Methods for diagnosis and intervention of hepatic disorders

摘要

The present disclosure concerns methods of administering and detecting a distinguishable agent in a sample from and assessing the condition of an organ in a subject. In a particular embodiment, the present invention concerns methods of detecting and comparing the cholate shunt, in a subject, preferably in a subject with chronic hepatitis C. In certain embodiments, the methods may comprise obtaining a sample from a subject such as a blood or saliva sample after administering an oral and intravenous dose of a distinguishable agent such as cholate and analyzing the sample clearance of the distinguishable agent from the subject and comparing the clearance levels in order to assess hepatic health. In another embodiment, the methods may comprise analyzing a sample from a subject for the presence of a distinguishable agent such as cholate and applying information obtained from analyzing the presence of the distinguishable agent to determine a treatment for a medical condition of the subject.

主权项

1. A method, which, when executed by a computer, cause the computer to carry out a method for quantitative testing of hepatic function by assessment of portal-systemic shunt which defines both functional hepatic reserve and alteration of the portal circulation in a subject suspected of having or developing a hepatic disorder, the method comprising:
processing blood samples collected at time points consisting of 2 to no more than 7 time points from a subject over a period consisting of no more than 90 minutes following intravenous administration of a first stable isotope distinguishable cholate and simultaneous oral administration of a second stable isotope distinguishable cholate to the subject; receiving first data representing a concentration of the intravenously administered first stable isotope distinguishable cholate in each of the blood samples; receiving second data representing a concentration of the orally administered second stable isotope distinguishable cholate in each of the blood samples; generating at least one model intravenous stable isotope cholate clearance curve; generating at least one model oral stable isotope cholate clearance curve; generating an individualized intravenous clearance curve from the concentration of the first cholate in each sample collected at time points consisting of 2 to no more than 7 over no more than 90 minutes by use of a computer algorithm curve fitting to the model intravenous stable isotope cholate clearance curve and computing the area under the individualized intravenous clearance curve (AUCiv), wherein AUC=area under the curve of the serum concentration; generating an individualized oral clearance curve from the concentration of the second cholate in each sample collected at time points consisting of 2 to no more than 7 over no more than 90 minutes comprising using a computer algorithm curve fitting to the model oral stable isotope cholic acid clearance curve and computing the area under the individualized oral clearance curve (AUCoral); comparing the AUCiv to the AUCoral to determine a ratio of clearance of the administered cholates in the subject comprising using a formula to calculate a cholate shunt value, and reporting the cholate shunt value as a measurement of first-pass hepatic elimination of cholate from the portal circulation in the subject.