Köller Adrian, Grzegorzewski Jan, Tautenhahn Hans-Michael, König Matthias
Institute for Theoretical Biology, Institute of Biology, Humboldt University, Berlin, Germany.
Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany.
Front Physiol. 2021 Nov 22;12:730418. doi: 10.3389/fphys.2021.730418. eCollection 2021.
The evaluation of hepatic function and functional capacity of the liver are essential tasks in hepatology as well as in hepatobiliary surgery. Indocyanine green (ICG) is a widely applied test compound that is used in clinical routine to evaluate hepatic function. Important questions for the functional evaluation with ICG in the context of hepatectomy are how liver disease such as cirrhosis alters ICG elimination, and if postoperative survival can be predicted from preoperative ICG measurements. Within this work a physiologically based pharmacokinetic (PBPK) model of ICG was developed and applied to the prediction of the effects of a liver resection under various degrees of cirrhosis. For the parametrization of the computational model and validation of model predictions a database of ICG pharmacokinetic data was established. The model was applied (i) to study the effect of liver cirrhosis and liver resection on ICG pharmacokinetics; and (ii) to evaluate the model-based prediction of postoperative ICG-R15 (retention ratio 15 min after administration) as a measure for postoperative outcome. Key results are the accurate prediction of changes in ICG pharmacokinetics caused by liver cirrhosis and postoperative changes of ICG-elimination after liver resection, as validated with a wide range of data sets. Based on the PBPK model, individual survival after liver resection could be classified, demonstrating its potential value as a clinical tool.
肝功能评估以及肝脏功能容量评估在肝病学和肝胆外科中都是至关重要的任务。吲哚菁绿（ICG）是一种广泛应用的测试化合物，在临床常规中用于评估肝功能。在肝切除术背景下，使用ICG进行功能评估的重要问题包括诸如肝硬化等肝脏疾病如何改变ICG清除，以及能否根据术前ICG测量预测术后生存率。在这项工作中，开发了一种基于生理的吲哚菁绿药代动力学（PBPK）模型，并将其应用于预测不同程度肝硬化情况下肝切除的效果。为了对计算模型进行参数化以及对模型预测进行验证，建立了一个ICG药代动力学数据库。该模型被应用于：（i）研究肝硬化和肝切除对ICG药代动力学的影响；以及（ii）评估基于模型对术后ICG-R15（给药后15分钟保留率）的预测，以此作为术后结果的衡量指标。关键结果是，通过大量数据集验证，准确预测了由肝硬化引起的ICG药代动力学变化以及肝切除术后ICG清除的变化。基于PBPK模型，可以对肝切除术后的个体生存情况进行分类，证明了其作为临床工具的潜在价值。
