Volume 29, Issue 9 pp. 727-736
ORIGINAL ARTICLE

Mortality and cause of death in persons with chronic hepatitis B virus infection versus healthy persons from the general population in Denmark

Signe Bollerup

Signe Bollerup

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark

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Sofie Hallager

Sofie Hallager

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark

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Frederik Engsig

Frederik Engsig

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark

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Amanda Mocroft

Amanda Mocroft

Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK

Centre of Excellence for Health, Immunity and Infections (CHIP) and PERSIMUNE, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Henrik Krarup

Henrik Krarup

Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark

Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark

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Lone G. Madsen

Lone G. Madsen

Department of Medical Gastroenterology, Zealand University Hospital, Koege, Denmark

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Peter Thielsen

Peter Thielsen

Department of Gastroenterology, Herlev Hospital, Herlev, Denmark

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Ulla Balslev

Ulla Balslev

Department of Infectious Diseases, Herlev Hospital, Herlev, Denmark

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Helene Mens

Helene Mens

Department of Lung- and Infectious diseases, North Zealand Hospital, Hilleroed, Denmark

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Toke S. Barfod

Toke S. Barfod

Department of Internal Medicine and Infectious Diseases, Zealand University Hospital, Roskilde, Denmark

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Mette R. Clausen

Mette R. Clausen

Department of Medical Gastroenterology and Hepatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Lise Hobolth

Lise Hobolth

Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark

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Alex L. Laursen

Alex L. Laursen

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark

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Britta Tarp

Britta Tarp

Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, Denmark

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Birgit T. Roege

Birgit T. Roege

Department of Internal Medicine, Kolding Hospital, Kolding, Denmark

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Jesper B. Hansen

Jesper B. Hansen

Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark

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Lone Mygind

Lone Mygind

Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark

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Peer B. Christensen

Peer B. Christensen

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark

Clinical Institute, University of Southern Denmark, Odense, Denmark

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Jan Gerstoft

Jan Gerstoft

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Nina Weis

Corresponding Author

Nina Weis

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Correspondence

Nina Weis, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Email: [email protected]

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First published: 27 May 2022
Citations: 1

Funding information

This study was funded by Manufacturer Vilhelm Pedersen and Wife's Foundation; Free research funds of University Hospital of Copenhagen, Amager and Hvidovre; Scholarship in memory of Carpenter Jørgen Holm and wife Elisa B. Hansen (20006–1948); Aase and Ejnar Danielsens Foundation and Scandinavian Society for Antimicrobial Chemotherapy Foundation (SLS-935536). Funding sources had no role in the design, interpretation or decision to publish this study.

Abstract

The study aimed to determine adjusted all-cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age- and sex-matched persons from the general population. We used nationwide registers to identify persons aged ≥18 years with chronic HBV infection in 2002–2017 in Denmark and included 10 age- and sex-matched controls for each. Follow-up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause-specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow-up of 7.7 years (range 0.0–15.5), 315 (5%) persons with—and 1525 (2%) without—chronic HBV infection died. The adjusted all-cause MRR was 1.5 (95% CI 1.2–2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6–17.7]), external causes (MRR 3.3 [2.5–4.7]), endocrine disease (MRR 3.2 [1.8–5.4]), genitourinary disease (MRR 3.2 [1.2–7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2–2.0]). In conclusion, this study showed an increased all-cause mortality in persons with chronic HBV infection in comparison with age- and sex-matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma).

CONFLICT OF INTERESTS

Peer Brehm Christensen (PBC) has received grants not related to this study from Abbvie, Gilead and MSD. Nina Weis (NW) has been clinical investigator, lecturer or member of advisory boards for Abbvie, Gilead, GSK and MSD, and has received unrestricted research grants not related to this study from Abbvie, Gilead and Novo Nordisk Foundation. Signe Bollerup (SB) received support for conference participation from Abbvie, Gilead and MSD. Amanda Mocroft (AM) received honoraria, travel support and consultancy fees from ViiV, Gilead and Eiland and Bonnin not related to this study.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from Statistics Denmark. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the author(s) with the permission of Statistics Denmark.

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