Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

Abstract

Purpose There are remarkable advances in the treatment of chronic hepatitis B (CHB) in the last few years. Unfortunately, prolonged antiviral treatment is associated with increasing risk of drug resistance/viral breakthrough (VBT), which may lead to flare-up and rapid decompensation. We have designed this study to predict the pretreatment and on-treatment factors responsible for development of VBT. Methods This study was conducted during the period of February 2000 to November 2007. We have included 423 patients who received lamivudine (LAM) therapy for at least 1 year and at least 2 follow-ups at 6 months' interval. Follow-up period was 12-78 months. Chi-square test, student's t test, and logistic regression analysis were performed to prove the validity. Results Of the 423 study cases, 367 (86.8%) were of male patients and 261 (61.7%) patients were HBeAg positive; the age of the patients was 30.8 ± 12.9 years. Development of VBT was 4. 4, 22.8, 45.3, and 74% at 1, 2, 3, and 4 or more years, respectively. Pretreatment high HBV DNA (P = 0.005) and female sex (P = 0.01) were associated with VBT and pretherapy ALT (P = 0.698), HBeAg status (P = 0.273), and age (P = 0.059) were not associated. Duration of treatment, failure to lose HBeAg at 1 year, and HBV DNA nonresponder at 6 months were significantly (P = 0.001) associated with development of VBT. Conclusion Persistence of HBeAg at 1 year and HBV DNA nonresponder at 6 months are good predictors of development of VBT.

Pretreatment and on-treatment indicators of virologic breakthrough of lamivudine therapy in chronic hepatitis B patients: an Egyptian study

“…However, this pre-treatment status did not significantly affect the development of VBT in the third year of treatment. These results disagree with those of studies conducted by Yuen (2001), Hadziyannis et al (2007), and Alam et al (2008), who found no significant relationship between the pre-treatment HBeAg status and rates of VBT.…”

“…We included in our analysis only those patients with ALT levels twice the normal limit. Our findings agree with those of Alam et al (2008) who also found no significant relationship between pre-treatment ALT levels and development of VBT.…”

“…This finding is similar to Chae et al (2007) and Alam et al (2008), who also reported that ALT levels during treatment were not predictive of VBT, presumably because VBT usually precedes biochemical breakthrough.…”

“…However, there was no significant positive correlation at 2 or 3 years of treatment. Alam et al(2008) reported a similar significant positive correlation between baseline HBV DNA levels and VBT in both HBeAg-positive and HBeAg-negative patients in a study of 423 patients followed up for 78 months (P = 0.005).…”

“…We observed a significant relationship between HBeAg status during treatment and development of VBT in the first and second years of treatment. Alam et al (2008) also observed that sustained HBeAg-positive status within 1 year of lamivudine therapy was highly predictive of future VBT.…”