Off-Treatment Hepatitis B Virus (HBV) DNA Levels and the Prediction of Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy in Patients With Chronic Hepatitis B: A Prospective Stop Study

J Infect Dis. 2017 Feb 15;215(4):581-589. doi: 10.1093/infdis/jix025.

Abstract

Background: The optimal management remains unknown after nucleos(t)ide analogue (NA) discontinuation in patients with chronic hepatitis B (CHB). This prospective study investigated the role of off-treatment viral kinetics in predicting relapse after discontinuation of NA therapy.

Methods: A total of 82 noncirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed. Patients with a hepatitis B virus (HBV) DNA level of >2000 IU/mL and an alanine aminotransferase (ALT) level of >2 times the upper limit of normal (clinical relapse) were retreated.

Results: Sixty patients were HBV envelope antigen (HBeAg) positive at the start of treatment, and 22 were HBeAg negative. Clinical relapse developed in 28 patients (2-year rates, 31% among HBeAg-positive patients and 53% among HBeAg-negative patients). Age of ≤35 years (hazard ratio [HR], 0.37; P = .026) and end-of-treatment HBsAg level of ≤200 IU/mL (HR, 0.39; P = .078) were independently associated with lower relapse rates. A high risk of biochemical relapse (defined as an ALT level of >2 times the upper limit of normal) was observed if the HBV DNA level was >200000 IU/mL when the level was initially elevated, compared with HBV DNA levels of >2000 to ≤200000 IU/mL (HR, 8.42; P < .001). The risk of biochemical relapse was also high in patients with persistent elevation in the HBV DNA level (confirmed to be >2000 IU/mL within 3 months), compared with the group with transient elevation (HR, 6.87; P < .001).

Conclusions: After NA discontinuation, a lower relapse rate was observed in younger patients and in those with low end-of-treatment HBsAg levels. The level and persistence of off-treatment elevated HBV DNA levels were useful in the prediction of a subsequent biochemical relapse and may thus be used to guide off-treatment management.

Keywords: Treatment cessation; antiviral agents; hepatitis B; off-treatment management.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / pharmacology*
  • Asian People
  • DNA, Viral / isolation & purification*
  • Endpoint Determination
  • Female
  • Follow-Up Studies
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / isolation & purification*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Limit of Detection
  • Liver / pathology
  • Male
  • Middle Aged
  • Nucleosides / pharmacology*
  • Nucleotides / pharmacology*
  • Prospective Studies
  • Recurrence
  • Risk Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Nucleosides
  • Nucleotides
  • Alanine Transaminase