Liver DiseasesEdMonHGNCT03995537
Monocytic Expression of HLA-DR After Liver Transplantation
An observational study of Liver Diseases and Liver Transplantation, run by Hospices Civils de Lyon at 3 sites in France.
Trial summary
A defect of the immune response has been described in patients with severe liver disease. This immune-paresis is partly driven by a compensatory anti-inflammatory response following a systemic inflammatory response syndrome and affects the innate immune response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Diseases, Liver Transplantation, Cirrhosis, Liver
- What is being tested?
- blood sample
- How many people
- 130 participants
- Where
- 3 sitesFrance
- Study dates
- 26 Feb 2020to 14 Jul 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with severe liver disease waiting for LT. Only patients with the most frequent LT indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral failure and fulminant hepatitis.
Who may be able to join
- Patients waiting for LT in the LT center of the Groupement Hospitalier Nord, and in the hepato-gastroenterology department of the Groupement hospitalier centre, Hospices Civils de Lyon, presenting :
- Cirrhosis
- Complicated with hepatocellular carcinoma
- Or chronically decompensated (recurrent gastrointestinal bleeding, refractory ascites, portopulmonary or hepatopulmonary syndrome, chronic liver failure)
- Or with acute decompensation, with or without multi-visceral failure
- Or fulminant hepatitis
- Patient eligible for the standard immunosuppression protocol (induction with anti-Interleukin-2 (IL2) (Day1 and Day4) and then corticosteroids for a minimum of 7 days associated with tacrolimus and mycophenolate mofetil)
- Patient having theoretical access to LT within <3 months (head of local and / or national waiting list)
Who cannot join
- Minor or adult patient under tutorship or curatorship
- Pregnant and lactating woman
- Patient without liberty
- Patient not affiliated to social security
- Refusal to participate in the study
- Patient enrolled in "super-emergency" outside working days
Show all 11Show fewer
- Patients waiting for LT without underlying liver disease (healthy liver HCC, cholangiocarcinoma, primary tumor metastases, amyloidosis, Rendu Osler disease, dominant biliary disease such as recurrent angiocholitis without underlying cirrhosis)
- Patient who already had a LT
- Patient who received a multi-organ transplant (liver + kidney / heart / lung / intestine)
- Patient on immunosuppressive therapy before hepatic transplant (other than corticosteroids)
- Patient not eligible for standard immunosuppression protocol
Trial locations and contacts
3 sites in 1 country.
France3 sites
Service d'hépato gastroentérologie hôpital Edouard Herriot Groupement hospitalier centre
Lyon, 69003
Hopital de la Croix-Rouse, service de réanimation chirurgicale
Lyon, 69004
Hospital de la Croix Rousse, service d'hépatologie
Lyon, 69004
About this study
A defect of the immune response has been described in patients with severe liver disease. This immune-paresis is partly driven by a compensatory anti-inflammatory response following a systemic inflammatory response syndrome and affects the innate immune response. The innate immune defect has been described in patients with advanced cirrhosis and more significantly in patients with acute liver failure or acute on chronic liver failure (ACLF). The monocytes/macrophages pro-inflammatory response and finally the antimicrobial response are thus strongly impaired, leading to higher sepsis risk. The monocytes/macrophages phenotype associated with these functional alterations has been widely described, with a weaker expression of Human Leukocyte Antigen - DR isotype (HLA-DR) on the monocytes surface, correlated with poor outcomes. The low monocytic expression of HLA-DR, its functional and clinical impact has been widely described in the context of septic shock with similar pathophysiological mechanisms.
Liver transplantation (LT) is often the only therapeutic option for patients with advanced liver failure. Post-transplant survival of the most severe patients is similar to the survival in the whole population of LT patients, but the complication rate remains higher, with a major risk of infection. Currently used immunosuppression protocols do not take into account the quality of pre-transplant immune response. Some treatments, such as corticosteroids, which are widely used for the induction of post-transplant immunosuppression, may affect the innate immune response. However, it has been shown that low expression of post-transplant monocyte HLA-DR was associated with a greater risk of septic complication.
Read more
The general objective of this study is to focus on the evolution of a robust marker of immune dysfunction, HLA-DR monocyte expression, before and following LT, and to analyse its post LT expression depending on the level of pre-transplant expression as well as its association with post-transplant complications. This study will bring new insights for the design of a prospective study on the relevance of adapting post-transplant immunosuppression protocols to HLA-DR expression on monocytes surface, which is a robust marker of the innate immune response.
Evaluation of innate immune dysfunction pre-LT by quantification of monocytic HLA-DR expression and monitoring of its post-LT kinetics may be relevant for assessing post-transplant immune status and adapting immunosuppressive therapy. A descriptive, observational study associating clinical and biological data is needed to confirm the relevance of HLA-DR expression quantification on the surface of monocytes in a population of selected patients, before and after LT. These data will allow setting up a prospective interventional study reporting the possible benefit of post-transplant immunosuppressive treatment modulation, according to the HLA-DR monocyte dosage and its kinetics evolution.
The main objective of this study is to describe the association between evolution of monocytic HLA-DR expression on monocytes/macrophages surface during the first month after LT and the occurrence of one of the 2 following clinical events reflecting a post LT immune dysfunction (acute cell rejection and sepsis).
- Conditions
- Liver Diseases, Liver Transplantation, Cirrhosis, Liver
- Being tested
- blood sample
- Keywords
- liver transplantation, Liver Diseases
- Medical subject headings
- Liver Diseases, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleBiological
Samples will be collected at the inclusion and repeated if necessary before LT, including one 4 mL EDTA sample and one 4 mL Heparin sample and one 2.5 mL PAXgene® sample, allowing the HLA-DR assay to be performed with also plasma aliquots and messenger RNAs.
Same samples will also be collected :
- between inclusion and LT in case of major clinical change
- During the pre-transplant follow-up 3 months after inclusion, for patients who have not been transplanted within 3 months after inclusion
- at day 1 after LT
- 2 times a week after the LT for a maximum of 1 month
Biological data will be collected at those different times.
| Study group | Role | What they receive |
|---|---|---|
| Patients with severe liver disease waiting liver transplant | Only patients with the most frequent LT indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral failure and fulminant hepatitis. Receives: Biological: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of receptors expressed by monocytes
Primary outcome will be the kinetics of HLA-DR expression on the monocytes / macrophages surface during the first month after LT as a function of pre-LT status (Nadir, normalization delay of HLA-DR expression) and its association with 2 clinical events reflecting post-LT immune dysfunction (acute cell rejection and sepsis).
Expression of HLA-DR is measured by the number of receptors expressed by monocytes and measured by flow cytometry at different times: at inclusion (D0), Month 3, Month 6, the day of LT and twice a week for 1 month in post LT.
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2019
- Study start26 Feb 2020
- Primary completion14 Jul 2023
- Study completion14 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver DiseasesStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03995537
- Sponsor's protocol ID
- 69HCL19_0116
- Other IDs
- 2019-A00954-53
- Acronym
- EdMonHG
- Status last verified
- Aug 2024
- First submitted
- 20 Jun 2019
- Last updated
- 28 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Delignette MC, Riff A, Antonini T, Soustre T, Bodinier M, Peronnet E, Venet F, Gossez M, Pantel S, Mabrut JY, Muller X, Mohkam K, Villeret F, Erard D, Dumortier J, Zoulim F, Heyer L, Guichon C, Blet A, Aubrun F, Monneret G, Lebosse F. Individual mHLA-DR trajectories in the ICU as predictors of early infections following liver transplantation: a prospective observational study. Crit Care. 2025 Feb 18;29(1):79. doi: 10.1186/s13054-025-05305-x.
PubMed 39966934
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monocytic Expression of HLA-DR After Liver Transplantation
- ClinicalTrials.gov ID
- NCT03995537
- Acronym / sponsor ID
- EdMonHG / 69HCL19_0116
- Conditions
- Liver Diseases, Liver Transplantation, Cirrhosis, Liver
- Keywords
- liver transplantation, Liver Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 26 Feb 2020 (actual)
- Primary completion
- 14 Jul 2023 (actual)
- Study completion
- 14 Jul 2023 (actual)
- First posted
- 24 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A defect of the immune response has been described in patients with severe liver disease. This immune-paresis is partly driven by a compensatory anti-inflammatory response following a systemic inflammatory response syndrome and affects the innate immune response. The innate immune defect has been described in patients with advanced cirrhosis and more significantly in patients with acute liver failure or acute on chronic liver failure (ACLF). The monocytes/macrophages pro-inflammatory response and finally the antimicrobial response are thus strongly impaired, leading to higher sepsis risk. The monocytes/macrophages phenotype associated with these functional alterations has been widely described, with a weaker expression of Human Leukocyte Antigen - DR isotype (HLA-DR) on the monocytes surface, correlated with poor outcomes. The low monocytic expression of HLA-DR, its functional and clinical impact has been widely described in the context of septic shock with similar pathophysiological mechanisms.
Liver transplantation (LT) is often the only therapeutic option for patients with advanced liver failure. Post-transplant survival of the most severe patients is similar to the survival in the whole population of LT patients, but the complication rate remains higher, with a major risk of infection. Currently used immunosuppression protocols do not take into account the quality of pre-transplant immune response. Some treatments, such as corticosteroids, which are widely used for the induction of post-transplant immunosuppression, may affect the innate immune response. However, it has been shown that low expression of post-transplant monocyte HLA-DR was associated with a greater risk of septic complication.
The general objective of this study is to focus on the evolution of a robust marker of immune dysfunction, HLA-DR monocyte expression, before and following LT, and to analyse its post LT expression depending on the level of pre-transplant expression as well as its association with post-transplant complications. This study will bring new insights for the design of a prospective study on the relevance of adapting post-transplant immunosuppression protocols to HLA-DR expression on monocytes surface, which is a robust marker of the innate immune response.
Evaluation of innate immune dysfunction pre-LT by quantification of monocytic HLA-DR expression and monitoring of its post-LT kinetics may be relevant for assessing post-transplant immune status and adapting immunosuppressive therapy. A descriptive, observational study associating clinical and biological data is needed to confirm the relevance of HLA-DR expression quantification on the surface of monocytes in a population of selected patients, before and after LT. These data will allow setting up a prospective interventional study reporting the possible benefit of post-transplant immunosuppressive treatment modulation, according to the HLA-DR monocyte dosage and its kinetics evolution.
The main objective of this study is to describe the association between evolution of monocytic HLA-DR expression on monocytes/macrophages surface during the first month after LT and the occurrence of one of the 2 following clinical events reflecting a post LT immune dysfunction (acute cell rejection and sepsis).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with severe liver disease waiting liver transplant | – | Biological: blood sampleOnly patients with the most frequent LT indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral failure and fulminant hepatitis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with severe liver disease waiting for LT. Only patients with the most frequent LT indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral failure and fulminant hepatitis.
Key inclusion criteria (8 listed)
- Patients waiting for LT in the LT center of the Groupement Hospitalier Nord, and in the hepato-gastroenterology department of the Groupement hospitalier centre, Hospices Civils de Lyon, presenting :
- Patient eligible for the standard immunosuppression protocol (induction with anti-Interleukin-2 (IL2) (Day1 and Day4) and then corticosteroids for a minimum of 7 days associated with tacrolimus and mycophenolate mofetil)
- Patient having theoretical access to LT within <3 months (head of local and / or national waiting list)
Key exclusion criteria (11 listed)
- Minor or adult patient under tutorship or curatorship
- Pregnant and lactating woman
- Patient without liberty
- Patient not affiliated to social security
- Refusal to participate in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sampleSamples will be collected at the inclusion and repeated if necessary before LT, including one 4 mL EDTA sample and one 4 mL Heparin sample and one 2.5 mL PAXgene® sample, allowing the HLA-DR assay to be performed with also plasma aliquots and messenger RNAs. Same samples will also be collected : * between inclusion and LT in case of major clinical change * During the pre-transplant follow-up 3 months after inclusion, for patients who have not been transplanted within 3 months after inclusion * at day 1 after LT * 2 times a week after the LT for a maximum of 1 month Biological data will be collected at those different times. | Biological | Patients with severe liver disease waiting liver transplant |
Primary outcome
number of receptors expressed by monocytes
Time frame: 7 months
Primary outcome will be the kinetics of HLA-DR expression on the monocytes / macrophages surface during the first month after LT as a function of pre-LT status (Nadir, normalization delay of HLA-DR expression) and its association with 2 clinical events reflecting post-LT immune dysfunction (acute cell rejection and sepsis). Expression of HLA-DR is measured by the number of receptors expressed by monocytes and measured by flow cytometry at different times: at inclusion (D0), Month 3, Month 6, the day of LT and twice a week for 1 month in post LT.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Derived from this study: PubMed 39966934Delignette MC, Riff A, Antonini T, Soustre T, Bodinier M, Peronnet E, Venet F, Gossez M, Pantel S, Mabrut JY, Muller X, Mohkam K, Villeret F, Erard D, Dumortier J, Zoulim F, Heyer L, Guichon C, Blet A, Aubrun F, Monneret G, Lebosse F. Individual mHLA-DR trajectories in the ICU as predictors of early infections following liver transplantation: a prospective observational study. Crit Care. 2025 Feb 18;29(1):79. doi: 10.1186/s13054-025-05305-x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Diseases and Liver Transplantation, run by Hospices Civils de Lyon at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of receptors expressed by monocytes (time frame: 7 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03995537, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.