Transplant Policy and Procedure Manual

I.                PURPOSE: This document serves to guide the pre-transplant evaluation and post-transplant surveillance and management of heart transplant recipients receiving hearts from donors with active HCV infection (nucleic acid test donor positive: NAT D+).

II.              POLICY: Please refer to the policy entitled Transplant Selection Criteria for patient eligibility for heart transplantation. Once a patient is determined to be suitable for listing, appropriate patients will be given the opportunity to accept a Hepatitis C+/NAT D-/+ donor heart based on the following criteria:

a. Absence of significant chronic liver disease (as defined below).

b. Available for follow-up for at least 1-year post-transplant.

c. Patient consents to accept HCV NAT D+ organ following the discussion of potential risks and benefits, and willingness to be treated for HCV infection with direct acting antiviral (DAA) medications following heart transplantation.

d. Patients are considered not eligible for HCV NAT D+ transplantation if significant chronic liver disease is present as determined by:

1.      advanced fibrosis or steatosis on Fibroscan® with confirmation of  disease on liver biopsy;

2.      evidence of significant synthetic liver dysfunction (INR, Platelets, Hepatic panel) as determined by treating physicians;

3.      contraindications, allergy or patient unwillingness to take direct acting anti-viral (DAA) therapy;

4.      recommendation by hepatologist against HCV NAT D+ heart transplantation.

III.           PROCEDURE:

Pre-transplant evaluation of eligibility for NAT D+ heart transplantation:

a.  Informed consent for NAT D+ heart acceptance, with specific discussion and documentation of risks of HCV infection and treatment.

b. Measurement of serum HCV antibody, HCV RNA quantification, and hepatitis B virus (HBV) testing (HBsAb, HBcAb, HBsAg) (Table).

c.      Liver imaging with Fibroscan®; abnormal scans (> 8 kPa or > 280 dB/m) will be referred for liver biopsy and consultation with a hepatologist.

d. Patients with mechanical circulatory support devices and/or pacemakers may need to be imaged using ultrasound with elastography due to the artifact produced by the device.

e.      If the patient is matched with HCV NAT D+ organ, detailed HCV donor data will be requested including, but not limited to, HCV history (new vs. old diagnosis, treatment history), HCV Quantitative PCR (if available), HCV Donor genotype (if available), and HBV serologies (HBsAb, HBcAb, HBsAg, if available). A designated transplant physician will carefully analyze this data prior to acceptance and implantation of donor organ.

Post-transplant Protocol:

f.       All HCV NAT D+ recipients will be tested for the emergence of quantitative HCV RNA at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 12 months following heart transplant (Table). Patients will be tested for the emergence of HCV antibody at 1, 3, 6 and 12 months. (Table) Once a patient is anti-HCV positive, further testing for antibodies is not required.

g.      In the event Hepatitis C viremia is detected (as evidenced by the presence of HCV RNA), the patients will be re-assessed for HCV genotype and HCV resistance (NS5A and NS3/4A) and for HBV co-infection with HBsAg and HBcAg testing, and will initiate therapy with pan-genotypic DAA under the direction of the hepatology service as soon as the patient is able to tolerate therapy.

h.      Drug-drug interactions of DAA medication and immunosuppression medications will be evaluated in consultation with Hepatology and the transplant pharmacist, and immunosuppression regimen will be adjusted accordingly with close drug-specific monitoring. Standard immunosuppression regimen with tacrolimus, mycophenolate and prednisone will be used unless otherwise indicated:

                                                  i. sofosbuvir/velpatasvir (SOF/VEL, Epclusa) is safe with all immunosuppressants;

                                                ii. other DAA medications will be assessed for drug-drug interactions before use.

i.       Other potential drug-drug interactions will also be addressed. Patients will be monitored for drug tolerance, side effects, kidney and liver function as per standard of care.

j.       Treated patients will be followed with quantitative HCV RNA testing after 4 and 12 weeks of therapy and assessed for sustained virologic response (SVR) at 12 and 24 weeks after completion of therapy as per AASLD-IDSA guidelines (American Association for the Study of Liver Diseases).

k.      Additional blood tests such as HCV genotyping, resistance testing and Fibroscans® might be indicated on a case by case basis.

l.   Patients who fail initial therapy with non-achievement of SVR may be candidates for additional therapy depending upon hepatology’s recommendations, HCV genotype, HCV resistance and insurance approval.

m. Patients will be tested for development of donor-specific antibody at 3 months, 6 months, 9 months and 12 months post-transplant.

 I.                REFERENCES

ASLD-IDSA guidelines. https://www.aasld.org/sites/default/files/PracticeGuidelines-HCV-November2018.pdf. Accessed 4/30/2019.

Moayedi Y, Fan CPS, Gulamhusein AF, et al. Current Use of Hearts From Hepatitis C Viremic Donors. Circ Heart Fail. 2018; 11: e005276.

Patel SR, Madan S, Saeed O et al. Cardiac transplantation from non-viremic hepatitis C donors.

J Heart Lung Transplant. 2018; 37: 1254-60.

Schlendorf KH, Zalawadiya S, Shah AS  et al. Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies. J Heart Lung Transplant. 2018; 37: 763-9.

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