Mechanisms and Management Strategies of Hepatocarcinogenesis Driven by Chronic Hepatitis B Comorbid with Type 2 Diabetes

Chronic hepatitis B (CHB) and Type 2 diabetes (T2DM) are major independent risk factors for Hepatocellular carcinoma (HCC). The bidirectional promotion between T2DM and CHB forms the biological basis for their synergistic carcinogenic effect. T2DM mainly accelerates the progression of CHB through mechanisms such as metabolic disorders, oxidative stress, chronic inflammation, and immunosuppression; CHB promotes the development of T2DM mainly through liver damage leading to dysfunction of the central glucose metabolism, HBx-driven gluconeogenesis, inhibition of the insulin signaling pathway, and potential β-cell damage. In comorbid conditions, these mechanisms intertwine to form a vicious cycle across four key aspects: metabolic and lipid disorders, activation of carcinogenic pathways, oxidative stress, and amplification of chronic inflammation, significantly accelerating the hepatocarcinogenesis. Regarding management strategies, we adopt the concept of three-level prevention, integrate various management plans and combine emerging drug therapies. We thus propose the establishment of a management strategy centered on "liver and glucose co-management" with multi-faceted joint control. This review aims to summarize the latest evidence on the mechanisms and management strategies by which the comorbidity of T2DM and CHB promotes the development of HCC, providing a theoretical basis for research on the mechanisms of this comorbidity and population-level HCC prevention strategies.