Chronic Liver Disease in Urea Cycle Disorders

Study Overview
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Brief Summary
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This is a pilot, cross-sectional study to assess liver stiffness and markers of hepatic injury, function, and fibrosis in patients with urea cycle disorders. This study will be conducted at 3 UCDC sites: Baylor College of Medicine in Houston, Texas, University of California San Francisco (UCSF), San Francisco, California and Seattle Children's Hospital, Seattle,Washington

Detailed Description
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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 purpose of this study is: 1) To determine whether liver stiffness is higher in individuals with ASS1D, ASLD, and ARG1D as compared to females with OTCD, and to assess liver stiffness in other UCDs (citrin deficiency, NAGSD, CPS1D, and males with OTCD), 2) To test whether markers of hepatocellular injury and function and novel serum biomarker panels for hepatic fibrosis provide evidence of chronic liver disease in individuals with ASS1D, ASLD, and ARG1D as compared to OTCD and to assess these sample markers of hepatocellular injury and function and novel serum biomarker panels for hepatic fibrosis in other UCDs (citrin deficiency, NAGSD, CPS1D, and males with OTCD).

Official Title
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Prospective Cross-Sectional Non-invasive Assessment of Chronic Liver Disease in Urea Cycle Disorders

Conditions
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Urea Cycle Disorder

Intervention / Treatment
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* Other: Diagnostic Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 5 years and < 60 years Weight ≥ 11 kg Males or females with a diagnosis of OTCD based on molecular or enzymatic testing. Males or females with a diagnosis of CPS1D, citrin deficiency, NAGSD, ASS1D, ASLD or ARG1D based on biochemical OR molecular, OR enzymatic testing Exclusion Criteria: History of hyperammonemia (blood ammonia greater than 100 micromoles/L) documented in the medical record or reported by the patient in the 30 days preceding enrollment visit History of Liver transplantation Current pregnancy Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, or alcohol liver disease

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Urea Cycle Disorders<br> | Other: Diagnostic Ultrasound<br>* All individuals will undergo a blood draw for measurement of biomarkers of liver disease and an ultrasound with shear-wave elastography.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver Stiffness as Measured by Shear Wave Elastography | Shear wave elastography in m/s is a measure of liver stiffness, a surrogate measure for hepatic fibrosis. Normal liverstiffness is < 1.35 m/s and abnormal liver stiffness is >1.35 m/s | One measurement made on the day of study visit | 
| Grey Scale Ultrasound Findings | Grey scale ultrasound findings | Baseline, once | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibrotest | Fibrotest is a blood test that is a surrogate measure for hepatic fibrosis. F0 is normal. >F0 predicts at least minimal fibrosis. | Baseline, once |