Letter to the Editor: The Concept of Real‐Time Spectroscopy for Liver Viability Assessment
Authors: Mauricio Flores Carvalho, Matteo Mueller, Paolo Muiesan, Philipp Dutkowski, Andrea Schlegel
Journal: Hepatology (2021)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the article by Ember et al., where the investigators explored the value of Raman spectroscopy to assess liver viability in a porcine model donated after circulator death (DCD) with subsequent normothermic regional perfusion (NRP).(1) The microvascular environment was analyzed through real‐time stimulated Raman spectroscopy (SRS) and histology. Trapped erythrocytes were quantified in ischemic liver areas through the intrinsic Raman signal of hemoglobin (excitation wavelength, 532 nm).(1) The investigators found a reduction of liver congestion with less red blood cells, stuck in the sinusoids after NRP. Removal of 10% of donor blood before treatment withdrawal and circulatory death was found to be protective and resulted in healthier sinusoids with less congestion.(1) Although the article targets the hot topic of viability assessment, a few points require clarification. The investigators suggest a reduction of donor blood volume before organ donation, to decrease organ injury for transplantation. However, any donor pretreatment, including heparin administration, before withdrawal of all supportive measures, is strictly prohibited in many countries. Following treatment withdrawal, DCD donors deteriorate until circulatory death occurs, with a subsequent mandatory stand‐off period (2‐30 minutes) worldwide. Super‐rapid donor laparotomy and cannulation with cold flush or NRP are only started after donor death confirmation. Any measures, which may accelerate natural donor deterioration, including a reduction of blood volume, is therefore a violation of the donation protocol. During combined thoracic‐abdominal DCD organ procurement, the donor blood, used for normothermic ex situ heart perfusion, is obtained after circulatory death.(2) Next, although we agree that a healthy microvasculature is important, it is only one contributor to liver viability, which should target the key players of liver function: mitochondria. Ischemia leads here to metabolite accumulation and energy loss.(3) At reperfusion, reactive oxygen species and flavin mononucleotides (FMNs) are released from mitochondrial complex‐I.(4) Additionally, this autofluoresecent, mitochondrial FMN can be easily quantified from various perfusates by real‐time fluorescence spectroscopy, as recently demonstrated during hypothermic oxygenated perfusion (HOPE; Fig. 1).(4) FMN concentration in HOPE perfusates has a high predictive accuracy for graft loss and posttransplant complications and was validated by mass spectometry.(5)FIG. 1: Real‐time spectroscopy for viability assessment before liver transplantation. Real‐time viability tests are currently a hot topic in solid organ transplantation. Various spectroscopic techniques are explored on tissues and perfusates. Donor and graft assessment is a staged procedure and involves multiple unspecific tests performed from donor to recipient center.( 1‐3 ) Fluorescence spectroscopy is a valuable tool for viability assessment from perfusates, obtained during machine perfusion. Mitochondrial molecules, including FMN, are released during reoxygenation of human tissue and represent mitochondrial function and injury to predict outcomes after transplantation of high‐risk donor organs.( 4 )In summary, various spectroscopic techniques are currently tested as important tools for future viability assessment. Author Contributions M.F.C., A.S.: Conception and design. M.F.C.: Acquisition of data. M.F.C., A.S.: Analysis and interpretation of data. M.F.C.: Drafting of the article. P.M., P.D., A.S.: Critical revision for important intellectual content. M.F.C., M.M., P.M., P.D., A.S.: Final approval of the published version.