Key Benefits:
Minister of Social Affairs, Health and Women ' s Rights,
Vu le Public Health Codeincluding articles R. 1211-14 and R. 1211-21;
Vu le Decree No. 2010-1625 of 23 December 2010 relating to health safety rules relating to the collection and use of elements and products of the human body, including Article 2;
Vu le Decree No. 2015-1747 of 23 December 2015 the derogatory recourse to grafting in cases of hepatitis C infectious markers in the donor;
Considering the amended decision of 23 December 2010 pursuant to the articles R. 1211-14, R. 1211-16, R. 1211-21 and R. 1211-22 the Public Health Code;
Considering the opinion of the National Drug and Health Products Safety Agency dated 4 November 2015, 9 November 2015 and 15 December 2015;
Based on the opinion of the Biomedicine Agency of 6 November 2015, 11 December 2015 and 16 December 2015,
Stop it!
The terms and conditions for the use of organs or donor cells carrying hepatitis C virus markers are set out in the Appendix to this Order.
Order 13 February 2012 pursuant to section R. 1211-21 of the Public Health Code relating to the conditions for the use of organs or cells from donor holders of hepatitis C virus markers is repealed.
The Director General of Health is responsible for the execution of this Order, which will be published in the Official Journal of the French Republic.
Annex
Preamble
Derogations allowing the use of donors with an infectious risk to hepatitis C (HCV) virus for the receiver have existed since 1997 for the transplant of heart, liver, lung and bone marrow in vital emergency situations. This derogatory device was extended in 2005 to situations involving the vital prognosis, without appropriate therapeutic alternatives, with respect to rein, heart, liver, lung transplants and transplants of hematopoietic stem cells, regardless of their origin (bone marrow, peripheral blood or placental blood) or mononuclear cells. This device, described in protocols implemented for a period of five years, was renewed in 2010 for an additional five years.
The assessment of the results of the transplants carried out under this derogatory device is contained in the report of the ANMS to the Minister for Health in accordance with theArticle 2 of Decree No. 2010-1625 of 23 December 2010.
In view of this assessment, it was possible to individualize two distinct transplant situations:
1. Hematopoietic stem cell transplants (SHCs) or mononucleated cells (NCMs) from donors with positive HCV serology (positive HCVs) and HCV genomic screening (HCV) confirmed negative.
These transplants are carried out pursuant to second paragraph of section R. 1211-14 of the Public Health Code.
They do not fall within the framework of the derogatory device to the ban of transplantation and are not subordinate to a condition of vital prognosis. They may be practised in all recipients if the foreseeable risk in the current state of scientific knowledge is not out of proportion to the expected benefit. The conditions for carrying out these transplants are described in paragraph I of this annex.
2. Organ transplants (including liver) from donors with positive anti-HCV antibodies (Anti-HCV+ Ac)
These transplants are carried out pursuant to third paragraph of section R. 1211-21 of the Public Health Code which determines the conditions of implementation.
Following the repeal of theArticle 2 of Decree No. 2010-1625 of 23 December 2010 by the Decree No. 2015-1747 of 23 December 2015 referred to above, they are now carried out on a perennial basis, but they remain a derogation from the transplant ban.
They can only be practiced if the patient's vital prognosis is engaged and the therapeutic alternatives become inappropriate.
A strict supervision of these transplants must be implemented. This guidance includes donor/receiver virological matching procedures as defined in the protocols described in this Order. In all cases, the patient must be previously informed and must give consent to the possibility of receiving a graft bearing HCV viral markers. It must also benefit from appropriate therapeutic care and post-greffe monitoring. The conditions for the conduct of these transplants are described in paragraph II of this annex.
The rapid development of effective treatments to cure a viral infection in HCV, as well as the collection of new data from the national or foreign experience, can lead to reconsidering the conditions for carrying out such transplants. Any developments to consider the completion of these grafts outside the derogatory framework provided for in section R. 1211-21 shall be conditioned on the handover to the Minister responsible for health of a report prepared by the ANSM in view of the synthesis of the results of these grafts transmitted by the Biomedicine Agency. This report that can be submitted at any time must be based on the evaluation:
1° Organ transplants carried out under theArticle R. 1211-21 of the Public Health Code the risk of transmission of hepatitis C virus;
2° The consequences of the treatments implemented for hepatitis C recipients who received a graft from donors carrying positive infectious markers for hepatitis C virus;
3° International literature data on the use of this category of donors.
I. - Conditions of use of hematopoietic stem cells (HSCs) or mononucleated cells (NCMs) from donors with positive HCV serology (positive HCVs) and HCV genomic testing (HCV)
1. Clinical prerequisites
The transplants of hematopoietic stem cells and mononucleated cells made from donor grafts with positive HCV serology (positive HCV antibody) and a genomic screening of HCV pregregates with confirmation of healing (HCHCV negative observed beyond three months after stopping an antiviral treatment if the donor has been treated or witnessed
2. Registry team information
The use of a graft from a donor with a positive HCV (positive HCV) serology and a negative confirmed HCV genomic screening must be brought to the attention of the transplant medical teams and the doctor who cares for the patient in the post transplant. All patient HCV status information must be clearly documented and easily accessible in the patient's medical file.
3. Information and consent
The patient's information must intervene as soon as possible. Indeed, it is imperative that he have all the elements that enable him to direct his choice knowingly. This information must be documented in the patient's medical file.
Informed consent of the patient is required before transplantation under the conditions provided for articles L. 1111-4 et seq. of the Public Health Code. In any case, the patient has the opportunity to withdraw at any time. In addition, the completion of this type of transplant within the framework of an intrafamilial donation implies that the potential donor consents to the disclosure to the recipient of medical information regarding his or her HIV status under HCV.
II. - Conditions of use of organs (including liver) from donors with positive anti-HCV antibodies (Anti-HCV+ Ac)
Grafts from live organ donors are treated differently, as the transplant is a scheduled activity and ensures the completeness of the medical balance of the donor. Taking into account these different criteria, it was possible to distinguish four derogatory transplant protocols that are the subject of B of this paragraph II.
A. - General conditions
1. Clinical prerequisites
Derogatory protocols should be implemented only when a patient has his/her active prognosis and the transplant alternatives become inappropriate, so that the expectation of another graft than that proposed in the derogatory context is prejudicial to his/her survival.
2. Protocols
(a) Use of deceased donors:
The derogatory device is primarily intended to respond to the context of a shortage of organs from deceased donors.
The procedures for the conduct of transplants using this category of donors are the subject of two protocols, which are specified in paragraph B of this chapter II.
(b) Use of living donors:
The removal of organs from live donor (possible for kidney, liver, lungs) remains limited. However, in specific situations, it may be necessary to use a live donor with positive infectious markers for HCV. In this programmed grafting context, the risk of sampling in the donor and also the risk of transmission to the recipient under the donor's HCV status.
The procedures for the conduct of transplants using this category of donors are the subject of two protocols, which are specified in paragraph B of this chapter II.
3. Information and collection of consent of the recipient and the living donor
The information and prior collection of the informed consent of the future recipient are essential prerequisites for the conduct of a derogatory transplant. The patient's information must intervene as soon as possible because it is imperative that the recipient (or his/her family, if any) have all the elements that enable him/her to guide his/her choice knowingly. Information should be provided on the impacts of this type of transplant, both on the expected benefits and the risks involved and on the therapeutics that may be proposed and the constraints related to the specific monitoring that will be undertaken. This information must be documented in the patient's medical file.
The information is provided to the transplant candidate on the possibility of a derogatory transplant at the time of registration on the national list of patients pending transplantation. Informed consent of the patient is required prior to transplantation under the conditions specified in the articles L. 1111-4 et seq. of the Public Health Code.
In any case, the future receiver must be able to withdraw at any time. In addition, the implementation of derogatory transplants as part of a lifetime donation provides that the potential donor is informed of the specific risks and gives consent to the recipient's disclosure of medical information regarding his or her immune status to HCV. This donor's consent is a prerequisite for the collection.
The terms of the collection of consent are explained in a letter of information prepared by the Biomedicine Agency.
4. Distribution and attribution of grafts
Derogatory transplants in relation to the risk of transmission of HCV shall not be in contradiction with the common principles and rules for the distribution and allocation of grafts. The possibility of entering a derogatory protocol should not exclude keeping its place in the national list of patients awaiting transplant.
5. Receiver Monitoring Protocol and Evaluation
Regular follow-up of recipients who have received a graft in the context of a derogatory protocol must be undertaken. A virological assessment, including in pregreffe, and then, every six months, the determination of viral load and the genotyping of the strain, if applicable, must be implemented for a minimum period of two years.
Data obtained in the context of derogatory transplants for HCV transmission risk are collected at the national level by the Biomedicine Agency. They serve as a basis for assessing each derogatory situation and updating these recommendations. A follow-up committee established by the Biomedicine Agency ensures monitoring of protocols and evaluation of results. The procedures for data transmission by transplant teams are explained in a letter of information prepared by the Biomedicine Agency.
6. Biovigilance
6.1. Incident reporting and adverse effects
Adverse events and effects, including those identified in the framework of long-term monitoring, must be reported in biovigilance in accordance with the existing regulatory provisions.
6.2. Sample libraries
The transplant of organs carried out within the framework of these derogatory transplants requires the creation of a donor's ultrasound in a biovigilance objective. Samples must be kept for a period of ten years.
The structures in charge of this ultrasound ensure the proper identification of the samples in accordance with the anonymity of the donors, the safety of the conservation of the samples and their accessibility.
(a) Abductions for the enchanting:
The material used for sampling is defined in relation to the structure in charge of the management of the squabbles. The samples for the enchantillothèque are carried out in conjunction with the removal of organs.
Must be taken:
- total blood on dry tube. This tube will separate and feed the serum;
- total blood on EDTA tube. This tube will separate and ignite plasma;
- total blood on EDTA tube for the storage and feeding of total blood.
The volume of samples taken is to be adjusted according to age, weight and clinical context to meet the requirements of the following point.
(b) Transport of samples:
In accordance with the requirements laid down by the structure in charge of the management of ultra-theqas, the time between sampling and freezing shall allow the subsequent operation of the sample for all purposes of expertise.
(c) Sample conservation:
Sample conservation request.
The transmission slip that will accompany the samples shall contain to a minimum the following information:
- the purpose of the sampling: "organ donor biovigilance ultrasound" as part of the application of theArticle R. 1211-21 of the Public Health Code ;
- name, name, date of birth of the donor or code;
- date and time of sampling;
- for donors to the arrested heart, specify the delay between the death and the removal;
- name of the breeder establishment and the applicant service;
- name of the prescriptor or coordinator;
- name of the breeder;
- date and time of arrival at the laboratory or biological center;
- justification in the absence of a sample or insufficient sample;
- modalities of conservation in the structures in charge of the management of the santillothèques.
Centrifugation:
The centrifugation of the tubes intended for the conservation of serum and plasma is implemented as quickly as possible in accordance with the procedures established by the structure in charge of the ultrasound.
The total blood: the EDTA tube(s) for the total blood retention will be homogenized by turns before moving to the next step.
Food: Samples must be connected according to the following distribution, a minima: 2 × 1 ml of serum; 2 × 1 ml of plasma; 2 × 1 ml of total blood.
Methods for processing samples for freezing and conservation are implemented in accordance with the procedures in place in the structure in charge of the management of shrines.
(d) Implementing a traceability system:
This system includes
- traceability of the steps implemented for the conservation of samples. The objective of this traceability is to find without delay the location of the samples;
- traceability of conservation temperatures throughout the storage period of samples.
B. Derogatory protocols for transplants
1. Deadline
In the particular case of liver transplants, only grafts with a Metavir score strictly below histologically appreciated F2 or any other validated non-invasive method may be offered to the graft. In the event of an assessment of fibrosis by a non-invasive method, the results of this assessment must have been obtained at least six months before the sampling and must correspond to a Metavir score strictly below F2. Subject to these conditions being met, the donor/receiver virological pairing procedures are those applicable to all organs.
For deceased donors, these matching arrangements are as follows:
(a) Organs from a donor with positive HCV serology (positive HCV antibodies) and a pregregate result of negative HCV genomic testing must be transplanted to recipients with positive HCV serology (positive HCVs), regardless of the outcome of their HCV DG (see protocol 1 in the tables below).
(b) Organs from a donor with positive HCV serology (positive HCV antibodies), and positive HCV genomic testing, or uninterpretable or unavailable in pregreffe, must be transplanted to positive HCV HCV recipients. A specific follow-up of these recipients must be implemented from the transplant and anti-viral treatment must be considered and discussed on a case-by-case basis by the teams in charge of the follow-up of transplanted patients (see protocol 2 in the tables below).
2. Living donor
In all cases, the impact of sampling in the living donor must also be appreciated by a panel of experts placed with the Biomedicine Agency who analyzes the situation on a case-by-case basis. Particular attention must be paid to the risks incurred by donors, regardless of the organ taken.
In the particular case of liver transplants, only grafts with a Metavir score strictly below histologically appreciated F2 or any other validated non-invasive method may be offered to the graft. In cases where a non-invasive method is used, the results of the evaluation of fibrosis, the results of this evaluation must correspond to a Metavir score strictly below F2. Subject to these conditions being met, the donor/receiver virological pairing procedures are those applicable to all organs.
For live donors, these modalities of matching are:
(a) Organs from a donor with positive HCV serology (positive HCV) and genomic testing of HCV (HCV) pregregate negative with confirmation of cure (HCB results in negative pregregates beyond three months after the cessation of antiviral treatment if the donor has been treated or testifying to a documented spontaneous recovery and which remain negative
(b) Organs from a donor with positive HCV serology (positive HCV) and genomic testing of HCV pregregs from the outset negative but without confirmation of healing (in treatment or delay less than three months since the cessation of treatment and which remain negative during the pre-sampling assessment), may be transplanted to receivers with positive HCSD serology of any
Summary table of HCV derogatory transplants with deceased donor:
| HCV DEROGATE PROTOCOLES DON'T REALLY | Any organ (*) | Positive anti-HCV results and negative HC DGV results | Protocol 1: Receiver with positive HCV serology (positive HCVs) regardless of the outcome of HCSB |
| Positive anti-HCVs and positive or uninterpretable HC DGVs | Protocol No. 2: Transferred Receiver (positive HCDG) | ||
| (*) Only liver grafts with a Metavir score strictly below F2 can be offered to the histologically appreciated graft or any other validated non-invasive method as the results of this evaluation must have been obtained at least six months before the sampling and correspond to a Metavir score strictly below F2. | |||
Summary table of HCV derogatory protocols with live donor:
The transplants will be restricted to therapeutic indications from a college of experts (*) that analyzes the situation on a case-by-case basis.
| HCV DEROGATE PROTOCOLES DONNECTIONS | Any body (**) | Positive HCV Aces and Confirmation of Healing (1) in Pregnant | Protocol #3: any HCV status of the receiver (naïve, positive HCV, regardless of the outcome of HCSB) |
| Positive HCV and negative HCV DGs without healing confirmation | Protocol #4: positive anti-HCV receiver, regardless of the outcome of HC DG | ||
| (*) Regardless of the organ collected, the transplanting physician must obtain the favourable opinion of this college of experts prior to grafting if the donor presents a Metavir rating of hepatic fibrosis greater than or equal to F2 valued histologically or by any other validated non-invasive method as the results of this evaluation correspond to a Metavir score strictly below F2. (**) Healing is defined by a negative HCV viral genomic screening beyond three months after stopping antiviral therapy when it is not a documented spontaneous cure, this screening must be performed by a standardized technique among the most sensitive of the market and remaining negative during the pre-sampling assessment. | |||
Done on December 23, 2015.
For the Minister and by delegation:
The Director General of Health,
B. Vallet
