Background

Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) which have been associated with an increased risk of hepatocellular carcinoma (HCC) and cirrhosis. Guideline-directed therapy for SLD includes vitamin E (VE), pioglitazone, and glucagon-like peptide 1 analogs (GLP1). We analyzed the incidence of HCC and cirrhosis following an SLD diagnosis on VE, pioglitazone, and GLP1s over 10 years.

Methods

This is a large, retrospective, population-based cohort study utilizing data from the TriNetX platform. Adult patients with a BMI of 30 or higher with MASH or MAFLD that were treated with VE, pioglitazone, or GLP1s excluding tirzepatide were included. Patients diagnosed with SLD before the index event, or those diagnosed with alcoholic liver disease, Wilson's disease, hereditary hemochromatosis, chronic hepatitis B and C, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, intrahepatic bile duct carcinoma, hepatoblastoma, and angiosarcoma were excluded.

Results

The GLP1 cohort included 34,614 patients, VE included 11,010 patients, pioglitazone included 2,765 patients, and control included 199,182 patients. The risk of progression from SLD to HCC and cirrhosis in the GLP1 cohort was significantly reduced compared to controls, VE, and pioglitazone. The pioglitazone cohorts HCC and cirrhosis risk was similar to controls and VE, but higher than GLP1s. The VE group showed higher risk of HCC and cirrhosis compared to controls and GLP1s, but insignificance compared to pioglitazone.

Conclusions

Compared to pioglitazone and VE, GLP1s are significantly better at reducing the risk of HCC and cirrhosis in patients with SLD.