Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia



Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to determine the HEV seroprevalence and risk factors among HD patients in Croatia.


A total of 394 HD patients from six medical facilities in five Croatian cities (three sites in the continental and three sites in the coastal region) were tested for HEV IgM/IgG antibodies using an enzyme-linked immunosorbent assay. Additionally, all samples were tested for HEV RNA by RT-PCR. Sociodemographic data and risk factors were collected using a questionnaire.


HEV IgG antibodies were detected in 110 (27.9%) patients. The seroprevalence varied significantly between dialysis centres, ranging from 5.2 to 43.4% (p = 0.001). HEV IgM antibodies were found in 0.04% of IgG positive patients. All patients tested negative for HEV RNA. Factors associated with HEV IgG seropositivity were age > 60 years (OR 8.17; 95% CI 1.08–62.14), living in the continental parts of the country (OR 2.58; 95% CI 1.55–4.30), and transfusion of blood products (OR 1.66; 95% CI 1.01–2.73). After adjusting for age and gender, patients from continental regions had higher odds of HEV seropositivity compared to patients from coastal regions (OR 2.88; 95% CI 1.71–4.85) and those who had RBC transfusions (OR 1.70, 95% CI 1.02–2.69) compared to those who did not.


The study showed a high HEV seropositivity among HD patients in Croatia, with significant variations between geographical regions. Continental area of residence and RBC transfusion were the most significant risk factors for HEV seropositivity. Due to the high seroprevalence, routine HEV screening among HD patients, especially in transplant candidates should be considered.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Clemente-Casares P, Ramos-Romero C, Ramirez-Gonzalez E, Mas A (2016) Hepatitis E virus in industrialized countries: the silent threat. Biomed Res Int 2016:9838041.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Baylis SA, Gärtner T, Nick S, Ovemyr J, Blümel J (2012) Occurrence of hepatitis E virus RNA in plasma donations from Sweden, Germany and the United States. Vox Sang 103(1):89–90.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Schlosser B, Stein A, Neuhaus R, Pahl S, Ramez B, Krüger DH, Berg T, Hofmann J (2012) Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient. J Hepatol 56(2):500–502.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Dalton HR, Stableforth W, Thurairajah P, Hazeldine S, Remnarace R, Usama W, Farrington L, Hamad N, Sieberhagen C, Ellis V, Mitchell J, Hussaini SH, Banks M, Ijaz S, Bendall RP (2008) Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. Eur J Gastroenterol Hepatol 20:784–790.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Blasco-Perrin H, Madden RG, Stanley A, Crossan C, Hunter JG, Vine L, Lane K, Devooght-Johnson N, Mclaughlin C, Petrik J, Stableforth B, Hussaini H, Phillips M, Mansuy JM, Forrest E, Izopet J, Blatchford O, Scobie L, Peron JM, Dalton HR (2015) Hepatitis E virus in patients with decompensated chronic liver disease: a prospective UK/French study. Aliment Pharmacol Ther 42:574–581.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Kamar N, Selves J, Mansuy JM, Ouezzani L, Péron JM, Guitard J, Cointault O, Esposito L, Abravanel F, Danjoux M, Durand D, Vinel JP, Izopet J, Rostaing L (2008) Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 358:811–817.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Dalton HR, Bendall RP, Keane FE, Tedder RS, Ijaz S (2009) Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med 361:1025–1027.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    von Felden J, Alric L, Pischke S, Aitken C, Schlabe S, Spengler U, Giordani MT, Schnitzler P, Bettinger D, Thimme R, Xhaard A, Binder M, Ayuk F, Lohse AW, Cornelissen JJ, de Man RA, Mallet V (2019) The burden of hepatitis E among patients with hematological malignancies: a retrospective european cohort study. J Hepatol 71:465–472

    Article  Google Scholar 

  9. 9.

    Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet C, Dumortier J, Cannesson A, Cassuto-Viguier E, Thervet E, Conti F, Lebray P, Dalton HR, Santella R, Kanaan N, Essig M, Mousson C, Radenne S, Roque-Afonso AM, Izopet J, Rostaing L (2011) Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 140:1481–1489.

    Article  PubMed  Google Scholar 

  10. 10.

    Zhang S, Chen C, Peng J, Li X, Zhang D, Yan J, Zhang Y, Lu C, Xun J, Li W, Ling Y, Huang Y, Chen L (2017) Investigation of underlying comorbidities as risk factors for symptomatic human hepatitis E virus infection. Aliment Pharmacol Ther 45:701–713.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Jeličić P, Jemeršić L, Brumen V, Janev-Holcer N, Prohić A, Barbić LJ, Tabain I, Stevanović V, Vilibić-Čavlek T (2017) Seroprevalence of hepatitis E in professionally exposed groups in Croatia: preliminary results. In: 7th International Congress “Veterinary Science and Profession”, Zagreb, 5–7 October, 2017, p. 55 (abstract). Accessed June 2019

  12. 12.

    Jeličić P, Vilibić-Čavlek T, Vilibić M, Jemeršić L, Kolarić B, Kučinar J, Barbić LJ, Stevanović V, Janev-Holcer N, Tabain I, Brumen V, Djaković I, Prohić A, Košec V, Kaić B (2017) Seroprevalence of hepatitis E in different population groups in Croatia. In: 7th Congress of Slovenian Microbiological Society, Bled, Slovenia, 20–22 September, 2017, p 155 (abstract). Accessed June 2019

  13. 13.

    Vilibic-Cavlek T, Vilibic M, Kolaric B, Jemersic L, Kucinar J, Barbic L, Bagaric A, Stevanovic V, Tabain I, Sviben M, Jukic V, Mlinaric-Galinovic G (2016) Seroepidemiology of hepatitis E in selected population groups in Croatia: a prospective pilot study. Zoonoses Public Health 63(6):494–502.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Miletić M, Vuk T, Hećimović A, Vidović MS, Jemeršić L, Jukić I (2019) Estimation of the hepatitis E assay-dependent seroprevalence among Croatian blood donors. Transfus Clin Biol.

    Article  PubMed  Google Scholar 

  15. 15.

    Mrzljak A, Dinjar-Kujundzic P, Vilibic-Cavlek T, Jemersic L, Prpic J, Dakovic-Rode O, Kolaric B, Vince A (2019) Hepatitis E seroprevalence and associated risk factors among liver transplant recipients in Croatia. Rev Soc Bras Med Trop 52:e20190302.

    Article  PubMed  Google Scholar 

  16. 16.

    Jothikumar N, Cromeans TL, Robertson BH, Meng XJ, Hill VR (2006) A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus. J Virol Methods 131:65–71

    CAS  Article  Google Scholar 

  17. 17.

    Hrvatsko drustvo za nefrologiju, dijalizu i transplantaciju. Accessed June 2019

  18. 18.

    International Registry in Organ Donation and Transplantation. Accessed June 2019

  19. 19.

    Owada Y, Oshiro Y, Inagaki Y, Harada H, Fujiyama N, Kawagishi N, Yagisawa T, Usui J, Akutsu N, Itabashi Y, Saito K, Watarai Y, Ichimaru N, Imamura R, Kyakuno M, Ide K, Shibuya Y, Okabe Y, Ono M, Sasaki K, Shiose A, Yamagishi K, Ohnishi H, Nagashima S, Takahashi M, Yuzawa K, Okamoto H, Ohkohchi N (2019) A nationwide survey of hepatitis E virus infection and chronic hepatitis in heart and kidney transplant recipients in Japan. Transplantation.

    Article  Google Scholar 

  20. 20.

    Haffar S, Bazerbachi F, Leise MD, Dillon JJ, Albright RC, Murad MH, Kamath PS, Watt KD (2017) Systematic review with meta-analysis: the association between hepatitis E seroprevalence and haemodialysis. Aliment Pharmacol Ther 46(9):790–799.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Jemeršić L, Keros T, Lj M, Lj B, Vilibić-Čavlek T, Jeličić P, Rode Đaković O, Prpić J (2017) Differences in hepatitis E virus (HEV) presence in naturally infected seropositive domestic pigs and wild boars—confirmation of wild boars having a key role in HEV epidemiology. Vet Arh 87(6):651–663

    Article  Google Scholar 

  22. 22.

    Prpić J, Černi S, Škorić D, Keros T, Brnić D, Cvetnić Ž, Jemeršić L (2015) Distribution and molecular characterization of hepatitis E virus in domestic animals and wildlife in Croatia. Food Environ Virol 7(3):195–205.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Lipej Z, Novosel D, Vojta L, Roić B, Simpraga M, Vojta A (2013) Detection and characterisation of hepatitis E virus in naturally infected swine in Croatia. Acta Vet Hung 61(4):517–528

    Article  Google Scholar 

  24. 24.

    van Gageldonk-Lafeber AB, van der Hoek W, Borlée F, Heederik DJ, Mooi SH, Maassen CB, Yzermans CJ, Rockx B, Smit LA, Reimerink JH (2017) Hepatitis E virus seroprevalence among the general population in a livestock-dense area in the Netherlands: a cross-sectional population-based serological survey. BMC Infect Dis 17:21.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    European Association for the Study of the Liver (2018) EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol 68(6):1256–1271

    Article  Google Scholar 

  26. 26.

    Courtney MG, O'Mahoney M, Albloushi S, Sachithanandan S, Walshe J, Carmody M, Donoghue J, Parfrey N, Shattock AG, Fielding J (1994) Hepatitis E virus anti-body prevalence. Lancet 344:1166

    CAS  Article  Google Scholar 

  27. 27.

    Irshad M, Peter S, Agarwal SK (2002) Transmission of hepatitis-E virus (HEV) infection via parenteral routes in Delhi, India. J Int Med Sci Acad 15:75–78

    Google Scholar 

  28. 28.

    Dalekos GN, Zervou E, Elisaf M, Germanos N, Galanakis E, Bourantas K, Siamopoulos KC, Tsianos EV (1998) Antibodies to hepatitis E virus among several populations in Greece: increased prevalence in an hemodialysis unit. Transfusion 38(6):589–595

    CAS  Article  Google Scholar 

  29. 29.

    Stefanidis I, Zervou EK, Rizos C, Syrganis C, Patsidis E, Kyriakopoulos G, Sdrakas L, Tsianas N, Rigopoulou EI, Liakopoulos V, Dalekos GN (2004) Hepatitis E virus antibodies in hemodialysis patients: An epidemiological survey in central Greece. Int J Artif Organs 27(10):842–847

    CAS  Article  Google Scholar 

  30. 30.

    Scotto G, Aucella F, Grandaliano G, Martinelli D, Querques M, Gesuete A, Infante B, Carri PD, Massa S, Salatino G, Bulla F, Fazio V (2015) Hepatitis E in hemodialysis and kidney transplant patients in south-east Italy. World J Gastroenterol 21(11):3266–3273.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Harrison A, Scobie L, Crossan C, Parry R, Johnston P, Stratton J, Dickinson S, Ellis V, Hunter JG, Prescott OR, Madden R, Lin NX, Henley WE, Bendall RP, Dalton HR (2013) Hepatitis E seroprevalence in recipients of renal transplants or haemodialysis in southwest England: a case-control study. J Med Virol 85:266–271.

    Article  PubMed  Google Scholar 

  32. 32.

    Hewitt PE, Ijaz S, Brailsford SR, Brett R, Dicks S, Haywood B, Kennedy IT, Kitchen A, Patel P, Poh J, Russell K, Tettmar KI, Tossell J, Ushiro-Lumb I, Tedder RS (2014) Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 384:1766–1773.

    Article  PubMed  Google Scholar 

  33. 33.

    Lee CC, Shih YL, Laio CS, Lin SM, Huang MM, Chen CJ, Chen CP, Chang CL, Chen LR, Tschen SY, Wang CH (2005) Prevalence of antibody to hepatitis E virus among haemodialysis patients in Taiwan: possible infection by blood transfusion. Nephron 99:c122–c127

    CAS  PubMed  Google Scholar 

  34. 34.

    Hewitt PE, Ijaz S, Brailsford SR, Brett R, Dicks S, Haywood B, Kennedy IT, Kitchen A, Patel P, Poh J, Russell K, Tettmar KI, Tossell J, Ushiro-Lumb I, Tedder RS (2014) Hepatitis E virus in blood components: A prevalence and transmission study in southeast England. Lancet 384:1766–1773

    Article  Google Scholar 

  35. 35.

    Slot E, Hogema BM, Riezebos-Brilman A, Kok TM, Molier M, Zaaijer HL (2013) Silent hepatitis E virus infection in Dutch blood donors, 2011 to 2012. Euro Surveill 18(31):20550

    Article  Google Scholar 

  36. 36.

    Sauleda S, Ong E, Bes M, Janssen A, Cory R, Babizki M, Shin T, Lindquist A, Hoang A, Vang L, Piron M, Casamitjana N, Koppelman M, Danzig L, Linnen JM (2015) Seroprevalence of hepatitis E virus (HEV) and detection of HEV RNA with a transcription-mediated amplification assay in blood donors from Catalonia (Spain). Transfusion 55:972–979

    CAS  Article  Google Scholar 

  37. 37.

    Mansuy JM, Sauné K, Rech H, Abravanel F, Mengelle C, L’Homme S, Destruel F, Kamar N, Izopet J (2015) Seroprevalence in blood donors reveals widespread, multi-source exposure to hepatitis E virus, southern France, October 2011. Euro Surveill 20(19):27–34

    CAS  Article  Google Scholar 

Download references


This study was supported by the ‘The Adris Foundation’ Grant for the project “Hepatitis E virus infection before and after solid–solid organ transplantation in Croatia”, Transplant Centre, Merkur University Hospital Merkur (to Anna Mrzljak). We thank Nena Peran, Irena Tomicic, Ljiljana Antolasic, Mirjana Siljan, Jolanka Prevendar, Ljiljana Ujevic, Zvjezdana Vranjes, Melita Jurcevic for their excellent technical support.

Author information




All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by AM, PD-K, MK, BK, MI, MG, LZ, IH, ZJ, BK, LJ, JP, MT, and TV-C. The first draft of the manuscript was written by AM and TV-C and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anna Mrzljak.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mrzljak, A., Dinjar-Kujundzic, P., Knotek, M. et al. Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia. Int Urol Nephrol 52, 371–378 (2020).

Download citation


  • Hepatitis E virus
  • Seroprevalence
  • Haemodialysis
  • Risk factors