Effect of Host and Viral Factors on Hepatitis B E Antigen-Positive Chronic Hepatitis B Patients Receiving Pegylated Interferon-Alpha-2a Therapy
Resource
ANTIVIRAL THERAPY v.16 n.5 pp.629-637
Journal
ANTIVIRAL THERAPY
Journal Volume
v.16
Journal Issue
n.5
Pages
629-637
Date Issued
2011
Date
2011
Author(s)
TSENG, TAI-CHUNG
YU, MING-LUNG
LIU, CHUN-JEN
LIN, CHIH-LIN
HUANG, YI-WEN
HSU, CHING-SHENG
LIU, CHEN-HUA
YANG, SHENG-SHUN
KAO, JIA-HORNG
CHEN, PEI-JER
CHEN, DING-SHINN
Abstract
Background: Pegylated interferon (PEG-IFN)-alpha-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- alpha-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-alpha-2 a 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 HLA-DPA1, HL4- 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 <2x10(6) 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-alpha-2a. Genetic variants in the HL4- DPA1 region may also affect treatment- induced HBeAg seroconversion.
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