Treatment outcomes and validation of the stopping rule for response to peginterferon in chronic hepatitis B: A Thai nationwide cohort study

J Gastroenterol Hepatol. 2016 Nov;31(11):1874-1881. doi: 10.1111/jgh.13378.

Abstract

Background and aims: Peginterferon has demonstrated effectiveness in clinical trials in patients with chronic hepatitis B (CHB). However, its efficacy in real-life settings remains unclear. We investigated the efficacy of peginterferon for CHB and validated the performance of previously identified response predictors in clinical practice.

Methods: We analyzed prospectively collected data from a Thai nationwide cohort of CHB patients treated with peginterferon alfa-2a (180 µg/week, 48 weeks).

Results: Among a total of 233 patients, mostly with genotype B or C, sustained response was observed in 23% of 135 hepatitis B e antigen (HBeAg)-positive patients (HBeAg seroconversion with hepatitis B virus [HBV] DNA < 2000 IU/mL) and 42% of 98 HBeAg-negative patients (HBV DNA < 2000 IU/mL with aminotransferase normalization) at 24 weeks after treatment. Age, sex, presence of cirrhosis, genotype, and pretreatment levels of aminotransferase, HBV DNA, and hepatitis B surface antigen (HBsAg) were not identified as significant predictors of sustained response. In HBeAg-positive patients, HBsAg > 20 000 IU/mL at week 12 provided a good stopping rule, with a negative predictive value of 96%. In HBeAg-negative patients, the performance of 12-week stopping rules of no decline in HBsAg with a < 2log10 decline in HBV DNA and a < 10% log10 decline in HBsAg showed modest negative predictive values of 80% and 66%, respectively, for achieving sustained response.

Conclusion: Outcomes in CHB patients treated with peginterferon in a clinical setting are similar to those demonstrated in clinical trials. Application of the early stopping rule based on HBsAg quantification may allow individualization of therapy, particularly in HBeAg-positive patients.

Keywords: antiviral therapy; chronic hepatitis B; peginterferon; quantitative HBsAg; stopping rule.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • Cohort Studies
  • DNA, Viral / blood
  • Drug Administration Schedule
  • Female
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / therapeutic use
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2a