This document discusses the transplantation of livers from hepatitis C virus (HCV) antibody-positive, HCV RNA-negative donors into HCV-negative recipients at a medical center between 2015-2017. Four cases of HCV transmission were observed. Various hypotheses for the transmission mechanism are discussed, including the possibility of an occult HCV infection or transient low-level viremia in donors. The timing of HCV testing in donors and lack of recipient RNA testing limit conclusions about the transmission mechanism. Taiwan has an estimated HCV antibody-positive rate of 4-5% in the general adult population, equivalent to 400,000-700,000 infected individuals.

1. 2018/08/16 9B Journal Reading
VS 何承懋 / PGY洪明道

3. Introduction & Background
2017, CDC,USA

4. Potential Organ Donors ?
Treatment

5. Introduction & Background
HCV Ab(+)
Non viremic

6. Molecular Diagnosis : Serological NAT Assays
Colin C; Sensitivity and specificity of third- generation hepatitis C virus antibody detection assays: an analysis of the literature. J Viral Hepat 2001

7. Recipient Selection
In 2015: Non-HCV status candidates
● HCV Ab(-)
● HCV Ab(+), undetectable NAT within 6 months prior to
transplantation
Informed Consent : 5% transmission rate

8. Donor Selection : Ab(+) , Virus(-)
The majority meet
Public Health Services (PHS)
Increased-Risk Criteria

9. Donor Selection : Ab(+) , Virus(-)
● Eclipse Phase of Reinfection ● Occult infection
HCV :
Serum (-)
Hepatocytes / mononuclear cells (+)
0.32% risk of HCV transmission

10. Donor Selection Tset
● 1 serum anti-HCV Ab test
● 1 serum HCV RNA test (NAT)
● May perform liver biopsy during transplantation
No executed prisoners or other institutionalized persons

11. HCV needle exposure transmission 3%

12. MMF
Transplantation
Tacrolimus ( trough 8~12 ng/ml)
HCV PCR
Screening
Corticosteroid
Antiviral Therapy if HCV(+)
Follow-up & Outcome measures
3 months
Tacrolimus ...
MMF ...

13. Result
● 26 / 125 (20.8%) liver transplants performed
● 2 simultaneous liver and kidney transplants
● 1 received two liver transplants (both seropositive nonviremic)

14. Histology did not reveal features
of viral hepatitis

16. Result

17. Case 1
● Recipient : 63 F, Primary sclerosing cholangitis
● Donor : 27 F, Anoxia related to a drug overdose
PHS increased risk (+)
● → Ledipasvir/sofosbuvir + ribavirin 33 days after (+)
→ SVR was achieved despite early discontinuation of ribavirin 2 weeks
because of adverse effects

18. Case 2
● Recipient : 61 F , Nonalcoholic steatohepatitis
● Donor : 32 M , Anoxia secondary to a heroin overdose
PHS increased risk(+)
● Biopsy : chronic HCV
● → 2-week course velpatasvir/sofosbuvir 31 days after (+)
→ End-of-treatment response, Follow-up for SVR is pending.

19. Case 3
● Recipient : 52 F , HIV, HCV, HCC
● Donor : 28 y.o. M , Anoxia presumed secondary to a heroin overdose
PHS increased risk(+)
● → Ledipasvir/sofosbuvir 14 days after(+)
→ Achieved SVR following 12 weeks of treatment

20. Molecular Analysis
Previous HCV ?
→
nonstructural protein 5B (NS5B)
phylogenetic analysis

21. Result
Only 1 patient
meet criteria
for molecular screening
2004
2005
2017

22. Case 4
● Recipient : 70 M ,
Nonalcoholic steatohepatitis complicated by portopulmonary hypertension
s/p transplant , primary graft non-function
→ 60 days retransplantation
● Donor: 26 M, Discovered unconscious with drug paraphernalia
PHS increased-risk(+)
● Multidrug-resistant infections
Renal failure from acute ATN necessitating hemodialysis
Died from pneumonia 9 months after

23. Discussion

24. Discussion -- Mechanisms
Hypothesis 1 : Eclipse period (Not favoured)
● Transmission rate : 16% >> 0.32%
● Meantime
28 other non-HCV Recipients &
PHS increased-risk, HCV-seronegative donors
→ none developed HCV viremia
Kucirka LM, et al. Risk of window period hepatitis-C infection in high infectious risk donors: systematic review and meta-analysis. Am J
Transplant

25. Discussion--Mechanism
Hypothesis 2 : Transient low-level viremia
● Occurs during the early phase of acute infection
(innate and cellular immune responses attempting to clear the virus)
● Described in chimpanzees experimentally infected with small HCV inocula
(mimic IDU)

26. Discussion--Mechanism
Hypothesis 3 : Occult infection
● Prevalence of OCI highly variable 0% ~ 95%
● Elmasry et al. : HCV RNA in liver tissue from 5 liver transplant recipients
(recurrent HCV, achieved SVR after treatment)
● Whitcomb et al. : 65 post SVR liver biopsies from patients ( recurrent HCV
after liver transplantation)
69% histologic features of active HCV infection, 1 confirmed (RNA)

27. ● The timing of NAT in donors
● One-time NAT of donors has limited predictive value
● Recipient RNA analysis not tested (may be viremic?, under 1%)
Discussion -- Other Factors

28. Epidemiological Data of Taiwan

29. ● 一般成人C型肝炎抗體陽性率估計約為4-5％
● C型肝炎感染者約40-70萬人
Epidemiological Data of Taiwan

30. Thank You For Listening

31. Molecular Diagnosis : Serological Assays
Colin C; Sensitivity and specificity of third- generation hepatitis C virus antibody detection assays:
an analysis of the literature. J Viral Hepat 2001