Electronic Health Informatics Data To Describe Clearance Dynamics of Hepatitis B Surface Antigen (HBsAg) and e Antigen (HBeAg) in Chronic Hepatitis B Virus Infection

被引:17
作者
Downs, Louise O. [1 ,2 ]
Smith, David A. [2 ,3 ]
Lumley, Sheila F. [1 ,2 ]
Patel, Meha [1 ]
McNaughton, Anna L. [2 ]
Mokaya, Jolynne [2 ]
Ansari, M. Azim [2 ]
Salih, Hizni [4 ]
Varnai, Kinga A. [3 ]
Freeman, Oliver [4 ]
Cripps, Sarah [5 ]
Phillips, Jane [6 ]
Collier, Jane [6 ]
Woods, Kerrie [3 ]
Channon, Keith [3 ]
Davies, Jim [4 ]
Barnes, Eleanor [2 ,3 ,6 ]
Jeffery, Katie [1 ]
Matthews, Philippa C. [1 ,2 ,3 ]
机构
[1] Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Infect Dis & Microbiol, Oxford, England
[2] Univ Oxford, Nuffield Dept Med, Medawar Bldg Pathogen Res, Oxford, England
[3] Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Natl Inst Hlth Res Hlth Informat Collaborat, NIHR Oxford Biomed Res Ctr, Oxford, England
[4] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford NIHR Biomed Res Ctr,Clin Informat Grp, Oxford, England
[5] Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Pharm Dept, Oxford, England
[6] Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Hepatol, Oxford, England
来源
MBIO | 2019年 / 10卷 / 03期
基金
英国医学研究理事会; 英国惠康基金;
关键词
biomarker; health informatics; hepatitis B virus; surface antigen; viral clearance; NATURAL-HISTORY; SERUM-LEVELS; SEROCLEARANCE; CARRIERS; THERAPY; REACTIVATION; PREDICTOR; RISK; HBV; DNA;
D O I
10.1128/mBio.00699-19
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
HBsAg and HBeAg have gained traction as biomarkers of control and clearance during chronic hepatitis B virus infection (CHB). Improved understanding of the clearance correlates of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR HIC), adopting an unbiased approach to the generation of a robust longitudinal data set for adults testing HBsAg positive from a large UK teaching hospital over a 6-year period (2011 to 2016 inclusive). Of 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. Among these 13, the HBsAg clearance rate in individuals on nucleos(t) ide analogue (NA) therapy (n = 4 [31%]; median clearance time, 150 weeks) was similar to that in individuals not on NA therapy (n = 9 [69%]; median clearance time, 157 weeks). Those who cleared HBsAg were significantly older and less likely to be on NA therapy than nonclearers (P = 0.003 and P = 0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (P = 0.025). HBeAg clearance occurred in individuals both on NA therapy (n = 24; median time, 49 weeks) and off NA therapy (n = 19; median time, 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematized approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and support improvements in clinical care. IMPORTANCE Advances in the diagnosis, monitoring, and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical data sets that can help to inform advances in patient care and provide insights that may help to inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been underrepresented in the literature. By tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualized clinical care and may provide important clues into the immune events that underpin disease control.
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页数:15
相关论文
共 42 条
  • [1] [Anonymous], 2016, GGPLOT2 ELEGANT GRAP
  • [2] Hepatitis B Surface Antigen Serum Levels Help to Distinguish Active From Inactive Hepatitis B Virus Genotype D Carriers
    Brunetto, Maurizia Rossana
    Oliveri, Filippo
    Colombatto, Piero
    Moriconi, Francesco
    Ciccorossi, Pietro
    Coco, Barbara
    Romagnoli, Veronica
    Cherubini, Beatrice
    Moscato, Giovanna
    Maina, Anna Maria
    Cavallone, Daniela
    Bonino, Ferruccio
    [J]. GASTROENTEROLOGY, 2010, 139 (02) : 483 - 490
  • [3] Chen Chien-Jen, 2007, Clin Liver Dis, V11, P797, DOI 10.1016/j.cld.2007.08.005
  • [4] THE NATURAL-HISTORY OF ASYMPTOMATIC HEPATITIS-B SURFACE-ANTIGEN CARRIERS
    DEFRANCHIS, R
    MEUCCI, G
    VECCHI, M
    TATARELLA, M
    COLOMBO, M
    DELNINNO, E
    RUMI, MG
    DONATO, MF
    RONCHI, G
    [J]. ANNALS OF INTERNAL MEDICINE, 1993, 118 (03) : 191 - 194
  • [5] Downs L, 2018, EASL INT LIV C 2018
  • [6] EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection
    Lampertico P.
    Agarwal K.
    Berg T.
    Buti M.
    Janssen H.L.A.
    Papatheodoridis G.
    Zoulim F.
    Tacke F.
    [J]. JOURNAL OF HEPATOLOGY, 2017, 67 (02) : 370 - 398
  • [7] Sustainable development goals for people and planet
    Griggs, David
    Stafford-Smith, Mark
    Gaffney, Owen
    Rockstroem, Johan
    Oehman, Marcus C.
    Shyamsundar, Priya
    Steffen, Will
    Glaser, Gisbert
    Kanie, Norichika
    Noble, Ian
    [J]. NATURE, 2013, 495 (7441) : 305 - 307
  • [8] Loss of hepatitis B surface antigen in a real-life clinical cohort of patients with chronic hepatitis B virus infection
    Habersetzer, Francois
    Moenne-Loccoz, Remy
    Meyer, Nicolas
    Schvoerer, Evelyne
    Simo-Noumbissie, Pauline
    Dritsas, Stavros
    Baumert, Thomas F.
    Doffoel, Michel
    [J]. LIVER INTERNATIONAL, 2015, 35 (01) : 130 - 139
  • [9] Long-term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide-naive chronic hepatitis B patients
    Hara, T.
    Suzuki, F.
    Kawamura, Y.
    Sezaki, H.
    Hosaka, T.
    Akuta, N.
    Kobayashi, M.
    Suzuki, Y.
    Saitoh, S.
    Arase, Y.
    Ikeda, K.
    Kobayashi, M.
    Watahiki, S.
    Mineta, R.
    Kumada, H.
    [J]. JOURNAL OF VIRAL HEPATITIS, 2014, 21 (11) : 802 - 808
  • [10] Huo T, 2000, EUR J GASTROEN HEPAT, V12, P6