US 12,332,255 B2
Methods for monitoring treatment of chronic liver disease
Gregory Thomas Everson, Englewood, CO (US); and Steve Mark Helmke, Denver, CO (US)
Assigned to The Regents of the University of Colorado, Denver, CO (US)
Filed by The Regents of the University of Colorado, Denver, CO (US)
Filed on Oct. 19, 2021, as Appl. No. 17/504,788.
Application 17/504,788 is a division of application No. 16/460,767, filed on Jul. 2, 2019, granted, now 11,181,536.
Application 16/460,767 is a continuation of application No. 15/673,191, filed on Aug. 9, 2017, granted, now 10,520,517.
Application 15/673,191 is a continuation of application No. 14/729,987, filed on Jun. 3, 2015, granted, now 9,759,731.
Application 14/729,987 is a continuation of application No. 14/078,058, filed on Nov. 12, 2013, granted, now 9,091,701.
Claims priority of provisional application 61/725,292, filed on Nov. 12, 2012.
Prior Publication US 2022/0034915 A1, Feb. 3, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 33/92 (2006.01); A61K 31/575 (2006.01); G16H 50/20 (2018.01); G16H 50/30 (2018.01)
CPC G01N 33/92 (2013.01) [A61K 31/575 (2013.01); G16H 50/20 (2018.01); G16H 50/30 (2018.01); G01N 2800/085 (2013.01)] 26 Claims
OG exemplary drawing
 
1. A method of predicting a response to a treatment of a chronic liver disease in a patient, comprising
determining a baseline Disease Severity Index (DSI) value in the patient having a chronic liver disease prior to the treatment; and
comparing the baseline DSI value in the patient to a DSI cutoff value, wherein a baseline DSI value in the patient below the DSI cutoff value indicates a higher predicted response rate to the treatment in the patient compared to a subject exhibiting a DSI value above the DSI cutoff value,
wherein the determining of the baseline DSI value in the patient comprises
performing a cholate liver function tests in the patient to obtain a portal hepatic filtration rate (portal HFR) value, a systemic hepatic filtration rate (systemic HFR) value, and optionally a cholate SHUNT test value; and
deriving the disease severity index (DSI) values from the cholate test results,
wherein the portal HFR test value in the patient is determined by a method comprising:
(a) receiving a plurality of blood or serum samples collected from the patient having a chronic liver disease, following oral administration of a dose of a first distinguishable cholate compound (doseoral) to the patient, wherein the samples have been collected from the patient over intervals of from two to seven time points spanning a period of time of no more than about 90 minutes after administration;
(b) measuring concentration of the first distinguishable cholate compound in each sample comprising HPLC-MS;
(c) generating an individualized oral clearance curve from the concentration of the first distinguishable cholate in each sample comprising using a computer algorithm curve fitting to a model distinguishable cholate clearance curve;
(d) computing the area under the individualized oral clearance curve (AUC) (mg/mL/min) and dividing the dose (in mg) by AUC of the orally administered first distinguishable cholate compound to obtain the oral cholate compound clearance in the patient; and
(e) dividing the oral cholate compound clearance by the weight of the patient in kg to obtain the portal HFR value in the patient (mL/min/kg); or,
wherein the portal HFR value in the patient is estimated from a cholate STAT test value in the patient.