Liver Function Measured by HepQuant-SHUNT in the Prediction of Outcomes in Patients With Heart Disease
Condition: Liver Disease; Cardiovascular Disease
MeSH terms: Liver Diseases; Cardiovascular Diseases; Heart Diseases
Study type: Interventional
Phase: Early Phase 1

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.
    

Detailed description: 
      Hypothesis The results of HepQuant in patients with CHD will correlate with outcomes of
      cardiac surgery (namely morbidity as defined by complications such as ischemic hepatitis,
      survival, need for heart transplantation, improvement of liver function post revision), and
      thus can be used for prognosis in this condition, either alone or in conjunction with other
      clinical, physiological, and laboratory prognostic scores, thereby giving clinical guidance
      concerning the need for heart transplantation and simultaneous liver transplantation..

      Primary Aim To assess the relationship between HepQuant testing results and clinical outcomes
      in patients with liver disease secondary to congenital heart disease (CHD) undergoing Fontan
      revisions.

      To assess the clinical outcomes of patients with liver disease secondary to acquired
      cardiomyopathy or valvular disease that will undergo extensive heart surgery or heart
      transplantation.

      Secondary Aim To assess whether HepQuant testing predicts clinical outcome in patients with
      Liver Disease and CHD when used in conjunction with other diagnostic tests, such as MELD,
      Child-Turcotte-Pugh (CTP), liver stiffness measurement (US with ARFI), and Fibrotest
      (Fibrosure).

      Study population Male and female Subjects (age 18 to 70 years) with liver disease secondary
      to congenital heart disease or cardiomyopathy.
    

Intervention name(s): Cholate testing
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): 13C-cholate; d4-cholate
Intervention MeSH terms: Cholic Acids
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Liver disease; cardiomyopathy; congenital heart disease