Hepatitis C Virus (HCV)

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Record number: 
Adverse Occurrence type: 
Estimated frequency: 
Frequency of this transmission event cannot be estimated currently because the study does not provide a review about this for technical reasons (first time report of three transmission clusters). Later studies estimate this risk as 1:1000 in donors with iv-drug abuse and increased risk for de-novo infection by HCV which is at time of NAT determination below the treshold of lower detection by the NAT-method used (see Notify record 1946) Summary of study provides proper estimate: HCV may be transmitted from organ donors to recipients even when the donors test negative by NAT. In all likelihood, this reflects the eclipse phase infection in donors with increased risk behaviors for the acquisition of HCV infection, especially injection drug users. Overall this risk is low and the use of the increased risk donors may be warranted given the younger age and better organ quality of some of these donors. Nevertheless, it is important to ensure that recipients understand the limitations of current testing strategies and the potential for transmission despite negative NAT. Early posttransplant screening of recipients with NAT for HCV RNA, along with protocols for monitoring and reporting of newly detected infections, are critical to identifying patients with new infections who may benefit from antiviral therapies.
Time to detection: 
Between 8 and 32 days during routine NAT surveillance of recipients of grafts from donors at increased risk for de-novo HCV-infection. Cluster 1: heart 30 days until routine NAT, kidney 8 days until routine NAT -> both genotype 2b (donor recipient); liver and second kidney: pre-infected with HCV genotype 3a and 1b and no genotype 2b detected. Cluster 2: kidney 32 days until routine NAT, other kidney NAT not-reactive after 3 months: -> genotype 1a in donor, 1b in recipient: either typing inaccurate or a potential infection with a recombinant genotype 1a/1b strain, Cluster 3: lung 14/66 days by routine NAT, kidney-pancreas 3/73 days unitl rorutine NAT, other kidney and heart NAT not reactive, other lung: early death -> donor and recipients genotype 1a (liver pre-infected with genotype 1a).
Alerting signals, symptoms, evidence of occurrence: 
See above. Of note in cluster 3, the HCV-NAT was done after 66 and 73 days and in the look back study of stored samples at 3 and 14 days NAT became reactive. Transmission evidence may be proved by phylogenetic similarity of donor's and recipients' genotype. Discussion of further clinical symptoms is not provided.
Demonstration of imputability or root cause: 
Three US clusters of HCV transmission from donors at increased risk for HCV infection (injection drug abuse) were followed up. Despite blood/serum NAT negative results HCV infection occured in 8 of 12 recipients -> HCV RNA was retrospectively detected in stored samples from donor immunologic tissue collected at organ procurement (splenocytes). Phylogenetic analysis showed two clusters of closely related HCV variants from recipients and donor (same genotype), in a thrid cluster there was a dfference between donor's and recipinet's genotype (2a vs. 2b). Method: Quasispecies analysis of hypervariable region-1 was used to establish genetic relatedness of recipient HCV variants. This study shows HCV transmissions from increased risk donors with negative NAT screening, indicating very recent donor HCV infection (eclispe period, where NAT in the blood compartment does not detect the virus while it may be spread at target tissue or PBMC). Recipient's informed consent and posttransplant screening for blood-borne pathogens are essential when considering increased risk donors.
Imputability grade: 
3 Definite/Certain/Proven
Suggest new keywords: 
Hepatitis C
NAT testing
recipient surveillance
increased risk donor
Reference attachment: 
Suggest references: 
1) 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.
Parts of this are cross referenced in 1710 and I would like to ensure that the requests are carried out. Otherwise this is ready to post. MG: Agree, please NOTIFY staff ensure the cross-referencing occurs and ready to post.
Expert comments for publication: 
The PHS Guidelines as well as the Council of Europe Guide to the Qualtiy and Safety of organs for transplantation recommend NAT surveillance of organ recipients after transplantation regarding HCV infection - especially in donors at increased risk for a recent HCV infection because during eclipse period blood NAT may be negative while infection can be transmitted. Secondly detection of HCV infection by NAT and initiating proper antiviral therapy before signifcant symptoms occur may simplify treatment to SVR in recipients (e.g. see Woolley AE, et al N Engl J Med. 2019 Apr 25;380(17):1606-1617 and Blumberg EA N Engl J Med. 2019 Apr 25;380(17):1669-1670)