Hepatitis delta infection among persons living with HIV in Europe

for EuroSIDA and SHCS

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Abstract

Background and Aims: A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons living with HIV (PLWH) in Europe. We analysed data from a large HIV cohort collaboration to characterize HDV epidemiological trends across Europe, as well as its impact on clinical outcomes. Methods: All PLWH with a positive hepatitis B surface antigen (HBsAg) in the Swiss HIV Cohort Study and EuroSIDA between 1988 and 2019 were tested for anti-HDV antibodies and, if positive, for HDV RNA. Demographic and clinical characteristics at initiation of antiretroviral therapy were compared between HDV-positive and HDV-negative individuals using descriptive statistics. The associations between HDV infection and overall mortality, liver-related mortality as well as hepatocellular carcinoma (HCC) were assessed using cumulative incidence plots and cause-specific multivariable Cox regression. Results: Of 2793 HBsAg-positive participants, 1556 (56%) had stored serum available and were included. The prevalence of HDV coinfection was 15.2% (237/1556, 95% confidence interval [CI]: 13.5%–17.1%) and 66% (132/200) of HDV-positive individuals had active HDV replication. Among persons who inject drugs (PWID), the prevalence of HDV coinfection was 50.5% (182/360, 95% CI: 45.3%–55.7%), with similar estimates across Europe, compared to 4.7% (52/1109, 95% CI: 3.5%–5.9%) among other participants. During a median follow-up of 10.8 years (interquartile range 5.6–17.8), 82 (34.6%) HDV-positive and 265 (20.1%) HDV-negative individuals died. 41.5% (34/82) of deaths were liver-related in HDV-positive individuals compared to 17.7% (47/265) in HDV-negative individuals. HDV infection was associated with overall mortality (adjusted hazard ratio 1.6; 95% CI 1.2–2.1), liver-related death (2.9, 1.6–5.0) and HCC (6.3, 2.5–16.0). Conclusion: We found a very high prevalence of hepatitis delta among PWID across Europe. Among PLWH who do not inject drugs, the prevalence was similar to that reported from populations without HIV. HDV coinfection was associated with liver-related mortality and HCC incidence.

Original languageEnglish
Pages (from-to)819-828
Number of pages10
JournalLiver International
Volume43
Issue number4
DOIs
Publication statusE-pub ahead of print - 10 Jan 2023

Bibliographical note

Funding Information:
We thank all participants, physicians and nurses associated with the SHCS and EuroSIDA. Open access funding provided by Inselspital Universitatsspital Bern. The SHCS: The members of the SHCS are Abela I., Aebi-Popp K., Anagnostopoulos A., Battegay M., Bernasconi E., Braun D. L., Bucher H. C., Calmy A., Cavassini M., Ciuffi A., Dollenmaier G., Egger M., Elzi L., Fehr J., Fellay J., Furrer H., Fux C. A., Günthard HF (President of the SHCS), Hachfeld A., Haerry D (deputy of ‘Positive Council’), Hasse B., Hirsch H. H., Hoffmann M., Hösli I., Huber M., Kahlert CR (Chairman of the Mother & Child Substudy), Kaiser L., Keiser O., Klimkait T., Kouyos R. D., Kovari H., Kusejko K (Head of Data Centre), Martinetti G., Martinez de Tejada B., Marzolini C., Metzner K. J., Müller N., Nemeth J., Nicca D., Paioni P., Pantaleo G., Perreau M., Rauch A. (Chairman of the Scientific Board), Schmid P., Speck R., Stöckle M. (Chairman of the Clinical and Laboratory Committee), Tarr P., Trkola A., Wandeler G., Yerly S. The EuroSIDA study group: The multi-centre study group, EuroSIDA (national coordinators in parenthesis). Albania: (A. Harxhi), University Hospital Center of Tirana, Tirana. Argentina: (M. Losso), M. Kundro, Hospital JM Ramos Mejia, Buenos Aires. Austria: (B. Schmied), Klinik Penzing, Vienna; R. Zangerle, Medical University Innsbruck, Innsbruck. Belarus: (I. Karpov), A. Vassilenko, Belarusian State Medical University, Minsk; V. M. Mitsura, Gomel State Medical University, Gomel; D. Paduto, Regional AIDS Centre, Svetlogorsk. Belgium: (N. Clumeck), S. De Wit, M. Delforge, Saint-Pierre Hospital, Brussels; E Florence, Institute of Tropical Medicine, Antwerp; L. Vandekerckhove, University Ziekenhuis Gent, Gent. Bosnia-Herzegovina: (V. Hadziosmanovic), Klinicki Centar Univerziteta Sarajevo, Sarajevo. Croatia: (J. Begovac), University Hospital of Infectious Diseases, Zagreb. Czech Republic: (L. Machala), D. Jilich, Faculty Hospital Bulovka, Prague; D. Sedlacek, Charles University Hospital, Plzen. Denmark: G. Kronborg, T. Benfield, Hvidovre Hospital, Copenhagen; J. Gerstoft, O. Kirk, Rigshospitalet, Copenhagen; C. Pedersen, I. S. Johansen, Odense University Hospital, Odense; L. Ostergaard, Skejby Hospital, Aarhus, L. Wiese, Sjællands Universitetshospital, Roskilde; L. N. Nielsen, Hillerod Hospital, Hillerod. Estonia: (K. Zilmer), West-Tallinn Central Hospital, Tallinn; Jelena Smidt, Nakkusosakond Siseklinik, Kohtla-Järve. Finland: (I. Aho), Helsinki University Hospital, Helsinki. France: (J.-P. Viard), Hôtel-Dieu, Paris; K. Lacombe, Hospital Saint-Antoine, Paris; C. Pradier, E. Fontas, Hôpital de l'Archet, Nice; C. Duvivier, Hôpital Necker-Enfants Malades, Paris. Germany: (J. Rockstroh), Universitäts Klinik Bonn; O. Degen, University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg; C. Hoffmann, H. J. Stellbrink, IPM Study Center, Hamburg; C. Stefan, JW Goethe University Hospital, Frankfurt; J. Bogner, Medizinische Poliklinik, Munich; G. Fätkenheuer, Universität Köln, Cologne. Georgia: (N. Chkhartishvili) Infectious Diseases, AIDS & Clinical Immunology Research Center, Tbilisi.Greece: (H. Sambatakou), Ippokration General Hospital, Athens; G. Adamis, N. Paissios, Athens General Hospital ‘G Gennimatas’, Athens. Hungary: (J. Szlávik), South-Pest Hospital Centre – National Institute for Infectology and Haematology, Budapest. Iceland: (M. Gottfredsson), Landspitali University Hospital, Reykjavik. Ireland: (E. Devitt), St. James's Hospital, Dublin. Israel: (L. Tau), D. Turner, M. Burke, Ichilov Hospital, Tel Aviv; E. Shahar, L. M. Wattad, Rambam Health Care Campus, Haifa; H. Elinav, M. Haouzi, Hadassah University Hospital, Jerusalem; D. Elbirt, AIDS Center (Neve Or), Rehovot. Italy: (A. D'Arminio Monforte), Istituto Di Clinica Malattie Infettive e Tropicale, Milan; G. Guaraldi, R. Esposito, I. Mazeu, C. Mussini, Università Modena, Modena; F. Mazzotta, A. Gabbuti, Ospedale S Maria Annunziata, Firenze; A. Lazzarin, A. Castagna, N. Gianotti, Ospedale San Raffaele, Milan; M. Galli, A. Ridolfo, Osp. L. Sacco, Milan. Lithuania: (V. Uzdaviniene) Vilnius University Hospital Santaros Klinikos, Vilnius; R. Matulionyte, Vilnius University, Faculty of Medicine, Department of Infectious Diseases and Dermatovenerology, Vilnius. Luxembourg: (T. Staub), R. Hemmer, Centre Hospitalier, Luxembourg. Netherlands: (Marc van der Valk), Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam. North Macedonia (J. Trajanovska), University Clinic for Infectious Diseases & Febrile Conditions, Mother Teresa 17, Skopje. Norway: (D. H. Reikvam), A. Maeland, J. Bruun, Oslo University Hospital, Ullevaal. Poland: (B. Knysz), B. Szetela, M. Inglot, Medical University, Wroclaw; E. Bakowska, Centrum Diagnostyki i Terapii AIDS, Warsaw; R. Flisiak, A. Grzeszczuk, Medical University, Bialystok; M. Parczewski, K. Maciejewska, B. Aksak-Was, Medical Univesity, Szczecin; M. Beniowski, E. Mularska, Osrodek Diagnostyki i Terapii AIDS, Chorzow; E. Jablonowska, J. Kamerys, K. Wojcik, Wojewodzki Szpital Specjalistyczny, Lodz; I. Mozer-Lisewska, B. Rozplochowski, Poznan University of Medical Sciences, Poznan. Portugal: (A. Zagalo), Hospital Santa Maria, Lisbon; K. Mansinho, Hospital de Egas Moniz, Lisbon; F. Maltez, Hospital Curry Cabral, Lisbon. Romania: (R. Radoi), C. Oprea, Carol Davila University of Medicine and Pharmacy Bucharest, Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest. Russia: D. Gusev, Medical Academy Botkin Hospital, St Petersburg; T. Trofimova, Novgorod Centre for AIDS, Novgorod, I. Khromova, Centre for HIV/AIDS & and Infectious Diseases, Kaliningrad; E. Kuzovatova, Academician I.N.Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology, Nizhny Novgorod; E. Borodulina, E. Vdoushkina, Samara State Medical University, Samara. Serbia: (J. Ranin), The Institute for Infectious and Tropical Diseases, Belgrade. Slovenia: (J. Tomazic), University Clinical Centre Ljubljana, Ljubljana. Spain: (J. M. Miro), J. M. Miró, M. Laguno, E. Martinez, F. Garcia, J. L. Blanco, M. Martinez-Rebollar, J. Mallolas, P. Callau, J. Rojas, A. Inciarta, Hospital Clinic – IDIBAPS University of Barcelona, Barcelona; S. Moreno, S. del Campo, Hospital Ramon y Cajal, Madrid; B. Clotet, A. Jou, R. Paredes, J. Puig, J. M. Llibre, J. R. Santos, Infectious Diseases Unit & IrsiCaixa AIDS Research Institute, Hospital Germans Trias I Pujol, Badalona; P Domingo, M. Gutierrez, G. Mateo, M. A. Sambeat, Hospital Sant Pau, Barcelona; J. M. Laporte, Hospital Universitario de Alava, Vitoria-Gasteiz. Sweden: (P. Novak), A. Thalme, A. Sönnerborg, Karolinska University Hospital, Stockholm; J. Brännström, Venhälsan-Sodersjukhuset, Stockholm; L. Flamholc, Malmö University Hospital, Malmö. Switzerland: (K. Kusejko), D. Braun, University Hospital Zurich; M. Cavassini, University Hospital Lausanne; A. Calmy, University Hospital Geneva; H. Furrer, University Hospital Bern; M. Battegay, University Hospital Basel; P. Schmid, Cantonal Hospital St. Gallen. Ukraine: A. Kuznetsova, Kharkov State Medical University, Kharkov; J. Mikhalik, Crimean Republican AIDS centre, Simferopol; M. Sluzhynska, Lviv Regional HIV/AIDS Prevention and Control CTR, Lviv. United Kingdom: A Milinkovic, St. Stephen's Clinic, Chelsea and Westminster Hospital, London; A. M. Johnson, S. Edwards, Mortimer Market Centre, London; A. Phillips, M. A. Johnson, A. Mocroft, Royal Free and University College Medical School, London (Royal Free Campus); C. Orkin, Royal London Hospital, London; A. Winston, Imperial College School of Medicine at St. Mary's, London; A. Clarke, Royal Sussex County Hospital, Brighton; C. Leen, Western General Hospital, Edinburgh. The following centers have previously contributed data to EuroSIDA: Medical University, Gdansk, Poland; Infectious Diseases Hospital, Sofia, Bulgaria; Hôpital de la Croix Rousse, Lyon, France; Hôpital de la Pitié-Salpétière, Paris, France; Unité INSERM, Bordeaux, France; Hôpital Edouard Herriot, Lyon, France; Bernhard Nocht Institut für Tropenmedizin, Hamburg, Germany; 1st I.K.A Hospital of Athens, Athens, Greece; Ospedale Riuniti, Divisione Malattie Infettive, Bergamo, Italy, Ospedale di Bolzano, Divisione Malattie Infettive, Bolzano, Italy; Ospedale Cotugno, III Divisione Malattie Infettive, Napoli, Italy; Dérer Hospital, Bratislava, Slovakia, Hospital Carlos III, Departamento de Enfermedades Infecciosas, Madrid, Spain, Kiev Centre for AIDS, Kiev, Ukraine, Luhansk State Medical University, Luhansk, Ukraine, Odessa Region AIDS Center, Odessa, Ukraine; St Petersburg AIDS Centre, St Petersburg, Russia; Infectology Centre of Latvia, Riga, Latvia; University di Roma la Sapienza, Rome, Italy; Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome, Italy. EuroSIDA Steering Committee: I. Karpov, M. Losso, J. Lundgren, J. Rockstroh, I. Aho, L. D. Rasmussen, P. Novak, G. Wandeler, C. Pradier, N. Chkhartishvili, R. Matulionyte, C. Oprea, J. D. Kowalska, J. Begovac, J. M. Miró, G. Guaraldi, R. Paredes; Chair: G. Wandeler; Co-Chair: R. Paredes; Study lead: L. Peters; Coordinating Centre Staff: L. Peters, J. F. Larsen, B. Neesgaard, N. Jaschinski, O. Fursa, D. Raben, D. Kristensen, A. H. Fischer, S. K. Jensen, T. W. Elsing, M. Gardizi, A Ahmed; Statistical Staff: A. Mocroft, A Phillips, J. Reekie, A. Cozzi-Lepri, A. Pelchen-Matthews, A. Roen, E. S. Tusch, W. Bannister.

Publisher Copyright:
© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.

Other keywords

  • HCC
  • Hepatitis Delta
  • HIV
  • PLWH
  • prevalence
  • Hepatitis D/epidemiology
  • Prevalence
  • Humans
  • Liver Neoplasms/epidemiology
  • Substance Abuse, Intravenous/complications
  • Hepatitis B Surface Antigens
  • Drug Users
  • Coinfection/epidemiology
  • Hepatitis Delta Virus/genetics
  • Hepatitis B/complications
  • Europe/epidemiology
  • HIV Infections/complications
  • Hepatitis A/complications
  • Carcinoma, Hepatocellular
  • Hepatitis B virus
  • Cohort Studies

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