Elevated testosterone increases risk of hepatocellular carcinoma in men with chronic hepatitis B and diabetes mellitus
Terry Cheuk‐Fung Yip, Grace Lai‐Hung Wong, Henry Lik‐Yuen Chan, Yee‐Kit Tse, Lilian Yan Liang, Vicki Wing‐Ki Hui, Hye Won Lee, Grace Lui, Alice P.S. Kong, Vincent Wai‐Sun Wong
Abstract
BACKGROUND AND AIM: Male sex is a risk factor for hepatocellular carcinoma (HCC). Diabetes mellitus (DM) is associated with a doubled risk of HCC in patients with chronic hepatitis B (CHB). We examined the relationship between serum total testosterone and HCC risk in male CHB patients with DM. METHODS: ≥ 6.5%, and/or fasting glucose ≥ 7 mmol/L in two measurements or ≥ 11.1 mmol/L in one measurement. RESULTS: Of 928 male CHB patients with DM, 83 (8.9%) developed HCC at a median (interquartile range) of 10.7 (6.1-14.6) years. Higher testosterone was associated with an elevated risk of HCC (adjusted hazard ratio [aHR] per 1 SD increase 1.23, 95% confidence interval [CI] 1.03-1.46, P = 0.024). The upper tertile of testosterone (aHR 1.86, 95% CI 1.02-3.39, P = 0.043), but not middle tertile (aHR 0.84, 95% CI 0.41-1.69 P = 0.620), was associated with a higher risk of HCC than the lower tertile. The cumulative incidence (95% CI) of HCC at 5, 10, and 15 years was 4.4% (2.5-7.2%), 12.4% (8.7-16.7%), and 19.1% (14.2-24.5%), respectively, in patients in the upper tertile of testosterone. By subgroup analysis, the association between testosterone and HCC was stronger in patients aged ≥ 50 years and those not receiving antiviral therapy. CONCLUSION: Higher serum testosterone is associated with a higher incidence of HCC in male CHB patients with DM.