Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B

J Infect Dis. 2021 Dec 1;224(11):1890-1899. doi: 10.1093/infdis/jiab241.

Abstract

Background: Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood.

Methods: This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.

Results: The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]).

Conclusion: HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.

Keywords: REAL-B; entecavir; functional cure; hepatitis B surface antigens; hepatitis B virus; tenofovir.

Publication types

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

MeSH terms

  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Bilirubin / blood
  • China / epidemiology
  • Cohort Studies
  • DNA, Viral
  • Fatty Liver
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Tenofovir / therapeutic use*
  • Treatment Outcome
  • Viremia

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • entecavir
  • Guanine
  • Tenofovir
  • Alanine Transaminase
  • Bilirubin