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. 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.

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.