The versatile interplay between steatotic liver disease and liver cancer

Steatotic liver diseases (SLDs), including metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as non-alcoholic fatty liver disease) and alcoholic liver disease, are the leading causes of chronic hepatitis, liver dysfunction, cirrhosis and liver cancer development. Severe manifestations of MASLD and alcoholic liver disease include metabolic dysfunction-associated steatohepatitis (MASH; formerly known as non-alcoholic steatohepatitis) and alcoholic steatohepatitis (ASH) or a combination thereof, termed metabolic dysfunction and alcohol-associated liver disease. While MASH-associated and ASH-associated liver cancers display common histopathological features, the underlying cellular and molecular pathophysiological mechanisms of each are distinct. Recent studies indicate that SLDs encompass previously unrecognized spectra of heterogeneous, metabolic, immunological and genetic diseases that, in combination with lifestyle measures and individual patient comorbidities, affect disease pathogenesis and therapy response. Here, we review the current knowledge of the molecular, genetic and cellular mechanisms underlying the transition of MASH or ASH to liver cancer as well as novel developments in liver cancer risk assessment in SLDs. We further discuss possible obstacles of differential diagnosis and outline current developments in the therapeutic management of both MASH-related and ASH-related liver cancer.