A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B

Ting Tsung Chang, Robert G. Gish, Robert De Man, Adrian Gadano, José Sollano, You Chen Chao, Anna S. Lok, Kwang Hyub Han, Zachary Goodman, Jin Zhu, Anne Cross, Deborah DeHertogh, Richard Wilber, Richard Colonno, David Apelian

Research output: Contribution to journalArticle

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Abstract

Background: Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV). Methods: In this phase 3, double-blind trial, we randomly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necro-inflammatory score, without worsening of fibrosis) at week 48. Secondary end points included a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferase level. Results: Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group (72 percent) and 195 of 314 patients in the lamivudine group (62 percent, P=0.009). More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67 percent vs. 36 percent, P<0.001) and normalization of alanine aminotransferase levels (68 percent vs. 60 percent, P=0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P<0.001). HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine (P=0.33). No viral resistance to entecavir was detected. Safety was similar in the two groups. Conclusions: Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lami vudine. The safety profile of the two agents is similar, and there is no evidence of viral resistance to entecavir.

Original languageEnglish
Pages (from-to)1001-1010
Number of pages10
JournalNew England Journal of Medicine
Volume354
Issue number10
DOIs
Publication statusPublished - 2006 Mar 9

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Lamivudine
Hepatitis B e Antigens
Chronic Hepatitis B
Hepatitis B virus
Alanine Transaminase
DNA
Serum
Safety
entecavir
Guanosine
Nucleosides
Fibrosis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Chang, T. T., Gish, R. G., De Man, R., Gadano, A., Sollano, J., Chao, Y. C., ... Apelian, D. (2006). A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. New England Journal of Medicine, 354(10), 1001-1010. https://doi.org/10.1056/NEJMoa051285
Chang, Ting Tsung ; Gish, Robert G. ; De Man, Robert ; Gadano, Adrian ; Sollano, José ; Chao, You Chen ; Lok, Anna S. ; Han, Kwang Hyub ; Goodman, Zachary ; Zhu, Jin ; Cross, Anne ; DeHertogh, Deborah ; Wilber, Richard ; Colonno, Richard ; Apelian, David. / A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. In: New England Journal of Medicine. 2006 ; Vol. 354, No. 10. pp. 1001-1010.
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abstract = "Background: Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV). Methods: In this phase 3, double-blind trial, we randomly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necro-inflammatory score, without worsening of fibrosis) at week 48. Secondary end points included a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferase level. Results: Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group (72 percent) and 195 of 314 patients in the lamivudine group (62 percent, P=0.009). More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67 percent vs. 36 percent, P<0.001) and normalization of alanine aminotransferase levels (68 percent vs. 60 percent, P=0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P<0.001). HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine (P=0.33). No viral resistance to entecavir was detected. Safety was similar in the two groups. Conclusions: Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lami vudine. The safety profile of the two agents is similar, and there is no evidence of viral resistance to entecavir.",
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Chang, TT, Gish, RG, De Man, R, Gadano, A, Sollano, J, Chao, YC, Lok, AS, Han, KH, Goodman, Z, Zhu, J, Cross, A, DeHertogh, D, Wilber, R, Colonno, R & Apelian, D 2006, 'A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B', New England Journal of Medicine, vol. 354, no. 10, pp. 1001-1010. https://doi.org/10.1056/NEJMoa051285

A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. / Chang, Ting Tsung; Gish, Robert G.; De Man, Robert; Gadano, Adrian; Sollano, José; Chao, You Chen; Lok, Anna S.; Han, Kwang Hyub; Goodman, Zachary; Zhu, Jin; Cross, Anne; DeHertogh, Deborah; Wilber, Richard; Colonno, Richard; Apelian, David.

In: New England Journal of Medicine, Vol. 354, No. 10, 09.03.2006, p. 1001-1010.

Research output: Contribution to journalArticle

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T1 - A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B

AU - Chang, Ting Tsung

AU - Gish, Robert G.

AU - De Man, Robert

AU - Gadano, Adrian

AU - Sollano, José

AU - Chao, You Chen

AU - Lok, Anna S.

AU - Han, Kwang Hyub

AU - Goodman, Zachary

AU - Zhu, Jin

AU - Cross, Anne

AU - DeHertogh, Deborah

AU - Wilber, Richard

AU - Colonno, Richard

AU - Apelian, David

PY - 2006/3/9

Y1 - 2006/3/9

N2 - Background: Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV). Methods: In this phase 3, double-blind trial, we randomly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necro-inflammatory score, without worsening of fibrosis) at week 48. Secondary end points included a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferase level. Results: Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group (72 percent) and 195 of 314 patients in the lamivudine group (62 percent, P=0.009). More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67 percent vs. 36 percent, P<0.001) and normalization of alanine aminotransferase levels (68 percent vs. 60 percent, P=0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P<0.001). HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine (P=0.33). No viral resistance to entecavir was detected. Safety was similar in the two groups. Conclusions: Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lami vudine. The safety profile of the two agents is similar, and there is no evidence of viral resistance to entecavir.

AB - Background: Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV). Methods: In this phase 3, double-blind trial, we randomly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necro-inflammatory score, without worsening of fibrosis) at week 48. Secondary end points included a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferase level. Results: Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group (72 percent) and 195 of 314 patients in the lamivudine group (62 percent, P=0.009). More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67 percent vs. 36 percent, P<0.001) and normalization of alanine aminotransferase levels (68 percent vs. 60 percent, P=0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P<0.001). HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine (P=0.33). No viral resistance to entecavir was detected. Safety was similar in the two groups. Conclusions: Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lami vudine. The safety profile of the two agents is similar, and there is no evidence of viral resistance to entecavir.

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Chang TT, Gish RG, De Man R, Gadano A, Sollano J, Chao YC et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. New England Journal of Medicine. 2006 Mar 9;354(10):1001-1010. https://doi.org/10.1056/NEJMoa051285