With regard to the non-modifiable risk factors, the following correlates are known: age, gender, type 2 diabetes mellitus (T2DM), genetic mutations (TERT, TP53, WNT or CTNNB1, KRAS, BRAF, SMAD4, FGFR2, IDH1 and IDH2, ARID1A, ARID2, PBRM1, BAP1, MLL3 or KMT2C, HDAC6, BRCA2, EGFR, and NTRKs), and clinical conditions such as Primary Sclerosing Cholangitis (PSC), biliary tree lithiasis, Cirrhosis, HBV and HCV, infectious Non Alcolic Fatty Liver Disease (NAFLD), and Inflammatory Bowel Disease (IBD) [9]. This evidence concerns the gene SMAD4 and type 2 diabetes mellitus.