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Low thyroid function predicts NASH, fibrosis in patients with fatty liver

Subclinical hypothyroidism and lower than normal thyroid function independently predicted advanced fibrosis and the risk for nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease, according to recently published data.

“The prevalence of NASH and advanced fibrosis associated with [thyroid-stimulating hormone levels] was significantly higher in subjects with subclinical hypothyroidism than in those with normal thyroid function,” the researchers wrote.

The researchers evaluated 426 patients (52% men; mean age = 53 years) with biopsy-proven NAFLD and classified the patients into a strict-normal thyroid function group (n = 282) and a low thyroid function group, which included patients with low-normal thyroid function (n = 84) and subclinical hypothyroidism (n = 59). They defined low-normal thyroid function as a higher plasma thyroid-stimulating hormone level and/or a lower free thyroxine (T₄) level within the euthyroid reference range.

Patients in the low thyroid function group had a higher prevalence of NASH (52.4% vs. 37.2%; P = .003) and advanced fibrosis (21% vs. 10.6%; P = .004) compared with those with strict-normal thyroid function. Similarly, patients with subclinical hypothyroidism had a higher prevalence of NASH (57.6% vs. 48.8%; P = .006) and advanced fibrosis (25.4% vs. 17.9%; P = .007) than those with low-normal thyroid function.

Specifically, subclinical hypothyroidism and low-normal thyroid function taken together were correlated with a 61% increase in risk for NASH (OR = 1.61; 95% CI, 1.04-2.5).

After adjusting for age, sex, BMI, smoking, hypertension, diabetes, cholesterol level, triglyceride levels and ratio of visceral and subcutaneous tissue, the researchers found an independent and dose-dependent relationship between the degree of thyroid dysfunction for subclinical hypothyroidism and NASH (OR = 2.17; 95% CI, 1.17-4.01). Adjustment for homeostasis model assessment of insulin resistance showed a similar association with subclinical hypothyroidism (OR= 2.17; 95% CI, 1.16-4.07), as did an adjustment for alanine aminotransferase and aspartate aminotransferase (OR = 2.3; 95% CI, 1.21-4.4).

Low-normal thyroid function and subclinical hypothyroidism also increased the risk for advanced fibrosis after the researchers adjusted for NAFLD and homeostasis model assessment of insulin resistance (OR = 2.23; 95% CI, 1.18-4.23) and after adjusting for ALT and AST (OR = 2.24; 95% CI, 1.17-4.28).

“According to the recent report, thyroid hormone receptor may regulate hepatic stellate cell activation, implicating the putative role of thyroid hormone signaling in liver fibrogenesis,” the researchers wrote. “Currently, an orally administered, small molecule liver-directed thyroid hormone receptor [beta] agonist with high liver uptake is under development for the treatment of NASH and familial hypercholesterolemia.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.