Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir

<jats:title>Summary</jats:title><jats:p>This study aimed to elucidate the temporal change and determinants for the risk of HCC in patients with chronic hepatitis B continuously receiving NUC. Through analysis of the national healthcare database in Taiwan, we screened a total of 65 426 infected patients receiving entecavir or tenofovir for at least 3 months and excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end‐stage renal failure or a diagnosis of HCC within 3 months of starting treatment. Eligible patients (N = 27 820) were followed until HCC occurrence, completion of the allowed 3‐year regimen or 31 December 2013. During a median follow‐up of 25.1 (12.1‐35.6) months, 802 patients developed HCC, with 1‐, 2‐ and 3‐year cumulative incidence of 1.82% (95% CI, 1.66‐1.99%), 3.05% (95% CI, 2.82‐3.28%) and 4.06% (95% CI, 3.77‐4.36%), respectively. HCC annual incidence decreased with an adjusted IRR of 0.73 (95% CI, 0.66‐0.80) per yearly interval and was associated with cirrhosis (IRR, 10.07; 95% CI, 6.00‐16.90 in age <40 years; 4.69; 95% CI, 3.94‐5.59 in age ≧40 years), age (IRR, 3.38; 95% CI, 2.10‐5.47 for 40‐50 years; 6.92; 95% CI, 4.27‐11.21 for 50‐60 years; 12.50; 95% CI, 7.71‐20.25 for ≧60 years; <40 years as reference), male sex (IRR, 1.71; 95% CI, 1.44‐2.04), HCV coinfection (IRR, 1.27; 95% CI, 1.02‐1.58) and diabetes (IRR, 1.24; 95% CI, 1.05‐1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B receiving entecavir or tenofovir declines over time and is determined by cirrhosis, age, male sex, HCV coinfection and diabetes.</jats:p>