Chronic Inflammation Injury Promotes Hepatocellular Carcinoma Development Via Up-Regulation O Gamma-H2ax

Hepatocellular carcinoma (HCC) is one of the most deadly cancers associated with chronic hepatitis. Inflammatory injury plays a key role in the development of HCC. To investigate the risk of HCC in patients with varying degrees of inflammation, we followed up a total of 2087 patients in this study and found that the incidence of hepatocarcinogenesis progressively increased as the stages increased sequentially from G1 to G4 (P<0.001). The risk of hepatocarcinogenesis was also associated with the age of the patient; the albumin (ALB), glutamyltranspeptidase (GGT), and platelet (PLT) levels; and the prothrombin time (PT). Immunohistochemical analysis demonstrated that the DNA damage response progressively increased as the inflammation degree progressed (G1-G4) (P<0.05). Furthermore our results showed gamma-H2AX was dramatically up-regulated in HCC tissues compared with adjacent normal tissues (P<0.001) and was closely correlated with poor outcomes (P<0.001). These findings provide pathological evidence that a persistent chronic inflammation-related DNA damage response might be a driving force of HCC. Based on these findings, the DNA damage response might be considered a promising diagnostic marker for identifying potential malignant transformation in Hepatitis B at the early stage. Patients with poor liver function parameters should receive active anti-viral and liver-protective therapy and be closely monitored.