Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection

Liver Int. 2019 Oct;39(10):1868-1875. doi: 10.1111/liv.14155. Epub 2019 Jul 10.

Abstract

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.

Methods: 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.

Results: 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.

Conclusions: Over 10 years, TDF had a favourable safety profile, was well tolerated, and resulted in continued maintenance of virological suppression with no documented resistance.

Keywords: TDF; hepatitis B; long-term.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Biomarkers / blood
  • DNA, Viral / blood
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Female
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Internationality
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage*
  • Organophosphonates / adverse effects
  • Tenofovir / administration & dosage*
  • Tenofovir / adverse effects
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphonates
  • Tenofovir
  • Adenine
  • adefovir dipivoxil

Associated data

  • ClinicalTrials.gov/NCT00117676
  • ClinicalTrials.gov/NCT00116805