Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study

J Hepatol. 2017 Nov;67(5):918-924. doi: 10.1016/j.jhep.2017.07.012. Epub 2017 Jul 21.

Abstract

Background & aims: There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients.

Methods: Non-cirrhotic HBeAg-negative patients who had received TDF for ≥4years, with suppressed HBV DNA for ≥3.5years, were randomly assigned to either stop (n=21) or continue (n=21) TDF monotherapy. Standard laboratory tests including HBV DNA viral load, HBsAg and alanine aminotransferase (ALT) measurements, and adverse event reporting were carried out during treatment and post-treatment follow-up for 144weeks.

Results: Of the patients who stopped TDF therapy, 62% (n=13) remained off-therapy to Week 144. Median HBsAg change in this group was -0.59log10IU/ml (range -4.49 to 0.02log10IU/ml) vs. 0.21log10IU/ml in patients who continued TDF therapy. Four patients (19%) achieved HBsAg loss. Patients stopping therapy had initial fluctuations in viral load and ALT; however, at Week 144, 43% (n=9) had either achieved HBsAg loss or had HBV DNA <2,000IU/ml. There were no unexpected safety issues identified with stopping TDF therapy.

Conclusions: This controlled study demonstrated the potential for HBsAg loss and/or sustained virological response in non-cirrhotic HBeAg-negative patients stopping long-term TDF therapy. Lay summary: Nucleos(t)ide analogue (NA) is usually a life-long therapy for HBV patients. This randomised controlled study investigated the discontinuation of tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Of the patients who stopped TDF therapy, 62% remained off-therapy to Week 144, of which 43% of patients had achieved either HBsAg loss or HBV DNA <2,000IU/ml. This offers a potential for long-term HBV-suppressed patients without cirrhosis to stop NA therapy under strict surveillance. Clinical trial number: NCT01320943.

Keywords: Finite therapy; HBeAg-negative; HBsAg loss; Tenofovir disoproxil fumarate.

Publication types

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

MeSH terms

  • Adult
  • Aftercare / methods
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • DNA, Viral / analysis
  • Drug Monitoring / methods
  • Female
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B virus* / drug effects
  • Hepatitis B virus* / genetics
  • Hepatitis B, Chronic* / diagnosis
  • Hepatitis B, Chronic* / drug therapy
  • Hepatitis B, Chronic* / immunology
  • Hepatitis B, Chronic* / virology
  • Humans
  • Male
  • Middle Aged
  • Tenofovir* / administration & dosage
  • Tenofovir* / adverse effects
  • Treatment Outcome
  • Viral Load* / drug effects
  • Viral Load* / methods
  • Withholding Treatment / statistics & numerical data*

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Tenofovir

Associated data

  • ClinicalTrials.gov/NCT01320943