Alagille Syndrome, Alpha 1-Antitrypsin Deficiency, Liver Diseases
Conditions
Keywords
Cholestatic Liver Disease, Cholestasis, Childhood Diseases, Genetic Diseases, Bile Acid Synthesis and Metabolism Defects, Progressive Familial Intrahepatic Cholestasis
Brief summary
Cholestasis is a condition in which bile is not properly transported from the liver to the small intestine. Cholestasis can be caused by an array of childhood diseases, including the genetic diseases Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis and metabolism defects, and progressive familial intrahepatic cholestasis (PFIC) or benign recurrent intrahepatic cholestasis(BRIC). This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.
Detailed description
Cholestasis is a rare condition that involves a reduction or obstruction of bile flow from the liver to the small intestine. When bile flow is hindered, a waste product pigment called bilirubin can escape into the bloodstream and build up to harmful levels. This may lead to the easily recognizable cholestatic symptoms of jaundice, itching, and impaired growth and eventually to more serious health problems. Four rare genetic liver disorders- ALGS, a-1AT, bile acid synthesis and metabolism defects, and PFIC-account for about 20% to 30% of all infant cases of cholestasis. These four disorders compose a group of related diseases that can cause significant growth problems during childhood, serious liver problems, the need for liver transplantation, and potentially death. More research on these rare liver diseases is necessary to develop a scientific basis for improvement in diagnostic techniques and treatments. Current diagnostic procedures are complex, and the development of simpler diagnostic tests would facilitate early diagnosis and treatment. This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases. Participants who have been previously enrolled into this study will be followed for 20 years, until transplanted, or death. Study visits will involve review of clinical information, family history, and any clinically indicated treatments and their outcomes; a physical exam; laboratory tests; and radiologic and imaging evaluations.
Interventions
None listed
Sponsors
Arbor Research Collaborative for Health
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Children and young adults diagnosed with one of the four cholestatic diseases from birth through 25 years old. 2. Siblings of participants with alpha-1-antitrypsin deficiency, who are affected with alpha-1-antitrypsin deficiency, but have no evidence of liver disease. 3. Both sexes, all races and ethnic groups. 4. Participant meets the enrollment criteria for one of the four cholestatic liver diseases. 5. Patient and/or parent/legal guardian have the ability to provide written informed consent for enrollment.
Exclusion criteria
1\. Inability to comply with the longitudinal follow-up described in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Demonstration of disease progression for each of the four cholestatic liver diseases of the study, including liver transplantation, death, growth failure, worsening liver function, and developmental complications of portal high blood pressure | Measured at baseline and annually through year 10 |
Secondary
| Measure | Time frame |
|---|---|
| Jaundice (total serum bilirubin of greater than 2.0 mg/dl) | Measured at baseline and annually through year 10 |
| Listing for liver transplantation | Measured at baseline and annually through year 10 |
| Calculated Pediatric End-Stage Liver Disease (PELD) score for participants less than 12 years of age or Model for End-Stage Liver Disease (MELD) score for participants 12 years of age or older | Measured at baseline and annually through year 10 |
| Health related quality of life | Measured at baseline and annually through year 10 |
| Growth (length and weight Z-score) | Measured at baseline and annually through year 10 |
| Bone mineral density (lumbar and spine total body) | Measured at baseline in ALGS and PFIC/BRIC subjects |
| Presence of hearing loss (ALGS and PFIC) | Measured at baseline |
Countries
Canada, United States
Contacts
STUDY_CHAIRKathleen Loomes, MD
Children's Hospital of Philadelphia
STUDY_DIRECTOREd Doo, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
PRINCIPAL_INVESTIGATORJohn Magee, MD
University of Michigan
PRINCIPAL_INVESTIGATORLisa Henn, PhD
Arbor Research Collaborative for Health
STUDY_DIRECTORKatrina Loh, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Outcome results
None listed