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Flares during long‐term entecavir therapy in chronic hepatitis B
Author(s) -
Chi Heng,
Arends Pauline,
Reijnders Jurriën G P,
Carey Ivana,
Brown Ashley,
Fasano Massimo,
Mutimer David,
Deterding Katja,
Oo Ye H,
Petersen Jörg,
Bommel Florian,
Knegt Robert J,
Santantonio Teresa A,
Berg Thomas,
Welzel Tania M,
Wedemeyer Heiner,
Buti Maria,
Pradat Pierre,
Zoulim Fabien,
Hansen Bettina E,
Janssen Harry L A
Publication year - 2016
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13377
Subject(s) - medicine , entecavir , hepatitis b virus , hbeag , gastroenterology , incidence (geometry) , hazard ratio , cumulative incidence , hepatitis b , cohort , virus , immunology , virology , hbsag , confidence interval , physics , lamivudine , optics
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 alanine aminotransferase (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 > 3× increase in ALT compared with baseline or lowest on‐treatment level and an absolute ALT > 3× ULN. Flares were designated as host‐induced (preceded by hepatitis B virus (HBV)‐DNA decline), virus‐induced (HBV‐DNA increase), or indeterminate (stable HBV‐DNA). Results Seven hundred and twenty‐nine 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 hepatitis B e antigen (HBeAg)‐positivity (HR 2.84; P = 0.005) and high HBV‐DNA (Hazard ratio (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 hepatitis B surface antigen ( 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.