Effect of host and viral factors on hepatitis B e antigen-positive chronic hepatitis B patients receiving pegylated interferon-α-2a therapy
Journal
Antiviral Therapy
Journal Volume
16
Journal Issue
5
Pages
629-637
Date Issued
2011
Author(s)
Yu M.-L.
Lin C.-L.
Huang Y.-W.
Hsu C.-S.
Kuo S.F.-T.
Pan C.J.-H.
Yang S.-S.
Su C.-W.
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. ?2011 International Medical Press.
SDGs
Other Subjects
alanine aminotransferase; hepatitis B(e) antigen; HLA DP antigen; HLA DPB1 antigen; peginterferon alpha2a; virus DNA; adult; alanine aminotransferase blood level; antiviral therapy; article; basal core promoter; controlled study; drug efficacy; female; gene mutation; gene sequence; genetic correlation; genetic variability; hepatitis B; Hepatitis B virus; human; major clinical study; male; nonhuman; outcome assessment; priority journal; prognosis; promoter region; seroconversion; single nucleotide polymorphism; stop codon; treatment duration; virus load; virus typing
Publisher
International Medical Press Ltd
Type
journal article