Chronic Liver Disease in Urea Cycle Disorders

Baylor College of Medicine28 enrolled

Overview

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

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).

Study Type

OBSERVATIONAL

Enrollment

Conditions

Urea Cycle Disorder

Interventions

Diagnostic UltrasoundOTHER

All individuals will undergo a blood draw for measurement of biomarkers of liver disease and an ultrasound with shear-wave elastography.

Eligibility

Sex: ALLMin age: 5 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age \> 5 years and \< 60 years 2. Weight ≥ 11 kg 3. 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: 1. 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 2. History of Liver transplantation 3. Current pregnancy 4. Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, or alcohol liver disease

Locations (1)

Baylor College of Medicine

Houston, Texas, United States

Outcomes

Primary Outcomes

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

Time frame: One measurement made on the day of study visit

Grey Scale Ultrasound Findings

Grey scale ultrasound findings

Time frame: Baseline, once

Secondary Outcomes

Fibrotest

Fibrotest is a blood test that is a surrogate measure for hepatic fibrosis. F0 is normal. \>F0 predicts at least minimal fibrosis.

Time frame: Baseline, once

Data from ClinicalTrials.gov

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