Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases

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.

Study Overview

• Status: Terminated
• Conditions: Hepatobiliary Diseases

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 Type: Observational
• Enrollment (Actual): 430

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medial Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy Controls: Subjects with no apparemt hepatobiliary diseases Patient Populaton: Subjects visiting the hepatology clinic in UNMC as part of their treatment of hepatobiliry diseases

Description

Healthy Controls

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy Controls; Male or female, age 19-65, no apparent signs of hepatobiliary diseases
Patients with hepatobiliary diseases; Male or female, age 19-65, visiting the UNMC hepatology clinic for treatment from hepatobiliary diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary bile acid indexes	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.	Healthy controls: 4 visits over 28 days. Patients: urine collction at every visit as decided in their course of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mayo model for end-stage liver disease score (MELD)	MELD score= 3.8*loge (bilirubin [mg/dL]) + 11.2*loge (INR) + 9.6*loge (creatinine [mg/dL]).	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)

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Yazen M Alnouti, PhD, University of Nebraska

Publications and helpful links

General Publications

• Simko V, Michael S. Urinary bile acids in population screening for inapparent liver disease. Hepatogastroenterology. 1998 Sep-Oct;45(23):1706-14.
• Makino I, Hashimoto H, Shinozaki K, Yoshino K, Nakagawa S. Sulfated and nonsulfated bile acids in urine, serum, and bile of patients with hepatobiliary diseases. Gastroenterology. 1975 Mar;68(3):545-53.
• Alme B, Bremmelgaard A, Sjovall J, Thomassen P. Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatorgaphy-mass spectrometry. J Lipid Res. 1977 May;18(3):339-62.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2011
• Primary Completion (Actual): September 2, 2022
• Study Completion (Actual): September 2, 2022

Study Registration Dates

• First Submitted: August 31, 2010
• First Submitted That Met QC Criteria: September 9, 2010
• First Posted (Estimated): September 13, 2010

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: alcoholic liver disease; chronic hepatitis C/B; primary biliary cirrhosis; primary sclerosing cholangitis; progressive familial intrahepatic cholestasis
• Additional Relevant MeSH Terms: Liver Diseases; Digestive System Diseases
• Other Study ID Numbers: 0487-10-EP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No