title: Noninvasive assessment of liver function.
abstract: OBJECTIVE
  It is our opinion that there is an unmet need in hepatology for a minimally or noninvasive test of liver function and physiology. Quantitative liver function tests define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high-affinity hepatic transporters exhibit high 'first-pass' hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways.
  
  
  RESULTS
  We highlight one quantitative liver function test, the dual cholate test, and introduce the concept of a disease severity index linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting.
  
  
  CONCLUSIONS
  It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy.
authors.affiliation: aUniversity of Colorado Denver School of Medicine, Aurora, Colorado, USA bLiver Unit, Biomedical Research Institute August Pi I Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain.
authors.forename: Steve
authors.initials: S
authors.lastname: Helmke
authors.forename: Jordi
authors.initials: J
authors.lastname: Colmenero
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
mesh_terms: D020355:Cholates / Q000378:metabolism*; D006301:Health Services Needs and Demand; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008107:Liver Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests / Q000379:methods; D008657:Metabolic Clearance Rate; D011237:Predictive Value of Tests; D012720:Severity of Illness Index
chemical_list: D020355:Cholates