|Title:||Association of Baseline Viral Factors with Response to Lamivudine Therapy in Chronic Hepatitis B Patients with High Serum Alanine Aminotransferase Levels||Authors:||TSENG, TAI-CHUNG
|Issue Date:||2009||Journal Volume:||v.14||Journal Issue:||n.2||Start page/Pages:||203-210||Source:||ANTIVIRAL THERAPY||Abstract:||
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 Hi 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 cordon 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 cordon mutation (G1896A), basal core promoter mutation (A1762T/G 1764A) 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 >5xULN, the PC stop codon mutation could predict a higher HBeAg seroclearance rate at the end of 12-18 months of therapy.
|Appears in Collections:||臨床醫學研究所|
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