EASTLUND TED - 28/02/2018 - 02:46

Record to update: 
Adverse Occurrence type: 
MPHO Type: 
Estimates Frequency: 
Cannot estimate: Within 15 days after heart transplantation, the patient developed “respiratory and limb weakness” and pneumonia progressing to fatal quadriparalysis and multi-organ failure, from HEV infection transmitted by a RBC transfusion given 12 days before the transplant operation. The report does not provide any information about the recipient outcomes of other blood components of the same blood donation, if any, such as platelets and plasma. Thus we cannot estimate the efficiency of the RBC and other components to carry and transmit HEV.
Time to detection: 
Within 27 days after RBC transfusion, acute flaccid paralysis developed.
Alerting signals, symptoms, evidence of occurrence : 
Within 27 days of receiving a RBC transfusion from an asymptomatic HEV-infected blood donor during ECMO and within 15 days after heart transplantation from an organ donor who was not infected by HEV, the patient developed “respiratory and limb weakness”. This was followed by severe pneumonia progressing to fatal quadriparalysis (“ acute inflammatory polyradiculopathy”), multidrug-resistant bacterial infections, respiratory failure, renal failure, and death 153 days after transplant. After testing archived samples of all 43 blood donors of transfusions given before transplant, one donor tested positive and HEV RNA and negative for anti-HEV. The patient tested negative for anti-HEV and HEV RNA at the time of transplant. The patient’s serum sample from postop day 56 was positive for HEV RNA. No samples were available from the patient following transfusion and transplantation prior to development of respiratory and limb paresis. Therefore the length of the seronegative incubation period could not be determined. HEV was documented in his CSF. Phylogenetic analysis of nucleic acid sequences of the HEV-3 strain obtained from the patient and the implicated blood donor revealed sequence homology. HEV hepatitis is usually transmitted by the fecal-oral route and from contaminated water. The HEV-3 genotype is infrequently found and usually found in animals (pigs, wild boar, deer), causing an asymptomatic infection but the patient had been hospitalized and not been exposed to animals.
Demonstration of imputability or root cause: 
Definite. The report documents transmission of HEV by blood transfusion to a heart recipient by demonstrating the same HEV-3 strain in the implicated blood donor and in the blood recipient. Phylogenetic analysis of nucleic acid sequences of the HEV-3 strain obtained from the patient and the implicated blood donor revealed sequence homology. HEV hepatitis is usually transmitted by the fecal-oral route and from contaminated water but has been transmitted by food and by kidney and liver transplantation and by transfusion to a liver recipient. The HEV-3 genotype is infrequently found and usually found in animals (pigs, wild boar, deer), causing an asymptomatic infection but the patient had been hospitalized and not been exposed to animals.
Imputability grade: 
3 Definite/Certain/Proven
Groups audience: 
Note: 
advise that you keep this one in the library
Suggest new keywords: 
HEV Hepatitis E Virus HEV RNA Anti-HEV Paralysis Paresis Tetraparesis Quadriparesis Hepatitis acute inflammatory polyradiculopathy red cell transfusion transfusion blood donor blood donor infection Respiratory failure Viral infection renal failure
Adverse occurrence description: 
Transfusion-Transmitted Hepatitis E Virus (HEV) causing fatal quadriparalysis in a heart transplant recipient
Suggest references: 
Schlosser B, Stein A, Neuhaus R, Pahl S, Ramez B, Krüger DH, Berg T, Hofmann J. Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient. J Hepatol. 2012 Feb;56(2):500-2. doi: 10.1016/j.jhep.2011.06.021. Epub 2011 Jul 26. Pourbaix A, Ouali N, Soussan P, Roque Afonso AM, Péraldi MN, Rondeau E, Peltier J Evidence of hepatitis E virus transmission by renal graft. Transpl Infect Dis. 2017 Feb;19(1). doi: 10.1111/tid.12624. Epub 2017 Jan 10. Coilly A, Haïm-Boukobza S, Roche B, Antonini TM, Pause A, Mokhtari C, Becq A, Farahmand H, Hauser L, Duclos-Vallée JC, Samuel D, Adam R, Roque-Afonso AM. Posttransplantation hepatitis E: transfusion-transmitted hepatitis rising from the ashes. Transplantation. 2013 Jul 27;96(2):e4-6. doi: 10.1097/TP.0b013e318296c9f7 Waldenström J, Castedal M, Konar J, Karason K, Lagging M, Norder H. Chronic hepatitis E infection with an emerging virus strain in a heart transplant recipient successfully treated with ribavirin: a case report. J Med Case Rep. 2015 Aug 26;9:180. doi: 10.1186/s13256-015-0655-z Guerra JAAA, Kampa KC, Morsoletto DGB, Junior AP, Ivantes CAP Hepatitis E: A Literature Review. J Clin Transl Hepatol. 2017 Dec 28;5(4):376-383. doi: 10.14218/JCTH.2017.00012. Epub 2017 Aug 18. Satake M, Matsubayashi K, Hoshi Y, Taira R, Furui Y, Kokudo N, Akamatsu N, Yoshizumi T, Ohkohchi N, Okamoto H, Miyoshi M, Tamura A, Fuse K, Tadokoro K. Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression. Transfusion. 2017 Feb;57(2):280-288. doi: 10.1111/trf.13994. Epub 2017 Jan 31. (RESULTS: Twenty established TT-HEV cases were recorded over the past 17 years. A lookback study verified that five of 10 patients transfused with known HEV-contaminated blood components acquired HEV infection. The minimal infectious dose of HEV through transfusion was 3.6 × 104 IU. Nine of the 19 TT-HEV cases analyzed had hematologic diseases. Only two cases showed the maximal alanine aminotransferase level of more than 1000 U/L. Two patients with hematologic malignancy and two liver transplant recipients had chronic liver injury of moderate severity. CONCLUSION: The infectivity of HEV-contaminated components was 50%. Immunosuppression likely causes the moderate illness of TT-HEV, but it may lead to the establishment of chronic sequelae. Kurihara T1, Yoshizumi T2, Itoh S1, Harimoto N1, Harada N1, Ikegami T1, Inagaki Y3, Oshiro Y3, Ohkohchi N3, Okamoto H4, Maehara YChronic hepatitis E virus infection after living donor liver transplantation via blood transfusion: a case report. Surg Case Rep. 2016 Dec;2(1):32. doi: 10.1186/s40792-016-0159-0. Epub 2016 Apr 8. (Abstract. This study describes a 41-year-old man with liver cirrhosis caused by non-alcoholic steatohepatitis and hepatocellular carcinoma within the Milan criteria. Living donor liver transplantation (LDLT) was performed, and he was discharged from the hospital on postoperative day (POD) 22. However, his alanine aminotransferase concentration began to increase on POD 60 and HEV infection was detected on POD 81. Retrospective assessments of stored blood samples showed that this patient became positive for HEV RNA on POD 3. The liver donor was negative for anti-HEV antibodies and HEV RNA. However, the platelet concentrate transfused into the liver recipient the day after LDLT was positive for HEV RNA. The patient remained positive for HEV infection for 10 months. Treatment with 800 mg/day ribavirin for 20 weeks reduced HEV RNA to an undetectable level. In conclusion, this report describes a patient infected with HEV through a blood transfusion after LDLT, who progressed to chronic hepatitis probably due to his immunosuppressed state and was treated well with ribavirin therapy)
Expert comments for publication: 
HEV hepatitis is usually transmitted by the fecal-oral route and from contaminated water but has been transmitted by food, by kidney transplantation, by liver transplantation and by transfusion to a liver recipient. Transplant physicians need to be aware that when a transplant recipient develops hepatitis or neurologic complications such as the acute inflammatory polyradiculopathy described in this case, and the cause is undetermined, they should consider HEV infection as a possible source. In a review by Guerra et al, the spectrum of neurologic complications of HEV infection has been wide and includes bilateral pyramidal signs, ataxia, proximal myopathy, encephalitis, cognitive dysfunction, peripheral demyelinating polyneuropathy, peripheral pain sensory neuropathy, Guillain-Barré syndrome, Bell’s palsy, acute transverse myelitis and acute meningoencephalitis Guerra JAAA, Kampa KC, Morsoletto DGB, Junior AP, Ivantes CAP Hepatitis E: A Literature Review. J Clin Transl Hepatol. 2017 Dec 28;5(4):376-383. doi: 10.14218/JCTH.2017.00012. Epub 2017 Aug 18. When the source of HEV infections is not the organ donor and transfusions have been given before or after transplantation, an evaluation of the blood donors is important.