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Fulminant hepatitis due to human adenovirus

Abstract

Purpose

To describe the demographics, clinical manifestations, treatment and outcomes of patients with human adenovirus (HAdV) hepatitis.

Methods

A case of fulminant HAdV hepatitis in a patient with chronic lymphocytic leukemia receiving rituximab and fludarabine is described. We conducted a comprehensive review of the English-language literature through May, 2012 in search of definite cases of HAdV hepatitis.

Results

Eighty-nine cases were reviewed. Forty-three (48 %) were liver transplant recipients, 19 (21 %) were bone marrow transplant recipients, 11 (12 %) had received chemotherapy, five (6 %) had severe combined immunodeficiency, four (4 %) were HIV infected, two had heart transplantation, and two were kidney transplant recipients. Ninety percent (46/51) of patients presented within 6 months following transplantation. Fever was the most common initial symptom. Abdominal CT scan revealed hypodense lesions in eight of nine patients. Diagnosis was made by liver biopsy in 43 (48 %), and on autopsy in 46 (52 %). The HAdV was isolated at other sites in 54 cases. Only 24 of 89 patients (27 %) survived: 16 whose immunosuppression was reduced, six with liver re-transplantation, and two who received cidofovir and intravenous immunoglobulin.

Conclusion

HAdV hepatitis can manifest as a fulminant illness in immunocompromised hosts. Definitive diagnosis requires liver biopsy. Early consideration of a viral etiology, reduction in immunosuppression, and liver transplantation can be potentially life-saving.

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References

  1. Echavarria M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev. 2008;21:704–15.

    PubMed Central  PubMed  Article  Google Scholar 

  2. Ison MG. Adenovirus infections in transplant recipients. Clin Infect Dis. 2006;43:331–9.

    PubMed  Article  Google Scholar 

  3. Matthes-Martin S, Feuchtinger T, Shaw PJ, Engelhard D, Hirsch HH, Cordonnier C, et al. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4. Transpl Infect Dis. 2011;14:555–63.

    Article  Google Scholar 

  4. Carrigan DR. Adenovirus infections in immunocompromised patients. Am J Med. 1997;102:71–4.

    CAS  PubMed  Article  Google Scholar 

  5. Abzug MJ, Levin MJ. Neonatal adenovirus infection: four patients and review of the literature. Pediatrics. 1991;87:890–6.

    CAS  PubMed  Google Scholar 

  6. Arav-Boger R, Echavarria M, Forman M, Charache P, Persaud D. Clearance of adenoviral hepatitis with ribavirin therapy in a pediatric liver transplant recipient. Pediatr Infect Dis J. 2000;19:1097–100.

    CAS  PubMed  Article  Google Scholar 

  7. Aterman K, Embil J, Easterbrook KB, Haldane EV, Crosby J. Liver necrosis, adenovirus type 2 and thymic dysplasia. Virchows Arch A Pathol. 1973;360:155–71.

    CAS  Article  Google Scholar 

  8. Benyesh-Melnick M, Rosenberg HS. The isolation of adenovirus type 7 from a fatal case of pneumonia and disseminated disease. J Pediatr. 1964;64:83–7.

    CAS  PubMed  Article  Google Scholar 

  9. Bertheau P, Parquet N, Ferchal F, Gluckman E, Brocheriou C. Fulminant adenovirus hepatitis after allogeneic bone marrow transplantation. Bone Marrow Transpl. 1996;17:295–8.

    CAS  Google Scholar 

  10. Brundler MA, Rodriguez-Baez N, Jaffe R, Weinberg AG, Rogers BB. Adenovirus ascending cholangiohepatitis. Pediatr Dev Pathol. 2003;6:156–9.

    PubMed  Article  Google Scholar 

  11. Cames B, Rahier J, Burtomboy G, de Ville de Goyet J, Reding R, Lamy M, et al. Acute adenovirus hepatitis in liver transplant recipients. J Pediatr. 1992;120:33–7.

    CAS  PubMed  Article  Google Scholar 

  12. Carmichael GP Jr, Zahradnik JM, Moyer GH, Porter DD. Adenovirus hepatitis in an immunosuppressed adult patient. Am J Clin Pathol. 1979;71:352–5.

    PubMed  Google Scholar 

  13. Chakrabarti S, Collingham KE, Fegan CD, Milligan DW. Fulminant adenovirus hepatitis following unrelated bone marrow transplantation: failure of intravenous ribavirin therapy. Bone Marrow Transpl. 1999;23:1209–11.

    CAS  Article  Google Scholar 

  14. Chakrabarti S, Mautner V, Osman H, Collingham KE, Fegan CD, Klapper PE, et al. Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery. Blood. 2002;100:1619–27.

    CAS  PubMed  Article  Google Scholar 

  15. Charles AK, Caul EO, Porter HJ, Oakhill A. Fatal adenovirus 32 infection in a bone marrow transplant recipient. J Clin Pathol. 1995;48:779–81.

    CAS  PubMed  Article  Google Scholar 

  16. Dombrowski F, Eis-Hubinger AM, Ackermann T, Blumel J, Spengler U, Pfeifer U. Adenovirus-induced liver necrosis in a case of AIDS. Virchows Arch. 1997;431:469–72.

    CAS  PubMed  Article  Google Scholar 

  17. Engelmann G, Heim A, Greil J, Schmitt CP, Flechtenmacher C, Daum E, et al. Adenovirus infection and treatment with cidofovir in children after liver transplantation. Pediatr Transpl. 2009;13:421–8.

    CAS  Article  Google Scholar 

  18. Faden H, Jockin H, Talty MR, Fazilli R, Barrett H. Fatal disseminated adenovirus infection featuring liver necrosis and prolonged viremia in an immunosuppressed child with malignant histiocytosis. Am J Pediatr Hematol/Oncol. 1985;7:15–20.

    CAS  Google Scholar 

  19. Fassas AB, Buddharaju LN, Rapoport A, Cottler-Fox M, Drachenberg C, Meisenberg B, et al. Fatal disseminated adenoviral infection associated with thrombotic thrombocytopenic purpura after allogeneic bone marrow transplantation. Leuk Lymph. 2001;42:801–4.

    CAS  Article  Google Scholar 

  20. Flomenberg P, Babbitt J, Drobyski WR, Ash RC, Carrigan DR, Sedmak GV, et al. Increasing incidence of adenovirus disease in bone marrow transplant recipients. J Infect Dis. 1994;169:775–81.

    CAS  PubMed  Article  Google Scholar 

  21. Gupta A, Philip A, Ranga K, Cappa J, Dougherty J, Lawlor M. An interesting case of adenoviral hepatitis in a cardiac transplant recipient. Transpl Infect Dis. 2013;12:84–6.

    Article  Google Scholar 

  22. Hale GA, Heslop HE, Krance RA, Brenner MA, Jayawardene D, Srivastava DK, et al. Adenovirus infection after pediatric bone marrow transplantation. Bone Marrow Transpl. 1999;23:277–82.

    CAS  Article  Google Scholar 

  23. Haura EB, Winden MA, Proia AD, Trotter JE. Fulminant hepatic failure due to disseminated adenovirus infection in a patient with chronic lymphocytic leukemia. Cancer Control. 2002;9:248–53.

    PubMed  Google Scholar 

  24. Hogan WJ, Edwards WD, Macon WR, Habermann TM. Fulminant hepatic failure secondary to adenovirus following fludarabine-based chemotherapy for non-Hodgkin’s lymphoma. Leuk Lymph. 2001;42:1145–50.

    CAS  Article  Google Scholar 

  25. Hough R, Chetwood A, Sinfield R, Welch J, Vora A. Fatal adenovirus hepatitis during standard chemotherapy for childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2005;27:67–72.

    PubMed  Article  Google Scholar 

  26. Ivan D, Frazier OH, Abrams J. Fatal disseminated adenoviral infection in an adult heart transplant patient. J Heart Lung Transpl. 2004;23:1209–12.

    Article  Google Scholar 

  27. Iyer A, Mathur R, Deepak BV, Sinard J. Fatal adenoviral hepatitis after rituximab therapy. Arch Pathol Lab Med. 2006;130:1557–60.

    PubMed  Google Scholar 

  28. Johnson PR, Yin JA, Morris DJ, Desai M, Cinkotai KI, McKeogh MM. Fulminant hepatic necrosis caused by adenovirus type 5 following bone marrow transplantation. Bone Marrow Transpl. 1990;5:345–7.

    CAS  Google Scholar 

  29. Kaur B, Gottardo NG, Keil AD, Hallam LA, Baker DL. A rare case of adenoviral fulminant hepatic necrosis after chemotherapy. Pediatr Hematol Oncol. 2002;19:361–71.

    PubMed  Article  Google Scholar 

  30. Koneru B, Atchison R, Jaffe R, Cassavilla A, Van Thiel DH, Starzl TE. Serological studies of adenoviral hepatitis following pediatric liver transplantation. Transpl Proc. 1990;22:1547–8.

    CAS  Google Scholar 

  31. Koneru B, Jaffe R, Esquivel CO, Kunz R, Todo S, Iwatsuki S, et al. Adenoviral infections in pediatric liver transplant recipients. JAMA. 1987;258:489–92.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  32. Krilov LR, Rubin LG, Frogel M, Gloster E, Ni K, Kaplan M, et al. Disseminated adenovirus infection with hepatic necrosis in patients with human immunodeficiency virus infection and other immunodeficiency states. Rev Infect Dis. 1990;12:303–7.

    CAS  PubMed  Article  Google Scholar 

  33. Ljungman P, Ehrnst A, Bjorkstrand B, Hellstrom E, Ingelman-Sundberg H, Juliusson G, et al. Lethal disseminated adenovirus type 1 infection in a patient with chronic lymphocytic leukemia. Scand J Infect Dis. 1990;22:601–5.

    CAS  PubMed  Article  Google Scholar 

  34. Longerich T, Haferkamp K, Tox U, Schirmacher P, Longerich T, Haferkamp K, et al. Acute liver failure in a renal transplant patient caused by adenoviral hepatitis superimposed on a fibrosing cholestatic hepatitis B. Hum Pathol. 2004;35:894–7.

    CAS  PubMed  Article  Google Scholar 

  35. McGrath D, Falagas ME, Freeman R, Rohrer R, Fairchild R, Colbach C, et al. Adenovirus infection in adult orthotopic liver transplant recipients: incidence and clinical significance. J Infect Dis. 1998;177:459–62.

    CAS  PubMed  Article  Google Scholar 

  36. Michaels MG, Green M, Wald ER, Starzl TE. Adenovirus infection in pediatric liver transplant recipients. J Infect Dis. 1992;165:170–4.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  37. Nakazawa H, Ito T, Makishima H, Misawa N, Okiyama W, Uehara T, et al. Adenovirus fulminant hepatic failure: disseminated adenovirus disease after unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia. Intern Med. 2006;45:975–80.

    PubMed  Article  Google Scholar 

  38. Neofytos D, Ojha A, Mookerjee B, Wagner J, Filicko J, Ferber A, et al. Treatment of adenovirus disease in stem cell transplant recipients with cidofovir. Biol Blood Marrow Transpl. 2007;13:74–81.

    CAS  Article  Google Scholar 

  39. Niemann TH, Trigg ME, Winick N, Penick GD. Disseminated adenoviral infection presenting as acute pancreatitis. Hum Pathol. 1993;24:1145–8.

    CAS  PubMed  Article  Google Scholar 

  40. Norris SH, Butler TC, Glass N, Tran R. Fatal hepatic necrosis caused by disseminated type 5 adenovirus infection in a renal transplant recipient. Am J Nephrol. 1989;9:101–5.

    CAS  PubMed  Article  Google Scholar 

  41. Ohbu M, Sasaki K, Okudaira M, Iidaka K, Aoyama Y. Adenovirus hepatitis in a patient with severe combined immunodeficiency. Acta Pathologica Japonica. 1987;37:655–64.

    CAS  PubMed  Google Scholar 

  42. Perez D, McCormack L, Petrowsky H, Jochum W, Mullhaupt B, Clavien PA. Successful outcome of severe adenovirus hepatitis of the allograft following liver transplantation. Transpl Infect Dis. 2007;9:318–22.

    CAS  PubMed  Article  Google Scholar 

  43. Purtilo DT, White R, Filipovich A, Kersey J, Zelkowitz L. Fulminant liver failure induced by adenovirus after bone marrow transplantation. N Engl J Med. 1985;312:1707–8.

    CAS  PubMed  Article  Google Scholar 

  44. Rodriguez FH Jr, Liuzza GE, Gohd RH. Disseminated adenovirus serotype 31 infection in an immunocompromised host. Am J Clin Pathol. 1984;82:615–8.

    PubMed  Google Scholar 

  45. Rothenberg M, Cheung R, Ahmed A. Adenovirus-induced acute liver failure. Dig Dis Sci. 2009;54:218–21.

    PubMed  Article  Google Scholar 

  46. Saad RS, Demetris AJ, Lee RG, Kusne S, Randhawa PS. Adenovirus hepatitis in the adult allograft liver. Transplantation. 1997;64:1483–5.

    CAS  PubMed  Article  Google Scholar 

  47. Shields AF, Hackman RC, Fife KH, Corey L, Meyers JD. Adenovirus infections in patients undergoing bone-marrow transplantation. N Engl J Med. 1985;312:529–33.

    CAS  PubMed  Article  Google Scholar 

  48. Somervaille TC, Kirk S, Dogan A, Landon GV, Mackinnon S. Fulminant hepatic failure caused by adenovirus infection following bone marrow transplantation for Hodgkin’s disease. Bone Marrow Transpl. 1999;24:99–101.

    CAS  Article  Google Scholar 

  49. Steiner I, Aebi C, Ridolfi Luthy A, Wagner B, Leibundgut K. Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50:647–9.

    PubMed  Article  Google Scholar 

  50. Terasako K, Oshima K, Wada H, Ishihara Y, Kawamura K, Sakamoto K, et al. Fulminant hepatic failure caused by adenovirus infection mimicking peliosis hepatitis on abdominal computed tomography images after allogeneic hematopoietic stem cell transplantation. Intern Med. 2012;51:405–11.

    PubMed  Article  Google Scholar 

  51. Varki NM, Bhuta S, Drake T, Porter DD. Adenovirus hepatitis in two successive liver transplants in a child. Arch Pathol Lab Med. 1990;114:106–9.

    CAS  PubMed  Google Scholar 

  52. Wang WH, Wang HL. Fulminant adenovirus hepatitis following bone marrow transplantation. A case report and brief review of the literature. Arch Pathol Lab Med. 2003;127:e246–8.

    PubMed  Google Scholar 

  53. Wigger HJ, Blanc WA. Fatal hepatic and bronchial necrosis in adenovirus infection with thymic alymphoplasia. N Engl J Med. 1966;275:870–4.

    CAS  PubMed  Article  Google Scholar 

  54. Zahradnik JM, Spencer MJ, Porter DD. Adenovirus infection in the immunocompromised patient. Am J Med. 1980;68:725–32.

    CAS  PubMed  Article  Google Scholar 

  55. Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947–54.

    PubMed  Article  Google Scholar 

  56. Hierholzer JC. Adenoviruses in the immunocompromised host. Clin Microbiol Rev. 1992;5:262–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Kojaoghlanian T, Flomenberg P, Horwitz MS. The impact of adenovirus infection on the immunocompromised host. Rev Med Virol. 2003;13:155–71.

    PubMed  Article  Google Scholar 

  58. Norvell JP, Blei AT, Jovanovic BD, Levitsky J. Herpes simplex virus hepatitis: an analysis of the published literature and institutional cases. Liver Transpl. 2007;13:1428–34.

    PubMed  Article  Google Scholar 

  59. Ljungman P. Prevention and treatment of viral infections in stem cell transplant recipients. Br J Haematol. 2002;118:44–57.

    CAS  PubMed  Article  Google Scholar 

  60. Martin-Garrido I, Carmona EM, Specks U, Limper AH. Pneumocystis pneumonia in patients treated with rituximab. Chest. 2013;144:258–65.

    CAS  PubMed  Article  Google Scholar 

  61. Safa G, Darrieux L. Cerebral toxoplasmosis after rituximab therapy. JAMA Intern Med. 2013;173:924–6.

    PubMed  Article  Google Scholar 

  62. Aksoy S, Harputluoglu H, Kilickap S, Dede DS, Dizdar O, Altundag K, et al. Rituximab-related viral infections in lymphoma patients. Leuk Lymph. 2007;48:1307–12.

    CAS  Article  Google Scholar 

  63. Isaacs D. Infectious risks associated with biologics. Adv Exp Med Biol. 2013;764:151–8.

    CAS  PubMed  Article  Google Scholar 

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Correspondence to H. R. Vikram.

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Ronan, B.A., Agrwal, N., Carey, E.J. et al. Fulminant hepatitis due to human adenovirus. Infection 42, 105–111 (2014). https://doi.org/10.1007/s15010-013-0527-7

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  • DOI: https://doi.org/10.1007/s15010-013-0527-7

Keywords

  • Adenovirus
  • Hepatic failure
  • Hepatitis
  • Acute liver failure
  • Rituximab