Effect of host and viral factors on hepatitis B e antigen-positive chronic hepatitis B patients receiving pegylated interferon-α-2a therapy

Tai Chung Tseng, Ming Lung Yu, Chun Jen Liu, Chih Lin Lin, Yi Wen Huang, Ching Sheng Hsu, Chen Hua Liu, Stephanie Fang Tzu Kuo, Corinna Jen Hui Pan, Sheng Shun Yang, Chien Wei Su, Pei Jer Chen, Ding Shinn Chen, Jia Horng Kao

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

Background: Pegylated interferon (PEG-IFN)-α-2a improves the hepatitis B e antigen (HBeAg) seroconversion rate in HBeAg-positive chronic hepatitis B patients. However, baseline factors predicting favourable responses to PEG-IFN-α-2a remain largely unknown. Methods: A total of 115 HBeAg-positive chronic hepatitis B patients who had a pre-therapy serum alanine aminotransferase (ALT) level over two times the upper limit of normal and received PEG-IFN-α-2a for 6-12 months were consecutively enrolled according to the local reimbursed guidelines. HBeAg seroconversion and combined response defined as HBeAg seroconversion, HBV-DNA level <20,000 IU/ml as well as ALT normalization at 6 months off therapy were primary and secondary therapeutic end points, respectively. Baseline viral factors, including viral load, genotype and major sequences of precore stop codon/ basal core promoter (BCP), and host factors, including three single nucleotide polymorphisms among the HLADPA1, HLA-DPB1 and IL28B regions, were determined to correlate with therapeutic end points. Results: HBeAg seroconversion and combined response rates were 26.1% and 18.3%, respectively. By multivariate analysis, BCP mutation (OR 8.04, 95% CI 2.00-32.28) and rs3077 G/G genotype (OR 3.49, 95% CI 1.12-10.84) were associated with a higher HBeAg seroconversion rate; BCP mutation (OR 9.28, 95% CI 1.92-44.99) and baseline viral load <2×106 IU/ml (OR 4.78, 95% CI 1.37-16.69) were associated with a higher combined response rate. Conclusions: BCP mutation is associated with higher HBeAg seroconversion and combined response rates at 6 months off therapy in HBeAg-positive chronic hepatitis B patients treated with PEG-IFN-α-2a. Genetic variants in the HLA-DPA1 region may also affect treatment-induced HBeAg seroconversion.

Original languageEnglish
Pages (from-to)629-637
Number of pages9
JournalAntiviral Therapy
Volume16
Issue number5
DOIs
Publication statusPublished - 2011
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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