Metabolic Associated Steatohepatitis (MASH) 

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as NASH, is a progressive liver disease driven by metabolic risk factors such as obesity, type 2 diabetes, and insulin resistance. It is marked by hepatic fat accumulation (steatosis), chronic inflammation, and hepatocellular injury, which can lead to fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. MASH lies at the severe end of the MASLD (metabolic dysfunction-associated steatotic liver disease) spectrum and is rapidly becoming a leading cause of liver transplantation globally. In the United States alone, an estimated 6 to 8 million people are affected, with prevalence expected to rise in parallel with increasing rates of metabolic syndrome. While lifestyle modification remains a cornerstone of care, effective pharmacologic therapies are still limited. Advances in human genetics have identified highly penetrant gene variants that influence disease risk, progression, and therapeutic responsiveness, offering new opportunities to develop precision therapies that directly address disease-driving biology. By leveraging these genetically validated pathways, a precision medicine approach can stratify patient populations and enable the development of more effective, disease-modifying treatments. As the molecular understanding of MASH continues to deepen, the disease is increasingly recognized as a high-value indication for next-generation gene therapies aimed at liver and metabolic disorders.