MASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges

Simple Summary Metabolic-dysfunction-associated steatotic liver disease (previously known as non-alcoholic fatty liver disease) is a term for a range of liver conditions in which excess fat builds up in the liver. This can eventually lead to liver inflammation, chronic liver disease and, in some cases, a form of liver cancer (hepatocellular carcinoma). This condition is increasing worldwide, with patients most at risk being overweight or obese or having type 2 diabetes. Hepatocellular carcinoma is seen in patients with this condition at different stages, and research is ongoing to identify why some patients appear to develop cancer at an earlier stage of liver disease than others, and how to best treat them, as there appear to be variations in how well patients respond depending on what caused the liver inflammation initially. Here, we summarise the research to date and discuss the potential rationale for what has been observed.Abstract Metabolic-dysfunction-associated steatotic liver disease (MASLD, previously known as non-alcoholic fatty liver disease (NAFLD)) represents a rapidly increasing cause of chronic liver disease and hepatocellular carcinoma (HCC), mirroring increasing rates of obesity and metabolic syndrome in the Western world. MASLD-HCC can develop at an earlier stage of fibrosis compared to other causes of chronic liver disease, presenting challenges in how to risk-stratify patients to set up effective screening programmes. Therapeutic decision making for MASLD-HCC is also complicated by medical comorbidities and disease presentation at a later stage. The response to treatment, particularly immune checkpoint inhibitors, may vary by the aetiology of the disease, and, in the future, patient stratification will be key to optimizing the therapeutic pathways.