Beware if you have HCV and a Underactive Thyroid

Underactive Thyroid Linked to Liver Cancer Risk
By Crystal Phend, Staff Writer, MedPage Today
Published: May 06, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco Earn CME/CE credit
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SAN FRANCISCO, May 6 -- Long-term hypothyroidism may nearly triple the risk of developing liver cancer, researchers found.
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■Note that the observational study could not prove causation.
The association was independent of established hepatocellular carcinoma risk factors, but significant only among women, according to Manal M. Hassan, M.D., Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues.

These case-control study findings shouldn't be surprising, the researchers wrote in the May issue of Hepatology.

Hypothyroidism has been linked to chronic liver diseases and implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), which is considered a predisposing condition for liver cancer.

This may result from the essential role of thyroid hormones in lipid mobilization and degradation and fatty acid oxidation, Dr. Hassan's group said. When they're out of balance, "all of these conditions may enhance the susceptibility to chronic inflammation, DNA damage, and hepatocellular carcinoma development."

In the study, an underactive thyroid increased hepatocellular carcinoma risk independent of hepatitis C virus (HCV) infection (adjusted odds ratio 2.0, 95% CI 1.2 to 3.3) and independent of diabetes (adjusted OR 1.9, 95% CI 1.2 to 3.3).

Together, though, these factors appeared to have more than an additive effect (adjusted OR 34.3 for hypothyroidism plus HCV and 7.9 for hypothyroidism plus diabetes, respectively).

"Screening and proper management of thyroid diseases in patients with diabetes or hepatitis C virus infection may help prevent hepatocellular cancer," they said.

The ongoing hospital-based case-control study involved 420 hepatocellular carcinoma patients newly diagnosed at M.D. Anderson.

The controls included 1,104 healthy, genetically unrelated family members (such as spouses and in-laws) of M.D. Anderson patients with cancers other than liver, gastrointestinal, lung, or head and neck.

Overall, more of the hepatocellular carcinoma cases than controls reported a history of thyroid disease (15.0% versus 12.1%).

Likewise, a history of hypothyroidism -- the most common type of thyroid disease -- was significantly more common among cases than controls (11.7% versus 8.0%, P=0.03).

Long-term hypothyroidism of more than three-years duration conferred a significant, 2.1-fold excess risk of liver cancer, compared with no history of thyroid disorders.

The multivariate analysis found the association only among women.

Women with a prior, long-term history of hypothyroidism for three to 10 years had a 2.6-fold higher risk of hepatocellular carcinoma (95% CI 1.0 to 7.2). For women with a history of hypothyroidism lasting more than 10 years, the risk was 2.9 times as high (P<0.001).

The two- to threefold increased risk of liver cancer remained for hypothyroidism in analyses controlling for obesity at different ages, for all established hepatocellular carcinoma risk factors, and even in analyses restricted to nondrinkers, nonsmokers, and those without hepatitis or diabetes.

The greater susceptibility of women than men with the same condition may be partially explained by the liver's role as a major target tissue for the proliferative effect of growth hormones, their receptors, and binding protein, the researchers suggested.

They noted that further prospective study is needed in different populations to validate the findings and to determine the underlying mechanisms.

While the self-reported thyroid disease may have been prone to recall bias, the investigators found no discrepancy in the medical records.

The study was supported by National Institutes of Health grants and the Texas Tobacco Settlement. The researchers reported no conflicts of interest.

Primary source: Hepatology
Source reference:
Hassan MM, et al "Association between hypothyroidism and hepatocellular carcinoma: a case-control study in the United States" Hepatology 2009; 49: 1563-70