# Adult Growth Hormone Deficiency and Metabolic Dysfunction-Associated Steatotic Liver Disease

## TL;DR

This review explores how adult growth hormone deficiency is linked to liver disease through metabolic issues and potential treatment options.

## Contribution

It highlights new insights into the direct and indirect effects of GH on liver steatosis and fibrosis in GHD patients.

## Key findings

- GH affects hepatocytes via the JAK2-STAT5 pathway, reducing hepatic steatosis.
- Low IGF-1 levels may contribute to hepatic fibrosis through effects on stellate cells.
- rhGH treatment shows potential benefits for liver steatosis and fibrosis in GHD patients.

## Abstract

Growth hormone (GH) deficiency (GHD) in adults presents with metabolic syndrome features, such as abdominal obesity, dysglycemia, atherogenic dyslipidemia and hypertension, which are closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD). This narrative review aims to critically summarize the available data on the link between adult GHD and MASLD, focusing on possible pathophysiological mechanisms, clinical associations and treatment considerations.

Experimental evidence supports a direct effect of GH on hepatocytes predominantly through the Janus kinase 2 (JAK2)–signal transducer and activator of transcription 5 (STAT5) pathway, which reduces hepatic steatosis. Hepatic steatosis in GHD may also be indirectly affected through the unfavorable effects of GHD on insulin resistance and metabolic syndrome features. Limited data show that low insulin-like growth factor-1 (IGF-1) concentrations may contribute to hepatic fibrosis by acting on hepatic stellate cells. Regarding clinical associations, MASLD is highly prevalent in adults with GHD, and, vice versa, lower or similar circulating GH/IGF-1 concentrations are reported in patients with MASLD compared with those without MASLD. Regarding treatment, favorable effects of recombinant GH (rhGH) on hepatic steatosis and, possibly, on hepatic fibrosis progression in patients with MASLD and GHD or with low IGF-1 concentrations have been demonstrated in interventional studies.

Existing findings may warrant more specifically designed studies to carefully assess the risk–benefit ratio of rhGH replacement in adults with GHD and MASLD.