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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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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.

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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

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Acknowledgments

This study was supported by Grants from Bristol-Myers Squibb and the Chinese Foundation for Hepatitis Prevention and Control (GHF 2011206).

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Authors and Affiliations

  1. Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China

    Shaohang Cai, Tao Yu & Jie Peng

  2. First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China

    Shaohang Cai

  3. Southwest Hospital, Third Military Medical University, Chongqing, China

    Yegui Jiang

  4. Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China

    Yonghong Zhang

  5. Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China

    Fangfang Lv

Authors
  1. Shaohang Cai
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  2. Tao Yu
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Corresponding author

Correspondence to Jie Peng.

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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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Cai, S., Yu, T., Jiang, Y. et al. 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. Clin Exp Med 16, 429–436 (2016). https://doi.org/10.1007/s10238-015-0373-2

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  • DOI: https://doi.org/10.1007/s10238-015-0373-2

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