NASH and hepatocellular carcinoma: immunology and immunotherapy.

The last 10 years have revolutionized our basic understanding of non-alcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining or exacerbating non-alcoholic steatohepatitis (NASH) - a disease that has been recently defined as auto-aggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carcinoma (HCC). Preliminary data from preclinical studies suggest that immunotherapy efficacy may be reduced in NASH-related HCC compared to viral HCC, however conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with carcinogenesis and therapeutic resistance is key to prevent progression to cirrhosis, improve monitoring and stratification of NASH according to predicted cancer risk and ultimately increase survival of NASH-HCC patients. In this review we summarize the state of the art in the field of NASH and NASH-HCC - with focus on immunobiology. We discuss pre-clinical and clinical findings underpinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulnerabilities in NASH-associated HCC.