Background Age-related differences of clinicopathologic features, outcomes, and molecular properties of hepatocellular carcinoma remain unclarified. Methods We classified patients who underwent hepatectomy for hepatocellular carcinoma into 3 groups by age bracket; younger group (<50 years), middle-aged group (50 to 79 years), and elderly group (≥80 years) and compared age-related features. Results Hepatitis viral infection was dominant in the younger group (hepatitis B virus [HBV]; 67%) and middle-aged group (hepatitis C virus [HCV]; 56%), whereas the elderly group showed a significantly higher rate without hepatitis virus infection (absence of HBV and HCV infection, 66%; P =.0001). There was a significantly greater proportion of age-associated pre-existing comorbidity in the elderly group (89%; P =.0004). Liver cirrhosis in the elderly group (24%) was significantly lower than other groups (younger, 67%; middle-aged, 50%; P =.0058). There was no significant difference in perioperative and postoperative outcomes among these groups. Microarray analysis revealed age-related upregulation of androgen and phosphatidylinositol 3-kinase pathways in the tumor tissue and downregulation of the fibrosis-related pathways in the noncancerous liver tissue. Conclusions Based on increased correlation with the absence of HBV and HCV infection and pre-existing comorbidity, the age-related carcinogenic pathways might play a critical role in elderly hepatocarcinogenesis.
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