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Liver disease progression and virological response: entecavir rescue still possible in the setting of rtM204I lamivudine-resistant mutation
  1. Poh Seng Tan1,2,
  2. Myat Oo Aung1,
  3. Yock Young Dan1,2,
  4. Yin Mei Lee1,2,
  5. Kieron Lim1,2,
  6. How Cheng Low1,2,
  7. Guan Huei Lee1,2,
  8. Maung Aye Thwin1,2,
  9. Charlene Soon1,
  10. Seng Gee Lim1,2
  1. 1Department of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
  2. 2Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  1. Correspondence to Dr Seng Gee Lim, Department of Gastroenterology and Hepatology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore; mdclimsg{at}

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We read with interest the paper by Zoutendijk et al who found that entecavir-induced virological response (VR) reduces the probability of liver disease progression (LDP) in chronic hepatitis B (CHB) patients with cirrhosis. They also found previous lamivudine treatment not to be a significant risk factor,1 but as a large number of lamivudine-experienced CHB patients exist, the impact of different types of lamivudine exposure on entecavir resistance in entecavir-treated real-world patients is not well documented, and can lead to suboptimal VR, virological breakthrough and entecavir resistance. We report here our long-term study, from 2005 to 2011, of 300 real-world entecavir-treated CHB patients, including 90 (30%) nucleos(t)ide-experienced cases. The baseline demographics are shown in table 1. Mean duration of entecavir therapy and follow-up was 30.5 (95% CI 28.6 to 32.4) and 32.7 (95% CI 30.8 to 34.6) months, respectively.

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Table 1

Baseline demographics of the entecavir-treatment cohort (n=300)

The cumulative probability of entecavir-induced VR was 96.5% by year 4. Similar to Zoutendijk's study, baseline liver disease severity did not influence VR rates in our cohort (p=0.72). Using Cox regression correcting for baseline factors, like lamivudine exposure and cirrhosis, only HBeAg-negative status (HR=2.07; 95% CI 1.56 to 2.75; p<0.001) and lower Hepatitis B …

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  • Contributors PST: acquisition of data, analysis and interpretation of data, drafting and finalising the manuscript. MOA: acquisition of data, analysis of data. YYD, YML, KL, HCL, GHL, MAT, CS: acquisition of data. SGL: study concept and design, study supervision, analysis and interpretation of data, critical revision of draft of manuscript, approval of final version of manuscript.

  • Funding The study was funded by a National University Hospital Research Grant, grant number: NBDT05DMED02 Gastro Fund. This funder was our hospital. It provided the funding as well as the facilities for this investigator-initiated study.

  • Competing interests Seng Gee Lim is on the Advisory Board of Novartis, Gilead Sciences, Merck Sharp and Dohme, Janssen, Archillion and Bristol Myers Squibb, and is on the speaker's Bureau for GlaxoSmithKline, Merck Sharpe and Dohme, and Bristol Myers Squibb. None of the other coauthors have any disclosures to declare.

  • Ethics approval This study was approved by the National Healthcare Group Institutional Review Board, and the study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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