1Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
2Department of Hepatology and Gastroenterology, King's College London, London, United Kingdom.
3Department of Hepatology and Gastroenterology, Imperial College London, London, United Kingdom.
4Clinic of Infectious Diseases, University of Foggia, Foggia, Italy.
5Centre for Liver Research, NIHR Biomedical Research Unit in Liver Disease, University of Birmingham & Queen Elizabeth Hospital, Birmingham, United Kingdom.
6Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.
7Ifi Institute, Asklepios Klinik St. Georg, Hamburg, Germany.
8Department of Hepatology, University Clinic Leipzig, Leipzig, Germany.
9Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
10Department of Hepatology, Hospital Vall de Hebron, Barcelona, Spain.
11Department of Hepatology, Hôpital de la Croix-Rousse Hospices Civils de Lyon, Lyon, France.
12Toronto Centre for Liver Disease, University Health Network, Toronto, Canada.
AbstractBACKGROUND 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.
This article is protected by copyright. All rights reserved.