Heng Chi1, Pauline Arends1, Jurriën G P Reijnders1, Ivana Carey2, Ashley Brown3, Massimo Fasano4, David Mutimer5, Katja Deterding6, Ye H Oo5, Jörg Petersen7, Florian van Bommel8, Robert J de Knegt1, Teresa A Santantonio4, Thomas Berg8, Tania M Welzel9, Heiner Wedemeyer6, Maria Buti10, Pierre Pradat11, Fabien Zoulim11, Bettina E Hansen1, Harry L A Janssen1,12. 1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 2. Department of Hepatology and Gastroenterology, King's College London, London, UK. 3. Department of Hepatology and Gastroenterology, Imperial College London, London, UK. 4. Clinic of Infectious Diseases, University of Foggia, Foggia, Italy. 5. Centre for Liver Research, NIHR Biomedical Research Unit in Liver Disease, University of Birmingham and Queen Elizabeth Hospital, Birmingham, UK. 6. Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany. 7. Ifi Institute, Asklepios Klinik St. Georg, Hamburg, Germany. 8. Department of Hepatology, University Clinic Leipzig, Leipzig, Germany. 9. Medizinische Klinik 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. 10. Department of Hepatology, Hospital Vall de Hebron, Barcelona, Spain. 11. Department of Hepatology, Hospices Civils de Lyon, Lyon, France. 12. Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
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 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.
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.
Authors: Hee Yeon Seo; Han Ah Lee; Soon Young Ko; Joon Ho Wang; Jeong Han Kim; Won Hyeok Choe; So Young Kwon Journal: Clin Mol Hepatol Date: 2017-05-08