Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Autor:	Wang T; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Nuffield Department of Medicine, University of Oxford, Oxford, UK., Campbell C; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Nuffield Department of Medicine, University of Oxford, Oxford, UK., Stockdale AJ; Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.; Tropical Infectious Diseases Unit, Royal Liverpool Hospital, Liverpool University Hospitals NHS Trust, Liverpool, UK., Todd S; Tropical Infectious Diseases Unit, Royal Liverpool Hospital, Liverpool University Hospitals NHS Trust, Liverpool, UK., McIntyre K; Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Trust, Liverpool, UK., Frankland A; Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Trust, Liverpool, UK., Jaworski J; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Glampson B; iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK.; Department of Surgery and Cancer, Imperial College London, London, UK., Papadimitriou D; iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK.; Department of Surgery and Cancer, Imperial College London, London, UK., Mercuri L; iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK.; Department of Surgery and Cancer, Imperial College London, London, UK., Mayer E; iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK.; Department of Surgery and Cancer, Imperial College London, London, UK., Jones CR; Department of Surgery and Cancer, Imperial College London, London, UK.; Department of Infectious Disease, Imperial College London, London, UK., Salih H; NIHR Oxford Biomedical Research Centre, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Roadknight G; NIHR Oxford Biomedical Research Centre, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Little S; NIHR Oxford Biomedical Research Centre, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Noble T; NIHR Oxford Biomedical Research Centre, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Várnai KA; NIHR Oxford Biomedical Research Centre, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Davis C; Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK., Heinson AI; Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK., George M; Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK., Borca F; Southampton Emerging Therapies and Technologies Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.; Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK., English L; NIHR University College London Hospitals Biomedical Research Centre, London, UK., Romão L; NIHR University College London Hospitals Biomedical Research Centre, London, UK., Ramlakhan D; NIHR University College London Hospitals Biomedical Research Centre, London, UK., Woods K; NIHR Oxford Biomedical Research Centre, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Davies J; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Department of Computer Science, University of Oxford, Oxford, UK., Nastouli E; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.; Department of Virology, UCLH, London, UK., Khakoo SI; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK., Gelson W; Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Cooke GS; iCARE Secure Data Environment, Digital Collaboration Space, Imperial College Healthcare NHS Trust, London, UK.; Department of Surgery and Cancer, Imperial College London, London, UK.; Faculty of Medicine, Department of Infectious Disease, Imperial College London, UK., Barnes E; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Nuffield Department of Medicine, University of Oxford, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Matthews PC; Nuffield Department of Medicine, University of Oxford, Oxford, UK.; NIHR Health Informatics Collaborative, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; The Francis Crick Institute, London, UK.; Division of Infection and Immunity, University College London, London, UK.; Department of Infectious Diseases, University College London Hospital, London, UK.
Jazyk:	angličtina
Zdroj:	JHEP reports : innovation in hepatology [JHEP Rep] 2024 Oct 09; Vol. 7 (1), pp. 101229. Date of Electronic Publication: 2024 Oct 09 (Print Publication: 2025).
DOI:	10.1016/j.jhepr.2024.101229
Abstrakt:	Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes. Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase, and with liver fibrosis/cirrhosis. Results: We retrieved data from 1,885 adults on NA treatment (median follow-up 6.2 years, IQR 3.7-9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5-17). Five VL classes were identified from the derivation cohort (n = 1,367, discrimination: 0.93, entropy: 0.90): class 1 'long term suppression' (n = 827, 60.5%), class 2 'timely virological suppression' (n = 254, 18.6%), class 3 'persistent moderate viraemia' (n = 140, 10.2%), class 4 'persistent high-level viraemia' (n = 44, 3.2%), and class 5 'slow virological suppression' (n = 102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n = 518). Alanine transaminase decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all p <0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had twofold increased hazards of fibrosis/cirrhosis compared with class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33-3.02). Conclusions: Heterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression. Impact and Implications: Treatment recommendations for people living with chronic hepatitis B virus (HBV) infection are becoming less stringent, meaning that more of the population will be eligible to receive therapy with nucleos(t)ide analogue agents. We explored outcomes of HBV treatment in a large UK dataset, describing different responses to treatment, and showing that the viral load is not completely suppressed after 1 year in about one in five cases, associated with an increased risk of liver complications. As treatment is rolled out more widely, patients and clinicians need to be aware of the potential for incomplete virologic responses. The findings can support the identification of high-risk individuals, improve early fibrosis and cirrhosis prediction, guide monitoring and preventive interventions, and support public health elimination goals. Competing Interests: GC reports personal fees from Gilead and Merck Sharp & Dohme, outside the submitted work. ST reports she has previously received Gilead Investigator-led grant for a viral hepatitis project. WG reports personal fees from GSK outside the submitted work. EB has consulted for, and received research grants from Roche and GSK. EB and PCM have academic collaborative partnerships with GSK. Other authors have no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details. (© 2024 The Author(s).)
Databáze:	MEDLINE
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