Methods for diagnosis and intervention of hepatic disorders

A method for assessment of hepatic function in a subject having, or suspected of having or developing, a hepatic disorder, the method comprising:

• (a) receiving a plurality of blood or serum samples collected from the subject following oral administration of a dose of a first distinguishable compound (doseoral) to the subject and intravenous co-administration of a dose of a second distinguishable compound (doseiv) to the subject, wherein the samples have been collected over intervals of no more than seven time points spanning a time period consisting of no more than 180 minutes after administration;
• (b) quantifying the concentration of the first and the second distinguishable compounds in each sample by a method comprising high-pressure liquid chromatography-mass spectrometry (HPLC-MS);
• (c) generating an individualized oral clearance curve from the concentration of the first distinguishable compound in each sample comprising using a computer algorithm curve fitting to a model oral distinguishable compound clearance curve and computing the area under the individualized oral clearance curve (AUCoral);
• (d) generating an individualized intravenous clearance curve from the concentration of the second distinguishable compound in each sample by use of a computer algorithm curve fitting to a model intravenous distinguishable compound clearance curve and computing the area under the individualized intravenous clearance curve (AUCiv);
• and
• (e) calculating the liver shunt fraction in the subject using the formula;
• AUCoral/AUCiv×Doseiv/Doseoral×100%;
• and
• (f) comparing the liver shunt fraction in the subject to a distinguishable compound liver shunt fraction cutoff value, wherein the liver shunt fraction in the subject compared to the cutoff value is an indicator of the hepatic function of the subject.