Disease severity index for assessment of chronic liver disease

A method of displaying likelihood or risk of future clinical outcome, disease severity, and/or disease status in a patient having or at risk of a chronic liver disease, the method comprising

• a. obtaining distinguishable bile acid test results in the patient comprising a portal hepatic filtration rate (portal HFR) value and a systemic hepatic filtration rate (systemic HFR) value from the patient at one or more test days;
• b. deriving one or more disease severity index (DSI) value(s) or mathematically transformed DSI value(s) of the patient from the portal and systemic HFR values or mathematically transformed portal and mathematically transformed systemic HFR values at the one or more test days;
• c. plotting the DSI value(s) or mathematically transformed DSI value(s) of the patient on a two-dimensional graphical plot, wherein the graphical plot is divided into a multiplicity of disease severity index (DSI) value zones predetermined by DSI values or mathematically transformed DSI values obtained from one or more groups of known subjects having a known clinical outcome, disease severity and/or disease status;
• and
• d. determining the location of each DSI value or mathematically transformed DSI value of the patient within the DSI value zones, wherein the location is indicative of likelihood or risk of experiencing a future clinical outcome, disease severity and/or disease status in the patient, wherein
• the portal HFR test value in the patient is determined by a method comprising
• (i) receiving a plurality of blood or serum samples collected from the patient having or at risk of a chronic liver disease, following oral administration of a dose of a distinguishable bile acid (doseoral) to the patient, wherein the samples have been collected from the patient over intervals of a period of time of no more than 180 minutes after administration;
• (ii) measuring concentration of the distinguishable bile acid in each sample;
• (iii) generating an individualized oral clearance curve from the concentration of the distinguishable bile acid in each sample comprising using a computer algorithm curve fitting to a model distinguishable bile acid clearance curve;
• (iv) 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 distinguishable bile acid to obtain the oral distinguishable bile acid clearance in the patient;
• and
• (v) dividing the oral distinguishable bile acid clearance by the weight of the patient in kg to obtain the portal HFR value in the patient (mL/min/kg).