Risk of Liver Cancer in MASLD: Role of Genetic Risk Scores

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the fastest growing cause of hepatocellular carcinoma (HCC). Several risk factors have been identified, including older age, male gender, Hispanic ethnicity, metabolic syndrome components, certain medications, tobacco and alcohol use. Genetic polymorphisms, such as PNPLA3 , TM6SF2 , and MBOAT7 variants, have been associated with increased risk of MASLD-related HCC. More recently, genetic risk scores (GRS) based on single-nucleotide polymorphisms (SNPs) have shown potential in predicting HCC risk. So far, there are a few studies that analyzed the impact of GRS in MASLD-related HCC, but they seem very promising in stratifying patients according to the risk of developing HCC. Although current GRS models have limitations, in the future, with a better understanding of these SNPs, and the discovery of other variants, they could integrate more comprehensive risk prediction models, including various data, such as etiology, fibrosis grade, serum markers, comorbidities and genetics, which will improve HCC risk prediction in MASLD.