1 Viral Hepatitis Research Unit, Hôpital Beaujon, Clichy, France.
2 Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada.
3 Gastroenterology and Hepatology Unit, Monash Health and Monash University, Melbourne, Australia.
4 Liver Unit, IFI-Institute for Interdisciplinary Medicine, Asklepios Klinik St Georg, Hamburg, Germany.
5 Department of Infectious Diseases and Hepatology, Medical University Bialystok, Bialystok, Poland.
6 Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
7 Helmholtz Center for Infection Research (HZI), Braunschweig, Hannover, Germany.
8 Viral Hepatitis Investigative Unit, University of Manitoba, Winnipeg, Canada.
9 Clinic of Gastroenterology, St Ivan Rilsky University Hospital, Medical University, Sofia, Bulgaria.
10 Liver Unit, University of Calgary, Calgary, Alberta, Canada.
11 Gilead Sciences Inc., Foster City, USA.
12 Gilead Sciences Europe Ltd., Uxbridge, UK.
13 Liver Unit, Hospital Universitario Vall d'Hebron and CIBEREHD del Instituto Carlos III, Barcelona, Spain.
BACKGROUND & AIMS:
Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B (CHB). We aimed to describe the efficacy and safety profiles of TDF treatment for up to 10 years in a well-described cohort of CHB patients.
Hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients from two randomised, double-blind trials (ClinicalTrials. gov: NCT00117676 and NCT00116805) completed 48 weeks of randomised treatment with TDF or adefovir dipivoxil. A subset of these patients was then eligible to receive open-label TDF treatment for up to 10 years. At Year 10, patients were assessed for virological suppression, alanine aminotransferase (ALT) normalisation, serological response, safety, and tolerability.
Of 641 randomised and treated patients, 585 (91%) entered the open-label extension phase with 203 (32%) patients completing Year 10 of the study. At Year 10, 118/118 (100%) of HBeAg-negative patients and 78/80 (98%) of HBeAg-positive patients with available data achieved hepatitis B virus (HBV) DNA <69 IU/mL, while 88/106 (83%) and 60/77 (78%) patients achieved ALT normalisation, respectively. Of the 23 patients with HBeAg status available at Year 10, 12 (52%) and six (27%) experienced HBeAg loss and seroconversion, respectively. No resistance to TDF was documented up to Year 10. In the period between Year 8 and Year 10, the safety profile of TDF was similar to previous reports, with few patients experiencing renal- or bone-related adverse events.
Over 10 years, TDF had a favourable safety profile, was well tolerated, and resulted in continued maintenance of virological suppression with no documented resistance.