Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression

Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor. However, the inflammasome-mediated cytokines associated with both diseases are central actors in liver cancer progression. The release of the pro-inflammatory cytokines IL-1 beta and IL-18 during inflammasome activation leads to several detrimental effects on the liver microenvironment. Considering the critical crosstalk between obesity, NASH, and HCC, this review will present the connections of IL-1 beta and IL-18 from obesity-associated NASH with HCC and will discuss approaches to using these cytokines as therapeutic targets against HCC.

Automated summary

Liver cancer, commonly known as hepatocellular carcinoma (HCC), is a highly lethal malignancy that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. The connection between these disorders and liver cancer is poorly understood, but inflammasome-mediated cytokines have been found to play a central role in HCC progression. The release of pro-inflammatory cytokines IL-1 beta and IL-18 during inflammasome activation has detrimental effects on the liver microenvironment. This review explores the connections between obesity-associated NASH and HCC, focusing on the potential therapeutic targeting of IL-1 beta and IL-18.