Repurposing levothyroxine for managing metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an entity closely linked to obesity and/or insulin resistance, projected to affect about half of the global adult population by 2040. New therapeutic strategies that are both effective and affordable are needed to address this impending public health crisis.

A narrative review was conducted to identify studies supporting the use of levothyroxine and thyroid hormone analogs in treating MASLD and metabolic dysfunction-associated steatohepatitis (MASH).

Clinical studies have identified clear pathophysiological links between low (or low-normal) thyroid function and increased risk of hepatic steatosis. Of the two main thyroid hormone receptor (THR) isoforms, THRα and THRβ, the latter primarily mediates the metabolic effects of thyroid hormones in the liver, which could greatly benefit patients with MASLD. Recently, selective analogs of hepatic THRβ receptors have been developed to treat MASLD, with early clinical data demonstrating an effective profile. However, due to the increasing prevalence of MASLD in both developed and developing countries, the high cost of branded drugs may hinder their widespread use.

Although the development of thyromimetics mainly aims to prevent activation of THRα in other tissues, there is evidence supporting the efficacy and safety of low-dose levothyroxine (LT4) therapy for treating MASLD. This review aims to systematically explore the potential of LT4 therapy as an alternative approach to managing MASLD.