NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy

The last 10 years have revolutionized our basic understanding of nonalcoholic 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 nonalco-holic steatohepatitis (NASH)-a disease that has been recently defined as autoaggressive. 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 with viral HCC; however, conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with car-cinogenesis 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 patients with NASH-HCC. In this review, we summarize the state of the art in the field of NASH and NASH-HCC with focus on immunobiology. We discuss preclinical and clinical findings under-pinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulner-abilities in NASH-associated HCC.

Automated summary

The past 10 years have brought about a revolution in our understanding of nonalcoholic fatty liver disease (NAFLD) and liver cancer. It has been discovered that various immune cells have a significant role in initiating and exacerbating nonalcoholic steatohepatitis (NASH), a newly defined autoaggressive disease. NASH is expected to become a leading cause of hepatocellular carcinoma (HCC) despite improved disease management. The effectiveness of immunotherapy in NASH-related HCC may be diminished compared to viral HCC, but further evidence is needed to support clinical translation of these findings.