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

INTRODUCTION: 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. METHODS: 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- 2 H] 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. RESULTS: 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. CONCLUSION: Concomitant use of statins alone or in combination with metformin was independently associated with preserved hepatic function (DSI) and reduced portal-systemic shunting (SHUNT%).