Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B

Hepatology. 2009 Apr;49(4):1141-50. doi: 10.1002/hep.22760.

Abstract

We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivudine alone. Serum HBsAg was quantified using the Architect assay (Abbott Diagnostics) at pretreatment, end of treatment (week 48), and 6 months after the end of treatment (week 72) in sera from 386 of the 537 patients who participated in the multinational study (peginterferon alfa-2a, 127; peginterferon alfa-2a plus lamivudine, 137; lamivudine monotherapy, 122). Pretreatment HBsAg levels varied according to genotype, with the highest levels present in patients infected with genotypes A (median, 4.11 log(10) IU/mL) and D (median, 3.85 log(10) IU/mL). Significant on-treatment decline in HBsAg was observed during treatment with peginterferon alfa-2a (alone or combined with lamivudine; mean decline at week 48, -0.71 and -0.67 log(10) IU/mL, respectively, P < 0.001), but not during treatment with lamivudine alone (-0.02 log(10) IU/mL). Significantly more patients treated with peginterferon alfa-2a (21%) or peginterferon alfa-2a plus lamivudine (17%) achieved HBsAg levels <100 IU/mL at the end of treatment compared with lamivudine (1%) (both P < 0.001 versus lamivudine). End-of-treatment HBsAg level correlated strongly with HBV DNA suppression to <or=400 copies/mL 6 months posttreatment. An HBsAg level <10 IU/mL at week 48 and on-treatment decline >1 log(10) IU/mL were significantly associated with sustained HBsAg clearance 3 years after treatment (both P < 0.0001).

Conclusion: On-treatment quantification of HBsAg in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a may help identify those likely to be cured by this therapy and optimize treatment strategies.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Drug Therapy, Combination
  • Female
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins
  • Retrospective Studies
  • Treatment Outcome

Substances

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