Liver Disease in Urea Cycle Disorders

Brief Title

Liver Disease in Urea Cycle Disorders

Official Title

Noninvasive Biomarkers of Hepatic Fibrosis in Urea Cycle Disorders

Brief Summary

      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.

Detailed 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

Study Type


Primary Outcome


Secondary Outcome



Urea Cycle Disorder


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

November 4, 2021

Completion Date

December 31, 2023

Primary Completion Date

December 31, 2023

Eligibility 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

        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




6 Years - 65 Years

Accepts Healthy Volunteers



Lindsay Burrage, MD, PhD, 832-822-4183, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Baylor College of Medicine


 Children's National Research Institute

Study Sponsor

Lindsay Burrage, MD, PhD, Principal Investigator, Baylor College of Medicine

Verification Date

December 2021