Chronic Liver Disease in Urea Cycle Disorders

Completed

Brief Summary: 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: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Urea Cycle Disorders	Diagnostic Ultrasound	-

Primary Outcome Measures

Name	Time	Method
Liver Stiffness as Measured by Shear Wave Elastography	One measurement made on the day of study visit	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
Grey Scale Ultrasound Findings	Baseline, once	Grey scale ultrasound findings

Secondary Outcome Measures

Name	Time	Method
Fibrotest	Baseline, once	Fibrotest is a blood test that is a surrogate measure for hepatic fibrosis. F0 is normal. \>F0 predicts at least minimal fibrosis.