Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver...

Previous studies suggest that hypothyroidism is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and its histological severity, but clinical outcome data are largely lacking. We aimed to study the impact of hypothyroidism on liver-related events (LREs).

Patients with MASLD were identified from a territory-wide registry in Hong Kong during 2000-2024. Thyroid status was determined using diagnosis codes and thyroid function tests. The primary outcome, LRE, was defined as a composite of hepatic decompensation, hepatocellular carcinoma, liver transplantation, and liver-related death.

A total of 20,478 patients with MASLD were included in the final analysis (mean age 56.4±13.2 years; 43.9% male). At baseline, 18,178 (88.8%) patients were euthyroid, 598 (2.9%) were hyperthyroid, and 1,702 (8.3%) were hypothyroid. Compared with euthyroid patients, both hyperthyroidism and overt hypothyroidism were associated with cirrhosis. At a median follow-up of 4.8 years, 179 patients developed LREs, and 26 died from liver disease. Compared with patients with normal serum thyroid-stimulating hormone (TSH) levels of 0.4-4 mIU/L, those with subclinical (4-10 mIU/L; adjusted time-dependent cause-specific hazard ratio [aCSHR], 2.49; 95% CI, 1.51-4.13) and overt hypothyroidism (>10 mIU/L; aCSHR, 4.91; 95% CI, 1.56-15.47) had an increased risk of LREs. Time-dependent, but not baseline, TSH and thyroid status were associated with LRE risk.

Subclinical and overt hypothyroidism are associated with an increased risk of LREs in a dose-dependent manner. The association with time-dependent but not baseline thyroid status underscores the importance of thyroid monitoring and suggests that correction of hypothyroidism may mitigate LRE risk.