Key Benefits:
Minister of Labour, Employment and Health,
Vu le Public Health Codeincluding its Article R. 1211-21 of the Public Health Code (third paragraph);
Considering the opinion of the Biomedicine Agency;
Considering the opinion of the French Health Products Safety Agency,
Stop it!
The protocols for the implementation of the exemption for the use of organs or donor cells carrying hepatitis B virus markers are listed in Appendix I to this Order.
The protocols for the implementation of the exemption for the use of organs or donor cells carrying hepatitis C virus markers are listed in Appendix II to this Order.
The Director General of Health, the Director General of the Agency for Biomedicine and the Director General of the French Health Safety Agency for Health Products are responsible for the execution of this Order, which will be published in the Official Journal of the French Republic.
A N N E X E I
PROTOCOLS FOR THE IMPLEMENTATION OF THE DEROGATION PERMITTING THE USE OF BODIES OR CELLULATIONS OF DONNOR PORTERS OF THE VIRUS OF HEPADITY B
Preamble
Derogations allowing the use of donors with an infectious risk to hepatitis B (HBV) virus for the receiver have existed since 1997 for the transplant of heart, liver, lung and bone marrow in vital emergency situations for the transplant candidate. This derogatory device was extended in 2005 (1) to situations involving the vital prognosis without appropriate therapeutic alternatives with respect to kidney transplants, heart, liver and lung, and stem cell transplants regardless of their origin (bone marrow, peripheral blood or placental blood) or mononuclear cells.
This device, implemented for a period of five years, was subject to certain donor-recognition conditions based on the donor's viral status as a protocol.
In France, as in other European states, organ shortage is a patent phenomenon that has steadily worsened for several years. The waiting times are extended ( Waiting media = 19.8 months for the kidney transplant) and 434 patients died pending a graft (data 2009, source Agency for Biomedicine).
The derogatory system implemented in January 2006 allowed, in less than three years, the completion of 617 additional organ transplants, including 366 kidney transplants, from 293 encephalic or living donors. These figures represent about 6% of the total organ transplant activity and saved the lives of many patients whose vital prognosis was engaged. In addition, the device also enabled the completion of 61 hematopoietic stem cell transplants in patients with short-term life prognosis.
In addition, although no cases of HBV transmission in recipients who received kidney transplant, heart or lung were observed, seroconversions in liver receivers occurred. In addition, there was a high frequency of occurrence, transient or prolonged, of anti-HBc antibodies in the population of kidney, lung or liver receivers with so-called non-immune profiles (antibodies anti-HBs negative) or "immunization" (positive HB antibodies). These antibody appearances occurred irrespective of the donor's status (antibodies anti-HBc isolated or associated with antibodies anti-HBs) and the elements available for the investigation of cases did not allow to formally exclude the hypothesis of an occult infection (organic manifestation without clinical manifestation) of the receiver by the VHB transmitted by the graft.
These various elements have justified the establishment of a new protocol that provides for the transplant of organ and cell (CSH and CMN) from donors with biological markers of HBV infection. Compliance with these protocols appears to be an essential element in ensuring the safety of recipients, taking into account the current context of organ shortages and stagnation of sampling activity observed in recent years.
Scope
The new regulatory framework distinguishes three types of situations depending on the serologic status of donors carrying a positive infection marker in relation to hepatitis B virus:
Donors with "old and healed" infection (Ag HBs ―, Ac anti-HBc +, Ac anti-HBs +):
Professionals can produce transplants of any organ other than the liver and hematopoietic stem cells and mononucleated cells from non-HBs antigen donors (Ag HBs) and presenting positive serology for anti-HBc Ac associated with positive serology for anti-HBs Ac. ;
Donors testifying to an earlier "contact" (Ag HBs – Ac HBs –, Ac HBc +):
By derogation and only in situations where the vital prognosis is engaged and when the therapeutic alternatives become inappropriate, professionals can perform transplants of any hematopoietic stem cells and mononucleated cells from a non-HBs antigen donor and presenting positive serology for isolated anti-HBc antibodies;
The particular case of liver donors with an "old and healed" infection (Ag HBs ―, Ac anti-HBc +, Ac anti-HBs +) or with an earlier "contact" (Ag HBs ―, Ac HBc +, Ac HBs ―):
Due to the tropism of the virus for the liver, these transplants can only be performed by derogation and only when the patient's vital prognosis is engaged and the therapeutic alternatives become inappropriate. Professionals can then perform liver transplants from a non-HBs antigen donor, presenting a positive serology for isolated anti-HBc antibodies or associated with positive serology for anti-HBs antibodies.
The use of donors with a "acute or chronic" profile (positive HBs antigen or VHB viremia) can only be justified as part of a vital emergency and is not the subject of these protocols.
Regardless of the donor's infection marker, transplants must be conducted in accordance with these protocols.
The purpose of these protocols is to accompany the medical teams in their choice and to allow them to ensure serological, virological and histological follow-up in the recipient having been transplanted from a graft with markers of hepatitis B virus infection.
In all cases, the patient must be previously informed and agree on the possibility of receiving a graft bearing viral markers under the common law conditions provided by the Act of 4 March 2002. It must also benefit from appropriate support and follow-up.
General conditions for grafting
1. Clinical prerequisites
The transplants of any organ made from grafts from donors with a so-called "old healed infection" (antigen HBs negative, antibodies positive, antibodies anti-HBs positive and if available in pregreffe, viral load negative HBV) or a profile known as "contact with HBV" (antigen negative HBs, antibodies anti-HBc positive; antibodies anti-HBs negative and if available in pregreffe, negative VHB viral load) can be performed in any immunized receiver vis-à-vis the VHB.
In addition, in particular cases of liver grafts from donors with anti-HBc antibodies (isolated or associated with anti-HBs antibodies) and other grafts from so-called "contact with HBV", the receiver's vital prognosis must be engaged and therapeutic alternatives become inappropriate.
Hematopoietic stem cell transplants and mononucleated cells produced from donor grafts with a so-called "old healed infection" profile (antigen HBs negative, antibodies anti-HBc positive, antibodies anti-HBs positive) or a profile known as "contact with VHB" (antigen HBs negative, antibodies anti-HBc positive); antibodies anti-HBs negative) can be performed in any receiver when VHB viral genomic screening shows the absence of viral replication in the donor. Two successive research is required to ensure the donor's absence of viremia. These examinations are, a contrario to the biological selection of organ donors, conciliable with the deadlines for obtaining the pregregate results in cells. The interpretation of this genomic profile must also take into account the stopping date of antiviral treatment.
2. Information and collection of patient consent
The information and informed consent of the patient must be required in advance under the conditions set out in sections L. 1111-4 (2) et seq. of Public Health Code.
It is indeed imperative that the patient have all the elements that enable him to direct his choice knowingly.
For organ transplants, the patient must be informed as soon as he is registered on the national waiting list on the possibility of being assigned a graft with a positive infectious marker for hepatitis B virus. This information should be used as soon as possible with respect to the transplants of hematopoietic stem cells and mononuclear cells.
This initial information must be supplemented by targeted information from the candidate to the transplant at the time of the proposal of such a graft. Targeted information should provide information on the impacts of this type of transplant, both on expected benefits and the risks involved and on the therapeutics that may be proposed and the therapeutic monitoring that will be undertaken.
The future receiver must also be informed of any additional constraints related to the allocation of grafts from HBV marker donors such as vaccination or pre-registered hepatitis B, as well as specific post-grecency follow-up measures where applicable.
In any case, the future receiver must be able to withdraw at any time.
This information must be documented in the patient's medical file.
In addition, it should be noted that the completion of this type of transplant as part of an intrafamilial donation provides that the potential donor consents to the recipient's disclosure of medical information regarding his or her immune status under the HBV. This donor's consent is a prerequisite for the collection.
3. Prophylaxis of HBV infection
1. Before grafting
The patient's transplant team doctor must verify the degree of his immunity from hepatitis B virus. Depending on the degree of protection assessed by the control of the Ac anti-HBs in the serum, the patient must benefit before the transplant, and as soon as possible, from a vaccine recall, or from a complete vaccination against the hepatitis B virus in accordance with existing vaccine schemes (3).
The effectiveness of vaccination must be verified before transplantation. In case of non-response to VHB vaccination, the patient will be able to benefit from a new anti-VHB vaccination attempt or an appropriate therapy to overcome non-response.
All of this information must be documented in the patient's medical file.
2. During the transplant
In case of non-protection against hepatitis B virus, the transplanted patient may, depending on its virological status and depending on the nature of the transplanted organ, receive appropriate antiviral treatment.
All of this information must be documented in the medical file.
4. Patient care and follow-up after transplant
The use of a graft from a donor carrying HPV markers must be documented and brought to the attention of medical and surgical transplant teams. In particular, it can be clearly and easily accessible in the patient's medical file.
The grafting team sets up a regular support and monitoring of the receiver.
In case of non-response to HBV vaccination, the transplanted patient will be able to benefit from a new attempt to immunize HBV.
A clinical, serological and virological follow-up of the transplanted patient is undertaken to define his status with regard to hepatitis B virus.
This follow-up is part of the general medical monitoring of recipients, however it must be adapted according to:
the nature of the graft;
- the serological profiles of the donor and the receiver;
- the clinical condition of the recipient and the prescribed therapeutics;
― the result of the donor's viral load.
All of this information must be documented in the patient's medical file.
5. Live donors
The legal health safety device allows for the removal of live donors despite positive infection markers against hepatitis B virus, which raises the issue of counterindicators to the donation in order to preserve the donor's health.
Although severe liver damage associated with infection is an obvious contraindication, a comprehensive list of contraindications is difficult to predict and is a case-by-case issue.
Also, for liver samples considered on donors carrying an infection with hepatitis B virus (for example, hepatitis B virus (forgeary or contact), transplant teams are invited to consult an ad hoc committee of experts placed with the Biomedicine Agency that will analyse the degree of motivation and the medical situation of the donor.
6. Biovigilance
General biovigilance provisions as defined in the Decree No. 2003-1206 of 12 December 2003 applies to all activities of transplantation and post-regime follow-up, including those conducted under section R. 1211-14-III.
As a result, any accident or error that may result in a adverse reaction in a patient, as well as any clinical or biological adverse reactions potentially attributable to the graft or transplant activity, must be reported promptly to the local health facility biovigilance correspondent.
Indeed, given the return of experience on the device of the derogatory transplant protocols established in 2005, it is particularly necessary that any incident or adverse effect be reported to the local biovigilance correspondent and be reported and investigated. Only the completeness of biovigilance declarations can be used to assess the use of grafts subject to these good practices.
7. Enchantillothèques : fabricthèque, cellulothèque,
plasma library, serothèque
The transplant of organs or cells carried out under paragraph III of Article R. 1211-14 requires the establishment, on the one hand, of a donor's santillothèque and, on the other hand, of a receiver's serothèque-plasmathèque in the context of biovigilance.
The donor's specimen imposes conservation at a minimum temperature of ―80 °C of 2 ml of serum, 2 ml of plasma, 2 ml of total blood as well as, in the case of organ transplants, a sample of liver tissue and this whatever type of transplanted organ, for a period of ten years.
The enchantillothèque of the receiver imposes conservation at a minimum temperature of ―80 °C of 2 ml of serum and 2 ml of plasma for a period of ten years.
Laboratories designated to support these sniffers trace the storage temperatures of the samples, the individual data attached to each sample. They ensure the development of computerization, security and accessibility of samples and associated data.
The following recommendations are intended to optimize and harmonize the practices of the different laboratories or biological centres in charge of these santillothèques.
Abductions for the donor enchantment.
The material used for sampling is defined in relation to the structure in charge of the management of squabbles in the biovigilance. The samples for the enchantillothèque are carried out in conjunction with the removal of organs or cells.
Must be taken:
10 ml of total blood on dry tube. This tube will separate and feed the serum;
10 ml of total blood on tube EDTA. This tube will separate and ignite plasma;
10 ml of total blood on EDTA tube for the storage and feeding of total blood.
In addition to organ transplants: a sample of liver tissue with sufficient volume for the subsequent realization, if any, of a viral load search. This sample may be used for the assessment of the quality of the hepatic parenchyma (fibrosis degree) in case of liver graft removal.
The volume of samples taken is to be adapted according to the age and weight of the donor.
Abductions for the receiver's serothèque-plasmathèque.
The material used for sampling will be defined in relation to the structure in charge of the management of the squabbles as part of the biovigilance. Samples for the serothèque-plasmathèque are made before organ transplant or the administration of cell therapy preparation.
Must be taken:
10 ml of total blood on dry tube. This tube will separate and feed the serum;
10 ml of total blood on tube EDTA. This tube will separate and feed the plasma.
Storage and transport of samples.
At temperature of +18 °C and +24 °C;
The period between sampling and freezing shall not exceed 6 hours.
Sample retention request.
The transmission slip that will accompany the samples shall contain a minimum the following information:
The purpose of the sampling: "biovigilance donor ultrasound" of organs or cells, "biovigilance receiver ultrasound" of organ or cells under Article R. 1211-14-III.
Name, first name, date of birth or code.
Date and time of sampling.
For donors to the arrested heart, specify the delay between death and 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.
Rationale for lack of sample or insufficient sample.
At laboratories (or biological centre) maintaining samples.
1.1. Centrifugation:
The centrifugation of tubes for the conservation of serum and plasma is implemented as soon as possible in the following ways:
800-1 600 g;
20 minutes.
1.2. Total blood:
The EDTA tube(s) for the total blood retention must be homogenized by reversals before moving to the next step.
1.3. The food:
To the extent that biovigilance investigations would require the deceleration of a sample, it is necessary to have a subsequent resource for a possible additional investigation. As a result, the samples shall be relative to the following distribution:
2 × 1 ml of serum;
2 × 1 ml of plasma;
2 × 1 ml of total blood;
2 fragments of liver tissue.
1.4. The identification of primary packagings:
At minima, the following information appears on primary packagings (cryotubes or any other device intended to preserve frozen samples): name, first name or code, sampling date, sample type (especially serum or plasma).
1.5. The freezing:
The samples (from the blood or tissue library) are frozen as quickly as possible at a minimum temperature of ―80 °C depending on the procedures implemented by the conservation centre.
The treatment of the hepatic parenchyma samples must subsequently allow the completion of the possible virological analyses, therefore the fixation of the tissues is not recommended.
2. Implementation of a traceability system:
(a) Traceability of storage temperatures throughout the sample storage period;
(b) Traceability of samples. This should include:
― to find without delay the location of the sample (chartography of freezers, vats, compartments, box with position of samples);
• to identify all non-conformities that have occurred since sampling;
―to have access to the conditions for the implementation of freezing or defrosting of the samples (delivery between death and removal of the donor(s) at the arrested heart, delay between sampling and freezing, reasons for possible decelerations, traceability of the movement history for samples from a given donor or receiver...)
3. Postgreffe analysis:
In postgreffe, it may be useful to keep samples collected during patient follow-up. The sample sampling period is left to the evaluation of the teams.
A N N E X E I
PROTOCOLS FOR THE IMPLEMENTATION OF THE DEROGATION PERMITTING THE USE OF BODIES OR CELLULATIONS OF DONNOR PORTERS OF THE VIRUS OF THE CETHERE
Preamble
Derogations allowing the use of donors with an infectious risk to the recipient against the hepatitis C virus (HCV) have existed since 1997, for the transplant of hematopoietic stem cells (HSCs) from the bone marrow in vital emergency situations and since 2005, for heart transplants, liver, lung and kidneys as well as for the transplants of HSC This latest situation has been the subject of regulatory guidance leading to the establishment of recommendations containing protocols, prepared by the French Health Products Safety Agency (AFSSAPS) on the basis of the advice of a group of multidisciplinary experts, published in the Official Journal of the French Republic of 11 March 2006.
Under the four years following the establishment of these protocols, AFSSAPS provided the Minister for Health with a report on the assessment of the transplants carried out in this framework so that the Minister would appreciate whether the device should be extended beyond December 22, 2010. The feedback on these exemptions has highlighted the need to maintain the HCV Protocols.
The continuation of this type of derogatory grafts has been advocated, on the one hand, of the prevalence of HCV in the general population and donor shortages and, on the other, of the potentially intrafamilial nature of HCV contamination for related donations. In all cases, the patient must be previously informed and must give consent to the possibility of receiving a viral marker(s). It must also benefit from appropriate therapeutic care and post-greffe monitoring.
In order to allow access to these protocols, a regulatory framework is put in place for five years to conduct the evaluation of these derogatory transplants, through national follow-up of recipients.
Regulatory framework regulating derogatory graft protocols against positive infectious markers for HCV
For the implementation of derogatory transplant protocols, the regulatory framework is as follows:
A decree in the Council of State introduces the principle of the protocols for the follow-up of the receivers and provides for the recommendations, subject to this document. The system in place will be the subject of a report four years after the issuance of the decree, its sustainability being subordinate to a favourable assessment of the data collected as part of the follow-up of the receivers;
An order mentions derogatory situations under HCV, i.e. the possible conditions for matching between the different virological status of donors and recipients.
Derogations from HCV that pre-existed in vital emergency situations for the receiver are maintained and are not the subject of these recommendations;
These recommendations are intended to guide teams who practice a graft in the context of a derogatory protocol. Each derogatory protocol is distinguished by a match between:
- one or more donor statutes under HCV;
- one or more of the Receiver status for HCV;
- a type of graft.
The liver grafts have been treated in isolation from other organs, since the donor's liver may have undergone reworking of the parenchyma which does not allow its therapeutic use. In addition, CSH (peripheral, bone marrow or placentary) and CMN are subject to specific derogatory protocols.
Taking into account these different criteria, it was possible to distinguish four derogatory transplant protocols.
For each of the derogatory transplant protocols, the recommendations relate to:
― the clinical context that can motivate the use of the derogatory protocol (one donor, intrafamilial framework, extension of the waiting for the transplant that affects the patient's survival, limitation of transplant indications...) and the nature of the information to be provided to the patient;
- the criteria for the use of the donor. These criteria are to be distinguished from viral markers that are mandatoryly sought as part of the biological qualification of donors. They therefore come in addition to the current biological qualification, in support of the decision to retain or exclude a donor carrying viral markers (results of liver biopsy, results of a genotyping...);
- the criteria for transplanting the patient in the context of the derogatory protocol. These criteria sought from the transplant candidate contribute to the transplant decision but are also used to anticipate the follow-up and treatment after transplantation;
― the therapeutic care that may be put in place in the receiver after the transplant;
― the parameters of therapeutic, virological and histological monitoring to be sought in the receiver.
A letter of information from the Biomedicine Agency outlines the practical modalities for the implementation of these exemptions.
General conditions of achievement
derogatory transplant protocols
1. Clinical prerequisites
Derogatory protocols should be implemented only when a patient has an urgent need for transplantation and that such an appropriate therapeutic alternative is possible for him, so that the expectation of another graft than that proposed in the derogatory context is prejudicial to his survival.
2. Information and collection of patient consent
The information and the prior collection of the informed consent of the patient are essential prerequisites for the course of the derogatory protocol. To this end, it is imperative that the patient (or his/her family) have all the elements that enable him/her to direct his/her choice knowingly.
It is recommended to provide general information on the possibility of a derogatory transplant at the time of registration on the national list of patients awaiting transplantation and to complete this initial information with targeted information from the candidate for transplantation, in the event of a graft assignment as part of a derogatory protocol. Targeted information should provide information on the impacts of this type of transplant, both on expected benefits and risks incurred and on the therapeutics that may be proposed and the specific monitoring that will be undertaken. In any case, the patient must be able to withdraw at any time.
It should be emphasized that the implementation of a derogatory protocol in the context of a non-anonymous donation poses the difficulty of receiving information while certain elements concerning the donor are subject to medical secrecy (serology.). In this context, the Order provides that the donor is informed of the disclosure to the recipient of medical information concerning him.
The terms of the collection of consent are explained in a letter of information prepared by the Biomedicine Agency.
3. Distribution and attribution of grafts
Derogatory transplant protocols should not be in contradiction with the common principles and rules for the distribution and attribution of grafts. The possibility of entering a derogatory protocol should not exclude keeping its place in the current national list of patients awaiting transplant.
4. Receiver Monitoring Protocol and Evaluation
Therapeutic, virological, serological and histological monitoring of recipients who have undergone a transplant in the context of a derogatory protocol must be undertaken. It is necessary to consider long-term follow-up and for certain virological statuses of receiver, or donor, a life-tracking. Indeed, events affecting the survival of grafts and recipients potentially attributable to HCV infections usually occur late after transplantation, which requires a specific monitoring distance from the transplant. Data obtained as part of this follow-up are collected at the national level by the Biomedicine Agency. They serve as a support for the evaluation of each derogatory protocol and the updating of these recommendations. A follow-up committee established by the Biomedicine Agency is responsible for the collection and operation of data.
The procedures for data transmission by transplant teams are explained in a letter of information prepared by the Biomedicine Agency.
5. Use of live donors
The extension of the derogatory device is primarily intended to respond to the context of a shortage of organs from deceased donors. In fact, the removal of organs in an intra-family situation on live donors (possible for kidney, liver, lungs) remains limited. These recommendations have been made specifically for the use of deceased organ donors.
In this derogatory context, live donors must be taken despite their infection, which raises the question of medical contraindications to the sampling. The list of these contraindications is difficult to predict. For HCV infection, severe liver damage is obvious medical contraindications, but some of the extra-hepatic manifestations of HCV infection may also counter-indicate sampling. In these situations (living organ donors or CSH donors), transplant teams are invited to consult an ad hoc committee of experts placed with the Biomedicine Agency that will analyze the degree of motivation and the medical situation of the donor.
6. Enchantillothèques : serothèque et biothèque
Since the establishment of the enchanting protocols is essential to the establishment of the derogatory protocols, it is necessary to rely on a serothèque and, if necessary, a biothèque (lopatic biopsy) of donors and recipients during the course of the derogatory transplant protocols. In fact, these biological samples find their immediate interest in conducting tests that cannot be performed prior to transplantation, but whose results condition the follow-up and treatment of the recipients. In addition, they could be subject to additional retrospective investigations in view of the long-term events observed in the recipients, during their virological and histological monitoring. The analysis of these data could lead to the clarification or modification of the recommendations issued at the start of the protocols.
Apart from the derogatory transplant protocols, it was once again emphasized that the establishment in France, in a coordinated manner, of serothèques and biothèques, is an indispensable element for good transplant practices. In fact, these samples are of interest in the evolution of emerging infection detection techniques that may be transmitted or reactivated to the detergents of a transplant. Moreover, they are also very useful for a retrospective understanding and analysis of the conditions of transmission of certain pathogens.
However, pending a regulatory framework for the structural organization of these santillothèques and the conditions for the conservation of the different samples, this document provides a first level of recommendations to the teams wishing to implement derogatory transplant protocols:
- samples of donor and receiver serum shall be taken and retained before the transplant. If necessary, hepatic biopsy samples must also be retained;
- if samples of donor and receiver serum are required immediately after the transplant, additional aliquots shall be provided for the storage of shrines;
– in postgreffe, it may be useful to keep samples collected during patient follow-up. The sample sampling period is left to the evaluation of the teams;
― the shelf life of the samples shall at least correspond to the period necessary for the follow-up of the receivers. For long-term follow-up, however, it must take into account the risk of denaturation of samples;
– the conditions for the storage of different samples must be consistent with the analyses that may be potentially required. For example, according to the objective of the examination on liver fragments (quantification of viral RNA by PCR in the liver or histological analysis), the conditions for handling the samples are different. Also, in the event that both types of examinations are required, it would be desirable to have unfixed sampling and frozen liquid nitrogen and fixed sampling. Similarly, in the case of serum, HCV genotyping in the donor and receiver requires a frozen sample at low temperature ( – 70 °C).
The following table mentions various possible purposes for biological samples. This non-exhaustive table is provided as an indication for the start-up of the derogatory grafting protocols, as further analysis may be required in view of the results of the receivers' follow-up.
You can consult the table in the
JOn° 299 of 26/12/2010 text number 36
Protocols
HCV marker holders
1. Derogatory situations for organ transplantation
In the absence of antiviral anti-HCV therapy that can be used in organ receivers, the patient's HCV status prior to transplantation was identified as a determining factor for inclusion/exclusion in derogatory transplant protocols using positive anti-HCV organ donors:
– only patients with chronic hepatitis C (positive HCV and positive HCCP), i.e., viral replication active at the time of transplantation, may be included in the protocols, if they are in the immediate need for transplantation;
– patients with negative serology and seropositive and non-tramic patients cannot be included in protocols. The use of positive anti-HCV organ donors remains unauthorised in this patient profile.
In terms of virological risk, the protocols distinguish between kidney, heart and lung transplants and, on the other hand, liver transplants; This risk is different for liver transplant as the donor's liver is the main reservoir and place of replication of HCV.
2. Derogatory situations for CSH grafting
(MO, CSP, CMN, cord blood)
The data in the literature show distinct levels of transmission risk depending on whether the seropositive donor is viremic or only bears antibodies. Given that it is technically possible to determine the donor's ARN-VHC status prior to the CSH graft, the level of transmission risk should be offset by the intended benefit of the graft to make the derogatory transplant decision. In other words, the higher the risk of transmission, the higher the expected profit of the transplant. The appreciation of the graft will have to take into account both the urgency necessary for the patient and the possible uniqueness of the donor.
As a result, the determining criteria for the inclusion/exclusion of a patient in derogatory protocols using positive anti-HCV donors are, on the one hand, the absence or presence of viremia in the donor and, on the other, the clinical situation of the patient pending transplantation:
― where the positive anti-HCV donor is not viremic (profile determined by two successive analyses by qualitative or quantitative CCP of sensitivity threshold equivalent to 15 days apart), the need for transplantation will be estimated taking into account the urgency for the patient and the possible uniqueness of the donor;
― when the donor is transferred, the need for transplantation will be estimated taking into account the urgency for the patient, the possible uniqueness of the donor, but also the transplant indication. Thus, with these donors, the derogatory protocols can only be considered in very limited graft indications relevant to a case-by-case analysis by an expert college.
In these situations, transplant teams are invited to consult an ad hoc expert committee with the Biomedicine Agency.
For each match between donors and recipients, the details of the various protocols are summarized as tables at the end of this document. For explicitation and justification of the various parameters taken into account in the protocols, it is also possible to refer to the report of the expert group on the Afssaps website (www.afssaps.sante.fr).
You can consult the table in the
JOn° 299 of 26/12/2010 text number 36
Two successive research is required to ensure the donor's absence of viremia. The interpretation of this profile must also take into account the stopping date of antiviral treatment.
You can consult the table in the
JOn° 299 of 26/12/2010 text number 36
You can consult the table in the
JOn° 299 of 26/12/2010 text number 36
You can consult the table in the
JOn° 299 of 26/12/2010 text number 36
You can consult the table in the
JOn° 299 of 26/12/2010 text number 36
Done in Paris, December 23, 2010.
Xavier Bertrand
