# ECM remodeling in hypothyroidism-associated MAFLD: mechanisms, clinical relevance, and therapeutic targets

## TL;DR

This paper explores how hypothyroidism contributes to liver disease through changes in the liver's structure and suggests new treatment approaches.

## Contribution

The paper identifies ECM remodeling as a novel mediator linking hypothyroidism and MAFLD, highlighting new therapeutic strategies.

## Key findings

- Altered thyroid hormone signaling promotes ECM remodeling through metabolic and inflammatory pathways.
- Hepatic stellate cell activation and immune reshaping are key in hypothyroidism-associated MAFLD.
- ECM-targeted therapies and THRβ agonists show promise as new treatment options.

## Abstract

Metabolic dysfunction–associated fatty liver disease (MAFLD) is a major chronic liver disease increasingly linked to endocrine and immunometabolic dysregulation. Hypothyroidism, both overt and subclinical, has emerged as a significant endocrine risk factor for MAFLD. Extracellular matrix (ECM) remodeling, a hallmark of fibrosis, represents a crucial but underexplored mediator in this process. This review highlights how altered thyroid hormone (TH) and thyroid-stimulating hormone (TSH) signaling promote ECM remodeling through metabolic, inflammatory, and fibrogenic pathways, with emphasis on hepatic stellate cell (HSC) activation and immune reshaping. We further summarize ECM-derived biomarkers and emerging therapeutic strategies, including THRβ agonists and ECM-targeted approaches.