Alpha-1 Antitrypsin Deficiency Adult Liver Study

NCT02014415 | Active Not Recruiting DMC

• 3 other identifiers: A1F-SLU-7113Alpha-1 Foundation22609
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

The investigators hypothesize that there is liver injury (inflammation, fibrosis, cirrhosis) in adults with Alpha-1 Antitrypsin Deficiency (AATD), which is asymptomatic, under-recognized, and undiagnosed. In addition, the investigators believe that the genetic and environmental factors that play an important role in the development of alpha-1 antitrypsin (AAT) liver disease, can be identified by comparing a cohort database of clinical disease information to linked biospecimen and DNA samples.

Conditions

Alpha-1 Antitrypsin Deficiency

Keywords

Alpha-1; AAT Deficiency; AATD; Liver; Fibrosis; Liver Transplant; Cirrhosis

Outcome Measures

Primary Outcomes (1)

• The risk and rate of histologic liver injury progression, as measured by liver biopsy, over a 5-year period.

  Liver biopsy performed in Year 1 and Year 5

Secondary Outcomes (10)

• Calculated Model for End-stage Liver Disease score (MELD)

  Calculated at baseline and annually through year 5

• Liver synthetic dysfunction defined by international normalized ratio (INR) > 1.3 or serum albumin < 3.2 gm/dL

  Measured at baseline and annually through year 5

• Presence of ascites (or treatment for ascites)

  Assessed at baseline and annually through year 5

• Development of complications of portal hypertension (e.g., variceal hemorrhage)

  Assessed at baseline and annually through year 5

• Jaundice (total serum bilirubin >2.0 mg/dl)

  Measured at baseline and annually through year 5

Study Arms (3)

Liver Biopsy

Participants will provide liver tissue specimens collected at the time of liver biopsy, to determine the rate of progression of liver injury in adults with Pi-ZZ Alpha-1 Antitrypsin Deficiency.

Procedure: Liver Biopsy (Biopsy Group Only)

Known Severe Liver Disease

Participants will provide samples of serum, plasma, and DNA at defined time points to determine what genetic and environmental modifiers and biomarkers are associated with severe clinical liver disease, such cirrhosis, portal hypertension and liver failure in adults with Pi-ZZ Alpha-1 Antitrypsin Deficiency.

Post Liver Transplant

Participants will provide a DNA sample to determine what genetic and environmental modifiers are associated with the need for liver transplantation in adults with Pi-ZZ Alpha-1 Antitrypsin Deficiency.

Interventions

Liver Biopsy (Biopsy Group Only) PROCEDURE

A percutaneous (needle) liver biopsy will be performed on subjects in the Liver Biopsy Group, in Year 1 and Year 5 of the study.

Liver Biopsy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pi-ZZ AAT deficient adults with either no previous history of liver disease, moderate-severe liver disease or post liver transplant. Biologic family members who are also Pi-ZZ and ≥ 18 years of age, will be offered enrollment into the study. The purpose of including family members is to determine if the natural history of the liver disease is consistent in a given family.

You may qualify if:

• Adults (≥ 18 years of age), with Alpha-1 Antitrypsin Deficiency
• Documented evidence Pi-ZZ phenotype or genotype
• Both genders, all races and ethnic groups
• Willingness to be followed for up to 5 years

You may not qualify if:

• Evidence of advanced liver disease defined by Child-Pugh Class B or C (score ≥ 7)
• Known advanced lung disease defined as forced expiratory volume at one second (FEV1) \< 40 % of Predicted
• History of Organ Transplantation
• Known congenital or metabolic liver disease (e.g.: Wilson's, glycogen storage, cystic fibrosis)or iron overload as evidenced by ≥ Grade 3 iron staining on a previous liver biopsy
• Evidence of chronic hepatitis B (marked by the presence of HBsAg in serum) or Hepatitis C (marked by the presence of anti-hepatitis C virus (HCV) or HCV RNA in serum)
• Vascular disorders of the liver (e.g.: cardiac sclerosis, acute or chronic Budd-Chiari, hepatoportal sclerosis, peliosis)
• Known HIV positivity
• Diagnosis of malignancy within the last 5 years
• Active substance abuse, that in the opinion of the study investigator, would interfere with adherence to study requirements
• Concomitant severe underlying systemic illness or medical condition which in the opinion of the investigator, would make the patient unsuitable for the study or would interfere with completion of follow-up
• Inability to comply with the longitudinal follow-up as outlined in the protocol
• Failure of the participant to sign informed consent or Health Insurance Portability and Accountability Act (HIPAA) documents
• Known Severe Liver Disease Group:
• Adults (≥ 18 years of age), with alpha-1-antitrypsin deficiency
• Documented evidence PI-ZZ phenotype or genotype

Sponsors & Collaborators

• St. Louis University: lead
• Alpha-1 Foundation: collaborator
• University of California: collaborator
• Boston University: collaborator
• University College, London: collaborator
• University of Massachusetts, Worcester: collaborator

Study Sites (3)

University of California

San Diego, California, 92103, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Related Publications (1)

• Suri A, Zhang Z, Neuschwander-Tetri B, Lomas DA, Heyer-Chauhan N, Burling K, Loomba R, Brenner DA, Nagy R, Wilson A, Carpenter D, Blomenkamp K, Teckman J. Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation. Liver Int. 2024 Dec;44(12):3204-3213. doi: 10.1111/liv.16094. Epub 2024 Sep 12.

  PMID: 39263815 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Samples of serum, plasma, and blood for genetic testing (Induced Pluripotent Stem Cells (iPS cells), microRNA and DNA) will be collected from subjects at defined time points. In addition, samples of liver tissue will be collected from participants in the Liver Biopsy Group.

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Fibrosis

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 Officials

• Jeffrey Teckman, MD

  St. Louis University

  STUDY CHAIR

• Andrew A Wilson, MD

  Alpha-1 Foundation

  STUDY DIRECTOR

• David A. Brenner, MD

  The University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Andrew A Wilson, MD

  Boston University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 7 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Professor of Biochemistry and Molecular Biology

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: December 18, 2013
• Study Start: December 1, 2013
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (3)