Thyroid hormones play an essential role in lipid mobilization, lipid degradation, and fatty acid oxidation. Hypothyroidism has been associated with nonalcoholic steatohepatitis; however, the association between thyroid diseases and hepatocellular carcinoma (HCC) in men and women has not been well established. We investigated the association between hypothyroidism and HCC risk in men and women in a case-control study, which included 420 eligible patients with HCC and 1104 healthy controls. We used multivariate unconditional logistic regression models to control for the confounding effects of established HCC risk factors. A long-term history of hypothyroidism (>10 years) was associated with a statistically significant high risk of HCC in women; after adjusting for demographic factors, diabetes, hepatitis, alcohol consumption, cigarette smoking, and family history of cancer, the odds ratio (OR) was 2.9 (95% confidence interval [CI], 1.3-6.3). Restricted analyses among hepatitis virus-negative subjects, nondrinkers, nondiabetics, nonsmokers, and nonobese individuals indicated a significant association between hypothyroidism and HCC, with an approximate two-fold to three-fold increased risk of HCC development. We observed risk modification among women with diabetes mellitus (OR ؍ 9.4; 95% CI ؍ 2.7-32.7) and chronic hepatitis virus infection (OR ؍ 31.2; 95% CI ؍ 6.3-153.2). A history of hyperthyroidism was not significantly related to HCC (OR ؍ 1.7; CI ؍ 0.6-5.1). We noted significant elevated risk association between hypothyroidism and HCC in women that was independent of established HCC risk factors. Experimental investigations are necessary for thorough assessment of the relationship between thyroid disorders and HCC. (HEPATOLOGY 2009;49: 1563-1570.) T he incidence of hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, 1 has been steadily increasing over the past two decades in the United States. 2 Chronic hepatitis C virus (HCV) infection and its underlying cirrhosis were suggested to be the reasons for this increase. Several extrahepatic conditions, however, have been associated with HCV infection, including mixed cryoglobulinemia, porphyria cutanea tarda, and membranoproliferative glomerulonephritis. In addition, patients with HCV are susceptible to autoimmune thyroid diseases before and after completion of interferon therapy, 6-8 suggesting an association between thyroid diseases and HCV.
Hypothyroidism has been observed in 5%-12% of patients with HCV 8 and is the most common thyroid disorder in the adult population, particularly among