Evaluation of liver maximum capacity measurements to monitor hepatocellular function during extended normothermic machine perfusion
Clarke, George Mao, Jingwen Hann, Angus Fan, Yiyu Gupta, Amita Kayani, Kayani Murphy, Nicholas Bangash, Mansoor N Casey, Anna L Wootton, Isla
Clarke, George
Mao, Jingwen
Hann, Angus
Fan, Yiyu
Gupta, Amita
Kayani, Kayani
Murphy, Nicholas
Bangash, Mansoor N
Casey, Anna L
Wootton, Isla
Affiliation
University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Ochre-Bio Ltd
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Publication date
2025-11-17
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Abstract
Background: Although lactate clearance provides important information regarding hepatocellular function during normothermic machine perfusion (NMP), the information inferred is adequate to exclude nonfunctioning grafts but is limited in evaluating comprehensive hepatocyte function. Liver maximum capacity (LiMAx), using C13-methacetin, has been adopted to assist in the functional assessment of the liver before major oncological resection. We evaluated the combined use of lactate clearance and LiMAx measurement to monitor liver function during extended-duration NMP.
Methods: Seven discarded donor livers underwent extended NMP for 87-184 h using a blood-based perfusate and a modified Liver Assist device incorporating hemofiltration. Hepatocellular function was assessed every 6 h using LiMAx: a fixed bolus of C13-methacetin was administered and the delta over baseline was measured. Lactate clearance capacity was tested every 24 h by administering 50% sodium lactate to achieve perfusate concentrations of 10-15 mmol/L.
Results: Initial lactate clearance to <2.5 mmol/L was achieved within 1.75-7.75 h post-NMP initiation. The median LiMAx value was 829 (range, 325-3130) µg/kg/h. Livers with efficient lactate clearance (<4 h) displayed stable LiMAx profiles with consistently low, flat delta over baseline curves, maintaining similar amplitude for 80 h of perfusion, indicative of preserved hepatocyte function. Conversely, livers with progressive reductions in LiMAx amplitude and curve flattening were associated with deteriorating function and eventual graft failure.
Conclusions: LiMAx enables real-time, longitudinal monitoring of hepatocyte metabolic activity during extended NMP. When combined with lactate clearance, it could offer a more comprehensive assessment of graft viability. Incorporating LiMAx into viability criteria could refine current decision-making frameworks for liver transplantation, particularly in marginal grafts.
Citation
Clarke G, Mao J, Hann A, Fan Y, Gupta A, Kayani K, Murphy N, Bangash MN, Casey AL, Wootton I, Lawson AJ, Mergental H, Afford SC, Dasari BVM. Evaluation of Liver Maximum Capacity Measurements to Monitor Hepatocellular Function During Extended Normothermic Machine Perfusion. Transplantation. 2025 Nov 17. doi: 10.1097/TP.0000000000005570. Epub ahead of print.
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Article