Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study

This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed type 2 diabetes patients on any antidiabetic agents in Taiwan before and after exclusion of chronic viral hepatitis, respectively. A total of 5832 and 1237 HCC cases were identified before and after exclusion of chronic viral hepatitis, respectively. Incident HCC risks were positively associated with any use of premixed insulin analogues (adjusted odds ratio (OR), 1.27; 95% CI 1.04 to 1.55) among total participants, especially among current users (adjusted OR, 1.45; 95% CI 1.12 to 1.89). However, the association between HCC occurrence and premixed insulin analogues diminished among participants without chronic viral hepatitis (adjusted OR, 1.35; 95% CI 0.92 to 1.98). We also observed a significant multiplicative interaction between chronic viral hepatitis and premixed insulin analogues on HCC risks (P = 0.010). Conclusions: Chronic viral hepatitis signifies the role of premixed insulin analogues in HCC oncogenesis. We recommend a closer liver surveillance among patients prescribed premixed insulin analogues with concomitant chronic viral hepatitis.