Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma

The prevalence of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is rapidly increasing, following the growing prevalence of NAFLD. The pathophysiological mechanisms of NAFLD-associated HCC are not fully elucidated. Emerging preclinical and limited clinical studies suggest that tumor necrosis factor-α (TNF-α) and adiponectin may contribute to the progression from NAFLD to HCC. This may render both TNF-α and adiponectin as appealing therapeutic targets in the setting of NAFLD-associated HCC, for which systemic immunotherapy, i.e., immune checkpoint inhibitors (ICIs), seems to be less effective compared to HCC of other etiologies. Therefore, anti-TNF biologics and/or adiponectin analogs or medications that increase endogenous adiponectin may be investigated combined with ICIs in the treatment of NAFLD-associated HCC.