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Clinical and Experimental Medicine

, Volume 16, Issue 3, pp 429–436 | Cite as

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

  • Shaohang Cai
  • Tao Yu
  • Yegui Jiang
  • Yonghong Zhang
  • Fangfang Lv
  • Jie Peng
Original Article

Abstract

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.

Keywords

Chronic hepatitis B High viral load Nucleos(t)ide analogs Virologic response 

Abbreviations

ADV

Adefovir dipivoxil

ALT

Alanine aminotransferase

CHB

Chronic hepatitis B

ETV

Entecavir

HBeAb

Hepatitis B e antibody

HBeAg

Hepatitis B e antigen

HBsAb

Hepatitis B surface antibody

HBsAg

Hepatitis B surface antigen

HBV

Hepatitis B virus

HVL

High baseline viral load

LAM

Lamivudine

NUC

Nucleos(t)ide analog

PCR

Polymerase chain reaction

ULN

Upper limit of normal

YMDD

Tyrosine-methionine-aspartate-aspartate

Notes

Acknowledgments

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

Ethical approval

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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Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Shaohang Cai
    • 1
    • 2
  • Tao Yu
    • 1
  • Yegui Jiang
    • 3
  • Yonghong Zhang
    • 4
  • Fangfang Lv
    • 5
  • Jie Peng
    • 1
  1. 1.Department of Infectious Diseases and Hepatology Unit, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.First Affiliated Hospital of Xiamen UniversityXiamenChina
  3. 3.Southwest HospitalThird Military Medical UniversityChongqingChina
  4. 4.Second Xiangya HospitalCentral South UniversityChangshaChina
  5. 5.Sir Run Run Shaw HospitalZhejiang UniversityHangzhouChina

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