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Journal Article Ahead of print 4 citations

PubMed: 42409322 DOI: 10.1016/j.jhep.2026.06.038

Declining but persistent hepatocellular cancer risk beyond 10 years of entecavir or tenofovir in chronic hepatitis B: Results of the PAGE-B cohort.

J Hepatol

Authors: George V Papatheodoridis, George Dalekos, Ramazan Idilman, Vana Sypsa, Maria Buti, Jose Luis Calleja, Spilios Manolakopoulos, Edo Dongelmans, Marta Borghi, Margarita Papatheodoridi, Nikolaos Gatselis, Zeynep Melekoğlu Ellik, Marta López-Gomez, Spyros Siakavellas, Sofia Paraskevopoulou, Kostas Galanis, Özge Koç, Rafael Esteban, Harry L A Janssen, Pietro Lampertico

Affiliations

  • 1(st) Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
  • Department of Medicine & Research Laboratory of Internal Medicine, General University Hospital of Larissa, European Reference Network on Hepatological Diseases, Larissa, Greece.
  • Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey.
  • Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece.
  • Hospital General Universitario Valle Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain.
  • Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain.
  • 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Hippokratio", Athens, Greece.
  • Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
  • Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  • 1(st) Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
  • Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Abstract

BACKGROUND AND AIMS

Long-term outcomes data of chronic hepatitis B (CHB) patients treated with high-genetic barrier nucleos(t)ide analogues (NA) beyond year-10 are scarce. We assessed the incidence and predictors of such long-term outcomes.

METHODS

The long-term PAGE-B cohort included 1644 Caucasians with CHB treated with entecavir/tenofovir. Cumulative incidence was estimated using Kaplan-Meier or cumulative incidence function accounting for competing events. Incidence rates (IR) per 100 person-years (/100 PYs) were estimated.

RESULTS

Of 1644 patients, 903 were followed beyond year-10 (mean:14±2 years). The 10- and 15-year cumulative incidence of hepatocellular carcinoma (HCC) was 10.9% and 13.2%, respectively, and the HCC IR was 1.25 before and 0.55/100 PYs after year-10 (P<0.001), with similar findings after inverse probability weighting. The IR of death or liver transplantation (LT) was relatively lower before than after year-10 (1.50 vs 1.95/100 PYs, P=0.069) and similar for liver-related death/LT in the two periods (0.74 vs 0.70/100 PYs, P=0.840). HCC development and baseline platelets were independently associated with LT-free liver-related or overall survival, which was also associated with older age and diabetes. The 10- and 15-year cumulative incidence of HBsAg loss on NA(s) was 8.3% and 14.3%, respectively; the IR of HBsAg loss was 0.94 before year-10 increasing to 1.42/100 PYs after year-10 (P=0.025). HBsAg loss was independently associated with older age and baseline HBeAg-positive. NA therapy was discontinued in 125 (7.6%) patients remaining HBsAg-positive.

CONCLUSIONS

Despite >10 years of NA therapy, CHB patients remain at risk for HCC, but the incidence rate declines significantly. HCC remains the main determinant of mortality. HBsAg loss rate increases after year-10, but it remains low being higher in older, initially HBeAg-positive patients.

MeSH

Liver Diseases, Tenofovir, Carcinoma, Hepatocellular, Incidence, Neoplasms, Hepatitis, Chronic, Liver, Therapeutics, Hepatitis B, Hepatitis B, Chronic, Hepatitis