Enhancers and attenuators of risk associations of chronic hepatitis B virus infection with hepatocellular carcinoma in type 2 diabetes

Chronic hepatitis B virus (HBV) infection promotes hepatocellular carcinoma (HCC) risk. In type 2 diabetes (T2D), use of insulin and statins was associated with reduced cancer risk while co-presence of low LDL cholesterol (LDLC <2.8 mmol/l) plus low triglyceride (TG; <1.7 mmol/l) increased cancer risk. There is experimental evidence showing that insulin insufficiency might promote HCC. In this study, we examined whether this lipid subphenotype and use of insulin or statins might modify the promoting effect of chronic HBV infection (indicated by the presence of hepatitis B surface antigen) on HCC. We analyzed data of 1319 T2D patients enrolled into the Hong Kong Diabetes Registry from December 1996 to January 2005 and followed up to 2005. Additive interaction was estimated using relative excess risk due to interaction and attributable proportion due to interaction. During 5782 person-years of follow-up, 1.74% (n=23) of patients developed HCC (incidence, 3.98; 95% confidence interval, 2.36-5.60/1000 person-years). HbA1c ≥7.0% and the lipid phenotype (LDLC <2.8 mmol/l plus TG <1.7 mmol/l) increased the hazard ratios (HRs) of chronic HBV infection for HCC from 3.74 to 74.96 and from 11.01 to 89.82 respectively with significant interactions. Use of insulin or statins decreased the HRs from 37.51 to 5.87 and from 64.94 to 16.99 respectively with significant interactions (all P values <0.05). These findings support our hypothesis that hyperglycemia and co-presence of low LDLC plus low TG might enhance, while insulin or statin usage might attenuate the promoting effect of chronic HBV infection on HCC in T2D.