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

Abstract

Background/Aims: 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). Methods: 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. Results: 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. Conclusions: 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.