Although Kupffer cells (macrophages) are known to promote an inflammatory response in the development of NASH, it has also been reported that injured hepatocytes produce pro-inflammatory cytokines and chemokines.47 Since hepatocyte-specific CGI-58 knockout mice exhibited inflammation and fibrosis in the liver, our experiment shows that KAL specifically down-regulates CGI-58 and induces TNFα in hepatocytes but not macrophages, and hepatocyte-specific CGI-58-overexpression could improve the hepatic steatosis and inflammation of KAL-Tg mice. Here, TNF is linked to metabolic dysfunction-associated steatohepatitis.