Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study

Patrick Marcellin, Edward J Gane, Maria Buti, Nezam H Afdhal, William Sievert, Ira M Jacobson, Mary Kay Washington, George Germanidis, John F Flaherty, Raul Aguilar Schall, Jeffrey D Bornstein, Kathryn M Kitrinos, G Mani Subramanian, John G McHutchison, E Jenny Heathcote

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. METHODS: After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (>/=2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (>/=1 unit decrease by Ishak scoring system). FINDINGS: Of 641 patients who received randomised treatment, 585 (91 ) entered the open-label phase, and 489 (76 ) completed 240 weeks. 348 patients (54 ) had biopsy results at both baseline and week 240. 304 (87 ) of the 348 had histological improvement, and 176 (51 ) had regression of fibrosis at week 240 (p/=1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p
Original languageEnglish
Pages (from-to)468 - 475
Number of pages8
JournalThe Lancet
Volume381
Issue number9865
DOIs
Publication statusPublished - 2013

Cite this

Marcellin, Patrick ; Gane, Edward J ; Buti, Maria ; Afdhal, Nezam H ; Sievert, William ; Jacobson, Ira M ; Washington, Mary Kay ; Germanidis, George ; Flaherty, John F ; Schall, Raul Aguilar ; Bornstein, Jeffrey D ; Kitrinos, Kathryn M ; Subramanian, G Mani ; McHutchison, John G ; Heathcote, E Jenny. / Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. In: The Lancet. 2013 ; Vol. 381, No. 9865. pp. 468 - 475.
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title = "Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study",
abstract = "Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. METHODS: After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (>/=2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (>/=1 unit decrease by Ishak scoring system). FINDINGS: Of 641 patients who received randomised treatment, 585 (91 ) entered the open-label phase, and 489 (76 ) completed 240 weeks. 348 patients (54 ) had biopsy results at both baseline and week 240. 304 (87 ) of the 348 had histological improvement, and 176 (51 ) had regression of fibrosis at week 240 (p/=1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p",
author = "Patrick Marcellin and Gane, {Edward J} and Maria Buti and Afdhal, {Nezam H} and William Sievert and Jacobson, {Ira M} and Washington, {Mary Kay} and George Germanidis and Flaherty, {John F} and Schall, {Raul Aguilar} and Bornstein, {Jeffrey D} and Kitrinos, {Kathryn M} and Subramanian, {G Mani} and McHutchison, {John G} and Heathcote, {E Jenny}",
year = "2013",
doi = "10.1016/S0140-6736(12)61425-1",
language = "English",
volume = "381",
pages = "468 -- 475",
journal = "The Lancet",
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Marcellin, P, Gane, EJ, Buti, M, Afdhal, NH, Sievert, W, Jacobson, IM, Washington, MK, Germanidis, G, Flaherty, JF, Schall, RA, Bornstein, JD, Kitrinos, KM, Subramanian, GM, McHutchison, JG & Heathcote, EJ 2013, 'Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study' The Lancet, vol. 381, no. 9865, pp. 468 - 475. https://doi.org/10.1016/S0140-6736(12)61425-1

Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. / Marcellin, Patrick; Gane, Edward J; Buti, Maria; Afdhal, Nezam H; Sievert, William; Jacobson, Ira M; Washington, Mary Kay; Germanidis, George; Flaherty, John F; Schall, Raul Aguilar; Bornstein, Jeffrey D; Kitrinos, Kathryn M; Subramanian, G Mani; McHutchison, John G; Heathcote, E Jenny.

In: The Lancet, Vol. 381, No. 9865, 2013, p. 468 - 475.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study

AU - Marcellin, Patrick

AU - Gane, Edward J

AU - Buti, Maria

AU - Afdhal, Nezam H

AU - Sievert, William

AU - Jacobson, Ira M

AU - Washington, Mary Kay

AU - Germanidis, George

AU - Flaherty, John F

AU - Schall, Raul Aguilar

AU - Bornstein, Jeffrey D

AU - Kitrinos, Kathryn M

AU - Subramanian, G Mani

AU - McHutchison, John G

AU - Heathcote, E Jenny

PY - 2013

Y1 - 2013

N2 - Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. METHODS: After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (>/=2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (>/=1 unit decrease by Ishak scoring system). FINDINGS: Of 641 patients who received randomised treatment, 585 (91 ) entered the open-label phase, and 489 (76 ) completed 240 weeks. 348 patients (54 ) had biopsy results at both baseline and week 240. 304 (87 ) of the 348 had histological improvement, and 176 (51 ) had regression of fibrosis at week 240 (p/=1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p

AB - Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. METHODS: After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (>/=2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (>/=1 unit decrease by Ishak scoring system). FINDINGS: Of 641 patients who received randomised treatment, 585 (91 ) entered the open-label phase, and 489 (76 ) completed 240 weeks. 348 patients (54 ) had biopsy results at both baseline and week 240. 304 (87 ) of the 348 had histological improvement, and 176 (51 ) had regression of fibrosis at week 240 (p/=1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p

UR - http://www.sciencedirect.com/science/article/pii/S0140673612614251

U2 - 10.1016/S0140-6736(12)61425-1

DO - 10.1016/S0140-6736(12)61425-1

M3 - Article

VL - 381

SP - 468

EP - 475

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9865

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