Liver Disease in Urea Cycle Disorders

Baylor College of Medicine

Status: Enrolling

Conditions: Citrullinemia 1; Hyperargininemia; Ornithine Transcarbamylase Deficiency; Urea Cycle Disorder; ARGI Deficiency; ASL Deficiency; Argininosuccinic Aciduria; ASS Deficiency

Study type: Observational

Funder types: Other

Identifiers

NCT04612764

H-50295

Details and patient eligibility

About

This is a multi-center, cross-sectional study to assess risk for liver fibrosis and hepatic injury in individuals with urea cycle disorders (UCDs) using serum biomarkers, Fibroscan, and MRE. This study will be conducted at 5 sites of the Urea Cycle Disorders Consortium: Baylor College of Medicine in Houston, TX, Seattle Children's Hospital in Seattle, WA, Children's Hospital Colorado in Aurora, CO, Children's Hospital of Philadelphia in Philadelphia, PA, and Children's National Medical Center in Washington D.C.

Full description

Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. With early diagnosis and improved treatments, the survival of individuals with UCDs has improved, and this improved survival has led to unmasking of some long-term complications such as hepatic dysfunction and progressive fibrosis in a subset of patients. Hepatic complications in UCDs are quite variable and dependent upon the specific metabolic defect.

Currently, there are no guidelines for monitoring hepatic complications or extent of liver disease in UCDs. The gold standard for staging of fibrosis or confirming cirrhosis has traditionally been liver biopsy, an invasive procedure with inherent risks, particularly in the setting of a UCD and compromised coagulation. Recently, non-invasive serum and imaging-based biomarkers have been introduced to assess hepatic fibrosis in adults and children who are at increased risk. Utilization of these technique in individuals with UCDs could be invaluable in both the research and clinical arenas.

The purpose of this study is:

1. To assess risk for increased fibrosis using serum biomarkers and/or VCTE in distal disorders (ASS1D, ASLD and ARG1D) as compared to OTCD 2 ) To assess risk for hepatic fibrosis (liver stiffness as measured by MRE) in individuals with UCDs who have abnormal serum biomarkers and/or VCTE as those who have normal values

Enrollment: 62 estimated patients

Sex: All

Ages: 6 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Stage A

Inclusion Criteria:

• Age > 6 years and < 65 years
• Weight ≥ 11 kg at time of screening
• A molecular or biochemical diagnosis of OTCD, ASS1D, ASLD, or ARG1D.

Exclusion Criteria:

• Prior liver transplantation
• Episode of acute hyperammonemia (≥100 umol/L) in the 30 days prior to enrollment
• Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, short gut, small bowel syndrome, alcohol liver disease, TPN requirement, or TPN-related cholestatic disease
• Adults with BMI ≥ 45 kg/m2
• Current pregnancy
• Open wound near expected Fibroscan® probe application site
• Use of implantable active medical device such as cardiac pacemaker or implantable cardioverter-defibrillator

Stage B Inclusion Criteria

• Participation in Stage A of this study

Exclusion Criteria

• Individuals with claustrophobia or other inability to complete
• Known diagnosis of hemochromatosis
• Presence of implants or devices incompatible with MRI
• Inability to breath-hold for 20 seconds for the elastography sequence
• Current pregnancy
• Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, short gut, small bowel syndrome, alcohol liver disease, TPN requirement, or TPN-related cholestatic disease
• Episode of documented acute hyperammonemia (ammonia ≥ 100 umol/L) in the 30 days prior to scheduled visit for Stage B