# Increased Risk Donor Toolkit

# Toolkit Purpose
This toolkit was developed to summarize recommendations on the use of Increased Risk Donors (IRDs) for organ transplantation as well as to provide useful information and guidance that could help Ontario increase organ utilization and improve access to organ transplantation for patients. It is intended for use by transplant physicians, hospital administration and transplant programs who are directly or indirectly involved with patient care in a transplant setting. This toolkit includes recommended tools and templates to support transplant programs in providing information to patients on the use of increased risk donors for transplantation.
The objectives of this toolkit are to:  Educate all healthcare providers along the transplant continuum about IRDs;  Provide guidance to healthcare administrators about incorporating IRDs into their clinical and administrative processes;  Provide information to healthcare providers to educate patients about IRDs;  Provide tools to support informed patient consent at the time of transplant.

# Toolkit Development Process
In March 2013, the Canadian Society of Transplantation (CST) and the Canadian National Transplant Research Program (CNTRP) held a conference and developed a framework guidance document that outlines recommendations for utilization of IRDs in Canada. The conference included experts from Canada in organ and tissue donation and transplantation, transplant infectious diseases, laboratory medicine, and epidemiology. Additional content expertise was provided by Health Canada, several major Canadian Organ Procurement Organizations (OPOs), and Canadian Blood Services (CBS). This toolkit is based on the recommendations developed by the CST/CNTRP Increased Risk Donor Working Group (2014) published in the journal Transplantation (CST/CNTRP Increased Risk Donor Working Group, 2014).
The process for the development of this toolkit included:  Detailed review of CST and CNTRP recommendations;  Literature research on current practices;  Review of TGLN policies and procedures;  Consultation sessions with transplant medical leads;
In 2017, TGLN's Infectious Disease Lead, Dr. Atul Humar, presented an algorithm that would increase the utilization of Hepatitis C Virus (HCV) positive organs based on new evidence on the efficacy of treatments for HCV (Feld, et al., 2015). Based on consensus from the Organ Specific Working Group representatives to move forward with the new algorithm, amendments to this version of the toolkit have been made to address the utilization of both HCV antibody positive, Nucleic Acid Testing (NAT) negative and HCV NAT positive donors in select populations.

# Introduction to Increased Risk Donors

# What is an Increased Risk Donor?
Increased Risk Donors (IRDs) are donors who may or may not test positive for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and HCV and/or identify certain lifestyle behaviours that are of higher risk who may transmit infectious diseases to transplant recipients. Donors who test negative for HIV, HBV, or HCV are still at risk for transmitting HIV, HCV, or HBV to recipients, due to a window period of time where the infection(s) is not detectable.
For the purpose of classification, the risk profile for HCV antibody positive, NAT negative donors who also have NAT negative results for HIV and HBV is similar to those who test negative for infections but identify with certain lifestyle behaviours. The risk associated with this donor profile is low due to treatment or spontaneous clearance, as evidenced by the NAT method, which is more specific and yields results earlier than other tests (Maylin, et al., 2008). Some exceptions to this may occur in the setting of liver transplant from donors who are HCV antibody positive / NAT negative.
For more information on NAT, see Section 3.1.2 and "The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation" in the American Journal of Transplantation (Levitsky, et al., 2017).

# Donation Protocols for Increased Risk Donors
TGLN is responsible for determining the safety of deceased organs for transplantation through donor screening, donor testing, and donor suitability assessment as per the Health Canada requirements for the Safety of Human Cells, Tissues, and Organs for Transplantation regulations (CTO regulations). All persons are considered to be a potential organ donor, regardless of age, health status, or social behavior. Potential donors that are referred to TGLN are assessed on an individual basis and go through a screening process as well as medical suitability testing to determine if organs are safe for transplantation. As part of the screening process, the family and/or close friends of every potential donor is asked a series of detailed questions about the social medical history of their loved one, and the donor's lifestyle is considered to assess the potential for the transmission of infectious disease to the recipient. Potential donors with identified increased risk behaviors may be eligible to donate, via a process of "exceptional distribution". Exceptional distribution is permitted if another standard organ is not immediately available, and the transplant physician has authorized the use of the organ based on their clinical judgment. The transplant program communicates the risk to the potential recipient so they can make an informed decision about whether to consent to accepting the offered organ.
The CTO regulations relating to exceptional distribution can be found in Appendix A.

# Criteria for Increased Risk Behaviour
Behavioural risk factors for HIV, HCV and HBV are assessed by a history and physical examination of the donor. Table 1 outlines the behaviours that are considered increased risk by the Canadian Standards Association.  or with a person known or suspected to have HIV, or clinically active HBV or clinically active HCV; f) persons who have been exposed, in the preceding 12 months*, to known or suspected HIV-, HBV-, and/or HCV-infected blood through percutaneous inoculation or through contact with an open wound, nonintact skin, or mucous membrane; g) persons who have been in youth correctional facility, jail, or prison for more than 72 consecutive hours in the preceding 12 months; h) persons who within 12 months- preceding donation have undergone tattooing, ear piercing, or body piercing in which sterile procedures were not used (e.g., contaminated instruments and/or ink were used, or shared instruments that had not been sterilized between uses were used); and i) persons who have had close contact within 12 months preceding donation with another person having clinically active HBV or clinically active HCV infection (e.g., living in the same household, where sharing of kitchen and bathroom facilities occurs regularly). - The 12 month period specified in Items f) and h) may be reduced to 6 months if nucleic acid testing (NAT) is used for the detection of HIV, HBV, and HCV.

# E.2:
The assessment of donors less than 11 years of age shall include the following risk factors and risk behaviours associated with HIV, HBV, and HCV: a) persons who have been exposed, in the preceding 12 months*, to known or suspected HIV-, HBV-, and/or HCV-infected blood through percutaneous inoculation or through contact with an open wound, nonintact skin, or mucous membrane; b) persons who within 12 months- of donation have undergone tattooing, ear piercing, or body piercing in which sterile procedures were not used (e.g., contaminated instruments and/or ink were used, or shared instruments that had not been sterilized between uses were used); c) persons who have had close contact within 12 months preceding donation with another person having clinically active viral hepatitis (e.g., living in the same household, where sharing of kitchen and bathroom facilities occurs regularly); d) persons who have been breastfed within the past 12 months  of donation by women with or a risk for HIV, HBV, and/or HCV; and e) persons less than 18 months of age who are born to women with or at risk for HIV, HBV, and/or HCV infection. - The 12 month period specified in Items a) and b) may be reduced to 6 months if NAT is used for the detection of HIV-1, HBV, and HCV.  It is only necessary to assess donors less than five years of age against the criteria in Item d).
Source: Canadian Standards Association, 2017.

# Risk Assessment of Increased Risk Donor Organs

# Infectious Disease Testing

# General Donor Testing Requirements
In order to evaluate the safety of organs for transplantation, TGLN facilitates infectious disease testing for all potential donors. STAT pre-transplant serological testing is required for:
- human immunodeficiency virus I/II (HIV I/II);  human T-cell lymphotropic virus (HTLV I/II);  venereal disease research lab test (VDRL);  hepatitis B surface antigen (HBsAg);  hepatitis C virus (HCV);  antibody to hepatitis B core antigen (anti-HBcAb);  cytomegalovirus (CMV); and,  West Nile virus (WNV) between May to October.
Additionally, retrospective (non-STAT) testing is required for:  Epstein Barr virus (EBV);  Toxoplasmosis IgG (toxo) for all potential heart donors For pediatric cases, maternal serology is required if the potential pediatric donor is  18 months of age and/or has been breast-fed within the last 12 months.
Test results are documented in the TGLN donor chart and reported to the appropriate transplant program(s) at the time of offer. Positive results do not automatically preclude donation as exceptional distribution may be considered. If the potential donor is assessed as being an increased risk, Nucleic Acid Testing (NAT) should be performed in addition to the required pre-transplant STAT serological testing.

# Nucleic Acid Testing
NAT is a method of testing for diseases in an individual's blood and it is the recommended method of infectious disease testing for living and deceased donors. It detects viruses earlier than other screening methods; thus, narrowing the detection window period of HIV, HCV, and HBV infections. Figure 1 below outlines the difference in pathogen detection window periods between serology and NAT testing methods. NAT aims to reduce the risk to the recipients in contracting diseases from organs that are recovered from deceased organ donors; in particular those donors that have been identified as having increased risk behavior. In general, NAT should be performed on deceased organ donors in circumstances where a decision is made to use exceptional distribution protocols from a donor with a history of increased risk behavior.
TGLN has implemented a process for requesting NAT testing for donors with confirmation of increased risk criteria having occurred as per Health Canada guidelines, especially if increased risk behaviors have occurred within the serology window period. Additionally, NAT should be requested for donors for which there is no way to confirm whether or not increased risk criteria has occurred in serology testing window period and who also have physical evidence of recent risk exposure. The process for requesting individual NAT testing based on the patient assessment can be found in Appendix B.

# Risk of Infection from Increased Risk Donor Organs
The potential risk for transmission of an infectious disease is the most important consideration in conducting a risk vs. benefit analysis when organs from IRDs become available. Residual risk estimates have been published based primarily on U.S. epidemiologic data. A systematic review of prevalence and incidence studies was conducted to determine the risk in a Canadian population (CST/CNTRP Increased Risk Donor Working Group, 2014).
Estimates of residual risk are provided in Tables 2 and Table 3 below per 10,000 donors if enzyme-linked immunosorbent assay (ELISA) or NAT is used for screening. Furthermore, the estimate is converted to a ratio to provide a number that can be more easily conveyed to patients during the informed consent process. Risk estimates assume the behaviour(s) occurred right up until the moment of donation. Additional factors may need to be considered when determining the actual risk to the patient, such as length of hospitalization prior to donation with risk generally decreasing as duration of hospitalization increases.   The diagram below shows the recommended sequence of activities in the IRD organ utilization process. Information and guidance on each of the activities are outlined in the following section.

# Guidance for Increased Risk Donor Organ Utilization 1) CONSIDER USE OF IRD ORGANS FOR SELECT TRANSPLANT PATIENTS
The number of organs and tissue needed in Ontario continues to be higher than the number available. When determining the risks vs. benefits of an organ from an IRD, physicians should consider the following facts:  There is a shortage of organs and tissue that can be used for transplant;  There are nearly 1,500 Ontarians waiting to get life-saving organ transplants;  Every three days, someone dies while waiting for an organ transplant;  The waiting times for organ transplants can be up to several years depending on the organ.
Given the significant discrepancy between donor organ supply and demand, the use of organs from IRDs should be considered for some patients. Using these organs offers an opportunity for shortening wait times while providing good outcomes. Furthermore, utilizing NAT testing during the screening process can further reduce the risk of disease transmission.
Physicians should consider the following factors when identifying potential candidates for organ transplant from an IRD: 1. Estimated time the patient may be on the wait list if he/she waits until the next offer.
- Estimated wait-list mortality if he/she waits until the next offer.
- Risk of becoming too sick that a transplant may not be possible.
Ultimately, the transplant physician must determine that the benefits of transplanting a particular patient with an IRD organ are greater than the risks. Otherwise, the patient should continue to wait for an organ from a standard donor.

# 2) CONSIDER USE OF HCV Ab +ve and NAT +ve ORGANS FOR SELECT TRANSPLANT PATIENTS
The HCV Donor Algorithm below outlines how donor organs should be considered for allocation. The Algorithm assumes that HIV NAT and HBV NAT results are also negative. *Risk of transmission may be higher in liver patients (Bari, et al., 2017) Use of HCV NAT positive organs should be considered in the following settings according to the order specified below. HCV NAT negative donors that are currently being treated for HCV or have only recently completed their HCV treatment should also be considered at the same risk level as NAT positive donors.

# HCV Donor Algorithm
- Preferentially use in HCV NAT positive recipients 2. Consider using in clinical trials evaluating the use of HCV NAT positive organs in NAT negative recipients 3. Consider use in selected cases of urgent need and special recipient considerations at the individual physician's discretion Stringent informed consent must be obtained and the availability of appropriate HCV drugs to treat transmission is mandatory. These recipients will be screened and monitored by transplant programs.

# 3) DISCUSSION OF IRD OPTIONS AT TIME OF LISTING
Information on the use of organs from IRDs should be provided to potential recipients at the time of listing and again at the time of offer. The discussion should take place with the transplant physician, although other members of the team may also be involved. The goal of the discussion is to ensure the patient is given the information, support and time needed to understand the option to accept an IRD organ and to make a decision that best reflects the patient's wishes.
The information provided to patients should be accurate and non-leading and the risk should be contextualized in a clear and understandable manner. In the discussion, the transplant physician should ensure, at a minimum, that the patient understands the:  Patient benefits of accepting an IRD organ vs. waiting for a standard organ;  Risk of acquiring an infectious disease;  Support available throughout and after the transplant;  Post-transplant monitoring and testing requirements;  Impact to wait list status from declining option;  The difference between willingness to consider an offer and offer acceptance.
Although a patient may decline this option at the time of listing, this could be reassessed throughout the waiting period and again at the time of offer as the patient's health status may change over time. The patient's decision should be noted in the medical chart and reviewed with the patient on a regular basis.

# 4) RECEIVING OFFER OF ORGAN FROM IRD
Organs from IRDs will be offered to transplant programs via a process of exceptional distribution. TGLN, as source establishment, is permitted to offer exceptionally distributed organs, if the following conditions are met:  an organ that has been determined safe for transplantation is not immediately available;  the transplant physician authorizes the exceptional distribution;  the transplant establishment obtains the informed consent of the recipient.
The organ(s) are distributed to a transplant program based on reasons related to the benefit of the recipient. Organs distributed via exceptional distribution are of a known risk, and adverse event reporting and investigation are not necessitated in the event of any reactions due to this known risk. TGLN will offer the organ(s) as per the allocation algorithm and indicate it as an exceptional distribution case. When making the offer to transplant programs, TGLN will ensure that the transplant physician is aware of the reason(s) for the exceptional distribution.
Exceptional distribution requires the transplant physician to authorize the use of the organ and obtain informed consent from the recipient (see following section). The decision by the transplant physician around utilization or non-utilization may take into account the timing of increased risk behaviour, the window period for the specific test used, the status of the recipient as well as other recipient-specific circumstances.
If the transplant physician decides to accept the IRD organ, TGLN will request and document the transplant physician's justification for accepting the organ in the Notice of Exceptional Distribution form (see Appendix C) and the clinical notes. TGLN will ensure that the TGLN portion of the form is complete and send the form to the transplant program Medical Director where it will be completed and returned to TGLN. TGLN will place a copy of the completed form in the TGLN donor chart.

# 5) OBTAIN INFORMED CONSENT AT TIME OF TRANSPLANT
Obtaining appropriate informed consent for potential recipients of organs from IRDs is essential. The informed consent must be obtained before the transplant takes place. To support the practitioner in providing their patient with accurate and timely information at the time of consent, a Frequently Asked Questions (FAQ) document for IRD and HCV NAT +ve donors have been developed. The information in the FAQ provides an overview of the risk and benefits in utilizing IRD and HCV NAT +ve donor organs.
A recommended template for a standardized informed consent script for IRD and HCV NAT +ve donors that can be read at the time of listing and of offer are provided in the Appendices. This script may be modified as needed to align with hospital specific practices. Standardizing the informed consent process may contribute to an increased utilization of organs.
It is essential to document the informed consent process. Hospital requirements may vary as to the format of documentation in the medical record and hospital specific protocols should be followed. A sample IRD Organ Informed Consent Form and HCV Positive Organ Informed Consent Form are also included in the Appendices.

# 6) FOLLOW-UP TESTING OF TRANSPLANT PATIENT
If organs from IRDs are utilized, post-transplant monitoring and testing of recipients is recommended for early detection of potential transmissions. Since delayed seroconversion may occur, post-transplant screening with NAT for HIV and HCV is recommended along with NAT or HBsAg testing for HBV. A potential proposed algorithm for testing is shown below in Table 5. In the unlikely case that the patient acquires an infection from the IRD organ, the infectious disease specialists should treat the patient as required. 

# Suggested IRD Protocol Development Guidelines
Utilization of IRDs may require formal changes to clinical and administrative processes within hospitals, including education of healthcare providers. Every hospital has different processes and procedures to implementing new protocols. The additional and potential use of HCV NAT positive donor organs in a select population of patients should be reconsidered within these protocols. Suggested guidelines for development of IRD protocols are:
- Review hospital based protocol development, approval, and implementation guidelines a. Typically, each hospital has protocol development guidelines. Refer to these prior to initiating the development or revision of existing protocols to ensure the IRD utilization protocol reflects the process required for your facility. b. Consider who should be involved and what the current process is in your hospital to initiate protocol development.

# Identify existing exceptional distribution protocols
a. Locate and review existing protocols on the use of IRDs; determine when the last revisions were completed.

# Review recommended IRD utilization process steps and compare with existing protocols
a. Identify any inconsistencies between existing and recommended process steps. b. Identify any information that may require revisions or changes in practices within the protocols. c. Review sample protocols, which have been provided as guidelines to integrate content requirements.
- Draft protocols to reflect all steps of the process, including the IRD utilization process identified by TGLN a. Draft IRD protocols to reflect donation process steps. b. Incorporate hospital-specific IRD practices.

# Proceed with hospital-specific process for approval and implementation of IRD utilization protocols
a. Follow hospital-specific process for revision, approval, and implementation of IRD protocols.
- Proceed with Steps 1 through 5 above to include hospital-specific process for NAT Testing in IRD, and HCV positive (Ab or NAT) organ recipients based on the approved policy for testing

# Conclusion
One donor can save up to eight lives and improve the lives of up to 75 people. Yet, there is a constant shortage of organs and tissue available for transplantation, and the demand for organs and tissue needed in Ontario continues to exceed the available supply. This document is intended to support transplant physicians and programs in the use of organs from IRDs so that more organ transplants can be given to patients who need them.
The use of organs from IRDs should be performed in a safe and ethical manner. This includes rigorous informed consent of potential recipients and appropriate testing of donors. It is recommended that transplant programs discuss their protocols with hospital senior leadership before finalizing policies to ensure that they are aligned with hospital requirements. Overall, a more standardized approach across Ontario and the rest of Canada should lead to optimized utilization practices and a significant increase in the number of organ transplants.
Patient FAQ -Getting an Organ from an Increased Risk Donor

# WHAT IS AN INCREASED RISK DONOR ORGAN?
This is an organ from a donor who identifies certain lifestyle behaviours that are of higher risk of transmitting infectious diseases to transplant recipients. These donors may test negative for infections, but they may still be a risk for spreading Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and Hepatitis B Virus (HBV) to transplant patients, due to a window period where the infection(s) cannot be detected from the tests. Organs are considered an increased risk if the donor has identified the following behaviours:  persons who have injected non-medical drugs into the blood, muscles, or under the skin in the last 5 years;  men who have had sex with another man in the last 12 months;  persons who have had sex in exchange for money or drugs in the last 5 years;  persons who have had sex with any persons described above or with a person who has or may have HIV, HBV or HCV infection in the last 12 months;  persons with a history of intranasal cocaine use in the last 6 months (unless they test HCV NAT negative);  persons who have been in contact with the blood and/or bodily fluids of a person who has or may have HIV, HBV, and/ or HCV in the last 12 months;  persons who have been in youth correctional facility, jail, or prison for more than 72 hours in the last 12 months;  persons with a tattoo or piercing where sterile procedures were not used in the last 12 months; and,  persons who have had close contact with another person having clinically active viral hepatitis (e.g., living in the same house where kitchen and bathroom are shared) in the last 12 months.
You might be offered an organ from a deceased donor that has an increased risk of passing on infections, such as HIV, HBV, and HCV. You will be informed if this is an increased risk organ when it is offered to you.

# WHAT IS THE DIFFERENCE BETWEEN AN ORGAN FROM AN INCREASED RISK DONOR AND ONE FROM A STANDARD DONOR?
The increased risk from the donor does not affect how well the organ will work. It means that the donor engaged in activities before their death that increase the chances of having an infection. All donors are screened for infectious diseases. This includes testing for HIV, Hepatitis B, and Hepatitis C. Even with negative test results, there is still a very small chance that an organ from an increased risk donor has an infection such as HIV or Hepatitis. There are treatments available for these diseases but they are not curable.
On average, increased risk donors tend to be of younger age with better organ function.

# WHY WOULD I THINK ABOUT ACCEPTING AN ORGAN FROM AN INCREASED RISK DONOR?
Deciding to accept an organ from an IRD may increase your chance of getting a transplant. These are the facts:  There is a constant shortage of organs and tissue that can be used for transplant.  There are nearly 1,500 Ontarians waiting to get life-saving organ transplants.  Every three days, someone dies while waiting for an organ transplant.  The waiting times for organ transplants can be up to several years depending on the organ.
You will only be offered an increased risk organ if a transplant doctor at your hospital feels that the benefits of transplanting you with the organ are greater than the risk. Otherwise the organ will not be offered to you. A transplant doctor will speak to you about the risks and benefits of accepting the increased risk organ versus waiting for another organ.

# HOW WILL I KNOW IF I DEVELOP AN INFECTION?
If you decide to accept the organ, you will be monitored after your transplant to be sure that you did not get an infection. In the unlikely case that you do get an infection, treatments are available. The infectious disease doctors will treat you, if needed.

# WHO DECIDES IF I SHOULD ACCEPT AN INCREASED RISK ORGAN?
The decision to accept the increased risk organ is YOURS. The right choice for you depends on the state of your health. You need to talk about this with your medical team and all your doctors. The best answer for you may change if the state of your health changes.
If you have questions about organs from IRDs, talk with a member of your healthcare team while you are waiting for your transplant. If you are offered an organ from an increased risk donor, it will be helpful to have already thought about this information.

# IF I DO NOT AGREE TO ACCEPT AN INCREASED RISK ORGAN, WILL IT HURT MY CHANCES OF GETTING A STANDARD ORGAN?
No. Everyone has a different level of how much risk they are willing to accept for themselves. The decision to accept the organ is yours. If you decide NOT to accept the organ, you will NOT lose your place on the waiting list.
You will only be offered the consideration of an HCV positive organ if a transplant doctor at your hospital has identified you in one of the three categories of patients listed above, you have consented, and appropriate HCV drugs to treat transmission are available.
Otherwise, the organ will not be offered to you. A transplant doctor will speak to you about the risks and benefits of accepting the HCV positive donor organ versus waiting for another organ.

# E. WHAT ARE THE RISKS OF RECEIVING AN HCV POSITIVE ORGAN AND HOW WILL I KNOW IF I DEVELOP AN INFECTION?
In the case of HCV NAT positive donors, if you decide to accept the organ, there is a 100% chance you will get HCV. The infectious disease doctors in partnership with the transplant physicians will treat you accordingly based on the access to drug coverage and perform regular blood tests.

# F. WHO DECIDES IF I SHOULD ACCEPT AN HCV POSITIVE ORGAN?
The decision to accept the HCV positive organ is YOURS. The right choice for you depends on the state of your health. You need to talk about this with your medical team and all your doctors. The best answer for you may change if the state of your health changes.
If you have questions, talk with a member of your healthcare team while you are waiting for your transplant.
If you are offered an HCV positive organ from a donor, it is because you consented to consider this type of organ at the time of listing.

# G. IF I DO NOT AGREE TO ACCEPT AN HCV POSITIVE DONOR ORGAN, WILL IT HURT MY CHANCES OF GETTING A STANDARD ORGAN?
No. Everyone has a different level of how much risk they are willing to accept for themselves. The decision to accept the organ is yours. If you decide NOT to accept the organ, you will NOT lose your place on the waiting list.

# Appendix A: CTO Regulations for Exceptional Distribution
CTO Regulations: Exceptional Distribution 40. A source establishment may distribute cells, tissues or organs that have not been determined safe for transplantation if all of the following conditions are met:
(a) a cell, tissue or organ that has been determined safe for transplantation is not immediately available; (b) the transplant physician or dentist, based on their clinical judgment, authorizes the exceptional distribution; and (c) the transplant establishment obtains the informed consent of the recipient. 41. (1) A source establishment that distributes cells, tissues or organs under section 40 must keep a copy of the notice of exceptional distribution in its records.
(2) The transplant establishment must keep a copy of the notice of exceptional distribution in its records.
(3) A notice of exceptional distribution must contain all of the following information:
(a) the name of the transplanted cell, tissue or organ; (b) the provisions of these Regulations with which the cell, tissue or organ is not in compliance at the time of its distribution; (c) the justification for the distribution that formed the basis for the transplant physician's or dentist's decision to authorize it; (d) the name of the source establishment that distributed the cell, tissue or organ;
(e) the name of the transplant establishment and of the transplant physician or dentist who authorized the distribution; and (f) the time and date of the written authorization of the distribution and a copy of the authorization signed by the transplant physician or dentist. 42. A source establishment that distributes a cell, tissue or organ under section 40 before the donor suitability assessment is complete must, after the distribution, complete the assessment, carry out any other appropriate follow-up testing and notify the relevant transplant establishment of the results.
Source: Safety of Human Cells, Tissues and Organs for Transplantation Regulations, 2015.

# Appendix B: Individual NAT Testing Algorithm

# Appendix C: Notice of Exceptional Distribution Form

# Appendix D: Patient FAQ on Getting an Organ from an IRD
The information in the following FAQ should be provided to the patient at the time of transplant assessment or listing and can also be used at the time of offer to ensure understanding of the risks and benefits of accepting an IRD organ. Patient FAQs, scripts, and forms for getting an HCV Ab+ or HCV NAT +ve donor organ follow in the next section.

# Appendix E: Template for Standardized Informed Consent Script for IRD Organs
The following script may be read, as written, to the patient at the time of the organ offer. The patient should be encouraged to ask questions to ensure that s/he understands and appreciates the content. The patient must verbally confirm that he/she is accepting this offer. The patient's affirmation should be documented in the patient's chart as applicable. Please see Appendix G to I for the patient FAQ, script, and form for getting an HCV NAT +ve donor organ.

# Script for Obtaining Informed Consent
You are being offered an organ from a deceased donor that the Canadian Standards Association guidelines defines as being at increased risk for transmitting infections, such as HIV, HBV, and HCV. There is always some risk with every donor. Please think back to discussions you have had about the risks in accepting an organ. The increased risk does not affect how well the organ works. Instead, we mean that this donor engaged in behaviors before their death that increase their chances of having an infection. You need to balance the slightly increased risk of accepting this organ with the likely benefits of being transplanted at this time instead of waiting for another organ. This donor has already had two types of screening for infections. They had required testing for HIV, hepatitis B, and Hepatitis C. They also had special testing for HIV, Hepatitis C, and Hepatitis B. All of the NAT test results were negative. Even with negative test results, there is still a very small chance that this donor has an infection such as HIV or hepatitis.
Based on information on similar donors with the same behaviors and negative test results, your risk of getting an infection may be in the range of: (only read statistics pertaining to this donor's specific behavior from Table 2, and Table 3. It is not necessary to name the behaviour, only the level of risk. If the donor has tested HCV antibody positive and NAT negative and all history is unknown, or there are no high risk behaviours, read out the highest risk rate which is IV Drug Use (liver patients are exceptions, who may be a higher risk).
A transplant physician at your hospital has carefully looked at information about this donor. She/he recommends that you consider this organ. In his/her opinion, the potential benefits of accepting the organ outweigh the risks of getting an infection from this donor. If you decide to accept this organ, you will be monitored after your transplant to be sure that you did not get an infection. IF you get an infection, treatments are available. The infectious disease doctors will treat you, if needed. Everyone has a different level of how much risk they are willing to accept for themselves The decision to accept this organ is yours. If you decide NOT to accept the organ, you will not lose your place on the waiting list.

# Do you have any questions?
Additional points may be discussed with the patient depending on type of transplant (e.g. kidney vs. non-kidney) and other factors. These points include: 1. Estimated time the patient may be on the wait list if he/she waits until the next offer 2. Estimated wait-list mortality if he/she waits until the next offer 3. Risk of becoming so sick a transplant may not be possible Note: A separate standardized informed consent template may be needed for kidney vs. non-kidney recipients given the availability of dialysis for support of end stage renal failure patients. Increased Risk Donor (IRD) organs may not meet the strict criteria of a standard organ donor.

# Appendix F: Sample IRD Organ Informed Consent Form
IRDs identify certain lifestyle behaviors that are of an increased risk of spreading illnesses to patients compared to standard donors.
Please take your time to make your decision about accepting an IRD organ. Feel free to ask questions.
Patient Sign-Off I, the undersigned, have been informed about the purpose, procedures, possible benefits and risks of accepting an IRD organ, and I have received a copy of this informed consent document. I have been given the opportunity to ask questions and I have been told that I can ask questions in the future. All my questions have been answered to my satisfaction. As a representative of this transplant program, I have explained the purpose, the procedures, the possible benefits and the risks that are involved with an organ from an Increased Risk Donor (IRD). Any questions that have been raised have been answered to the best of my knowledge.  You are waiting for an organ transplant  Your doctor feels that you will benefit from having an IRD organ. An IRD organ may allow you to be transplanted sooner, rather than waiting a longer period of time for a standard criteria organ.

# Appendix G: Patient FAQ on Getting an Organ from a HCV NAT Positive Donor or HCV Antibody Positive (with Recent Antiviral Treatment)
The information in the following FAQ should be provided to the patient at the time of transplant assessment or listing and can be used again at the time of offer to ensure understanding of the risks and benefits of accepting a Hepatitis C Virus (HCV) NAT positive organ.

# WHAT DETERMINES AN HCV POSITIVE ORGAN?
Hepatitis C is a virus that enters through a person's blood stream and can affect the liver. This is an organ from a donor who has tested negative for Human Immunodeficiency Virus (HIV), and Hepatitis B Virus (HBV) and fits one of the following two profiles:
A. HCV antibody positive, NAT negative results with recent or unknown history of treatment:
The donor is currently on HCV treatment, less than 12 weeks have elapsed since completion of HCV treatment, or HCV treatment history is unknown.

# B. Donor NAT test results are positive for HCV
A patient may be asked to consider an organ from a deceased donor that is HCV NAT positive by either of the above definitions if they fit into one of the following categories:
1) HCV NAT positive recipient 2) Participant in clinical trials for HCV NAT negative recipients 3) Selected cases and special recipient considerations
The risk of transmission from a donor who tested HCV NAT positive is 100%.

# C. WHAT IS THE DIFFERENCE BETWEEN AN HCV POSITIVE ORGAN AND A STANDARD DONOR ORGAN?
An organ that comes from an HCV positive donor does not affect how well the organ will work (however, the risk of transmission may be higher for liver recipients). The difference is that by receiving an HCV positive organ, a treatment protocol will be required. The evidence shows that HCV treatments are effective in 95-99% of the HCV population (Feld, et al., 2015;Levitsky, et al., 2017). New therapies called direct acting antivirals (DAAs) are pills that act on the virus itself to get rid of it from the body.
The new treatment requires a shorter time (between 8 to 24 weeks), has reduced side effects, and appears to be effective at all stages of the disease.
After your surgery, an infectious disease physician or hepatologist may also be involved in your care and you will require some additional blood work at 2 weeks, 6 weeks, 1 month, 3 months, and 1 year to track the Hepatitis C virus in your blood. All other care and the transplant surgery will be the same.

# D. WHY WOULD I THINK ABOUT ACCEPTING AN HCV POSITIVE ORGAN?
Deciding to accept an organ from an HCV positive donor may increase your chance of getting a transplant. These are the facts:  There is a constant shortage of organs and tissue that can be used for transplant.  There are nearly 1,500 Ontarians waiting to get life-saving organ transplants.  Every three days, someone dies while waiting for an organ transplant.  The waiting times for organ transplants can be up to several years depending on the organ.

# Appendix H: Template for Standardized Informed Consent Script for HCV Antibody Positive (with Recent Antiviral Treatment) and HCV NAT Positive Donor Organs
The following script may be read, as written, to the patient at the time of the organ listing and again at offer. Please note that once a patient has consented and the program has accepted the organ, the "Notice of Exceptional Distribution" will still need to be completed. The patient should be encouraged to ask questions to ensure that s/he understands and appreciates the content. The patient must verbally confirm that he/she is accepting this offer. The patient's affirmation should be documented in the patient's chart as applicable.

# Script for Obtaining Informed Consent
You are being offered an organ from a deceased donor that has tested positive for the Hepatitis C Virus (HCV). We look at the combination of two types of testing and the history of any recent treatments for HCV in the donor to determine whether the donor organ classifies as HCV+. If you get HCV, treatments are available and the infectious disease doctors will treat you if needed.
The results for this donor indicate they are negative for HIV and HBV, and are (choose 1 of the following): a) Considered HCV positive due to a positive HCV NAT result b) Considered HCV positive due to a recent history of HCV antiviral treatment in the donor and a positive HCV antibody result You are being considered to receive an organ from a deceased donor who is HCV positive because you fit one of the following categories: 1. HCV NAT positive recipient 2. Participant in a clinical trial for HCV NAT negative recipients 3. Selected cases and special recipient considerations
There is always some risk with every donor and the risk of transmission may be higher in liver patients (Bari, et al., 2017). You need to balance the risk of accepting this organ with the likely benefits of being treated effectively post-transplant instead of waiting for another organ.
A transplant physician at your hospital has carefully looked at information about this donor. She/he recommends that you consider this organ. In his/her opinion, the potential benefits of accepting the organ outweigh the risks of getting an infection from this donor. If you decide to accept this organ, you will be monitored after your transplant for your viral status. The hepatologist or infectious disease doctors will treat you if needed. Everyone has a different level of how much risk they are willing to take. The decision to accept this organ is yours. If you decide NOT to accept the organ, you will not lose your place on the waiting list.

# Do you have any questions?
Additional points may be discussed with the patient depending on type of transplant (e.g. kidney vs. non-kidney) and other factors. These points include: 1. Estimated time the patient may be on the wait list if he/she waits until the next offer 2. Estimated wait-list mortality if he/she waits until the next offer 3. Risk of becoming so sick a transplant may not be possible Note: A separate standardized informed consent template may be needed for kidney vs. non-kidney recipients given the availability of dialysis for support of end stage renal failure patients. HCV positive organs may not meet the strict criteria of a standard organ donor. The donor organ has tested either HCV Nucleic Acid Testing (NAT) positive OR HCV antibody (Ab) positive with a history of recent or unknown treatment.
Please take your time to make your decision about accepting an HCV donor organ. Feel free to ask questions.
Patient Sign-Off I, the undersigned, have been informed about the purpose, procedures, possible benefits and risks of accepting an HCV positive donor organ, and I have received a copy of this informed consent document. I have been given the opportunity to ask questions and I have been told that I can ask questions in the future. All my questions have been answered to my satisfaction.
 Yes, I am willing to accept an organ from an HCV Antibody (Ab) positive, NAT negative donor with a history of recent or unknown treatment  Yes, I am willing to accept an organ from an HCV NAT positive donor  You are waiting for an organ transplant  Your doctor feels that you will benefit from having an HCV donor organ. An HCV donor organ may allow you to be transplanted sooner, rather than waiting a longer period of time for a standard criteria organ.

# Glossary of Terms
HCV Antibody Test: A blood test that detects antibodies to Hepatitis C Virus (HCV) in the blood and identifies if HCV is currently in the blood or was in the blood in the past. The HCV Antibody Test cannot determine if the infection is acute or long-term (chronic).
Canadian National Transplant Research Program: a national initiative designed to increase organ and tissue donation in Canada and enhance the survival and quality of life of Canadians who receive transplants.
Canadian Society of Transplantation: the professional organization for physicians, surgeons, scientists and allied health professionals dedicated to leading, advancing, and advocating for patient care, research, and education in donation and transplantation in Canada.
Canadian Standards Association: a not-for-profit standards organization which develops and published standards in a variety of areas and provides training and advisory services.
Direct Acting Antivirals (DAA): Direct Acting Antivirals are Hepatitis C Virus (HCV) treatments that are made up of different combinations of drugs and target the virus in the blood.
Exceptional Distribution: the process and conditions under sections 40 to 42 of the CTO regulations whereby a source establishment may distribute cells, tissues or organs that have not been determined safe for transplantation.
Enzyme-Linked Immunosorbent Assay (ELISA): is a common laboratory technique which is used to measure the concentration of an analyte (usually antibodies or antigens) in solution.
Hepatitis B Virus (HBV): a DNA virus belonging to the Hepadnaviridae family of viruses. The virus causes the disease hepatitis B, a viral infection that attacks the liver and can cause both acute and chronic disease.
Hepatitis C Virus (HCV): a small, enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The virus causes the disease Hepatitis C, a bloodborne virus that can cause both acute and chronic hepatitis infection.
Human Immunodeficiency Virus (HIV): a retrovirus that infects cells of the immune system, destroying or impairing their function.
Increased Risk Behaviour: certain lifestyle behaviours that are of higher risk of transmitting infectious diseases to transplant recipients.
Increased Risk Donor (IRD): organ or tissue donor who identifies certain lifestyle behaviours that meet the criteria for being a higher risk of transmitting infectious diseases to transplant recipients.
Informed Consent: process for getting permission before conducting a healthcare intervention on a person.
Nucleic Acid Testing (NAT): a molecular technique used to detect a virus or a bacterium. It detects viruses earlier than other screening methods; thus, narrowing the detection window period.

# Public Health Ontario Laboratory (PHOL):
The provincial laboratory of Public Health Ontario (PHO), which is a governing body who strives to prevent illness and improve health through scientific evidence and expert guidance that shapes policy and practices in Ontario. There are 11 laboratory sites in Ontario.
Residual Risk: the risk of infectious disease transmission when the screening test is negative.
Serology: a blood test to detect serum antibodies or antibody-like substances that appear specifically in association with certain diseases.
Source Establishment: entity responsible for the processing of cells, tissues and organs, whether the processing is carried out by the source establishment itself or by another establishment, and for determining whether the cells, tissues and organs are safe for transplantation.

# Sustained Virologic Response (SVR):
When the Hepatitis C Virus (HCV) is not detected in the blood after a certain amount of time (12 weeks) after completing treatment, sustained virologic response (SVR) is achieved.
Trillium Gift of Life Network (TGLN): a not-for-profit agency of the Government of Ontario that plans, promotes, coordinates and supports organ and tissue donation and transplantation across Ontario.
Window Period: the time between first infection and when a test can reliably detect that infection.