Association of baseline viral factors with response to lamivudine therapy in chronic hepatitis B patients with high serum alanine aminotransferase levels.
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 >5xULN, the PC stop codon mutation could predict a higher HBeAg seroclearance rate at the end of 12-18 months of therapy.
Tseng
Tai-Chung
TC
Division of Hepatogastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, Taipei, Taiwan.
Liu
Chun-Jen
CJ
Wang
Chia-Chi
CC
Chen
Pei-Jer
PJ
Lai
Ming-Yang
MY
Chen
Ding-Shinn
DS
Kao
Jia-Horng
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D018389:Codon, Nonsense; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019562:Viral Load
D018389:Codon, Nonsense; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase