Link between type 2 diabetes mellitus and hepatocellular carcinoma

Abstract

Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) have a strong bidirectional relationship. T2DM increases the risk of developing HCC, mainly through the nonalcoholic steatohepatitis pathway, but a significant proportion of patients develop HCC without developing cirrhosis. The identification of HCC in T2DM patients is difficult considering the low incidence of HCC and the high prevalence of T2DM. However, considering the alarming increase in the incidence of diabetes mellitus in the global population, effective strategies are urgently needed to identify patients at high risk. Nonetheless, various classes of drugs, such as sodium-glucose cotransporter-2 inhibitors and incretin analogs, may be promising for reducing the risk of nonalcoholic steatohepatitis and HCC development in T2DM patients in the future. In this review, we discuss all these facets of the relationship between HCC and T2DM, and we summarize future directions.

Keywords: Cancer; Hepatocellular carcinoma; Nonalcoholic fatty liver disease; Steatohepatitis; Type 2 diabetes mellitus

Core Tip: Type 2 diabetes mellitus increases the hepatocellular carcinoma (HCC) risk and also impacts the treatment response of HCC. The molecular pathways of diabetes, development of its complications are interconnected with HCC. However, only a subset of HCC cases in type 2 diabetes mellitus are driven by nonalcoholic fatty liver disease, suggesting the involvement of additional pathogenic pathways. Newer generation anti-diabetic and anti-obesity drugs like sodium-glucose cotransporter-2 inhibitors and incretin analogues can hold promises in the future.