August 09, 2018
2 min read

Primary hypothyroidism associated with increased risk for NAFLD

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Giovanni Targher
Giovanni Targher

The presence of primary hypothyroidism is associated with a 42% increased risk for image-defined or biopsy-proven nonalcoholic fatty liver disease, or NAFLD, with risk increasing across different definitions for diagnosing hypothyroidism, according to findings from a meta-analysis published in Thyroid.

“To date, several observational studies have explored the association between primary subclinical/overt hypothyroidism and imaging-defined or biopsy-proven NAFLD,” Alessandro Mantovani, MD, of the section of endocrinology, diabetes and metabolism at Universitaria Integrata of Verona, Italy, and colleagues wrote in the study background. “However, the findings from such studies have been conflicting so far, with some studies reporting that the prevalence of primary hypothyroidism, especially subclinical hypothyroidism, was extremely common among patients with NAFLD, [with] other studies failing to find any significant association between hypothyroidism and risk of NAFLD.”

Mantovani and colleagues analyzed data from12 cross-sectional and three longitudinal studies enrolling 44,140 participants between January 2000 and March 2018 that examined the association between primary hypothyroidism and NAFLD (diagnosed via imaging or biopsy) that reported ORs or HRs for any association. Researchers pooled all adjusted ORs and HRs to calculate an overall estimated effect size using random-effects modeling.

Thirteen studies recruited adults and two studies recruited children or adolescents with overweight or obesity. Diagnosis of NAFLD was based on liver biopsy (n = 3 studies), ultrasound (n = 11 studies) or CT scan (n = 1 study). Diagnoses of primary hypothyroidism were based on either self-report with use of levothyroxine replacement therapy or serum thyroid hormone measurements. Seven studies were conducted in Asia, five were conducted in Europe and three were conducted in the United States. Mean age across studies was 45 years, with 6,067 participants with primary hypothyroidism and 7,810 participants with NAFLD.

Researchers found that the presence of hypothyroidism was associated with an increased risk for prevalent NAFLD (OR = 1.42; 95% CI, 1.15-1.77), independent of age, sex, BMI and common metabolic risk factors. In analyzing the association between the presence of hypothyroidism and risk for severe NAFLD, researchers observed a 2.7-fold higher risk for nonalcoholic steatohepatitis or advanced fibrosis in adults with primary hypothyroidism (OR = 2.73; 95% CI, 1.9-3.93), independent of age, sex, BMI or metabolic factors. However, the presence of subclinical hypothyroidism was not associated with increased incident risk for ultrasound-diagnosed NAFLD during a median of 5 years (HR = 1.29; 95% CI, 0.89-1.86). Findings persisted in sensitivity analyses, according to researchers.


The researchers noted that this risk tended to increase across the different definitions used for diagnosing hypothyroidism (ie, a self-reported history of hypothyroidism with use of levothyroxine replacement therapy; newly diagnosed overt biochemical hypothyroidism; or newly diagnosed subclinical hypothyroidism) and appeared to further increase with a greater severity of NAFLD, reaching a risk of nearly three times greater in the presence of nonalcoholic steatohepatitis or advanced fibrosis on liver histology.

“These findings may have clinical practice implications for the potential screening of hypothyroidism and NAFLD,” Giovanni Targher, MD, associate professor of endocrinology and diabetes at Universitaria Integrata of Verona, told Endocrine Today. “Indeed, the results of this meta-analysis suggest that patients with NAFLD should probably be screened for primary hypothyroidism and that NAFLD should be looked for in all patients with hypothyroidism, given that these patients are at higher risk of more advanced histologic forms of NAFLD (ie, non-alcoholic steatohepatitis and advanced fibrosis).” – by Regina Schaffer

For more information:

Giovanni Targher, MD, can be reached at University and Azienda Ospedaliera Universitaria Integrata of Verona, Department of Medicine, Piazzale A. Stefani, 137126, Verona, Italy;

Disclosures: The authors report no relevant financial disclosures.