Status:
Ready to upload
Record number:
1710
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
In HCV infected stem cell donors the frequency of HCV transmission to the recipient depends on the viraemic status of the donor: whenever the donor is viraemic (NAT reactive) transmission will most likely be for 100% for sure, whenever the donor is not viraemic (NAT negative) transmission will be low - the wording unlikely needs to be confirmed by further studies. In this report (dated from the era before DAA became available) a donor with sustained virological response (SVR; HCV-NAT negative; n1) after treatment with ribavirin/PEG-regime did not transmit HCV to the recipient whereas donors without successful treatment (HCV-NAT reactive; n2) transmitted HCV. Of note, frequency estimate should be based on the NAT result and not anti-HCV result as in one case without HCV transmission the author observed a temporary anti-HCV reactivity from month 1 to month 5 post transplant - which might be a passively acquired reactivity and not based on infection (the authors did not mention the issue of passenger lymphocytes which has been observed as an issue in organ transplant since 2015 in other reports as one explanation beyond the issue of passive antibody transfer).
Time to detection:
Case 1: Donor viremic at day of HSCT -> recipient with liver dysfunction 1 month post HSCT and anti-HCV-seroconversion 1 month post HSCT (no data about recipient HCV-NAT status) No treatment of HCV infection in recipient reported at time of study
Case 2: Donor not viremic at day of HSCT -> recipient remained NAT negative after HSCT (follow up > 2 years); transient anti-HCV reactivity month 1-5 post HSCT not related to infection
Case 3: Donor viremic at day of HSCT -> recipient NAT reactive 1 week post HSCT, viral load increased to log 5 until month 2 post HSCT (with liver dysfunction). No treatment of HCV infection in recipient possible at time of study
Additional case to be considered in study of Tomblyn et al: Donor not viremic -> recipient remained not viremic
Alerting signals, symptoms, evidence of occurrence:
NAT reactive result in donor at HSCT should alert for risk of transmission; NAT reactive result in recipient (as soon as 1 week post HSCT with continuous follow up) should alert for infection. Typical symptoms of liver dysfunction of HCV infection are self speaking and may be absent in immunosuppressed patients. NAT result will be sufficient to determine occurrence.
Of note, where a donor is at higher risk of infection, consider the NAT not reactive situation: despite successful treatment with SVR and/or spontaneous clearance, HCV can persist or that the donor is in eclipse period before NAT becomes reactive. This is not mentioned in the study, but should be considered carefully (-> see Notify record 1826)
Demonstration of imputability or root cause:
HCV NAT reactive result in donor before HSCT and HCV NAT reactive result post HSCT in recipient are most likely related to HCV transmission
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Keywords:
References:
Suggest new keywords:
Hepatitis C
stem cell transplant
transmission
treatment of donor
Reference attachment:
Suggest references:
Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant. Hsiao HH et al. Transpl Infect Dis. 16(6):1003-6, 2014 Dec.
Note:
Carl-Ludwig (first Review): Internal comment: I hope you can agree to drifting off the contents of the article - unfortunately I know a little bit too much about organs and HCV but not enough about HSCT and HCV
.
Please add following references to this case: a) record 1826 "Transmission of Hepatitis C Virus From Organ Donors Despite Nucleic Acid Test Screening. Suryaprasad et al. American Journal of Transplantation. 15(7):1827-1835, July 2015. 2) Single-Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs Distinguishes Modes and Models of Virus Transmission and Early Diversification. Li H et al. J Virol. 90(1):152-66, 2016 Jan." b) Tomblyn M, Chen M, Kukreja M, et al. No increased mortality from donor or recipient hepatitis B- and/or hepatitis C-positive serostatus after related-donor allogeneic hematopoietic cell transplantation. Transpl Infect Dis 2012; 14: 468–478.
IUL started 2nd review and made some initial changes but will have to allocate to record.
MG: Asking please for the cross-referencing to be checked by the NOTIFY staff.
EP: cross-reference competed
Expert comments for publication:
This study is from 2014 and refers to the practice before Direct Acting Antivirals (DAA) became available. Therefore nowadays treatment options before HSCT in the donor and recipient after HSCT need to be re-evaluated. It is currently not proven whether already not reactive HCV NAT in HSCT donor will be sufficient to prevent HCV transmssion or whether SVR has to be awaited (2019).
An important finding, that this study confirms in one case, is that HCV-non-viremic donors do not transmit HCV to the recipient when we take into account the limitations known to be associated to such a result (see Notify record 1826).
It should not be surprising that HCV is transmissible by HSCT given it is transmissible via blood, and according to a 2011 review (Revie D, Salahuddin SZ. Human cell types important for hepatitis C virus replication in vivo and in vitro: old assertions and current evidence. Virol J. 2011 Jul 11;8:346. doi: 10.1186/1743-422X-8-346. PMID: 21745397; PMCID: PMC3142522.): "The in vivo studies described above have provided an impressive amount of evidence that HCV infects not only hepatocytes, but many other extrahepatic sites that include B cells, T cells, and macrophages/monocytes. The life cycle of HCV is unclear, but may involve cycling between liver and other tissues. A complex life cycle could help explain why it takes a long time for HCV-infected individuals to progress to liver and other diseases."