Impact of Levothyroxine on Progression to and Complications of Cirrhosis in MASH.

PURPOSE

Resmetirom, a liver-targeted thyroid hormone receptor-β (THR-β) agonist, used to treat MASH, shares a similar mechanism of action with levothyroxine, a nonselective (THR-α/β) receptor agonist used to treat hypothyroidism. Given the potential effect of levothyroxine on THR-β, we hypothesized that it may have beneficial effects in MASH patients.

METHODS

We used TriNetX to examine patients aged ≥ 18 years with MASH treated with levothyroxine from 1/1/16 to 1/1/25. Patients prescribed levothyroxine (levothyroxine group) were compared to those not receiving them (control group). Patients with previous cirrhosis or liver transplant were excluded. To control for disease severity and underlying comorbidities, propensity score matching (PSM) was performed.

RESULTS

Of 109,268 patients with MASH, 17,629 (16%) received levothyroxine. Following PSM, we examined 15,076 patients in each group. MASH patients with or without levothyroxine treatment were predominantly White females, with a mean [SD] bilirubin, INR, and creatinine of 0.6 [0.7], 1.1 [0.4], and 0.9 [1.2], respectively. Comorbidities, BMIs, and MASH therapies including GLP-1s, SGLT-2s, and statins were similar in both groups. Over a mean [SD] follow-up of 2.8 [1.8] years, patients receiving levothyroxine had a similar rate of progression to cirrhosis (HR: 1.08; 95% CI 0.97-1.21; p = 0.16) as patients not on levothyroxine. In patients who developed cirrhosis, those receiving levothyroxine had a small, but statistically significantly higher risk of developing any portal hypertensive complication (HR: 1.33; 95% CI 1.18-1.49; p < 0.001) than those not receiving levothyroxine.

CONCLUSION

MASH patients prescribed levothyroxine had a similar rate of progression to cirrhosis and a slightly higher rate of portal hypertension complications than those not prescribed levothyroxine.