Liver DysfunctionINTERLIVERNCT03193151
Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation
An observational study of Liver Dysfunction, run by University of Alberta at 15 sites in 5 countries.
Trial summary
INTERLIVER is a prospective observational study of the relationship of the molecular phenotype of 300 liver transplant biopsies to the histologic phenotype and the clinical features and outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Dysfunction
- What is being tested?
- liver biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 300 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 19 Dec 2017to Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: This study aims to recruit 300 biopsies from liver transplant patients for clinical indications and the standard of care biopsies.
Who may be able to join
- biopsy for clinical indications
Who cannot join
- no consent, pregnant women
Trial locations and contacts
15 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
15 sites in 5 countries
United States8 sites, 1 recruiting
- Completed
University of Maryland School of Medicine
Baltimore, Maryland, 21201
- Completed
Northwestern Memorial Hospital
Chicago, Illinois, 60611
- Completed
Baylor University Medical Center, Annette C. and Harold C. Simmons Transplant Institute
Dallas, Texas, 75246
- Recruiting
Henry Ford Transplant Institute
Detroit, Michigan, 48202
Dilip Moonka, MD, DMOONKA1@hfhs.org
Sierra Foley, SFoley3@hfhs.org
- Withdrawn
Vanderbilt University Medical Center, Vanderbilt Transplant Center
Nashville, Tennessee, 37232
- Completed
Transplant Surgery, VCU Medical Center
Richmond, Virginia, 23298
- Completed
University of California San Francisco, Transplant Research Unit
San Francisco, California, 94143
- Completed
Division of Transplant Surgery, University of Washington
Seattle, Washington, 98195
Poland4 sites
- Completed
Dep. of Nephrology, Transplantation & Internal Med., Samodzielny Publiczny Szpital Kliniczny im. A. Mieleckiego
Katowice, 40-027
- Completed
Independent Public Composite Regional Hospital
Szczecin, 71-455
- Completed
Warsaw Medical University, Jesus the Child Clinical Hospital
Warsaw, 02-005
- Completed
Warsaw Medical University, Independent Public Clinical Hospital
Warsaw, 02-097
Australia1 site
- Completed
Centenary Institute of Cancer Medicine & Cell Biology, Royal Prince Alfred Hospital
Camperdown, NSW 2050
Canada1 site
- Completed
University of Alberta, Laboratory Medicine and Pathology
Edmonton, Alberta, T6G 2R7
United Kingdom1 site
- Completed
Institute for Liver Science, King's College London
London, SE5 9NU
About this study
Official title: Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation, a Multicenter Study
INTERLIVER is a prospective observational study of the relationship of the molecular phenotype of 300 liver transplant biopsies to the histologic phenotype and the clinical features and outcomes. A segment of a biopsy performed as standard-of-care for indications, or by center protocol, will be used for gene expression study.
Read the detailed description
The current standard for biopsy-based diagnoses of dysfunction of liver transplants is histology (the Banff system), an arbitrary international empirical consensus based on lesions and rules, similar in principle to the kidney, heart, and lung histology systems. Recent data-driven approaches using molecular and conventional technologies indicate that such systems frequently produce incorrect diagnoses - perhaps 40-50% in abnormal kidney or heart transplant biopsies and even more in lung biopsies, with great potential for harm to patients due to inappropriate treatment.
To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype, and combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The MMDx, developed first in kidney transplant biopsies because phenotypes are well established, will now be adapted to liver transplant biopsies. The present study will develop a Reference Set of liver biopsies, adapt the MMDx system to assess and report molecular phenotype of liver biopsies; and validate and refine this system in 300 unselected prospectively collected for clinical indications and a standard of care biopsies from North American and European Centers. In addition to demonstrating the real-time feasibility and potential value of this System in patient care, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback to improve its utility.
Thanks to increasing interest and support from participating centers, INTERLIVER has already received 856 biopsies from 740 participants and will extend the Reference Set to 900 biopsies.
- Conditions
- Liver Dysfunction
- Being tested
- liver biopsy
- Keywords
- Liver transplant, global gene expression, molecular diagnostics
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
liver biopsyProcedure or surgery
5 mm fragment of liver transplant biopsy taken for clinical indication
What is being measured
The primary outcome is the main question the study is designed to answer.
Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in liver transplant biopsies, in a reference set of 100 biopsies
Based on the reference set, create molecular classifier that predicts antibody mediated and T cell mediated rejection for next 200 biopsies
Measured: two years
Secondary outcomes (1)
Assign in real time (two working days upon biopsy receipt) molecular scores (probability) of T cell mediated rejection and antibody mediated rejection.
The molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample when compared to the reference set.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start19 Dec 2017
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Liver DysfunctionStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Philip Halloran, University of Alberta
- Investigators
- Philip F Halloran, MD, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03193151
- Sponsor's protocol ID
- ATAGC04
- Acronym
- INTERLIVER
- Status last verified
- Jun 2026
- First submitted
- 15 Jun 2017
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Madill-Thomsen KS, Halloran PF. Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope(R) Diagnostic System (MMDx). Clin Sci (Lond). 2024 Jun 5;138(11):663-685. doi: 10.1042/CS20220530.
PubMed 38819301Madill-Thomsen KS, Gauthier PT, Abouljoud M, Bhati C, Bruno D, Ciszek M, Durlik M, Feng S, Foroncewicz B, Grat M, Jurczyk K, Levitsky J, McCaughan G, Maluf D, Montano-Loza A, Moonka D, Mucha K, Myslak M, Perkowska-Ptasinska A, Piecha G, Reichman T, Tronina O, Wawrzynowicz-Syczewska M, Zeair S, Halloran PF. Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study. Transplantation. 2025 Aug 1;109(8):1367-1382. doi: 10.1097/TP.0000000000005269. Epub 2025 Jan 9.
PubMed 39780312Madill-Thomsen K, Abouljoud M, Bhati C, Ciszek M, Durlik M, Feng S, Foroncewicz B, Francis I, Grat M, Jurczyk K, Klintmalm G, Krasnodebski M, McCaughan G, Miquel R, Montano-Loza A, Moonka D, Mucha K, Myslak M, Paczek L, Perkowska-Ptasinska A, Piecha G, Reichman T, Sanchez-Fueyo A, Tronina O, Wawrzynowicz-Syczewska M, Wiecek A, Zieniewicz K, Halloran PF. The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study. Am J Transplant. 2020 Aug;20(8):2156-2172. doi: 10.1111/ajt.15828. Epub 2020 Apr 9.
PubMed 32090446Madill-Thomsen KS, Abouljoud M, Bhati C, Ciszek M, Durlik M, Feng S, Foroncewicz B, Francis I, Grat M, Jurczyk K, Klintmalm G, Krasnodebski M, McCaughan G, Miquel R, Montano-Loza A, Moonka D, Mucha K, Myslak M, Paczek L, Perkowska-Ptasinska A, Piecha G, Reichman T, Sanchez-Fueyo A, Tronina O, Wawrzynowicz-Syczewska M, Wiecek A, Zieniewicz K, Halloran PF. The molecular phenotypes of injury, steatohepatitis, and fibrosis in liver transplant biopsies in the INTERLIVER study. Am J Transplant. 2022 Mar;22(3):909-926. doi: 10.1111/ajt.16890. Epub 2021 Dec 3.
PubMed 34780106Gauthier PT, Gerhardt LM, Jahn L, Hinze C, Halloran PF. Digital cytometry of leukocyte landscapes reveals shared correlates of rejection across organ transplants. J Clin Invest. 2026 Sep 22:e208686. doi: 10.1172/JCI208686. Online ahead of print.
PubMed 42771484Halloran PF. Integrating molecular and histologic interpretation of transplant biopsies. Clin Transplant. 2021 Apr;35(4):e14244. doi: 10.1111/ctr.14244. Epub 2021 Feb 17. No abstract available.
PubMed 33595110
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation, a Multicenter Study
- ClinicalTrials.gov ID
- NCT03193151
- Acronym / sponsor ID
- INTERLIVER / ATAGC04
- Conditions
- Liver Dysfunction
- Keywords
- Liver transplant, global gene expression, molecular diagnostics
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- 19 Dec 2017 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 20 Jun 2017 (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.
INTERLIVER is a prospective observational study of the relationship of the molecular phenotype of 300 liver transplant biopsies to the histologic phenotype and the clinical features and outcomes. A segment of a biopsy performed as standard-of-care for indications, or by center protocol, will be used for gene expression study.
Detailed description
The current standard for biopsy-based diagnoses of dysfunction of liver transplants is histology (the Banff system), an arbitrary international empirical consensus based on lesions and rules, similar in principle to the kidney, heart, and lung histology systems. Recent data-driven approaches using molecular and conventional technologies indicate that such systems frequently produce incorrect diagnoses - perhaps 40-50% in abnormal kidney or heart transplant biopsies and even more in lung biopsies, with great potential for harm to patients due to inappropriate treatment.
To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype, and combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The MMDx, developed first in kidney transplant biopsies because phenotypes are well established, will now be adapted to liver transplant biopsies. The present study will develop a Reference Set of liver biopsies, adapt the MMDx system to assess and report molecular phenotype of liver biopsies; and validate and refine this system in 300 unselected prospectively collected for clinical indications and a standard of care biopsies from North American and European Centers. In addition to demonstrating the real-time feasibility and potential value of this System in patient care, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback to improve its utility.
Thanks to increasing interest and support from participating centers, INTERLIVER has already received 856 biopsies from 740 participants and will extend the Reference Set to 900 biopsies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This study aims to recruit 300 biopsies from liver transplant patients for clinical indications and the standard of care biopsies.
Key inclusion criteria (1 listed)
- biopsy for clinical indications
Key exclusion criteria (1 listed)
- no consent, pregnant women
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 |
|---|---|---|
| liver biopsy5 mm fragment of liver transplant biopsy taken for clinical indication | Procedure or surgery | – |
Primary outcome
Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in liver transplant biopsies, in a reference set of 100 biopsies
Time frame: two years
Based on the reference set, create molecular classifier that predicts antibody mediated and T cell mediated rejection for next 200 biopsies
1 secondary outcome
Assign in real time (two working days upon biopsy receipt) molecular scores (probability) of T cell mediated rejection and antibody mediated rejection.
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Background: PubMed 38819301Madill-Thomsen KS, Halloran PF. Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope(R) Diagnostic System (MMDx). Clin Sci (Lond). 2024 Jun 5;138(11):663-685. doi: 10.1042/CS20220530.
- Results publication: PubMed 39780312Madill-Thomsen KS, Gauthier PT, Abouljoud M, Bhati C, Bruno D, Ciszek M, Durlik M, Feng S, Foroncewicz B, Grat M, Jurczyk K, Levitsky J, McCaughan G, Maluf D, Montano-Loza A, Moonka D, Mucha K, Myslak M, Perkowska-Ptasinska A, Piecha G, Reichman T, Tronina O, Wawrzynowicz-Syczewska M, Zeair S, Halloran PF. Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study. Transplantation. 2025 Aug 1;109(8):1367-1382. doi: 10.1097/TP.0000000000005269. Epub 2025 Jan 9.
- Results publication: PubMed 32090446Madill-Thomsen K, Abouljoud M, Bhati C, Ciszek M, Durlik M, Feng S, Foroncewicz B, Francis I, Grat M, Jurczyk K, Klintmalm G, Krasnodebski M, McCaughan G, Miquel R, Montano-Loza A, Moonka D, Mucha K, Myslak M, Paczek L, Perkowska-Ptasinska A, Piecha G, Reichman T, Sanchez-Fueyo A, Tronina O, Wawrzynowicz-Syczewska M, Wiecek A, Zieniewicz K, Halloran PF. The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study. Am J Transplant. 2020 Aug;20(8):2156-2172. doi: 10.1111/ajt.15828. Epub 2020 Apr 9.
- Results publication: PubMed 34780106Madill-Thomsen KS, Abouljoud M, Bhati C, Ciszek M, Durlik M, Feng S, Foroncewicz B, Francis I, Grat M, Jurczyk K, Klintmalm G, Krasnodebski M, McCaughan G, Miquel R, Montano-Loza A, Moonka D, Mucha K, Myslak M, Paczek L, Perkowska-Ptasinska A, Piecha G, Reichman T, Sanchez-Fueyo A, Tronina O, Wawrzynowicz-Syczewska M, Wiecek A, Zieniewicz K, Halloran PF. The molecular phenotypes of injury, steatohepatitis, and fibrosis in liver transplant biopsies in the INTERLIVER study. Am J Transplant. 2022 Mar;22(3):909-926. doi: 10.1111/ajt.16890. Epub 2021 Dec 3.
- Derived from this study: PubMed 42771484Gauthier PT, Gerhardt LM, Jahn L, Hinze C, Halloran PF. Digital cytometry of leukocyte landscapes reveals shared correlates of rejection across organ transplants. J Clin Invest. 2026 Sep 22:e208686. doi: 10.1172/JCI208686. Online ahead of print.
- Derived from this study: PubMed 33595110Halloran PF. Integrating molecular and histologic interpretation of transplant biopsies. Clin Transplant. 2021 Apr;35(4):e14244. doi: 10.1111/ctr.14244. Epub 2021 Feb 17. No abstract available.
- Individual participant dataSharing planned: No
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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.
Philip F Halloran, MD, PhD principal investigator
University of Alberta
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Dysfunction, run by University of Alberta at 15 sites in 5 countries.
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 1 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Poland, Australia, Canada, United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Konrad S Famulski, PhD (1 780 492 1725, konrad@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in liver transplant biopsies, in a reference set of 100 biopsies (time frame: two years). 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 NCT03193151, which also lists 6 linked publications.
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 4 Jun 2026.