Association of baseline viral factors with response to lamivudine therapy in chronic hepatitis B patients with high serum alanine aminotransferase levels
Journal
Antiviral Therapy
Journal Volume
14
Journal Issue
2
Pages
203-210
Date Issued
2009
Author(s)
Abstract
Background: With the exception of alanine aminotransferase (ALT) level, baseline factors predictive of therapeutic response to lamivudine in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remain unknown. We thus studied the influence of pre-therapy viral factors on end-of-treatment responses to lamivudine. Methods: A total of 116 treatment-naive HBeAg-positive CHB patients who had pre-therapy ALT level >5x the upper limit of normal (ULN) and received lamivudine for 12-18 months were enrolled. HBeAg seroclearance and combined HBeAg seroclearance, ALT normalization and undetectable hepatitis B virus DNA at the end of therapy were defined as primary and secondary endpoints, respectively. Pre-therapy viral factors including viral load, genotype, precore (PC) stop codon status, basal core promoter status and pre-S deletion were determined to correlate with therapeutic endpoints. Results: The frequency of patients with detectable PC stop codon mutation (G1896A), basal core promoter mutation (A1762T/G1764A) and pre-S deletion at baseline was 22.4%, 21.6% and 12.1%, respectively. After the end of 12-18 months of lamivudine therapy, the overall HBeAg seroclearance rate was 56.0%. Patients with HBeAg seroclearance had a higher prevalence of baseline PC stop codon mutation than those without (30.8% versus 11.8%; P=0.015). By using multivariate analyses, the odds ratio of patients with the PC stop codon mutation to develop HBeAg seroclearance was 3.33 (P=0.024). The presence of the PC stop codon mutation also correlated with the combined response. Conclusions: For lamivudine-treated HBeAg-positive CHB patients with pre-therapy ALT levels >5×ULN, the PC stop codon mutation could predict a higher HBeAg seroclearance rate at the end of 12-18 months of therapy. ? 2009 International Medical Press.
SDGs
Other Subjects
adenosine; alanine aminotransferase; guanosine; hepatitis B(e) antigen; lamivudine; thymine; virus DNA; alanine aminotransferase; hepatitis B(e) antigen; lamivudine; RNA directed DNA polymerase inhibitor; virus DNA; adult; alanine aminotransferase blood level; article; clinical trial; cohort analysis; disease association; drug efficacy; drug response; female; follow up; gene deletion; gene frequency; gene mutation; genotype; hepatitis B; Hepatitis B virus; human; major clinical study; male; nonhuman; prediction; prevalence; priority journal; promoter region; stop codon; virus detection; virus load; adolescent; aged; antiviral resistance; blood; genetics; immunology; middle aged; prediction and forecasting; virology; Adolescent; Adult; Aged; Alanine Transaminase; Codon, Nonsense; DNA, Viral; Drug Resistance, Viral; Female; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Male; Middle Aged; Predictive Value of Tests; Reverse Transcriptase Inhibitors; Viral Load
Publisher
International Medical Press Ltd
Type
journal article