1. FACILITATOR VERSION Case Four: I just have antibodies to this
Educational Workshops 2015
FACILITATOR VERSION Case Four: I just have antibodies to this
We are grateful to William Tong, Consultant
Virologist, Barts Health NHS Trust, London for
composing this case.

2. Background 34 Year old woman Lupus nephritis diagnosed since 2001
Developed ESRF and commenced HD Sept 2005
Received a deceased donor renal transplant 13/2/2009
Donor was known to be an IVDU but serological screening was negative for BBV
The recipient was aware of the higher risk and accepted the transplant.

3. Post-transplant Progress
Recurrent ureteric stenosis requiring nephrostomy with continuous leakage
CMV D+ R-
Active CMV infection September successfully treated with valganciclovir
CMV viral load not detected since 2011
Stable on prednisolone, cyclosporin and MMF

4. Surprise finding !
Routine BBV screening on 15/5/2014 – found to be HCV IgG positive
Patient was known to be HCV IgG and RNA negative before the transplant
Case note review:
had a negative HCV IgG test in 2013
LFT was normal throughout

5. Where did she acquire HCV?

6. Where did she acquire HCV?
No obvious risk factors
No longer on haemodialysis
Single sexual partner who is HCV negative
No history of intravenous drug use
No history of Travel
Possible leads
Multiple procedures
? Blood transfusion
Acquired from the donor

7. What can be done to find out?

8. What can be done to find out?
To test serial samples retrospectively to establish timing of infection

9. Results of retrospective testing
No of weeks (yrs) from Renal Transplantation
HCV RNA (IU/ml)
HCV RNA (log value)
HCV IgG
HCV genotype
Event
-22
Neg
-13 -9
Date of Transplant 2
132606
5.12 4
6.32 9
774150
5.89 13
892774
5.95 45
195 (3.8)
7.56 3a
215 (4.1)
244 (4.7)
6.74
274 (5.3)
Pos
HCV Diagnosis made  
277 (5.3)
6.53
280 (5.4)
6.14

10. What else can we do to establish source of HCV infection?

11. What else can we do to establish source of HCV infection?
Retrieve donor samples
Sample from the donor has to be stored for at least 10 years and sample from the recipient for 30 years

12. Donor test results HCV antibody: NOT detected HCV RNA: detected
HCV genotype = 3a

13. What further proof is there that the donor is the source?

14. What further proof is there that the donor is the source?
Only 1 base difference out of 328 bp between donor and recipient in NS5b region of HCV. (99.7% homology)
Consistent with transmission between these two individuals

15. Patient progress Persistent normal LFT US liver showed coarse texture
Waiting for interferon free, all oral treatment for HCV

16. Summary and lessons
A case of transmission of HCV through renal transplantation
Screening using HCV IgG failed to identify an infected donor during the sero-conversion phase
PCR generally not available at time of donation – organ viability limits time available for testing
Should the blood be tested for PCR even if it does not affect decision re donation as it will affect recipient follow up strategy?
A positive HCV RNA result after donation would prompt PCR testing in the recipient
A negative PCR result would provide reassurance
Early diagnosis of HCV is useful because of availability of potent new direct acting agents
Will there be a role for prophylaxis in the future?

17. Summary and lessons
Immunocompromised patients with chronic hepatitis C could have persistent normal LFT
Delayed seroconversion often occurs in immunocompromised individuals
The recipient was sero-negative when tested for HCV IgG in 2013 (4 years after the initial infection)
PCR testing is required to make the diagnosis – who should be screened?
Transplant recipients and immunocompromised should be monitored using HCV RNA and HCV antigen rather than HCV IgG (especially if at risk of acquisition)