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Adverse Occurrence type:
Estimated frequencies vary, with significant limitations due to methodology and assays used. In this paper, two recipients were cited, with probable transmission only to the combined liver and kidney recipient and not to the kidney only recipient.
Time to detection:
7 months to start of symptoms, 8 months to diagnosis
Alerting signals, symptoms, evidence of occurrence:
Donor: A 57 year old male with history of hypertension and diabetes mellitus, classified as increased risk due to history of drug use, sex in exchange for money, and men who have sex with men (MSM) behavior. Cause of death was intracranial hemorrhage. Pre-organ transplant routine screening results included evidence of previous hepatitis B infection and no evidence of HCV or HIV infection. The donor’s state of residency and country of birth were not documented. Recipient 1: A 56 year old female underwent combined liver and right kidney; eight months after transplantation she presented with a four week history of progressively worsening abdominal pain initially. Ascit fluid was obtained by abdominal paracentesis, with negative cultures and cytology. Abdominal CT identified a peri-pancreatic mesenteric mass and a biopsy revealed proliferation of spindle cells with prominent chronic inflammatory cell infiltrate including numerous plasma cells consistent with Kaposi's sarcoma (KS); HHV8 infection was confirmed by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) testing for sex chromosomes X and Y in the mesenteric tissue was performed revealed XX female chromosomes indicating the tumor was recipient in origin. Tacrolimus was changed to sirolimus, with resolution of ascites, mesenteric mass and abdominal pain within 6 months. Recipient 2 (left kidney): a 62 year old male with kidney failure secondary to diabetes mellitus, at 10 months post-transplant, there was no evidence of HHV8 seroconversion or any symptoms.
Demonstration of imputability or root cause:
Pre-transplant donor and recipient samples were tested for IgG antibodies to HHV-8 using two enzyme immunoassays (EIAs, ORF K8.1 and ORF 65 viral genes) and a whole cell immunofluorescence assay (IFA). These three in-house CDC (Centers for Disease Control and Prevention USA) tests have a combined sensitivity of 96.3% and specificity of 97.5%. Donor was seropositive, seroconversion was demonstrated in one of the recipients (recipient 1), supporting a donor-derived transmission; HHV-8 prevalence is low in the US general population at 3-6% and concentrated in the MSM community where the prevalence varies between 15 to 50%.
Fatal disseminated Kaposi's sarcoma following human herpesvirus 8 primary infections in liver-transplant recipients
Suggest new keywords:
increased risk donor;Kidney transplant; liver transplant; immunohistochemistry; ascites; spindle cells; immunofluorescence assay; ORF 65; ORF K8.1
Fluorescence in situ hybridization; tacrolimus; sirolimus
1) Donor derived Kaposi's sarcoma in a liver-kidney transplant recipient. et al. Am J Transplant. 2017 Sep 23. 2) Marcelin AG, Roque-Afonso AM, Hurtova M, et al. Fatal disseminated Kaposi's sarcoma following human herpesvirus 8 primary infections in liver-transplant recipients. Liver transplantation 2004;10:295-300. 3) Chiereghin et al. Multicenter Prospective Study for Laboratory Diagnosis of HHV8 Infection in Solid Organ Donors and Transplant Recipients and Evaluation of the Clinical Impact After Transplantation. Transplantation. 2017 Aug;101(8):1935-1944
I left this case as a separate entry to others as the risk for the donor seems not to have been birth or residency in an endemic country. Also, FISH study of the tumour adds interest. Availability of serology in D/R, and discussion about difficulties with current serological methods available.
Expert comments for publication:
There is sparse seroprevalence data in various groups at increased risk of HHV8 infection in non-endemic countries; these pools of individuals contribute to the increased risk of donor acquired HHV8 infection or reactivation in previously infected recipients. The challenges with HHV8 serology are also highlighted, with further information also available through many other publications, eg Marcelin et al 2004, Chiereghin et al 2017. In terms of clinical management of the affected recipient, this case is another example of control of symptomatic HHV8 infection by switching from calcineurin inhibitors (CNI) to sirolimus which is now considered the first-line treatment of KS for transplant recipients.