Natural Course and Molecular Basis of Alpha 1- Antitrypsin Deficiency-associated Liver Disease.

NCT07639996 | Not Yet Recruiting

• 1 other identifier: Alpha 1 antitrypsin deficiency
• Study Type: observational
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

• To define the course of AATD-associated liver disease.
• To use the obtained samples for biomedical research which includes:
• Search for serum-based disease biomarkers and the associated molecular pathways.
• Multi-omic spatial analysis of human AATD-LD.

Conditions

Alpha 1-antitrypsin Deficiency (AATD)

Outcome Measures

Primary Outcomes (1)

• Search for serum-based disease biomarkers and the associated molecular pathways

  Eight months of performing serum proteomics to identify biomarkers that reflect liver disease severity and predict poor outcomes

Secondary Outcomes (1)

• Multi-omic spatial analysis of human AATD-LD.

  Eight months of conduction of spatial multi-omic analyses comparing pediatric and adult liver tissues. This will include proteomic and transcriptomic mapping to understand how AAT accumulation and ductular reactions differ between the two forms.

Interventions

Multi-omic spatial analysis DIAGNOSTIC_TEST

conduction of spatial multi-omic analyses comparing pediatric and adult liver tissues. This will include proteomic and transcriptomic mapping to understand how AAT accumulation and ductular reactions differ between the two forms.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Adult patients (≥18 years) with genetically confirmed alpha-1 antitrypsin deficiency (Pi\*ZZ genotype). * Availability of longitudinal clinical follow-up data (minimum 5 years) within the AATD consortium. * At least one documented liver assessment including liver stiffness measurement (LSM) and serum-based fibrosis markers. * Availability of stored serum samples for proteomic analysis. * For translational analyses: availability of liver tissue samples (pediatric or adult) and/or induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells.

You may qualify if:

• Adult patients (≥18 years) with genetically confirmed alpha-1 antitrypsin deficiency (Pi\*ZZ genotype).
• Availability of longitudinal clinical follow-up data (minimum 5 years) within the AATD consortium.
• At least one documented liver assessment including liver stiffness measurement (LSM) and serum-based fibrosis markers.
• Availability of stored serum samples for proteomic analysis.
• For translational analyses: availability of liver tissue samples (pediatric or adult) and/or induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells.

You may not qualify if:

• Presence of other chronic liver diseases (e.g., viral hepatitis, autoimmune hepatitis) that may confound fibrosis assessment.
• Incomplete clinical, laboratory, or follow-up data.
• Poor-quality or insufficient biological samples for proteomic or molecular analyses.
• Patients lost to follow-up or with unreliable longitudinal data

Sponsors & Collaborators

• Assiut University: lead

Related Publications (10)

• Townsend SA, Edgar RG, Ellis PR, Kantas D, Newsome PN, Turner AM. Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease. Aliment Pharmacol Ther. 2018 Apr;47(7):877-885. doi: 10.1111/apt.14537. Epub 2018 Feb 15.

  PMID: 29446109 BACKGROUND

• Tafaleng EN, Chakraborty S, Han B, Hale P, Wu W, Soto-Gutierrez A, Feghali-Bostwick CA, Wilson AA, Kotton DN, Nagaya M, Strom SC, Roy-Chowdhury J, Stolz DB, Perlmutter DH, Fox IJ. Induced pluripotent stem cells model personalized variations in liver disease resulting from alpha1-antitrypsin deficiency. Hepatology. 2015 Jul;62(1):147-57. doi: 10.1002/hep.27753. Epub 2015 Apr 13.

  PMID: 25690322 BACKGROUND

• Strnad P, McElvaney NG, Lomas DA. Alpha1-Antitrypsin Deficiency. N Engl J Med. 2020 Apr 9;382(15):1443-1455. doi: 10.1056/NEJMra1910234. No abstract available.

  PMID: 32268028 BACKGROUND

• Ruiz M, Lacaille F, Schrader C, Pons M, Socha P, Krag A, Sturm E, Bouchecareilh M, Strnad P. Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency. Semin Liver Dis. 2023 Aug;43(3):258-266. doi: 10.1055/a-2122-7674. Epub 2023 Jul 4.

  PMID: 37402396 BACKGROUND

• Patel D, McAllister SL, Teckman JH. Alpha-1 antitrypsin deficiency liver disease. Transl Gastroenterol Hepatol. 2021 Apr 5;6:23. doi: 10.21037/tgh.2020.02.23. eCollection 2021.

  PMID: 33824927 BACKGROUND

• Ncube A, Bewersdorf L, Spitzhorn LS, Loerch C, Bohndorf M, Graffmann N, May L, Amzou S, Fromme M, Wruck W, Strnad P, Adjaye J. Generation of two Alpha-I antitrypsin deficiency patient-derived induced pluripotent stem cell lines ISRM-AATD-iPSC-1 (HHUUKDi011-A) and ISRM-AATD-iPSC-2 (HHUUKDi012-A). Stem Cell Res. 2023 Sep;71:103171. doi: 10.1016/j.scr.2023.103171. Epub 2023 Jul 23.

  PMID: 37506509 BACKGROUND

• Kaserman JE, Hurley K, Dodge M, Villacorta-Martin C, Vedaie M, Jean JC, Liberti DC, James MF, Higgins MI, Lee NJ, Washko GR, San Jose Estepar R, Teckman J, Kotton DN, Wilson AA. A Highly Phenotyped Open Access Repository of Alpha-1 Antitrypsin Deficiency Pluripotent Stem Cells. Stem Cell Reports. 2020 Jul 14;15(1):242-255. doi: 10.1016/j.stemcr.2020.06.006. Epub 2020 Jul 2.

  PMID: 32619491 BACKGROUND

• Hamesch K, Mandorfer M, Pereira VM, Moeller LS, Pons M, Dolman GE, Reichert MC, Schneider CV, Woditsch V, Voss J, Lindhauer C, Fromme M, Spivak I, Guldiken N, Zhou B, Arslanow A, Schaefer B, Zoller H, Aigner E, Reiberger T, Wetzel M, Siegmund B, Simoes C, Gaspar R, Maia L, Costa D, Bento-Miranda M, van Helden J, Yagmur E, Bzdok D, Stolk J, Gleiber W, Knipel V, Windisch W, Mahadeva R, Bals R, Koczulla R, Barrecheguren M, Miravitlles M, Janciauskiene S, Stickel F, Lammert F, Liberal R, Genesca J, Griffiths WJ, Trauner M, Krag A, Trautwein C, Strnad P; European Alpha1-Liver Study Group. Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation. Gastroenterology. 2019 Sep;157(3):705-719.e18. doi: 10.1053/j.gastro.2019.05.013. Epub 2019 May 20.

  PMID: 31121167 BACKGROUND

• Greene CM, Marciniak SJ, Teckman J, Ferrarotti I, Brantly ML, Lomas DA, Stoller JK, McElvaney NG. alpha1-Antitrypsin deficiency. Nat Rev Dis Primers. 2016 Jul 28;2:16051. doi: 10.1038/nrdp.2016.51.

  PMID: 27465791 BACKGROUND

• Fromme M, Schneider CV, Trautwein C, Brunetti-Pierri N, Strnad P. Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder. J Hepatol. 2022 Apr;76(4):946-958. doi: 10.1016/j.jhep.2021.11.022. Epub 2021 Nov 27.

  PMID: 34848258 BACKGROUND

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 10, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: June 10, 2026

Record last verified: 2026-05