Liver Function Measured by HepQuant-SHUNT in the Prediction of Outcomes in Patients With Heart Disease

Summary

Background: It is still difficult to predict the outcome in patients requiring Fontan Revisions and in those who have evidence of congestive hepatopathy and probable cirrhosis requiring major cardiac surgery including heart transplant. Over the years, many prognostic indices have been derived from laboratory results of blood tests, clinical and physiological variables (or some combination thereof), from liver imaging to liver histology, which has issues of sampling error, medical risks and technical difficulty. None of these have proved entirely satisfactory. Predicting morbidity or survival is particularly important when deciding about Fontan revisions versus the need for heart transplantation. What is needed here is a truly reliable test of liver function that can help predict outcome, on the basis of a single measurement within few days of a planned revision. For this purpose, it is desirable that the chosen tests of liver performance be safe, non-invasive, easy to perform, have a rapid turnaround for results, and be readily repeatable.

Tests of hepatic elimination of various exogenous substances have been described, such as galactose elimination capacity (GEC), indocyanine green (ICG) clearance, lidocaine metabolism to monoethylglycinexylidide (MEGX), and other tests that rely on liver metabolic capacity. None of these metabolic or clearance tests achieved widespread acceptance or use, mostly because their performance and analyses were cumbersome.

HepQuant,LLC has developed a platform of tests of liver function which include Systemic Hepatic Filtration Rate (HFR), Portal HFR, SHUNT, and Disease Severity Index (DSI)1,2. HepQuant tests specifically target the hepatic uptake of cholate and use a single noninvasive test of 90 minutes duration to quantify the systemic circulation, portal circulation, and portal-systemic shunt and to derive a DSI in intact human subjects. HepQuant tests can assess all stages and etiologies of liver disease. In chronic HCV patients HepQuant testing can predict which patients will respond to antiviral therapy and can measure the improvement in hepatic function that occurs after successful antiviral therapy. Patients who did not respond were followed for an average of 5 years and up to 8 years, and baseline HepQuant testing could predict clinical outcomes (CTP progression, variceal bleeding, encephalopathy, ascites, liver-related death) with 87% sensitivity and 71% specificity.

Conditions

• Liver Disease
• Cardiovascular Disease

Interventions

DRUG

Cholate testing

The patient receives simultaneously an oral dose of d4-cholate and an IV dose of 13C-cholate, which are stable isotopes; there is no radioactivity or radiation exposure.

Sponsors & Collaborators

• University of Colorado, Denver

  collaborator OTHER

• Northwestern University

  lead OTHER

Principal Investigators

• Daniel Ganger, MD · Northwestern University

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-09-01

Primary Completion

2018-05-01

Completion

2018-05-01