McRae Michael P, Helmke Steve M, Burton James R, Everson Gregory T
Custom Diagnostic Solutions LLC, Houston, Texas.
HepQuant LLC, Denver, Colorado.
Transl Res. 2023 Feb;252:53-63. doi: 10.1016/j.trsl.2022.08.002. Epub 2022 Aug 7.
The HepQuant SHUNT test quantifies hepatic functional impairment from the simultaneous clearance of cholate from the systemic and portal circulations for the purpose of monitoring treatment effects or for predicting risk for clinical outcome. Compartmental models are defined by distribution volumes and transfer rates between volumes to estimate parameters not defined by noncompartmental analyses. Previously, a noncompartmental analysis method, called the minimal model (MM), demonstrated reproducible and reliable measures of liver function (Translational Research 2021). The aim of this study was to compare the reproducibility and reliability of a new physiologically based compartmental model (CM) vs the MM. Data were analyzed from 16 control, 16 nonalcoholic steatohepatitis (NASH), and 16 hepatitis C virus (HCV) subjects, each with 3 replicate tests conducted on 3 separate days. The CM describes transfer of cholates between systemic, portal, and liver compartments with assumptions from measured or literature-derived values and unknown parameters estimated by nonlinear least-squares regression. The CM was compared to the MM for 6 key indices of hepatic disease in terms of intraclass correlation coefficient (ICC) with a lower acceptable limit of 0.7. The CM correlated well with the MM for disease severity index (DSI) with R (95% confidence interval) of 0.96 (0.94-0.98, P < 0.001). Acceptable reproducibility (ICC > 0.7) was observed for 6/6 and 5/6 hepatic disease indices for CM and MM, respectively. SHUNT, a measure of the absolute bioavailability, had ICC of 0.73 (0.60-0.83, P = 0.3095) for MM and 0.84 (0.76-0.90, P = 0.0012) for CM. The CM, but not the MM, allowed determination of anatomic shunt and hepatic extraction and improved the within individual reproducibility.
HepQuant SHUNT检测通过同时清除体循环和门静脉循环中的胆酸盐来量化肝功能损害，以监测治疗效果或预测临床结局风险。房室模型由分布容积和容积之间的转移速率定义，用于估计非房室分析未定义的参数。此前，一种称为最小模型（MM）的非房室分析方法已证明对肝功能的测量具有可重复性和可靠性（《转化研究》，2021年）。本研究的目的是比较一种新的基于生理学的房室模型（CM）与MM的可重复性和可靠性。分析了16名对照受试者、16名非酒精性脂肪性肝炎（NASH）受试者和16名丙型肝炎病毒（HCV）受试者的数据，每位受试者在3个不同日期进行3次重复检测。CM通过测量值或文献值以及非线性最小二乘法回归估计的未知参数，描述了胆酸盐在体循环、门静脉和肝脏房室之间的转移。根据组内相关系数（ICC），将CM与MM在肝病的6个关键指标方面进行比较，可接受的下限为0.7。对于疾病严重程度指数（DSI），CM与MM具有良好的相关性，R（95%置信区间）为0.96（0.94 - 0.98，P < 0.001）。CM和MM分别在6/6和5/6的肝病指标上观察到了可接受的重复性（ICC > 0.7）。作为绝对生物利用度指标的SHUNT，MM的ICC为0.73（0.60 - 0.83，P = 0.3095），CM的ICC为0.84（0.76 - 0.90，P = 0.0012）。CM能够确定解剖分流和肝脏摄取，而MM不能，并且CM提高了个体内的重复性。
