title: Hepatitis delta-associated mortality in HIV/HBV-coinfected patients.
abstract: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes.
  
  
  
  All HIV-infected patients with a positive hepatitis B surface antigen test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC).
  
  
  
  Of 818 patients with a positive hepatitis B surface antigen tests, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% CI: 12.9-18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (60.6% vs. 9.1%) and to have a positive hepatitis C virus (HCV) serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41-3.84), liver-related death (7.71, 3.13-18.97) and with the occurrence of HCC (9.30, 3.03-28.61). Results were similar when persons who inject drugs or HCV-coinfected patients were excluded from the analyses.
  
  
  
  The prevalence of HDV in hepatitis B surface antigen-positive patients in the Swiss HIV Cohort Study (SHCS) is high and HDV infection is independently associated with mortality and liver-related events, including HCC.
  
  
  
  Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, eight times more likely to die from a liver-related cause and nine times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection.
authors.affiliation: Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Charles
authors.initials: C
authors.lastname: Béguelin
authors.affiliation: Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
authors.affiliation: Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Sahli
authors.affiliation: Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Suter-Riniker
authors.affiliation: Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lüthi
authors.affiliation: Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland; Institute of Medical Virology, University of Zurich, Switzerland.
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.affiliation: Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.affiliation: Division of Infectious Diseases, Regional Hospital Lugano, Switzerland.
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St.Gallen, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schmid
authors.affiliation: Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland; Institute of Medical Virology, University of Zurich, Switzerland.
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Braun
authors.affiliation: Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.affiliation: Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.affiliation: Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Switzerland. Electronic address: gilles.wandeler@ispm.unibe.ch.
authors.forename: Gilles
authors.initials: G
authors.lastname: Wandeler
mesh_terms: D000328:Adult; D060085:Coinfection / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000453:epidemiology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D003699:Hepatitis D / Q000401:mortality / Q000821:virology; D003698:Hepatitis Delta Virus / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016016:Proportional Hazards Models; D013557:Switzerland / Q000453:epidemiology
chemical_list: D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens
keywords: Clinical; Coinfection; Hepatitis delta virus; Human immunodeficiency virus; Mortality; Outcome; Prevalence