@article{3125684,
    title = "The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B",
    author = "Papatheodoridis, G.V. and Idilman, R. and Dalekos, G.N. and Buti, M. and Chi, H. and van Boemmel, F. and Calleja, J.L. and Sypsa, V. and Goulis, J. and Manolakopoulos, S. and Loglio, A. and Siakavellas, S. and Keskın, O. and Gatselis, N. and Hansen, B.E. and Lehretz, M. and de la Revilla, J. and Savvidou, S. and Kourikou, A. and Vlachogiannakos, I. and Galanis, K. and Yurdaydin, C. and Berg, T. and Colombo, M. and Esteban, R. and Janssen, H.L.A. and Lampertico, P.",
    journal = "Annals of Hepatology",
    year = "2017",
    volume = "66",
    number = "5",
    pages = "1444-1453",
    publisher = "John Wiley and Sons Inc",
    doi = "10.1002/hep.29320",
    keywords = "alpha fetoprotein;  entecavir;  hepatitis B surface antigen;  tenofovir;  virus DNA;  antivirus agent;  entecavir;  guanine;  tenofovir, adult;  alcohol consumption;  antiviral therapy;  Article;  cancer incidence;  cancer risk;  Caucasian;  chronic hepatitis B;  cohort analysis;  disease severity;  female;  follow up;  human;  liver cell carcinoma;  liver cirrhosis;  liver stiffness;  major clinical study;  male;  priority journal;  transient elastography;  treatment duration;  aged;  analogs and derivatives;  Carcinoma, Hepatocellular;  clinical trial;  complication;  Europe;  Hepatitis B, Chronic;  incidence;  Liver Neoplasms;  middle aged;  multicenter study;  risk factor;  virology, 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",
    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). © 2017 by the American Association for the Study of Liver Diseases."
}