Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases

Terminated

• Conditions: Hepatobiliary Diseases

• Registration Number: NCT01200082
• Lead Sponsor: University of Nebraska

Brief Summary

The investigators hypothesize that the extent of sulfation of toxic BAs and their urinary elimination can be used as a biomarker to predict the severity and prognosis of hepatobiliary diseases. The investigators rationale in this project is that the discovery of biomarkers specific to liver injury would provide the foundation for a specific and non-invasive tool to evaluate disease prognosis, determine patients with higher risk of developing end-stage liver diseases, and determine patients with higher risk of recurrence of hepatobiliary complications after liver transplant.

Patients on the liver transplant list are continuously monitored during their hospitalization and are scheduled for follow-up visits for 12 months after their release post-surgery. Disease progression will be evaluated by monitoring MELD scores, survival, incidence of liver transplant, and incidence of complications related to hepatobiliary conditions such as fluid retention, GI bleeding, encephalopathy, and biliary stricture complications.

Detailed Description

The investigators propose the following specific aims to test the investigators hypothesis:

Specific Aim #1: Establish a baseline of individual and total urinary BAs and BA-sulfates in healthy controls and patients with hepatobiliary diseases. A baseline reference of the average and distribution of the percentage of urinary BA-sulfates will be determined in healthy subjects and in patients with hepatobiliary diseases including chronic hepatitis C/B, alcoholic liver disease, hereditary, drug-induced, and autoimmune hepatobiliary diseases. The investigators working hypothesis is that patients' capability to sulfate total or specific BAs, as determined by the percentage of total or specific BAs excreted in the sulfate form, can predict the severity of hepatobiliary diseases, as determined by mayo model for end-stage liver disease (MELD) score and compensation status(compensated and decompensated). Patients with higher MELD score are considered to be at higher risk of developing severe hepatobiliary complications.

Specific Aim #2: Determine the relationship between BA sulfation and the progression of hepatobiliary diseases. This is an exploratory aim to collect preliminary data on the relationship between urinary BAs and the progression of hepatobiliary diseases in liver-transplant and non-liver-transplant patients, as monitored over a1-year period. The investigators working hypothesis is that patients' capabilities of sulfating BAs determine the progression of the disease.

Study Timeline

• Study First Submitted: 2010-08-31
• Study First Submitted QC: 2010-09-09
• Study First Posted: 2010-09-13
• Study Start: 2011-11
• Primary Completion: 2022-09-02
• Study Completion: 2022-09-02
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-28
• Last Update Posted: 2023-10-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 430

Inclusion Criteria

• Male or female, age 19-65, no apparent signs of hepatobiliary diseases

Exclusion Criteria

• Levels higher than 50, 56, 78 U/L for ALT, AST, and GGT, respectively.

Patient Population

Inclusion Criteria:

• Male or female, age 19-65, visiting the UNMC hepatology clinic for treatment from hepatobiliary diseases

Exclusion Criteria:

• MELD score less than 6

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Urinary bile acid indexes	Healthy controls: 4 visits over 28 days. Patients: urine collction at every visit as decided in their course of treatment	Bile acids (BAs), the end products of cholesterol metabolism, are synthesized in liver and excreted into bile, which flows to the small intestine via the bile duct. Most of the BAs are reabsorbed from the intestine into the portal circulation and undergo enterohepatic recirculation with minimal levels detected in urine and blood under normal conditions.

Secondary Outcome Measures

Name	Time	Method
mayo model for end-stage liver disease score (MELD)	Healthy controls: 1st visit only (1 week). Patients: every time a MELD score is required by hepatologists as partrt of their regular course of treatment (1 year)	MELD score= 3.8\*loge (bilirubin \[mg/dL\]) + 11.2\*loge (INR) + 9.6\*loge (creatinine \[mg/dL\]).

Trial Locations

Locations (1)

University of Nebraska Medial Center; 🇺🇸 Omaha, Nebraska, United States