Hepatitis B Virus (HBV), Lung Transplant Recipient
Conditions
Keywords
HBV Disease, EVLP, lung transplant
Brief summary
The aim of the study is to show that transplantation of lungs from Hepatitis B-infected donors is safe when using EVLP with UV light inactivation plus antivirals
Detailed description
The success of transplantation is significantly hindered by the lack of sufficient available donors. Many potential donor organs are not fully utilized in clinical transplantation because donors have chronic viral infections. Currently, donors with chronic hepatitis B virus (HBV) infection are utilized by typically providing nucleoside analogues such as entecavir or lamivudine plus/minus several doses of HBIG. The entecavir or lamivudine are typically given either life-long in liver transplants or for 1 year in non-liver transplants. Donors with chronic HBV infection are Core Antibody positive (HBcAb +ve). These donors carry chronic virus but may be NAT positive or NAT negative. HBcAb+ve donors are routinely used, but NAT positive donors are typically not used. The Toronto lung transplant program commonly applies Ex Vivo Lung Perfusion (EVLP) to organs. This allows for treatment of organs prior to transplantation. The investigators have shown that UV light administered on the EVLP circuit can substantially decrease the amount of infectious virus. Such a strategy was previously employed with hepatitis C virus. The aim of the study is to show that transplantation of organs from HBV NAT+ve donors is safe with the use of UV light treatment on EVLP combined with post-transplant antivirals for the recipient (HBIG and entecavir). The investigators hypothesize that rates of HBV transmission to recipients will be prevented by the use of this approach and any HBV transmission that does occur will be readily treatable. This will be a small pilot study to determine the feasibility of this approach. If successful, the knowledge from this study can have an important impact on patients awaiting lung transplantation by providing a novel strategy for the use of HBV-positive organ donors, simplified through a shorter course of approved antivirals.
Interventions
DRUGEntecavir
Recipients will receive 1mg administered orally, beginning pre-transplant as soon as the patient arrives to the hospital for surgery, and then 1mg post-operatively administered orally or via nasogastric tube once daily for 28 days.
BIOLOGICALHBIG
Recipients will receive 4500 IU intravenously pre-transplant and then at day 3 and 7 post-transplant (3 doses total).
DEVICEEVLP UV Light Treatment
UV light therapy will be administered to the organ during EVLP prior to transplantation. For minimum 2 hours, maximum 6 hours (duration determined by time clinically required for EVLP based on standard clinical assessment of lung).
Sponsors
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
The antiviral used are both approved drugs (entecavir and HBIG) but being used for a new indication
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Donor Inclusion Criteria * Donor lung suitable for transplantation * HBV SAg positive and/or HBV NAT+ donor Donor
Exclusion criteria
* HIV positive * HTLV 1/2 positive; * Any medical issues in the donor that would normally clinically exclude the donor (e.g. history of cancer, evidence of organ dysfunction, etc). Recipient inclusion Criteria: * Recipients eligible and listed for lung transplant * HBV NAT negative * Provides written informed consent * Has received at least 3 prior doses of Hepatitis B vaccine or anti-HBs\>=10 IU/mL * Patients with other co-morbid conditions (such as diabetes, autoimmune disease, renal dysfunction) will remain eligible provided they are otherwise medically suitable for transplantation. The exception to this will be patients with significant liver disease as outlined below. Recipient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of transplantation using HBV positive donors reflected by negative HBV NAT at 6 months post-transplant | At 6 months post-transplant | Participant blood samples will be taken at days 3 and 7, then weekly for the first 4 weeks, then every two weeks until 12 weeks post-transplant, then at month 6 after transplantation. Blood samples will be tested for HBV DNA via Nucleic Acid Amplification. |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of acute liver dysfunction for infected patients | From enrollment until 2 years post-transplant |
| Interval of time from transplantation to viremia development | From enrollment until 2 years post-transplant |
| HBV suppression rates after treatment for infected patients | From time of infection until end of treatment or up to 2 years post-transplant |
| Incidence of any HBV donor to recipient transmission | From enrollment until 2 years post-transplant |
| Adverse reactions to antiviral therapy | From enrollment until 2 years post-transplant |
| In-hospital mortality | From hospital admission until date of discharge or date of death from any cause, whichever comes first, assessed up to 2 years |
| 1-year graft and patient survival | Measured 1 year post-transplant |
| Organ function at 1 year (FEV1) | Measured 1 year post-transplant |
| Development of anti-HBV antibodies (anti-HBs, anti-HBc) | From enrollment until 2 years post-transplant |
| Correlation between donor viremia level, and recipient infection | From enrollment until up to 2 years post-transplant |
Countries
Canada
Contacts
Primary ContactAtul Humar, MD, FRCPC
Outcome results
None listed