Comparison of entecavir monotherapy and de novo lamivudine and adefovir combination therapy in HBeAg-positive chronic hepatitis B with high viral load: 48-week result
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This study compared virologic response to entecavir monotherapy and de novo lamivudine plus adefovir (LAM + ADV) combination therapy in patients with chronic hepatitis B (CHB) with high viral load (HVL). Hepatitis B e antigen (HBeAg)-positive patients [hepatitis B virus (HBV) DNA levels >1 × 107 copies/ml] were assigned to LAM + ADV or entecavir treatment. The primary efficacy endpoint measure of the multicenter prospective cohort study was proportion of patients with CHB with virologic response, defined as HBV DNA <300 copies/ml at week 48. During treatment, 39.1 % (18/46) of patients in the LAM + ADV group and 48.1 % (25/52) of those in the entecavir group achieved virologic response in week 48 (P = 0.37). A baseline alanine aminotransferase (ALT) level ≥5 × ULN (upper limit of normal) or baseline serum HBV DNA level <8 log10 IU/ml could predict virologic response at week 48 (P = 0.025). The mean reduction in HBV DNA was comparable (P = 0.45); no significant difference was found in the proportion of ALT normalization (P = 0.46) or HBeAg seroconversion (P = 0.88). Two cases of genotypic resistance were found (rtM204 V + rtL180 M and rtA181T/V) in the LAM + ADV group, with a resistance rate of 4.3 %; there was no genotypic resistance in the entecavir group (P = 0.13). De novo LAM + ADV combination therapy is as effective as entecavir monotherapy in HBeAg-positive patients with CHB with HVL. Moreover, genotypic resistance was only found in the LAM + ADV group at week 48. Baseline ALT levels ≥5 ULN or baseline serum HBV DNA levels <8 log10 IU/ml were favorable predictors of virologic response in CHB with HVL.
KeywordsChronic hepatitis B High viral load Nucleos(t)ide analogs Virologic response
Chronic hepatitis B
Hepatitis B e antibody
Hepatitis B e antigen
Hepatitis B surface antibody
Hepatitis B surface antigen
Hepatitis B virus
High baseline viral load
Polymerase chain reaction
Upper limit of normal
This study was supported by Grants from Bristol-Myers Squibb and the Chinese Foundation for Hepatitis Prevention and Control (GHF 2011206).
Compliance with Ethical Standards
The Institutional Review Board of Nanfang Hospital, Southern Medical University, had approved the study (ID: ZHF2011206). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for inclusion in the study.
Conflict of interest
Shaohang Cai, Tao Yu, Yegui Jiang, Yonghong Zhang, Fangfang Lv, and Jie Peng declare that they have no financial or personal relationships with other people or organizations that could inappropriately influence this work.
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