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.

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.

Post-transplant Progress Recurrent ureteric stenosis requiring nephrostomy with continuous leakage CMV D+ R- Active CMV infection September 2009 - successfully treated with valganciclovir CMV viral load not detected since 2011 Stable on prednisolone, cyclosporin and MMF

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

Where did she acquire HCV?

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

What can be done to find out?

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

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 2070763 6.32 9 774150 5.89 13 892774 5.95 45 2105611 195 (3.8) 36389475 7.56 3a 215 (4.1) 244 (4.7) 5517845 6.74 274 (5.3) Pos HCV Diagnosis made   277 (5.3) 3357571 6.53 280 (5.4) 1365923 6.14

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

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 30 years

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

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

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

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

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?

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)