Metabolic-associated steatohepatitis (MASH) impacts an estimated 15 million people in the U.S. alone, significantly raising their risk for cirrhosis, hepatocellular carcinoma, and eventual liver transplantation. Previously known as non-alcoholic steatohepatitis (NASH), MASH represents the most advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD), a chronic condition now affecting 30% to 40% of the U.S. adult population.[1]
In MASLD, fat accumulation, or microvesicular steatosis, exceeds 5% without an identifiable cause such as excessive alcohol consumption, toxins or virus.[2]
Progression from MASLD to MASH: Understanding a growing health crisis
About one in seven patients with MASLD (previously called non-alcoholic fatty liver disease or NAFLD) will progress to MASH, a condition marked by steatosis, hepatocellular injury, and inflammation, with or without fibrosis.[3]
This progression dramatically increases the risk of severe liver complications: within a decade, up to 50% of patients with MASH may develop cirrhosis.[4] Further, the progression to MASH increases the annual incidences of liver-specific mortality and hepatic carcinoma exponentially, rising from 0.77 and 0.44 per 1,000 person-year for MASLD, respectively, to 11.77 and 5.29 per 1,000 person-year for MASH, respectively.[5] In the next decade, MASH is projected to become the most common reason for liver transplants and hepatocellular carcinoma in the U.S.[6],[7]
Decoding MASH risk factors: Obesity, diabetes, and metabolic dysregulation
While the precise pathogenesis of MASH remains incompletely understood, metabolic dysregulation, genetics, and the gut microbiome all appear to contribute to disease progression.[8]
Obesity is the predominant risk factor for MASLD and MASH, with MASLD affecting 75% of individuals with obesity and 90% of those with morbid obesity. MASLD and MASH can also occur in individuals with normal or low body weight, however.
Type 2 diabetes mellitus compounds the risk of developing MASH. A recent study found that 58% of randomly selected individuals with type 2 diabetes had MASH and 38% had advanced fibrosis.[9] Individuals with hypertension and hyperlipidemia also face an increased risk for MASLD and MASH with fibrosis, further highlighting the connection between metabolic health and liver disease.
Better understanding and addressing the metabolic drivers of MASH and MASLD will be essential for reducing the burden of liver-related morbidity and mortality in the coming years.
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