Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B

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Journal of Hepatology

Volume 54, Issue 2, February 2011, Pages 236-242

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doi:10.1016/j.jhep.2010.06.043 European Association for the

Study of the Liver Published by Elsevier Ireland Ltd. Cited By in Scopus (0)

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Research Article

Entecavir treatment in patients with severe acute exacerbation of chronic

hepatitis B

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Wai-Sun Wonga, b, Grace Lai-Hung Wonga, b, Kar-Lum Yiua, b, Angel

Mei-Ling Chima, b, Shirley Ho-Ting Chua, b, Hoi-Yun Chana, b, ph Jao-Yiu

Sunga, b and Henry Lik-Yuen Chan, a, b,

a Department of Medicine and Therapeutics, The Chinese University of Hong Kong,

Hong Kong

b Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong

Received 29 April 2010; revised 28 June 2010; accepted 29 June 2010.

Available online 7 September 2010.

Background & Aims

Severe acute exacerbation of chronic hepatitis B is a unique clinical

presentation with significant morbidity and mortality. Lamivudine was used in

most previous studies, but the drug was limited by the development of

resistance. Our objective is to study the safety and efficacy of entecavir in

patients with severe acute exacerbation.

Methods

Consecutive patients with severe acute exacerbation of chronic hepatitis B were

recruited from 1998 to 2009. All patients had serum alanine aminotransferase and

bilirubin increased beyond 10 and 3 times the upper limit of normal,

respectively. The primary endpoint was overall mortality at week 48. Virological

and biochemical responses were also studied.

Results

Thirty-six patients and 117 patients were treated with entecavir and lamivudine,

respectively. By week 48, 7 (19%) patients in the entecavir group and 5 (4%)

patients in the lamivudine group died (adjusted hazard ratio 5.1, 95% confidence

interval 1.5–17.2, p = 0.010). Similarly, the entecavir group had higher

liver-related mortality (adjusted hazard ratio 4.0, 95% confidence interval

1.0–15.7, p = 0.044). Despite a lower prevalence of cirrhosis, more patients in

the entecavir group developed prolonged jaundice, hepatic encephalopathy, and

ascites. Entecavir resulted in more rapid and complete viral suppression, with

71% of patients achieving undetectable hepatitis B virus (HBV) DNA at week 48,

compared to 40% in the lamivudine group (p = 0.007). However, rapid HBV DNA

reduction at week 4 was associated with prolonged jaundice.

Conclusions

Entecavir treatment is associated with increased short-term mortality in

patients with severe acute exacerbation of chronic hepatitis B but achieves

better virological response in the long run.