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

• DOI: 10.1002/hep.29320
• Publication Date: 2017-06-16T16:32:36Z
• Authors: George V. Papathe...; Ramazan Idilman; George N. Dalekos; Maria Buti; Heng Chi; Florian van Boemmel; Jose Luis Calleja; Vana Sypsa; John Goulis; Spilios Manolakop...; Alessandro Loglio; Spyros Siakavellas; Onur Keskın; Nikolaos Gatselis; Bettina E. Hansen; Maria Lehretz; Juan de la Revilla; Savvoula Savvidou; Anastasia Kourikou; Ioannis Vlachogia...; Kostantinos Galanis; Cihan Yurdaydin; Thomas Berg; Massimo Colombo; Rafael Esteban; Harry L.A. Janssen; Pietro Lampertico
• Keywords: Adult; Male; Carcinoma, Hepatocellular; Guanine; Incidence; EMC OR-01; Liver Neoplasms; Middle Aged; adult; aged; antiviral agents; carcinoma, hepatocellular; cohort studies; europe; european continental ancestry group; female; guanine; hepatitis b, chronic; humans; incidence; liver neoplasms; male; middle aged; risk factors; tenofovir; hepatology; Antiviral Agents; White People; 3. Good health; Cohort Studies; Europe; Hepatitis B, Chronic; SDG 3 - Good Health and Well-being; Risk Factors; Humans; Female; Tenofovir; Aged

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 = 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 = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 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. (Hepatology 2017;66:1444–1453).