to antiviral therapy, some studies have concluded that pre-existing hypothyroidism is not a contraindication to interferon therapy and that the possibility of secondary hyperthyroidism is low, and even if pre-existing hypothyroidism is aggravated, the effect on the body is less after replacement therapy. Pre-treatment goiter, females and positive thyroid autoantibodies are predictive factors for the development of hypothyroidism. In patients with pre-existing hyperthyroidism, especially those with positive thyrotropin receptor antibodies (TRAb), interferon therapy is currently considered to be administered with caution because it may induce Graves’ disease, lead to severe metabolic disorders, aggravate the patient’s liver function abnormalities, and complicate treatment. For new onset of hyperthyroidism during treatment, the principle of treatment should be decided depending on its clinical manifestations. The thyroid antibodies TGAb and TPOAb are predictors of the onset and progression of thyroid disease after interferon therapy, while the guiding effect of TRAb on treatment has not been reported. However, in the context of clinical practice, it is not recommended to continue interferon therapy for TRAb-positive hyperthyroidism; TRAb-negative patients can continue interferon therapy along with symptomatic treatment, and thyroid function and patient status should be closely monitored.1 Thyroid function monitoring during interferon therapy for hepatitis C Patients with hepatitis C should be tested for thyroid hormones and thyroid autoantibodies before interferon therapy. If the TSH and TRAb are detected at the end of interferon therapy, and if they are abnormal, the relevant treatment will be performed; ② if the TSH is normal and the thyroid autoantibodies are positive, the TSH will be followed up every two months until the end of interferon therapy. If the TSH is normal but the thyroid autoantibodies are positive, the type of thyroid abnormality should be further defined and treated accordingly. 2. Treatment of hypothyroidism in combination with hepatitis C Patients with hypothyroidism should be tested for thyroid autoantibodies and if: 1) the thyroid autoantibodies are negative, short-term treatment with levothyroxine and If: (1) the thyroid autoantibodies are negative, the patient should be treated with levothyroxine for a short period of time and thyroid function should be monitored closely and interferon therapy should be continued; (2) if the thyroid autoantibodies are positive, the patient should be treated with levothyroxine for a long period of time and thyroid function should be monitored closely and interferon therapy should be continued. 3. If symptoms are controlled, continue interferon therapy and monitor thyroid function along with beta-blocker therapy; if symptoms are not controlled, stop interferon therapy until thyroid function returns to normal. In patients with severe Graves’ disease, interferon therapy should be discontinued until thyroid function returns to normal, and radioactive iodine therapy should be administered if necessary. In conclusion, whether hepatitis C combined with abnormal thyroid function is a contraindication to interferon therapy should be analyzed on a case-by-case basis, and there is hope for a durable virological response if standardized therapy (including antiviral and treatment of thyroid disease) is administered with the patient’s informed consent and safety. (This article was published in China Medical Tribune in November 2012)