SIMulation supported LIVer Assessment for donor organs (SimLivA) - Continuum-biomechanical modeling for staging of ischemia reperfusion injury during liver transplantation

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Background: Liver transplantation (LTx) is the only curative treatment option for acute and chronic end-stage liver disease. Demographic change and western lifestyle result in an increasing rate of elderly multi-morbid potential recipients and donors. Liver grafts from such donors, so-called marginal liver grafts, are often affected by hepatic steatosis compromising the quality of the donor organ substantially. One reason is the alteration of the tissue structure, resulting in an impaired perfusion, which in turn affects hepatic metabolism and organ function. In case of a marginal graft, the surgeon is faced with the clinical decision to either accept or reject the organ, significantly increasing the postoperative risk for the recipient or increasing the risk of death on the waiting list, respectively. Two major challenges for marginal grafts are the storage between procurement of the organ and transplantation (cold ischemia time) and damage after reperfusion (ischemia reperfusion injury or IRI).Goal: Our co-designed interdisciplinary project “SIMulation supported LIVer Assessment for donor organs (SimLivA)” aims to mathematically model the impact of mechanical alterations of the (steatotic) marginal liver graft and cold ischemia on early IRI. We address the following research questions: (i) How to co-design computational methods, experimental studies, clinical processes, and technical workflows? (ii) How to improve the multiscale continuum-biomechanical model for prediction of IRI? (iii) How to obtain experimental and clinical data that are essential to quantify the relationship between steatosis, ischemia and reperfusion injury? (iv) How to evaluate the clinical usability of the model?Methods: To achieve these goals, we will extend and adapt our coupled continuum-biomechanical multiphase and multi-scale PDE-ODE model of the liver lobule to numerically simulate IRI in dependence of the degree of steatosis and ischemia duration. Experimental and clinical data acquisition for model parameterization and validation is designed in close collaboration with modeling. A proof-of-concept trial for clinical applicability will be performed. Our model couples structure, perfusion and function of the liver via the interplay between mechanical properties of the graft, hepatic sinusoidal perfusion and the affected molecular pathways, which might facilitate these decision processes and is urgently needed. This will be the first step towards an in-silico clinical decision support tool to reach a better decision pro or contra the marginal organ by in-silico predicting hepatic damage and early graft function.