The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B

Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long-term therapy with potent nucleos(t) ide analogues is currently unclear. We therefore assessed the HCC incidence beyond year 5 of entecavir/ tenofovir (ETV/ TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10-center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV/ TDF for 1 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5-10 (median, 6.8) years. HCCs have been diagnosed in 101/ 1,951 (5.2%) patients within the first 5 years and 17/ 1,205 (1.4%) patients within 5-10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P 5 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P 5 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P 5 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV/ TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness 12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender-Hepatitis B score at baseline or year 5 developed HCC. Conclusion: The HCC risk decreases beyond year 5 of ETV/ TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially 50 years), lower platelets, and liver stiffness 12 kPa at year 5 represent the main risk factors for late HCC development.