Compartmental Cholate Analysis for Extracorporeal Liver Function
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Solution Overview
Problem
Existing methods for evaluating liver function in extracorporeal liver perfusion systems are laborious and lack efficient methods to distinguish the functional capabilities of a human liver and an extracorporeal liver, limiting the efficacy of liver support options for patients with liver failure.
Innovation Solution
A method is provided for determining hepatic clearance in a system comprising a human patient supported on an extracorporeal liver perfusion system, involving the administration of distinguishable cholate compounds and measuring their concentrations in various compartments to calculate relative liver function, using compartmental models and differential equations to derive blood flow rates and clearance rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing liver support options are used, then patients with liver failure receive treatment, but the efficacy is limited and mortality risk remains high
Solution Approach 1:
The patent segments liver function assessment into distinct compartments (systemic circulation, portal circulation, extracorporeal liver, native liver) allowing independent evaluation of each component's contribution to overall liver function. This enables precise identification of which liver components are functioning and which require support, improving the reliability of liver support therapy.
Solution Approach 2:
The patent introduces distinguishable cholate compounds as intermediaries to trace and measure blood flow and clearance through different liver compartments. These compounds serve as mediators that enable indirect measurement of liver function parameters without directly interfering with liver physiology, thereby improving assessment accuracy.
2Measurement precision
If cholate SHUNT tests are used to monitor liver function, then treatment effects can be predicted, but the sample processing and analysis using GC-MS or HPLC-MS is laborious
Solution Approach 1:
The patent extracts only the essential measurement information (cholate compound concentrations in different compartments) needed for liver function assessment, separating this from the complex sample processing requirements of traditional methods. By focusing on compartmental concentration differences rather than complete metabolic profiling, the method reduces processing complexity while maintaining measurement precision.
Solution Approach 2:
The patent changes the measurement parameters from comprehensive metabolic analysis to specific compartmental concentration measurements of distinguishable cholate compounds. This parameter change simplifies the analytical requirements while providing equally precise or more specific information about liver function and treatment effects.
3Measurement precision
If distinguishable cholate compounds are administered to evaluate liver function, then relative liver function can be determined, but multiple blood samples from multiple compartments must be collected and analyzed
Solution Approach 1:
The patent merges the assessment of multiple liver functions (systemic clearance, portal clearance, extracorporeal liver function, native liver function) into a single integrated compartmental analysis framework. By administering distinguishable cholate compounds and measuring their distribution across compartments simultaneously, the method determines relative liver function for all compartments in one unified analysis, improving productivity without sacrificing measurement precision.
Data Source
AI summary
Methods are provided for effectively distinguishing the abilities of a human liver and an extracorporeal liver in an extracorporeal liver perfusion system to extract cholate and, thus, measure relative liver function.