Metabolic dysfunction-associated steatotic liver disease and the cardiovascular system

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty-liver disease, is an important and rising health issue with a link with atherosclerotic cardiovascular (CV) disease (CVD), affecting ∼25–30 % of the adults in the general population; in patients with diabetes, its prevalence culminates to ∼70 %; its evolutive form, nonalcoholic steatohepatitis, is estimated to be the main cause of liver transplantation in the future. MASLD is a multisystem disease that affects, besides the liver, extra-hepatic organs and regulatory pathways; it raises the risk of type 2 diabetes mellitus (T2D), CVD, and chronic kidney disease; the disease may also progress to hepatocellular carcinoma. Its diagnosis requires hepatic steatosis and at least one cardiometabolic risk factor and the exclusion of both significant alcohol consumption and other competing causes of chronic liver disease. Beyond CV events, associated metabolic comorbidities comprise obesity (∼50 %), T2D (∼20 %), hyperlipidemia (∼70 %), hypertension (∼40 %), and metabolic syndrome (∼40 %). Among the various clinical events, CV events mostly determine prognosis as they are the leading cause of death in these patients. Regarding management, statins exert beneficial effects in improving liver injury; silybin, derived from Silybum marianum, has some protective effects; lifestyle modification, such as weight loss, dietary changes, physical exercise, and abstention from alcohol use combined with optimal management of comorbidities are most helpful. Bariatric surgery may be an option in persons with MASLD and obesity. Adults with non-cirrhotic MASLD and significant liver fibrosis may be candidates for targeted treatment with resmetirom, which has histological efficacy on steatohepatitis and fibrosis with an acceptable safety and tolerability profile, whereas, no MASLD-targeted pharmacotherapy can be beneficial in the cirrhotic stage, whereby other measures may include metabolic drugs, nutritional counseling, surveillance for portal hypertension and hepatocellular carcinoma, and finally, liver transplantation in decompensated cirrhosis.