Although TGR5 promoter methylation is age-related and higher in patients older than 60, methylation may serve as a potential diagnostic for both acute-on-chronic hepatitis B liver failure and hepatocellular carcinoma.207 Besides direct phenotypic association between hepatic pathology and CpG methylation of the TGR5 promoter, not much research has been conducted directly on the factors driving TGR5 epigenetic regulation. This evidence concerns the gene GPBAR1 and hepatocellular carcinoma.