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

George V. Papatheodoridis, Ramazan Idilman, George N. Dalekos, Maria Buti, Heng Chi, Florian van Boemmel, Jose Luis Calleja, Vana Sypsa, John Goulis, Spilios Manolakopoulos, Alessandro Loglio, Spyros Siakavellas, Onur Keskın, Nikolaos Gatselis, Bettina E. Hansen, Maria Lehretz, Juan de la Revilla, Savvoula Savvidou, Anastasia Kourikou, Ioannis VlachogiannakosKostantinos Galanis, Cihan Yurdaydin, Thomas Berg, Massimo Colombo, Rafael Esteban, Harry L.A. Janssen, Pietro Lampertico

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish
Pages (from-to)1444-1453
Number of pages10
JournalHepatology
Volume66
Issue number5
DOIs
Publication statusPublished - Nov 1 2017

ASJC Scopus subject areas

  • Hepatology

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