Association of Dipeptidyl Peptidase-4 Inhibitors Use with Reduced Risk of Hepatocellular Carcinoma in Type 2 Diabetes Patients with Chronic HBV Infection

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) was the sixth most common cancer and the third leading cause of cancer death worldwide in 2020. Several studies have demonstrated that both chronic hepatitis B virus (HBV) infection and type 2 diabetes mellitus (T2DM) are important risk factors for HCC. Treatment with antiglycemic agents in patients with various chronic liver diseases has been well studied, but there are relatively few related studies on dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), especially in patients with coexisting T2DM and chronic HBV infection. This long-term retrospective population-based cohort study aimed to investigate whether the use of DPP-4 inhibitors decreases the risk of developing HCC in patients with coexisting T2DM and chronic HBV infection. Our study presents a preliminary confirmation that DPP-4 inhibitors have a beneficial effect in decreasing the risk of HCC in the treatment of T2DM patients with chronic HBV infection. ABSTRACT: Previous studies have indicated that HBV infection and T2DM are the factors that increase the risk of developing HCC. The experimental evidence has shown that antiglycemic agents may reduce the risk of HCC. However, the effect of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) on the risk of HCC in T2DM patients with chronic HBV infection remains unclear. In this retrospective cohort study, we extracted patients with T2DM and chronic HBV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The cases were divided into DPP-4 inhibitors use and non-use groups, according to whether they received DPP-4 inhibitors treatment, and the risk of HCC was compared between the two groups. At the end of the follow-up, approximately 2.33% of DPP-4 inhibitors users had received an HCC diagnosis compared with 3.33% of non-DPP-4 inhibitors users (p < 0.0001). After multivariate adjustment, DPP-4 inhibitors users showed a significant reduction in HCC risk (adjusted hazard ratios (aHRs): 0.53; 95% confidence intervals (CIs): 0.44–0.65). In conclusion, this population-based retrospective cohort study indicated that, in T2DM patients with chronic HBV infection, the use of DPP-4 inhibitors significantly reduced the risk of developing HCC compared with non-DPP-4 inhibitors use.