Human Herpesvirus 6 and the Liver

Linda Cook


Human Herpesvirus 6 (HHV-6) is an interesting member of the herpesvirus family that infects humans.  There are 2 HHV-6 species, designated HHV-6A and HHV-6B, which infect humans with most clinical disease caused by HHV-6B.  The virus is ubiquitous and most infections take place in very young children, where the infection is either asymptomatic or mild and result in a syndrome called Exanthem subitum with fever and a characteristic skin rash.  Occasionally the infection can result in CSF infection and encephalitis.  Much less commonly, the infection can cause more severe damage to internal organs and rarely liver or other organ failure.  A total of 12 pediatric and 11 adult case reports of liver failure in the context of HHV-6 infections are reviewed in this paper.  These reports highlight the need to better characterize this rare complication and determine the frequency of occurrence as well as identify possible therapies to prevent complete organ failure.  Significant organ disease is also described during HHV-6 reactivation episodes secondary to hematopoietic and solid organ transplant, and is possibly more common in liver than in hematopoietic transplantation.  Because of the relatively new descriptions of significant disease post-transplant caused by HHV-6, much work is left to be done to improve diagnosis of this reactivation disease and define the best therapies to be used.  A very important component of this process should be the improvement of laboratory diagnostics to standardize the assay across laboratories and establish clinical cut-off values to clarify the detection of latent virus vs active HHV-6 disease replication.  Because of the unique ability of HHV-6 to establish latency via integration into host chromosomal telomers, laboratory testing needs to be improved to be able to distinguish between latent, inactive, chromosomal HHV-6, and active HHV-6 replication associated with clinical disease and organ damage. 



HHV-6, Acute liver disease, post-transplant infections

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Pruksananonda P, Hall CB, Insel RA, McIntyre K, Pellett PE, Long CE, et al. Primary human herpesvirus 6 infection in young children. N Engl J Med. 1992;326(22):1445-50,10.1056/NEJM199205283262201.10.1056/NEJM199205283262201.

Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, et al. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med. 1994;331(7):432-8,10.1056/NEJM199408183310703.10.1056/NEJM199408183310703.

Salahuddin SZ, Ablashi DV, Markham PD, Josephs SF, Sturzenegger S, Kaplan M, et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986;234(4776):596-601.

Albright AV, Lavi E, Black JB, Goldberg S, O'Connor MJ, Gonzalez-Scarano F. The effect of human herpesvirus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia. J Neurovirol. 1998;4(5):486-94.

He J, McCarthy M, Zhou Y, Chandran B, Wood C. Infection of primary human fetal astrocytes by human herpesvirus 6. J Virol. 1996;70(2):1296-300.

Cermelli C, Concari M, Carubbi F, Fabio G, Sabbatini AM, Pecorari M, et al. Growth of human herpesvirus 6 in HEPG2 cells. Virus Res. 1996;45(2):75-85.

Inagi R, Guntapong R, Nakao M, Ishino Y, Kawanishi K, Isegawa Y, et al. Human herpesvirus 6 induces IL-8 gene expression in human hepatoma cell line, Hep G2. J Med Virol. 1996;49(1):34-40,10.1002/(SICI)1096-9071(199605)49:1<34::AID-JMV6>3.0.CO;2-L.10.1002/(SICI)1096-9071(199605)49:1<34::AID-JMV6>3.0.CO;2-L.

Locatelli G, Santoro F, Veglia F, Gobbi A, Lusso P, Malnati MS. Real-time quantitative PCR for human herpesvirus 6 DNA. J Clin Microbiol. 2000;38(11):4042-8.

Ljungman P, Wang FZ, Clark DA, Emery VC, Remberger M, Ringden O, et al. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Br J Haematol. 2000;111(3):774-81.

Palleau S, Boutolleau D, Bonnafous P, Agut H, Gautheret-Dejean A. Polymorphonuclear leukocytes mainly contribute to human herpesvirus-6 load in the peripheral blood of patients. Clin Infect Dis. 2006;42(9):1342-3,10.1086/503303.10.1086/503303.

Achour A, Boutolleau D, Slim A, Agut H, Gautheret-Dejean A. Human herpesvirus-6 (HHV-6) DNA in plasma reflects the presence of infected blood cells rather than circulating viral particles. J Clin Virol. 2007;38(4):280-5,10.1016/j.jcv.2006.

Kong H, Baerbig Q, Duncan L, Shepel N, Mayne M. Human herpesvirus type 6 indirectly enhances oligodendrocyte cell death. J Neurovirol. 2003;9(5):539-50,10.1080/13550280390241241.10.1080/13550280390241241.

Yoshikawa T, Ihira M, Suzuki K, Suga S, Matsubara T, Furukawa S, et al. Invasion by human herpesvirus 6 and human herpesvirus 7 of the central nervous system in patients with neurological signs and symptoms. Arch Dis Child. 2000;83(2):170-1.

Yoshikawa T, Asano Y. Central nervous system complications in human herpesvirus-6 infection. Brain Dev. 2000;22(5):307-14.

Ishikawa K, Hasegawa K, Naritomi T, Kanai N, Ogawa M, Kato Y, et al. Prevalence of herpesviridae and hepatitis virus sequences in the livers of patients with fulminant hepatitis of unknown etiology in Japan. J Gastroenterol. 2002;37(7):523-30,10.1007/s005350200081.10.1007/s005350200081.

Tajiri H, Tanaka-Taya K, Ozaki Y, Okada S, Mushiake S, Yamanishi K. Chronic hepatitis in an infant, in association with human herpesvirus-6 infection. J Pediatr. 1997;131(3):473-5.

Chevret L, Boutolleau D, Halimi-Idri N, Branchereau S, Baujard C, Fabre M, et al. Human herpesvirus-6 infection: a prospective study evaluating HHV-6 DNA levels in liver from children with acute liver failure. J Med Virol. 2008;80(6):1051-7,10.1002/jmv.21143.10.1002/jmv.21143.

Ozaki Y, Tajiri H, Tanaka-Taya K, Mushiake S, Kimoto A, Yamanishi K, et al. Frequent detection of the human herpesvirus 6-specific genomes in the livers of children with various liver diseases. J Clin Microbiol. 2001;39(6):2173-7,10.1128/JCM.39.6.2173-2177.2001.10.1128/JCM.39.6.2173-2177.2001.

Schmitt K, Deutsch J, Tulzer G, Meindi R, Aberle S. Autoimmune hepatitis and adrenal insufficiency in an infant with human herpesvirus-6 infection. Lancet. 1996;348(9032):966.

Harma M, Hockerstedt K, Lautenschlager I. Human herpesvirus-6 and acute liver failure. Transplantation. 2003;76(3):536-9,10.1097/01.TP.0000069233.13409.DF.10.1097/01.TP.0000069233.13409.DF.

Sobue R, Miyazaki H, Okamoto M, Hirano M, Yoshikawa T, Suga S, et al. Fulminant hepatitis in primary human herpesvirus-6 infection. N Engl J Med. 1991;324(18):1290,10.1056/NEJM199105023241818.10.1056/NEJM199105023241818.

Kondo K, Kondo T, Okuno T, Takahashi M, Yamanishi K. Latent human herpesvirus 6 infection of human monocytes/macrophages. J Gen Virol. 1991;72 ( Pt 6):1401-8,10.1099/0022-1317-72-6-1401.10.1099/0022-1317-72-6-1401.

Luppi M, Barozzi P, Morris C, Maiorana A, Garber R, Bonacorsi G, et al. Human herpesvirus 6 latently infects early bone marrow progenitors in vivo. J Virol. 1999;73(1):754-9.

Luppi M, Marasca R, Barozzi P, Ferrari S, Ceccherini-Nelli L, Batoni G, et al. Three cases of human herpesvirus-6 latent infection: integration of viral genome in peripheral blood mononuclear cell DNA. J Med Virol. 1993;40(1):44-52.

Arbuckle JH, Pantry SN, Medveczky MM, Prichett J, Loomis KS, Ablashi D, et al. Mapping the telomere integrated genome of human herpesvirus 6A and 6B. Virology. 2013;442(1):3-11,10.1016/j.virol.2013.

Arbuckle JH, Medveczky MM, Luka J, Hadley SH, Luegmayr A, Ablashi D, et al. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc Natl Acad Sci U S A. 2010;107(12):5563-8,10.1073/pnas.0913586107.10.1073/pnas.0913586107.

Gravel A, Dubuc I, Wallaschek N, Gilbert-Girard S, Collin V, Hall-Sedlak R, et al. Cell Culture Systems To Study Human Herpesvirus 6A/B Chromosomal Integration. J Virol. 2017;91(14),10.1128/JVI.00437-17.10.1128/JVI.00437-17.

Leong HN, Tuke PW, Tedder RS, Khanom AB, Eglin RP, Atkinson CE, et al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol. 2007;79(1):45-51,10.1002/jmv.20760.10.1002/jmv.20760.

Mori T, Tanaka-Taya K, Satoh H, Aisa Y, Yamazaki R, Kato J, et al. Transmission of chromosomally integrated human herpesvirsus 6 (HHV-6) variant A from a parent to children leading to misdiagnosis of active HHV-6 infection. Transpl Infect Dis. 2009;11(6):503-6,10.1111/j.1399-3062.2009.00430.x.10.1111/j.1399-3062.2009.00430.x.

Boutolleau D, Agut H, Gautheret-Dejean A. Human herpesvirus 6 genome integration: a possible cause of misdiagnosis of active viral infection? J Infect Dis. 2006;194(7):1019-20; author reply 21-3,10.1086/506951.10.1086/506951.

Endo A, Watanabe K, Ohye T, Suzuki K, Matsubara T, Shimizu N, et al. Molecular and virological evidence of viral activation from chromosomally integrated human herpesvirus 6A in a patient with X-linked severe combined immunodeficiency. Clin Infect Dis. 2014;59(4):545-8,10.1093/cid/ciu323.10.1093/cid/ciu323.

Pantry SN, Medveczky MM, Arbuckle JH, Luka J, Montoya JG, Hu J, et al. Persistent human herpesvirus-6 infection in patients with an inherited form of the virus. J Med Virol. 2013;85(11):1940-6,10.1002/jmv.23685.10.1002/jmv.23685.

Gravel A, Hall CB, Flamand L. Sequence analysis of transplacentally acquired human herpesvirus 6 DNA is consistent with transmission of a chromosomally integrated reactivated virus. J Infect Dis. 2013;207(10):1585-9,10.1093/infdis/jit060.10.1093/infdis/jit060.

Sedlak RH, Hill JA, Nguyen T, Cho M, Levin G, Cook L, et al. Detection of Human Herpesvirus 6B (HHV-6B) Reactivation in Hematopoietic Cell Transplant Recipients with Inherited Chromosomally Integrated HHV-6A by Droplet Digital PCR. J Clin Microbiol. 2016;54(5):1223-7,10.1128/JCM.03275-15.10.1128/JCM.03275-15.

Sedlak RH, Cook L, Huang ML, Magaret A, Zerr DM, Boeckh M, et al. Identification of chromosomally integrated human herpesvirus 6 by droplet digital PCR. Clin Chem. 2014;60(5):765-72,10.1373/clinchem.2013.217240.10.1373/clinchem.2013.217240.

Wood ML, Royle NJ. Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health. Viruses. 2017;9(7),10.3390/v9070184.10.3390/v9070184.

Flamand L. Pathogenesis from the reactivation of chromosomally integrated human herpesvirus type 6: facts rather than fiction. Clin Infect Dis. 2014;59(4):549-51,10.1093/cid/ciu326.10.1093/cid/ciu326.

Pantry SN, Medveczky PG. Latency, Integration, and Reactivation of Human Herpesvirus-6. Viruses. 2017;9(7),10.3390/v9070194.10.3390/v9070194.

Clark DA. Clinical and laboratory features of human herpesvirus 6 chromosomal integration. Clin Microbiol Infect. 2016;22(4):333-9,10.1016/j.cmi.2015.

Collin V, Flamand L. HHV-6A/B Integration and the Pathogenesis Associated with the Reactivation of Chromosomally Integrated HHV-6A/B. Viruses. 2017;9(7),10.3390/v9070160.10.3390/v9070160.

Quintela A, Escuret V, Roux S, Bonnafous P, Gilis L, Barraco F, et al. HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns. J Infect. 2016;72(2):214-22,10.1016/j.jinf.2015.

Hill JA, Magaret AS, Hall-Sedlak R, Mikhaylova A, Huang ML, Sandmaier BM, et al. Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6. Blood. 2017;130(8):1062-9,10.1182/blood-2017-03-775759.10.1182/blood-2017-03-775759.

Morissette G, Flamand L. Herpesviruses and chromosomal integration. J Virol. 2010;84(23):12100-9,10.1128/JVI.01169-10.10.1128/JVI.01169-10.

Zhang E, Bell AJ, Wilkie GS, Suarez NM, Batini C, Veal CD, et al. Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres. J Virol. 2017,10.1128/JVI.01137-17.10.1128/JVI.01137-17.

Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, et al. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Methods. 2002;100(1-2):27-35.

Jeulin H, Salmon A, Gautheret-Dejean A, Agut H, Bordigoni P, Fortier B, et al. Contribution of human herpesvirus 6 (HHV-6) viral load in whole blood and serum to investigate integrated HHV-6 transmission after haematopoietic stem cell transplantation. J Clin Virol. 2009;45(1):43-6,10.1016/j.jcv.2009.

Huang LM, Kuo PF, Lee CY, Chen JY, Liu MY, Yang CS. Detection of human herpesvirus-6 DNA by polymerase chain reaction in serum or plasma. J Med Virol. 1992;38(1):7-10.

Secchiero P, Carrigan DR, Asano Y, Benedetti L, Crowley RW, Komaroff AL, et al. Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. J Infect Dis. 1995;171(2):273-80.

Nitsche A, Muller CW, Radonic A, Landt O, Ellerbrok H, Pauli G, et al. Human herpesvirus 6A DNA Is detected frequently in plasma but rarely in peripheral blood leukocytes of patients after bone marrow transplantation. J Infect Dis. 2001;183(1):130-3,10.1086/317651.10.1086/317651.

Zerr DM, Gooley TA, Yeung L, Huang ML, Carpenter P, Wade JC, et al. Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients. Clin Infect Dis. 2001;33(6):763-71,10.1086/322642.10.1086/322642.

Yoshikawa T. Human herpesvirus 6 infection in hematopoietic stem cell transplant patients. Br J Haematol. 2004;124(4):421-32.

Al Fawaz T, Ng V, Richardson SE, Barton M, Allen U. Clinical consequences of human herpesvirus-6 DNAemia in peripheral blood in pediatric liver transplant recipients. Pediatr Transplant. 2014;18(1):47-51,10.1111/petr.12176.10.1111/petr.12176.

Scheurer ME, Pritchett JC, Amirian ES, Zemke NR, Lusso P, Ljungman P. HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis. Bone Marrow Transplant. 2013;48(4):574-80,10.1038/bmt.2012.180.10.1038/bmt.2012.180.

Fernandez-Ruiz M, Kumar D, Husain S, Lilly L, Renner E, Mazzulli T, et al. Utility of a monitoring strategy for human herpesviruses 6 and 7 viremia after liver transplantation: a randomized clinical trial. Transplantation. 2015;99(1):106-13,10.1097/TP.0000000000000306.10.1097/TP.0000000000000306.

Violago L, Jin Z, Bhatia M, Rustia E, Kung AL, Foca MD, et al. Human herpesvirus-6 viremia is not associated with poor clinical outcomes in children following allogeneic hematopoietic cell transplantation. Pediatr Transplant. 2015;19(7):737-44,10.1111/petr.12572.10.1111/petr.12572.

Ono Y, Ito Y, Kaneko K, Shibata-Watanabe Y, Tainaka T, Sumida W, et al. Simultaneous monitoring by real-time polymerase chain reaction of epstein-barr virus, human cytomegalovirus, and human herpesvirus-6 in juvenile and adult liver transplant recipients. Transplant Proc. 2008;40(10):3578-82,10.1016/j.transproceed.2008.

Pischke S, Gosling J, Engelmann I, Schlue J, Wolk B, Jackel E, et al. High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis. J Hepatol. 2012;56(5):1063-9,10.1016/j.jhep.2011.

Guardia-Silva AC, Stucchi RS, Sampaio AM, Milan A, Costa SC, Boin IF. Detection of cytomegalovirus and human herpesvirus-6 DNA in liver biopsy specimens and their correlation with rejection after liver transplantation. Transplant Proc. 2012;44(8):2441-4,10.1016/j.transproceed.2012.

Boutolleau D, Bonduelle O, Sabard A, Devers L, Agut H, Gautheret-Dejean A, et al. Detection of human herpesvirus 7 DNA in peripheral blood reflects mainly CD4+ cell count in patients infected with HIV. J Med Virol. 2005;76(2):223-8,10.1002/jmv.20345.10.1002/jmv.20345.

Guardia AC, Stucchi RS, Sampaio AM, Milan A, Costa SC, Pavan CR, et al. Human herpesvirus 6 in donor biopsies associated with the incidence of clinical cytomegalovirus disease and hepatitis C virus recurrence. Int J Infect Dis. 2012;16(2):e124-9,10.1016/j.ijid.2011.

Phan TL, Lautenschlager I, Razonable RR, Munoz FM. HHV-6 in liver transplantation: A literature review. Liver Int. 2017,10.1111/liv.13506.10.1111/liv.13506.

Abdel Massih RC, Razonable RR. Human herpesvirus 6 infections after liver transplantation. World J Gastroenterol. 2009;15(21):2561-9.

Ylinen E, Lehtinen S, Jahnukainen T, Karlsson T, Loginov R, Mannonen L, et al. Human herpes virus 6 infection in pediatric organ transplant patients. Pediatr Transplant. 2017;21(4),10.1111/petr.12905.10.1111/petr.12905.

Kouri V, Correa C, Martinez PA, Sanchez L, Alvarez A, Gonzalez G, et al. Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation. Springerplus. 2014;3:247,10.1186/2193-1801-3-247.10.1186/2193-1801-3-247.

Yoshikawa T, Ihira M, Suzuki K, Suga S, Iida K, Saito Y, et al. Human herpesvirus 6 infection after living related liver transplantation. J Med Virol. 2000;62(1):52-9.

Griffiths PD, Ait-Khaled M, Bearcroft CP, Clark DA, Quaglia A, Davies SE, et al. Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus. J Med Virol. 1999;59(4):496-501.

Lautenschlager I, Linnavuori K, Hockerstedt K. Human herpesvirus-6 antigenemia after liver transplantation. Transplantation. 2000;69(12):2561-6.

Montejo M, Ramon Fernandez J, Testillano M, Valdivieso A, Aguirrebengoa K, Varas C, et al. Encephalitis caused by human herpesvirus-6 in a liver transplant recipient. Eur Neurol. 2002;48(4):234-5,66172.66172.

Costa FA, Soki MN, Andrade PD, Bonon SH, Thomasini RL, Sampaio AM, et al. Simultaneous monitoring of CMV and human herpesvirus 6 infections and diseases in liver transplant patients: one-year follow-up. Clinics (Sao Paulo). 2011;66(6):949-53.

Ohashi M, Yoshikawa T, Asonuma K, Iwasaki T, Nishiyama Y, Asano Y, et al. Human herpesvirus 6 fulminant hepatic failure treated by living donor liver transplantation. Pediatr Int. 2004;46(6):730-2,10.1111/j.1442-200x.2004.01989.x.10.1111/j.1442-200x.2004.01989.x.

Harma M, Hockerstedt K, Lyytikainen O, Lautenschlager I. HHV-6 and HHV-7 antigenemia related to CMV infection after liver transplantation. J Med Virol. 2006;78(6):800-5,10.1002/jmv.20626.10.1002/jmv.20626.

Sampaio AM, Guardia AC, Milan A, Sasaki AN, Andrade PD, Bonon SH, et al. Co-infection and clinical impact of human herpesvirus 5 and 6 in liver transplantation. Transplant Proc. 2012;44(8):2455-8,10.1016/j.transproceed.2012.

DesJardin JA, Cho E, Supran S, Gibbons L, Werner BG, Snydman DR. Association of human herpesvirus 6 reactivation with severe cytomegalovirus-associated disease in orthotopic liver transplant recipients. Clin Infect Dis. 2001;33(8):1358-62,10.1086/323336.10.1086/323336.

Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg. 1996;15(4):250-7.

Descamps V, Bouscarat F, Laglenne S, Aslangul E, Veber B, Descamps D, et al. Human herpesvirus 6 infection associated with anticonvulsant hypersensitivity syndrome and reactive haemophagocytic syndrome. Br J Dermatol. 1997;137(4):605-8.

Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-97,10.1016/j.amjmed.2011.

Ishida T, Kano Y, Mizukawa Y, Shiohara T. The dynamics of herpesvirus reactivations during and after severe drug eruptions: their relation to the clinical phenotype and therapeutic outcome. Allergy. 2014;69(6):798-805,10.1111/all.12410.10.1111/all.12410.

Cho YT, Yang CW, Chu CY. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System. Int J Mol Sci. 2017;18(6),10.3390/ijms18061243.10.3390/ijms18061243.

Shiohara T, Ushigome Y, Kano Y, Takahashi R. Crucial Role of Viral Reactivation in the Development of Severe Drug Eruptions: a Comprehensive Review. Clin Rev Allergy Immunol. 2015;49(2):192-202,10.1007/s12016-014-8421-3.10.1007/s12016-014-8421-3.

Descamps V, Ranger-Rogez S. DRESS syndrome. Joint Bone Spine. 2014;81(1):15-21,10.1016/j.jbspin.2013.

Asano Y, Yoshikawa T, Suga S, Nakashima T, Yazaki T, Fukuda M, et al. Reactivation of herpesvirus type 6 in children receiving bone marrow transplants for leukemia. N Engl J Med. 1991;324(9):634-5,10.1056/NEJM199102283240915.10.1056/NEJM199102283240915.

Imbert-Marcille BM, Tang XW, Lepelletier D, Besse B, Moreau P, Billaudel S, et al. Human herpesvirus 6 infection after autologous or allogeneic stem cell transplantation: a single-center prospective longitudinal study of 92 patients. Clin Infect Dis. 2000;31(4):881-6,10.1086/318142.10.1086/318142.

Yoshikawa T, Asano Y, Ihira M, Suzuki K, Ohashi M, Suga S, et al. Human herpesvirus 6 viremia in bone marrow transplant recipients: clinical features and risk factors. J Infect Dis. 2002;185(7):847-53,10.1086/339411.10.1086/339411.

Zerr DM, Corey L, Kim HW, Huang ML, Nguy L, Boeckh M. Clinical outcomes of human herpesvirus 6 reactivation after hematopoietic stem cell transplantation. Clin Infect Dis. 2005;40(7):932-40,10.1086/428060.10.1086/428060.

Ogata M, Kikuchi H, Satou T, Kawano R, Ikewaki J, Kohno K, et al. Human herpesvirus 6 DNA in plasma after allogeneic stem cell transplantation: incidence and clinical significance. J Infect Dis. 2006;193(1):68-79,10.1086/498531.10.1086/498531.

de Pagter PJ, Schuurman R, Meijer E, van Baarle D, Sanders EA, Boelens JJ. Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation. J Clin Virol. 2008;43(4):361-6,10.1016/j.jcv.2008.

Lau YL, Peiris M, Chan GC, Chan AC, Chiu D, Ha SY. Primary human herpes virus 6 infection transmitted from donor to recipient through bone marrow infusion. Bone Marrow Transplant. 1998;21(10):1063-6,10.1038/sj.bmt.1701230.10.1038/sj.bmt.1701230.

Zerr DM, Gupta D, Huang ML, Carter R, Corey L. Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34(3):309-17,10.1086/338044.10.1086/338044.

Sashihara J, Tanaka-Taya K, Tanaka S, Amo K, Miyagawa H, Hosoi G, et al. High incidence of human herpesvirus 6 infection with a high viral load in cord blood stem cell transplant recipients. Blood. 2002;100(6):2005-11.

Chevallier P, Hebia-Fellah I, Planche L, Guillaume T, Bressolette-Bodin C, Coste-Burel M, et al. Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source. Bone Marrow Transplant. 2010;45(7):1204-11,10.1038/bmt.2009.326.10.1038/bmt.2009.326.

Mori Y, Miyamoto T, Nagafuji K, Kamezaki K, Yamamoto A, Saito N, et al. High incidence of human herpes virus 6-associated encephalitis/myelitis following a second unrelated cord blood transplantation. Biol Blood Marrow Transplant. 2010;16(11):1596-602,10.1016/j.bbmt.2010.

Inazawa N, Hori T, Nojima M, Saito M, Igarashi K, Yamamoto M, et al. Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay. J Med Virol. 2017;89(2):358-62,10.1002/jmv.24621.10.1002/jmv.24621.

Greco R, Crucitti L, Noviello M, Racca S, Mannina D, Forcina A, et al. Human Herpesvirus 6 Infection Following Haploidentical Transplantation: Immune Recovery and Outcome. Biol Blood Marrow Transplant. 2016;22(12):2250-5,10.1016/j.bbmt.2016.

Hill JA, Myerson D, Sedlak RH, Jerome KR, Zerr DM. Hepatitis due to human herpesvirus 6B after hematopoietic cell transplantation and a review of the literature. Transpl Infect Dis. 2014;16(3):477-83,10.1111/tid.12208.10.1111/tid.12208.

Kuribayashi K, Matsunaga T, Iyama S, Takada K, Sato T, Murase K, et al. Human herpesvirus-6 hepatitis associated with cyclosporine-A encephalitis after bone marrow transplantation for chronic myeloid leukemia. Intern Med. 2006;45(7):475-8.

Dewhurst S, McIntyre K, Schnabel K, Hall CB. Human herpesvirus 6 (HHV-6) variant B accounts for the majority of symptomatic primary HHV-6 infections in a population of U.S. infants. J Clin Microbiol. 1993;31(2):416-8.

Fujino M, Ohashi M, Tanaka K, Kato T, Asano Y, Yoshikawa T. Rhabdomyolysis in an infant with primary human herpesvirus 6 infection. Pediatr Infect Dis J. 2012;31(11):1202-3,10.1097/INF.0b013e318266b3c9.10.1097/INF.0b013e318266b3c9.

Yoshikawa T, Ihira M, Suzuki K, Suga S, Kito H, Iwasaki T, et al. Fatal acute myocarditis in an infant with human herpesvirus 6 infection. J Clin Pathol. 2001;54(10):792-5.

Asano Y, Yoshikawa T, Suga S, Yazaki T, Kondo K, Yamanishi K. Fatal fulminant hepatitis in an infant with human herpesvirus-6 infection. Lancet. 1990;335(8693):862-3.

Tajiri H, Nose O, Baba K, Okada S. Human herpesvirus-6 infection with liver injury in neonatal hepatitis. Lancet. 1990;335(8693):863.

Takikawa T, Hayashibara H, Harada Y, Shiraki K. Liver dysfunction, anaemia, and granulocytopenia after exanthema subitum. Lancet. 1992;340(8830):1288-9.

Mendel I, de Matteis M, Bertin C, Delaporte B, Maguer D, Collandre H, et al. Fulminant hepatitis in neonates with human herpesvirus 6 infection. Pediatr Infect Dis J. 1995;14(11):993-7.

Aita K, Jin Y, Irie H, Takahashi I, Kobori K, Nakasato Y, et al. Are there histopathologic characteristics particular to fulminant hepatic failure caused by human herpesvirus-6 infection? A case report and discussion. Hum Pathol. 2001;32(8):887-9,10.1053/hupa.2001.26477.10.1053/hupa.2001.26477.

Nobili V, Vento S, Dionisi C, Sartorelli MR, Russo C, Marcellini M. Acute liver failure as presenting feature of tyrosinemia type 1 in a child with primary HHV-6 infection. J Gastroenterol Hepatol. 2006;21(1 Pt 2):339,10.1111/j.1440-1746.2006.04045.x.10.1111/j.1440-1746.2006.04045.x.

Nobili V, Pietrobattista A, Francalanci P, Giovannoni I, Marcellini M, Vento S. Human herpesvirus type 6 hepatitis or familiar intrahepatic cholestasis: the importance of follow-up. BMJ Case Rep. 2009;2009,10.1136/bcr.08.2008.0623.10.1136/bcr.08.2008.0623.

Schenke C, Alejandre-Alcazar MA, Holter W, Korn K, Papadopoulos T, Kohler H. Aplastic anemia following hepatitis associated with human herpesvirus 6. J Pediatr Gastroenterol Nutr. 2010;51(4):527-9,10.1097/MPG.0b013e3181e9636e.10.1097/MPG.0b013e3181e9636e.

Durand P, Debray D, Mandel R, Baujard C, Branchereau S, Gauthier F, et al. Acute liver failure in infancy: a 14-year experience of a pediatric liver transplantation center. J Pediatr. 2001;139(6):871-6,10.1067/mpd.2001.119989.10.1067/mpd.2001.119989.

Tsunoda T, Inui A, Iwasawa K, Oikawa M, Sogo T, Komatsu H, et al. Acute liver dysfunction not resulting from hepatitis virus in immunocompetent children. Pediatr Int. 2017;59(5):551-6,10.1111/ped.13249.10.1111/ped.13249.

Harma M, Hockerstedt K, Lautenschlager I. The long-term outcomes of patients transplanted due to acute liver failure with hepatic human herpesvirus-6 infection. Transplant Proc. 2013;45(5):1910-2,10.1016/j.transproceed.2013.

Kirchesch H, Mertens T, Burkhardt U, Kruppenbacher JP, Hoffken A, Eggers HJ. Seroconversion against human herpesvirus-6 (and other herpesviruses) and clinical illness. Lancet. 1988;2(8605):273-4.

Dubedat S, Kappagoda N. Hepatitis due to human herpesvirus-6. Lancet. 1989;2(8677):1463-4.

Akashi K, Eizuru Y, Sumiyoshi Y, Minematsu T, Hara S, Harada M, et al. Brief report: severe infectious mononucleosis-like syndrome and primary human herpesvirus 6 infection in an adult. N Engl J Med. 1993;329(3):168-71,10.1056/NEJM199307153290304.10.1056/NEJM199307153290304.

Cacheux W, Carbonell N, Rosmorduc O, Wendum D, Paye F, Poupon R, et al. HHV-6-related acute liver failure in two immunocompetent adults: favourable outcome after liver transplantation and/or ganciclovir therapy. J Intern Med. 2005;258(6):573-8,10.1111/j.1365-2796.2005.01567.x.10.1111/j.1365-2796.2005.01567.x.

Grima P, Chiavaroli R, Calabrese P, Tundo P, Grima P. Severe hepatitis with autoimmune features following a HHV-6: a case report. Cases J. 2008;1(1):110,10.1186/1757-1626-1-110.10.1186/1757-1626-1-110.

Chang YL, Parker ME, Nuovo G, Miller JB. Human herpesvirus 6-related fulminant myocarditis and hepatitis in an immunocompetent adult with fatal outcome. Hum Pathol. 2009;40(5):740-5,10.1016/j.humpath.2008.

Maggi U, Russo R, Conte G, Chiumello D, Lunghi G, Maggioni M, et al. Fulminant multiorgan failure due to varicella zoster virus and HHV6 in an immunocompetent adult patient, and anhepatia. Transplant Proc. 2011;43(4):1184-6,10.1016/j.transproceed.2011.

Cleron B, Argote C, Chevrier A. [Fulminant hepatitis and multiorgan failure induced by HHV-6 infection in an immunocompetent 24-year-old woman]. Ann Fr Anesth Reanim. 2014;33(12):707-8,10.1016/j.annfar.2014.

Charnot-Katsikas A, Baewer D, Cook L, David MZ. Fulminant hepatic failure attributed to infection with human herpesvirus 6 (HHV-6) in an immunocompetent woman: A case report and review of the literature. J Clin Virol. 2016;75:27-32,10.1016/j.jcv.2015.

Mason A, Sallie R, Perrillo R, Rayner A, Xu L, Dohner DE, et al. Prevalence of herpesviridae and hepatitis B virus DNA in the liver of patients with non-A, non-B fulminant hepatic failure. Hepatology. 1996;24(6):1361-5,10.1002/hep.510240608.10.1002/hep.510240608.



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