# HMG-CoA Reductase Inhibitors (Statins) May Preserve Hepatic Function and Reduce Portal-Systemic Shunting in Compensated Advanced Chronic Liver Disease: Results From the SHUNT-V Study

## TL;DR

This study found that statins may help preserve liver function and reduce shunting in people with advanced chronic liver disease.

## Contribution

The study identifies statins as a potential therapeutic for preserving liver function in compensated cirrhosis.

## Key findings

- Statins were independently associated with preserved hepatic function and reduced portal-systemic shunting.
- Combined use of lipid-lowering and anti-diabetic drugs reduced disease severity by 19%.
- MASLD/MASH subjects had similar clinical scores to those with other liver disease etiologies.

## Abstract

Factors associated with decline of hepatic function and increase in portal-systemic shunting, which herald clinical outcome in persons with compensated cirrhosis, are poorly characterized. We used cholate challenge to evaluate the associations of liver disease etiology, concomitant diabetes, and maintenance drug therapy, with the degree of hepatic dysfunction and portal-systemic shunting.

In the SHUNT-V study, there were 255 subjects with compensated (Child-Pugh class A) cirrhosis who underwent cholate challenge, involving oral administration of [2,2,4,4-2H] cholate and measurement of its serum concentrations at 20 and 60 minutes. Test outputs included a disease severity index (DSI) to assess global liver function and SHUNT% to assess portal systemic shunting.

Eighty-seven percent of subjects were overweight, 65% were obese, 48% had metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), 51% had type 2 diabetes mellitus, 49% were taking anti-diabetic drugs, and 45% were taking lipid-lowering drugs. Laboratory values and clinical scores of MASLD/MASH subjects were similar to subjects with other etiologies for liver disease. In univariable regression, MASLD/MASH, diabetes mellitus, metformin, and statins were associated with lower DSI and SHUNT%. In multivariable regression, lower DSI was attributable to statins (P = 0.0354) and metformin (P = 0.0561). The combined use of lipid-lowering and anti-diabetic drugs, compared with no use, was associated with 19% reduction in DSI.

Concomitant use of statins alone or in combination with metformin was independently associated with preserved hepatic function (DSI) and reduced portal-systemic shunting (SHUNT%).