Hepatitis C Positive Donor Into Hepatitis C Negative Recipients
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Hepatitis, Hepatitis |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 2/10/2019 |
| Start Date: | February 28, 2019 |
| End Date: | December 31, 2019 |
| Contact: | David Bruno, MD |
| Email: | dbruno@som.umaryland.edu |
| Phone: | 410-328-2691 |
An Open-label Pilot Study to Determine the Safety and Efficacy of Hepatitis C Uninfected Recipients of Renal and Liver Transplants From a Currently Infected or Previously Infected Hepatitis C Donor
Despite many efforts to increase the size of the donor pool, there is a large and growing
disparity between the number of donor kidneys and livers available for transplantation and
the number of patients on the transplant waiting list. New donor pools are needed to satisfy
the lack of available donor organs, along with expanded criteria for the existing donor
pools.
A new standard of care now exists at most local and regional transplant centers. This new
standard of care is based on the use of multiple direct-acting antiviral agents (DAAs) for
treatment of hepatitis C virus (HCV) that have been approved by the Food and Drug
Administration (FDA) for the treatment of hepatitis C and are associated with high HCV cure
rates and minimal side effect profiles. The efficacy and tolerability of these medications
has allowed the expansion of the available donor pool by making HCV antibody positive non
viremic organs and HCV-viremic organs (when HCV is detectable in the blood) available to
HCV-naive recipients on the organ transplantation waiting list. Expansion of this donor pool
may decrease time on the waiting list and improve quality of life and survival while waiting
for organ transplantation.
Study Aim:
We propose a clinical protocol to utilize solid organs from exposed and/or HCV-viremic organ
donors for transplantation into HCV negative recipients.
The primary purpose of the clinical protocol is to:
Collect prospective standard of care laboratory data on the results of these interventions
disparity between the number of donor kidneys and livers available for transplantation and
the number of patients on the transplant waiting list. New donor pools are needed to satisfy
the lack of available donor organs, along with expanded criteria for the existing donor
pools.
A new standard of care now exists at most local and regional transplant centers. This new
standard of care is based on the use of multiple direct-acting antiviral agents (DAAs) for
treatment of hepatitis C virus (HCV) that have been approved by the Food and Drug
Administration (FDA) for the treatment of hepatitis C and are associated with high HCV cure
rates and minimal side effect profiles. The efficacy and tolerability of these medications
has allowed the expansion of the available donor pool by making HCV antibody positive non
viremic organs and HCV-viremic organs (when HCV is detectable in the blood) available to
HCV-naive recipients on the organ transplantation waiting list. Expansion of this donor pool
may decrease time on the waiting list and improve quality of life and survival while waiting
for organ transplantation.
Study Aim:
We propose a clinical protocol to utilize solid organs from exposed and/or HCV-viremic organ
donors for transplantation into HCV negative recipients.
The primary purpose of the clinical protocol is to:
Collect prospective standard of care laboratory data on the results of these interventions
Once the donor is accepted for transplantation and the recipient enrolled in the innovative
clinical practice, donor HCV Ab status will be requested to initiate HCV RNA viral load
testing.
Donor data will be recorded as per our standard practice and as mandated by UNOS. Our
University of Maryland Medical Center team will be responsible for the donor operation as per
standard of care.
Hep C Ab + NAT - Donor to Naïve Recipient This group will be monitored as illustrated in
figure 1. Hep C Ab+ NAT+ Donor to Naïve Recipient HCV RNA levels, liver biochemistries, and
renal function will be measured 3 days after transplant. HCV Genotype will be determined
after HCV RNA is >1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until
HCV treatment is initiated.
Due to risk of HBV reactivation with DAA therapy, Hepatitis B surface antigen, surface
antibody and core antibody status will be determined prior to HCV therapy. In patients with a
prior exposure to HBV (i.e. positive HBV core antibody), Hepatitis B surface antigen levels
will be monitored throughout therapy.
All patients will be seen in the Hepatology clinic within 4 weeks of transplant to establish
care and follow-up.
HCV Therapy DAA therapy will be prescribed to all patients according to AASLD and IDSA joint
guidelines, after giving consideration to the transplanted organ, renal function, and HCV
genotype. All regimens exclude administration of ribavirin.
Therapy will be initiated as soon as possible (pending initiation of oral intake and
insurance approval) following organ transplantation.
DAAs will be prescribed, after which medications will then be delivered to the patient's home
or to the bedside.
If therapy is delayed beyond the 4-week appointment with Hepatology post-transplant, a
protocol to monitor for infection, new-onset diabetes mellitus, glomerulonephritis and severe
cholestatic hepatitis will be implemented. This protocol will include weekly blood work to
include: CBC with differential, hepatic function panel, basic metabolic panel, and
coagulation studies.
Liver Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
- Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
- Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30
Kidney Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
- Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30 HCV Follow-Up HCV RNA, complete
blood count (CBC) and liver biochemistries will be checked 4 weeks, 8 weeks, and 12
weeks after starting therapy. In patients previously exposed to HBV, HBV surface antigen
will be followed qualitatively at the same intervals.
HCV RNA will also be checked 12 weeks after completion of therapy to define cure, or
sustained virologic response. As part of long-term follow-up, HCV RNA will be checked
annually at routine post-transplant visits.
If SVR is not achieved, a second, and if needed, third antiviral regimen will be provided to
the participant at no cost.
Transplant, Post-Operative, Immunosuppression Follow Up All will be as per UMMC standard of
care. Unless otherwise contraindicated, tacrolimus immune suppression will be favored, due to
drug-drug interactions associated with DATs and cyclosporine.
clinical practice, donor HCV Ab status will be requested to initiate HCV RNA viral load
testing.
Donor data will be recorded as per our standard practice and as mandated by UNOS. Our
University of Maryland Medical Center team will be responsible for the donor operation as per
standard of care.
Hep C Ab + NAT - Donor to Naïve Recipient This group will be monitored as illustrated in
figure 1. Hep C Ab+ NAT+ Donor to Naïve Recipient HCV RNA levels, liver biochemistries, and
renal function will be measured 3 days after transplant. HCV Genotype will be determined
after HCV RNA is >1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until
HCV treatment is initiated.
Due to risk of HBV reactivation with DAA therapy, Hepatitis B surface antigen, surface
antibody and core antibody status will be determined prior to HCV therapy. In patients with a
prior exposure to HBV (i.e. positive HBV core antibody), Hepatitis B surface antigen levels
will be monitored throughout therapy.
All patients will be seen in the Hepatology clinic within 4 weeks of transplant to establish
care and follow-up.
HCV Therapy DAA therapy will be prescribed to all patients according to AASLD and IDSA joint
guidelines, after giving consideration to the transplanted organ, renal function, and HCV
genotype. All regimens exclude administration of ribavirin.
Therapy will be initiated as soon as possible (pending initiation of oral intake and
insurance approval) following organ transplantation.
DAAs will be prescribed, after which medications will then be delivered to the patient's home
or to the bedside.
If therapy is delayed beyond the 4-week appointment with Hepatology post-transplant, a
protocol to monitor for infection, new-onset diabetes mellitus, glomerulonephritis and severe
cholestatic hepatitis will be implemented. This protocol will include weekly blood work to
include: CBC with differential, hepatic function panel, basic metabolic panel, and
coagulation studies.
Liver Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
- Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
- Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30
Kidney Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
- Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30 HCV Follow-Up HCV RNA, complete
blood count (CBC) and liver biochemistries will be checked 4 weeks, 8 weeks, and 12
weeks after starting therapy. In patients previously exposed to HBV, HBV surface antigen
will be followed qualitatively at the same intervals.
HCV RNA will also be checked 12 weeks after completion of therapy to define cure, or
sustained virologic response. As part of long-term follow-up, HCV RNA will be checked
annually at routine post-transplant visits.
If SVR is not achieved, a second, and if needed, third antiviral regimen will be provided to
the participant at no cost.
Transplant, Post-Operative, Immunosuppression Follow Up All will be as per UMMC standard of
care. Unless otherwise contraindicated, tacrolimus immune suppression will be favored, due to
drug-drug interactions associated with DATs and cyclosporine.
Inclusion Criteria:
- RECIPIENT INCLUSION CRITERIA
- Patients undergoing solid organ transplantation, including liver, kidney, and
simultaneous liver-kidney who are not chronically infected with HCV
- No evident contraindication for organ transplantation
- HCV RNA negative (can be isolated HCV antibody positive provided the patient will
have no history of previously treated HCV)
- Age 18-75 years at the time of transplantation
- Signed Informed Consent Form
- No identified living organ donor
- Able to travel to the University of Maryland for routine post-transplant and HCV
follow-up visits
- Men and women must agree to use at least one barrier method to prevent any
secretion exchange
- No active illicit drug use
DONOR INCLUSION CRITERIA
• Qualitative HCV nucleic acid test (NAT) positive and/or Hepatitis C antibody positive HCV
donors offered to the University of Maryland.
Exclusion Criteria:
RECIPIENT EXCLUSION CRITERIA
- History of prior solid organ transplantation
- HIV infection
- HBV surface antigen or DNA positive. Organs from HCV positive donors who are also
Hepatitis B core antibody positive (hepatitis B surface antigen negative) can be used.
These patients will however need to undergo prophylaxis for HBV according to their
respective organ specific criteria and during treatment for hepatitis C due to the
increased risk of reactivation of hepatitis B with DAA therapy
- Waitlisted for a multi-organ transplant (with the exception of simultaneous
liver-kidney transplant)
- HCV RNA positive (can be isolated HCV antibody positive provided the patient will have
no history of previously treated HCV)
- Prior direct-acting antiviral (DAA) treatment for HCV. Patients previously treated
with interferon-based regimens may be included.
DONOR EXCLUSION CRITERIA
- Every donor that is considered unsuitable by the transplant surgeon for any reason.
- Hepatocellular carcinoma
- HIV infection
- Use of HCV positive livers to be determined according to current existing criteria
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