Non-alcoholic fatty liver disease (NAFLD) is fat accumulation in the liver that can progress to steatohepatitis (NASH, also called MASH), inflammation and liver-cell injury on top of the fat. Its management addresses the two forces that drive the disease and its mortality: the metabolic dysfunction that injures the liver, and the cardiovascular risk that accompanies it.
Lifestyle
A healthy diet and regular exercise form the foundation of treatment for almost everyone with NAFLD, whether or not weight loss is needed, because they improve cardiovascular and metabolic health as well as the liver.
Weight loss is the single most effective intervention. Losing 3–5% of body weight improves steatosis, but around 7–10% is generally needed to improve steatohepatitis, and at least 10% to improve fibrosis. Weight loss is difficult to sustain, so nutrition support and follow-up are part of treatment. Exercise has hepatic and cardiometabolic benefit even without weight loss, and regular moderate activity for about 150 minutes per week is a reasonable target. People with cirrhosis need a different approach that protects protein intake and accounts for physical limitations.
Diet composition matters in its own right: reducing fructose and sugar-sweetened drinks limits de novo lipogenesis, the liver’s own fat production, and heavy alcohol use should be avoided. In lean patients with NAFLD, weight loss may not be appropriate, but dietary change and exercise can still help.
Metabolic comorbidity
Because cardiovascular disease and metabolic dysfunction shape the outcome in NAFLD, treating the conditions that travel with it improves both liver and cardiovascular outcomes. Statins are safe across the spectrum of NAFLD, including compensated cirrhosis (cirrhosis without complications such as ascites), and reduce cardiovascular morbidity and mortality, so they should not be withheld because of raised liver enzymes. Blood pressure and lipids should be treated to the usual targets, and patients who are overweight or obese should be screened for obstructive sleep apnea (OSA).
Drug therapy
Drug therapy is aimed at steatohepatitis, alongside lifestyle change and control of metabolic risk factors. No single drug treats all of NAFLD, and the choice usually follows which need dominates. Four drugs or classes have some evidence in NASH:
- Resmetirom, an oral thyroid hormone receptor-β agonist, is the first drug approved for MASH (metabolic dysfunction-associated steatohepatitis). In 2024 it was approved for noncirrhotic MASH with moderate to advanced fibrosis (F2–F3); in a phase 3 randomised trial it improved steatohepatitis and fibrosis compared with placebo. It is not for use in decompensated cirrhosis.
- Pioglitazone improves histology and insulin sensitivity in NASH with or without diabetes, and can be considered in patients with type 2 diabetes or biopsy-proven NASH.
- Vitamin E at 800 IU/day improves histology in non-diabetic adults with biopsy-proven NASH, though it has not been shown to improve fibrosis.
- GLP-1 receptor agonists (glucagon-like peptide-1 receptor agonists) such as semaglutide improve steatosis and help resolve steatohepatitis while promoting weight loss, but a benefit on fibrosis is not established.
Other drugs have been tried without success. Metformin, ursodeoxycholic acid, DPP-4 (dipeptidyl peptidase-4) inhibitors and silymarin have been studied in NASH and should not be used as treatments for it, because they do not offer a meaningful histological benefit.
Bariatric surgery and transplantation
Procedures matter at the advanced end of the disease. Bariatric surgery can resolve NASH and improve fibrosis in patients who meet the criteria for metabolic weight-loss surgery, and it reduces mortality from cardiovascular disease and malignancy. Decompensated cirrhosis (cirrhosis with complications of liver failure or portal hypertension) is a contraindication outside specialised transplant centres.
When NAFLD has progressed to decompensated cirrhosis or hepatocellular carcinoma, liver transplantation is the definitive option. Because the metabolic syndrome persists after transplantation, NAFLD and NASH commonly recur in the graft, so metabolic risk factors need continued management.