Hepatocellular carcinoma (HCC), a leading cause of cancer-related death in the world, was assessed to have a global incidence rate of 9.3 per 100,000 person-years with an approximately equivalent mortality rate of 8.5 in 2018 with substantial variations in different areas (1). The main risk factors for HCC have been attributed to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcoholic cirrhosis, non-alcoholic fatty liver disease (NAFLD), alfatoxin, and aristolochic acid (2). Despite extensive vaccination for HBV and aggressive administration of anti-viral treatments against HBV and HCV, the International Agency for Research on Cancer reckons that 1,436,744 new patients will be diagnosed to have liver and intrahepatic bile duct cancer in 2040 on the basis of annual projections (3) with 75%-85% as HCC and 10%-15% as intrahepatic cholangiocarcinoma (4). Prevention of HCC and reduction of its death rate therefore become an urgent need in public health.
Interestingly, a recent dose-response meta-analysis disclosed that an extra two-cups of coffee per day reduced the risk of HCC by 35% without significant intervention from liver disease stage, body mass index, alcohol drinking, and viral hepatitis B or C infection (5). The inverse correlation between coffee consumption and HCC risk was shortly supported by another similar dose-response study reporting a 15% reduction in HCC risk by one cup of coffee per day (6). Following these, in a succeeding umbrella review of meta-analyses of observational studies accommodating 36 summary associations for 26 cancer sites, highly suggestive evidence was shown for an inverted relationship between coffee intake and the risk of HCC (7). However, the potential mechanism of coffee’s beneficial effect on reducing HCC development remains to be explicated and requires resolution in spite of thoroughly reviewing relevant literatures (8). Herein, an attempt to explain the causality will be made based on recent advancement of research on inflammasomes, the supramolecular cytoplasmic structures which drive immune responses and inflammation.