Flares during long-term entecavir therapy in chronic hepatitis B

Heng Chi; Pauline Arends; Jurriën G P Reijnders; Ivana Carey; Ashley Brown; Massimo Fasano; David Mutimer; Katja Deterding; Ye H Oo; Jörg Petersen; Florian van Bommel; Robert J de Knegt; Teresa A Santantonio; Thomas Berg; Tania M Welzel; Heiner Wedemeyer; Maria Buti; Pierre Pradat; Fabien Zoulim; Bettina Hansen; Harry L A Janssen; VIRGIL Surveillance Study Group

doi:10.1111/jgh.13377

Flares during long-term entecavir therapy in chronic hepatitis B

Heng Chi, Pauline Arends, Jurriën G P Reijnders, Ivana Carey, Ashley Brown, Massimo Fasano, David Mutimer, Katja Deterding, Ye H Oo, Jörg Petersen, Florian van Bommel, Robert J de Knegt, Teresa A Santantonio, Thomas Berg, Tania M Welzel, Heiner Wedemeyer, Maria Buti, Pierre Pradat, Fabien Zoulim, Bettina HansenHarry L A Janssen, VIRGIL Surveillance Study Group

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

BACKGROUND AND AIM: The incidence and consequences of flares during first-line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of ALT flares during long-term entecavir (ETV) in chronic hepatitis B (CHB).

METHODS: CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as >3x increase in ALT compared with baseline or lowest on-treatment level, and an absolute ALT >3x upper limit of normal. Flares were designated as host-induced (preceded by HBV DNA decline), virus-induced (HBV DNA increase), or indeterminate (stable HBV DNA).

RESULTS: 729 patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline HBeAg-positivity (HR 2.84; p = 0.005) and high HBV DNA (HR 1.30; p = 0.003) predicted flares. There were 12 (40%) host-induced, 7 (23%) virus-induced, and 11 (37%) indeterminate flares. Host-induced flares occurred earlier than virus-induced (median: 15 vs. 83 weeks; p = 0.027) or indeterminate flares (15 vs. 109 weeks; p = 0.011). Host-induced flares were associated with biochemical remission, and HBeAg (n = 3) and HBsAg (n = 2) seroconversions were exclusively observed among patients with these flares. Virus-induced flares were associated with ETV resistance (n = 2) and non-compliance (n = 1).

CONCLUSION: The incidence of ALT flares during ETV was low in this real-life cohort. ETV can be safely continued in patients with host-induced flares. Treatment adherence and drug resistance must be assessed in patients with virus-induced flares. This article is protected by copyright. All rights reserved.

Original language	English
Journal	Journal of Gastroenterology and Hepatology
DOIs	https://doi.org/10.1111/jgh.13377
Publication status	Published - 24 Mar 2016

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10.1111/jgh.13377

Intrahepatic Signals Involve in the Recruitment and Differentiation of IL-17 Secreting T Cells and Regulatory T Cells in Chronic Hepatitis - Fellowship
Oo, Y.
Medical Research Council
4/01/12 → 5/01/18
Project: Research Councils

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Chi, H., Arends, P., Reijnders, J. G. P., Carey, I., Brown, A., Fasano, M., Mutimer, D., Deterding, K., Oo, Y. H., Petersen, J., van Bommel, F., de Knegt, R. J., Santantonio, T. A., Berg, T., Welzel, T. M., Wedemeyer, H., Buti, M., Pradat, P., Zoulim, F., ... VIRGIL Surveillance Study Group (2016). Flares during long-term entecavir therapy in chronic hepatitis B. Journal of Gastroenterology and Hepatology. https://doi.org/10.1111/jgh.13377

@article{484082954342496bb98ae46540ccd76d,

title = "Flares during long-term entecavir therapy in chronic hepatitis B",

abstract = "BACKGROUND AND AIM: The incidence and consequences of flares during first-line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of ALT flares during long-term entecavir (ETV) in chronic hepatitis B (CHB).METHODS: CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as >3x increase in ALT compared with baseline or lowest on-treatment level, and an absolute ALT >3x upper limit of normal. Flares were designated as host-induced (preceded by HBV DNA decline), virus-induced (HBV DNA increase), or indeterminate (stable HBV DNA).RESULTS: 729 patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline HBeAg-positivity (HR 2.84; p = 0.005) and high HBV DNA (HR 1.30; p = 0.003) predicted flares. There were 12 (40%) host-induced, 7 (23%) virus-induced, and 11 (37%) indeterminate flares. Host-induced flares occurred earlier than virus-induced (median: 15 vs. 83 weeks; p = 0.027) or indeterminate flares (15 vs. 109 weeks; p = 0.011). Host-induced flares were associated with biochemical remission, and HBeAg (n = 3) and HBsAg (n = 2) seroconversions were exclusively observed among patients with these flares. Virus-induced flares were associated with ETV resistance (n = 2) and non-compliance (n = 1).CONCLUSION: The incidence of ALT flares during ETV was low in this real-life cohort. ETV can be safely continued in patients with host-induced flares. Treatment adherence and drug resistance must be assessed in patients with virus-induced flares. This article is protected by copyright. All rights reserved.",

author = "Heng Chi and Pauline Arends and Reijnders, {Jurri{\"e}n G P} and Ivana Carey and Ashley Brown and Massimo Fasano and David Mutimer and Katja Deterding and Oo, {Ye H} and J{\"o}rg Petersen and {van Bommel}, Florian and {de Knegt}, {Robert J} and Santantonio, {Teresa A} and Thomas Berg and Welzel, {Tania M} and Heiner Wedemeyer and Maria Buti and Pierre Pradat and Fabien Zoulim and Bettina Hansen and Janssen, {Harry L A} and {VIRGIL Surveillance Study Group}",

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month = mar,

day = "24",

doi = "10.1111/jgh.13377",

language = "English",

journal = "Journal of Gastroenterology and Hepatology",

issn = "0815-9319",

publisher = "Wiley",

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Chi, H, Arends, P, Reijnders, JGP, Carey, I, Brown, A, Fasano, M, Mutimer, D, Deterding, K, Oo, YH, Petersen, J, van Bommel, F, de Knegt, RJ, Santantonio, TA, Berg, T, Welzel, TM, Wedemeyer, H, Buti, M, Pradat, P, Zoulim, F, Hansen, B, Janssen, HLA & VIRGIL Surveillance Study Group 2016, 'Flares during long-term entecavir therapy in chronic hepatitis B', Journal of Gastroenterology and Hepatology. https://doi.org/10.1111/jgh.13377

TY - JOUR

T1 - Flares during long-term entecavir therapy in chronic hepatitis B

AU - Chi, Heng

AU - Arends, Pauline

AU - Reijnders, Jurriën G P

AU - Carey, Ivana

AU - Brown, Ashley

AU - Fasano, Massimo

AU - Mutimer, David

AU - Deterding, Katja

AU - Oo, Ye H

AU - Petersen, Jörg

AU - van Bommel, Florian

AU - de Knegt, Robert J

AU - Santantonio, Teresa A

AU - Berg, Thomas

AU - Welzel, Tania M

AU - Wedemeyer, Heiner

AU - Buti, Maria

AU - Pradat, Pierre

AU - Zoulim, Fabien

AU - Hansen, Bettina

AU - Janssen, Harry L A

AU - VIRGIL Surveillance Study Group

PY - 2016/3/24

Y1 - 2016/3/24

N2 - BACKGROUND AND AIM: The incidence and consequences of flares during first-line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of ALT flares during long-term entecavir (ETV) in chronic hepatitis B (CHB).METHODS: CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as >3x increase in ALT compared with baseline or lowest on-treatment level, and an absolute ALT >3x upper limit of normal. Flares were designated as host-induced (preceded by HBV DNA decline), virus-induced (HBV DNA increase), or indeterminate (stable HBV DNA).RESULTS: 729 patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline HBeAg-positivity (HR 2.84; p = 0.005) and high HBV DNA (HR 1.30; p = 0.003) predicted flares. There were 12 (40%) host-induced, 7 (23%) virus-induced, and 11 (37%) indeterminate flares. Host-induced flares occurred earlier than virus-induced (median: 15 vs. 83 weeks; p = 0.027) or indeterminate flares (15 vs. 109 weeks; p = 0.011). Host-induced flares were associated with biochemical remission, and HBeAg (n = 3) and HBsAg (n = 2) seroconversions were exclusively observed among patients with these flares. Virus-induced flares were associated with ETV resistance (n = 2) and non-compliance (n = 1).CONCLUSION: The incidence of ALT flares during ETV was low in this real-life cohort. ETV can be safely continued in patients with host-induced flares. Treatment adherence and drug resistance must be assessed in patients with virus-induced flares. This article is protected by copyright. All rights reserved.

AB - BACKGROUND AND AIM: The incidence and consequences of flares during first-line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of ALT flares during long-term entecavir (ETV) in chronic hepatitis B (CHB).METHODS: CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as >3x increase in ALT compared with baseline or lowest on-treatment level, and an absolute ALT >3x upper limit of normal. Flares were designated as host-induced (preceded by HBV DNA decline), virus-induced (HBV DNA increase), or indeterminate (stable HBV DNA).RESULTS: 729 patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline HBeAg-positivity (HR 2.84; p = 0.005) and high HBV DNA (HR 1.30; p = 0.003) predicted flares. There were 12 (40%) host-induced, 7 (23%) virus-induced, and 11 (37%) indeterminate flares. Host-induced flares occurred earlier than virus-induced (median: 15 vs. 83 weeks; p = 0.027) or indeterminate flares (15 vs. 109 weeks; p = 0.011). Host-induced flares were associated with biochemical remission, and HBeAg (n = 3) and HBsAg (n = 2) seroconversions were exclusively observed among patients with these flares. Virus-induced flares were associated with ETV resistance (n = 2) and non-compliance (n = 1).CONCLUSION: The incidence of ALT flares during ETV was low in this real-life cohort. ETV can be safely continued in patients with host-induced flares. Treatment adherence and drug resistance must be assessed in patients with virus-induced flares. This article is protected by copyright. All rights reserved.

U2 - 10.1111/jgh.13377

DO - 10.1111/jgh.13377

M3 - Article

C2 - 27008918

SN - 0815-9319

JO - Journal of Gastroenterology and Hepatology

JF - Journal of Gastroenterology and Hepatology

ER -

Flares during long-term entecavir therapy in chronic hepatitis B

Abstract

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Intrahepatic Signals Involve in the Recruitment and Differentiation of IL-17 Secreting T Cells and Regulatory T Cells in Chronic Hepatitis - Fellowship

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