Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, affecting around 30% of Americans. It encompasses a spectrum of conditions, with non-alcoholic fatty liver (NAFL) being the milder form characterized by fat accumulation in the liver. Non-alcoholic steatohepatitis (NASH) is the more severe form, marked by inflammation and liver cell injury. NASH can progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) and is expected to surpass hepatitis C as the leading cause of liver transplantation within the next 5 to 15 years.

The pathophysiology of NASH involves metabolic imbalances, including excess dietary fat, increased free fatty acids from adipose tissue, and increased liver fat production. This leads to fat accumulation in the liver, mitochondrial stress, and inflammation, ultimately resulting in fibrosis. Treatment approaches include lifestyle changes such as weight loss and exercise, which are often challenging to sustain. As a result, pharmacotherapy is needed, with novel drugs targeting various pathways under investigation. Current therapies include PPAR agonists, bile acid modulators, and lipid-altering agents, alongside ongoing research into inflammation, fibrosis, and gut-related treatments.

Reference: Oseini AM, Sanyal AJ. Therapies in non-alcoholic steatohepatitis (NASH). Liver Int. 2017 Jan;37 Suppl 1(Suppl 1):97-103. doi: 10.1111/liv.13302. PMID: 28052626; PMCID: PMC5492893.