Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B

Ting Tsung Chang, Yun Fan Liaw, Shun Sheng Wu, Eugene Schiff, Kwang Hyub Han, Ching Lung Lai, Rifaat Safadi, Samuel S. Lee, Waldemar Halota, Zachary Goodman, Yun Chan Chi, Hui Zhang, Robert Hindes, Uchenna Iloeje, Suzanne Beebe, Bruce Kreter

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Abstract

One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores ≥2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a ≥1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. Conclusion: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.

Original languageEnglish (US)
Pages (from-to)886-893
Number of pages8
JournalHepatology
Volume52
Issue number3
DOIs
StatePublished - Sep 1 2010

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Chronic Hepatitis B
Fibrosis
Hepatitis B e Antigens
Biopsy
Therapeutics
Nucleosides
Liver
entecavir
Lamivudine
Alanine Transaminase
Hepatitis B virus
Histology
DNA

ASJC Scopus subject areas

  • Hepatology

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Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. / Chang, Ting Tsung; Liaw, Yun Fan; Wu, Shun Sheng; Schiff, Eugene; Han, Kwang Hyub; Lai, Ching Lung; Safadi, Rifaat; Lee, Samuel S.; Halota, Waldemar; Goodman, Zachary; Chi, Yun Chan; Zhang, Hui; Hindes, Robert; Iloeje, Uchenna; Beebe, Suzanne; Kreter, Bruce.

In: Hepatology, Vol. 52, No. 3, 01.09.2010, p. 886-893.

Research output: Contribution to journalArticle

Chang, TT, Liaw, YF, Wu, SS, Schiff, E, Han, KH, Lai, CL, Safadi, R, Lee, SS, Halota, W, Goodman, Z, Chi, YC, Zhang, H, Hindes, R, Iloeje, U, Beebe, S & Kreter, B 2010, 'Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B', Hepatology, vol. 52, no. 3, pp. 886-893. https://doi.org/10.1002/hep.23785
Chang, Ting Tsung ; Liaw, Yun Fan ; Wu, Shun Sheng ; Schiff, Eugene ; Han, Kwang Hyub ; Lai, Ching Lung ; Safadi, Rifaat ; Lee, Samuel S. ; Halota, Waldemar ; Goodman, Zachary ; Chi, Yun Chan ; Zhang, Hui ; Hindes, Robert ; Iloeje, Uchenna ; Beebe, Suzanne ; Kreter, Bruce. / Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. In: Hepatology. 2010 ; Vol. 52, No. 3. pp. 886-893.
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abstract = "One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores ≥2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86{\%} had a normalized alanine aminotransferase level. Histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96{\%} of patients, and a ≥1-point improvement in the Ishak fibrosis score was found in 88{\%} of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. Conclusion: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.",
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T1 - Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B

AU - Chang, Ting Tsung

AU - Liaw, Yun Fan

AU - Wu, Shun Sheng

AU - Schiff, Eugene

AU - Han, Kwang Hyub

AU - Lai, Ching Lung

AU - Safadi, Rifaat

AU - Lee, Samuel S.

AU - Halota, Waldemar

AU - Goodman, Zachary

AU - Chi, Yun Chan

AU - Zhang, Hui

AU - Hindes, Robert

AU - Iloeje, Uchenna

AU - Beebe, Suzanne

AU - Kreter, Bruce

PY - 2010/9/1

Y1 - 2010/9/1

N2 - One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores ≥2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a ≥1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. Conclusion: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.

AB - One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores ≥2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a ≥1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline. Conclusion: The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.

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DO - 10.1002/hep.23785

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