Inclusion Criteria: 

• Signed and dated information consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Adult male or female, age at entry at least 18 years
• Adequate peripheral venous access for intravenous catheter
• Ability to take the oral dose of d4-cholate
• Ability to hold morning doses of medications (Non-Selective Beta Blocker, ARB and/or Ace Inhibitor) for the 90 minute duration of the HepQuant SHUNT Test
• Meets at least one of the following criteria for CLD:
  • Abnormal liver enzymes (AST, ALT, or alkaline phosphatase), or, abnormal direct bilirubin, albumin, or INR (liver-related) of greater than 6 months duration. These subjects must also have platelet count < 175,000 μL-1:
  • Fibrosis stage 3 (F3) or higher by liver biopsy (by METAVIR, Batts-Ludwig, or Brunt-Kleiner). Patients with F3 fibrosis must have platelet count < 175,000 μL-1;
  • Fibrosis stage 3 or higher by elastography (FibroScan, SuperSonic, or MRE). Patients with F3 fibrosis must have platelet count < 175,000 μL-1;
  • Fibrosis stage 3 or higher by FDA-approved laboratory panels. Patients with F3 fibrosis must have platelet count < 175,000 μL-1;
  • Child-Pugh class A or B cirrhosis;
  • HVPG of 6 mmHg or higher;
  • Radiologic imaging consistent with either cirrhosis or portal hypertension .
• Has one of the following diagnoses of CLD:
  • Hepatitis C virus (HCV) infection with documentation of a prior positive HCV RNA. Patients who achieved virologic cure are eligible to participate as long as they have CLD as defined above;
  • Hepatitis B virus (HBV) infection defined by positive HBsAg;
  • Non-alcoholic steatohepatitis (NASH);
  • Cryptogenic cirrhosis ;
  • Alcoholic liver disease;
  • Cholestatic liver disease:
    • Primary biliary cholangitis (PBC);
    • Primary sclerosing cholangitis (PSC).
• Autoimmune hepatitis.
• Inherited disorders causing CLD:
  • Hereditary hemochromatosis;
  • Alpha-1-antitrypsin deficiency;
  • Wilson disease.
• Scheduled, or in the process of being scheduled for EGD

• Indications for EGD. A key inclusion criteria is that the subject must have been selected and scheduled or in the process of being scheduled for EGD for the indication of either screening or surveillance for esophageal varices. Patients who are known to have had large esophageal varices on prior endoscopy or who have undergone treatment for varices, either radiologically (TIPS), surgically (Portal-Systemic Shunt), or endoscopically (banding or sclerotherapy) are excluded. Patients with prior endoscopic diagnosis of small esophageal varices who are undergoing EGD for surveillance of varices may be included.

Exclusion Criteria: 

• Unable to give informed consent.
• Unable to obtain venous access for administration of intravenous cholate.
• Unable to absorb orally-administered cholate (examples could include underlying severe gastroparesis or having undergone extensive small bowel resection, conditions or post-operative state that could impair the absorption of the orally administered d4-cholate).
• Known hypersensitivity to human serum albumin.
• Known hypersensitivity to any of the components of the HepQuant SHUNT Liver Diagnostic Kit.
• Acute hepatitis, Acute Liver Failure, or Acute on Chronic Liver Failure.
• Acute drug-induced liver disease (DILI).
• Noncirrhotic causes for portal hypertension and varices.
• Ongoing active alcoholic hepatitis.
• Child-Pugh class C defined by Child-Pugh score 10 or higher.
• Dialysis .
• Active infection or febrile illness within the last month.
• Documented history of esophageal or gastric variceal hemorrhage.
• Documented history of treatment of varices.
• Documented history of endoscopic findings of large esophageal varices.
• Hepatocellular carcinoma beyond Milan or UCSF criteria.
• Thrombosis of main portal vein.
• Liver transplant recipient.
• Pregnancy.
• Women who are breast-feeding.
• Serious intercurrent medical or surgical illness, such as acute myocardial infarction, acute cerebral hemorrhage, sepsis, or other immediate life-threatening illness.
• NPO (nothing through the mouth) status.