# US 12,007,383 B2 · Method for assessment of hepatic function and portal blood flow > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,007,383 B2 - Document ID: US12007383B2 - Status: Granted - Kind: B2 - Application number: 16/878,510 - Filed: 2020-05-19 - Published: 2020-10-22 - Granted: 2024-06-11 - Earliest claimed: 2011-05-31 - Assignees: The Regents of the University of Colorado, a body corporate - Applicants: The Regents of the University of Colorado - Inventors: Gregory Thomas Everson; Steve Mark Helmke - Web page: https://patentgrep.com/patent/US12007383B2 ## CPC - G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)} - A61J 1/05: for collecting, storing or administering blood, plasma or medical fluids {(multiple bags systems for separating or storing blood components A61M1/0209); Infusion or perfusion containers} - G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} - G01N 2800/085: Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin - Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract A method for estimating portal blood flow and hepatic function in a subject is provided. In one example, the STAT test is an in vitro simplified, convenient test intended for screening purposes that can reasonably estimate the portal blood flow from a single blood sample taken 60 minutes after orally administered deuterated-cholate. The test can be administered to a patient having, or suspected of having, Chronic Hepatitis C, Primary Sclerosing Cholangitis (PSC), Non-Alcoholic Fatty Liver Disease (NAFLD), or any chronic liver disease. ## Claims ### Claim 1 A method of risk assessment for determining liver disease severity, disease progression, stage of disease, disease prognosis, fibrosis stage, and/or response to treatment in a patient having, suspected of having, or at risk of having a chronic liver disease, comprising receiving a sample consisting of a single blood or serum sample from the patient obtained at a single, specific time point less than 3 hours after oral administration of a single distinguishable agent to the patient, wherein no other distinguishable agent is intravenously co-administered, wherein the distinguishable agent is capable of exhibiting hepatic extraction of at least 60% in first pass through the liver of a healthy subject following oral administration, and wherein the distinguishable agent is a distinguishable bile acid or bile acid conjugate; measuring the concentration of the distinguishable agent in the sample, wherein the measuring comprises quantifying the concentration of the distinguishable agent in the sample by GC-MS, LC-MS, scintillation spectroscopy, autoanalyzer, luminescence, or ELISA; and comparing the concentration of the distinguishable agent in the sample to a cutoff value or cutoffs of values from a known patient population(s), and/or to the concentration of the distinguishable agent in one or more earlier samples from the same patient over time, wherein the concentration of distinguishable agent in the sample compared to the cutoff value or cutoffs of values from a known patient population(s), and/or to the concentration of the distinguishable agent in one or more earlier samples from the same patient over time is an estimation of portal blood flow in the patient. ### Claim 2 (depends on 1) The method of claim 1, wherein an increase in the concentration of the distinguishable agent in the sample compared to one or more earlier samples from the same patient over time indicates liver disease progression in the patient, the method further comprising additional testing selected from the group consisting of an additional liver function test and an additional clinical screening procedure. ### Claim 3 (depends on 2) The method of claim 2, wherein the additional clinical screening procedure is selected from the group consisting of liver biopsy, histological assessment, endoscopy, radiologic imaging, elastography, biomarker panel, metabolic test, Model for End Stage Liver Disease (MELD) score, Childs-Turcotte-Pugh (CTP) score, fibrosis test, and hepatocellular carcinoma (HCC) screening. ### Claim 4 (depends on 1) The method of claim 1, further comprising assigning the concentration of the distinguishable agent in the patient sample to one of a multiplicity of ranges defined by the cutoff value or cutoffs of values from the known patient population(s) to obtain a test result, said multiplicity of ranges comprising at least two ranges comprising a range below a first cutoff value, and a range above a second cutoff value. ### Claim 5 (depends on 4) The method of claim 4, wherein the liver disease is selected from the group consisting of chronic hepatitis C; chronic hepatitis B; cytomegalovirus; Epstein Barr virus; primary sclerosing cholangitis (PSC); alcoholic liver disease; drug toxicity; autoimmune liver disease; primary biliary cirrhosis; cryptogenic cirrhosis; hemochromatosis; Wilson's disease; alpha-1-antitrypsin deficiency; cholestatic liver disease; hepatocellular carcinoma (HCC); and non-alcoholic fatty liver disease (NAFLD). ### Claim 6 (depends on 5) The method of claim 5, wherein the test result differentiates stage of non-alcoholic fatty liver disease (NAFLD) into simple fatty liver (hepatic steatosis) and non-alcoholic steatohepatitis (NASH), and or is predictive of fibrosis score, presence or absence of varices, cirrhosis, and clinical decompensation. ### Claim 7 (depends on 5) The method of claim 5, wherein the drug toxicity is selected from the group consisting of methotrexate toxicity, amiodarone toxicity, and nitrofurantoin toxicity. ### Claim 8 (depends on 4) The method of claim 4, wherein the first cutoff value and the second cutoff value are different, and one or more intermediate ranges are between the first and second cutoff values. ### Claim 9 (depends on 4) The method of claim 4, wherein the first cutoff value and the second cutoff value are the same. ### Claim 10 (depends on 1) The method of claim 1, wherein the treatment is selected from the group consisting of lifestyle modification; diet modification; antiviral treatment; pharmacotherapy; treatment of portal hypertension; hepatic resection; and liver transplantation. ### Claim 11 (depends on 1) The method of claim 1, wherein the orally administered distinguishable agent is capable of exhibiting hepatic extraction of at least about 80% in first pass through the liver of a healthy subject following oral administration. ### Claim 12 (depends on 1) The method of claim 1, wherein the distinguishable agent is a distinguishable bile acid. ### Claim 13 (depends on 12) The method of claim 12, wherein the distinguishable bile acid is a distinguishable cholate, deoxycholate, lithocholate, or chenodeoxycholate compound. ### Claim 14 (depends on 13) The method of claim 13, wherein the distinguishable cholate compound is an isotopically labeled cholic acid. ### Claim 15 (depends on 14) The method of claim 14, wherein the isotopically labeled cholic acid is a stable isotope labeled cholic acid. ### Claim 16 (depends on 15) The method of claim 15, wherein the stable isotope labeled cholic acid is selected from 24-13C cholic acid or 2,2,4,4-H2H cholic acid. ### Claim 17 (depends on 1) The method of claim 1, wherein the single blood or serum sample is collected at one time point selected from about 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, or 180 minutes, or any time point in between, after oral administration of the distinguishable agent. ### Claim 18 (depends on 17) The method of claim 17, wherein the single blood or serum sample is collected at one time point selected from about 45, about 60 or about 90 minutes after oral administration of the distinguishable agent. ### Claim 19 (depends on 18) The method of claim 18, wherein the single blood or serum sample is collected at about 60 minutes after oral administration of the distinguishable agent. ### Claim 20 (depends on 1) The method of claim 1, wherein the method further comprises estimating portal hepatic filtration rate (portal HFR) in the patient comprising: converting the concentration of the distinguishable agent in the sample (μM) by using an equation into an estimated portal HFR (mL/min/kg) in the patient; and comparing the estimated portal HFR in the patient to a portal HFR (FLOW) cutoff value or cutoffs of values established from known patient population or to a previous estimated portal HFR (mL/min/kg) in the patient over time to assess liver disease severity, disease progression, and/or response to treatment in the patient. ### Claim 21 (depends on 20) The method of claim 20, wherein a decrease in estimated portal HFR in the patient over lime is indicative of liver disease progression.