Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality

Fodor, Margot; Woerdehoff, Adriana; Peter, Wolfgang; Esser, Hannah; Oberhuber, Rupert; Margreiter, Christian; Maglione, Manuel; Cardini, Benno; Resch, Thomas; Weißenbacher, Annemarie; Sucher, Robert; Zoller, Heinz; Tilg, Herbert; Öfner, Dietmar; Schneeberger, Stefan

doi:10.3389/fsurg.2021.693288

Cited by 9 publications

(9 citation statements)

References 29 publications

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“…It is noteworthy that the majority of EAD grafts in this study met only one EAD criterion, AST > 2000 U/L during the first week post-LT. Fodor et al previously noted that bilirubin and INR have a stronger predictive capacity for patient and graft survival compared to AST [26]. Similarly, Wang et al also noted that EAD outcomes varied by the number of observed criteria, with outcomes of recipients having one criterion being superior to those with two or three criteria [22].…”

Section: Discussionmentioning

confidence: 98%

“…These studies have shown inferior patient and graft survival as well as increased resource utilization such as ventilator days, occurrence of renal failure, and longer hospital length of stay [11][12][13][14][15]. The rising prevalence of EAD with the use of nonconventional grafts, such as those from DCD donors, is arguably expected; however, increasingly favorable outcomes have also been demonstrated with such donors despite the presence of at-risk variables [4,5,18,[24][25][26]. In this series, 31.8% of grafts were from DCD donors and post-transplant outcomes were similar in regard to resource utilization (ICU and hospital length of stay), prevalence of AKI, and patient and graft survival.…”

Section: Discussionmentioning

confidence: 99%

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Decreasing Significance of Early Allograft Dysfunction with Rising Use of Nonconventional Donors

et al. 2022

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Background and Objectives: Early allograft dysfunction (EAD) is considered a surrogate marker for adverse post-liver transplant (LT) outcomes. With the increasing use of nonconventional donors, EAD has become a more frequent occurrence. Given this background, we aimed to assess the prevalence and impact of EAD in an updated cohort inclusive of both conventional and nonconventional liver allografts. Materials and Methods: Perioperative and one-year outcomes were assessed for a total of 611 LT recipients with and without EAD from Mayo Clinic Arizona. EAD was defined as the presence of one or more of the following: bilirubin > 10 mg/dL on day 7, INR > 1.6 on day 7, or ALT and/or AST > 2000 IU/L within the first 7 days of LT. Results: Within this cohort, 31.8% of grafts (n = 194) came from donation after circulatory death (DCD) donors, 17.7% (n = 108) were nationally shared, 16.4% (n = 100) were allocated as post-cross clamp, and 8.7% contained moderate steatosis. EAD was observed in 52.2% (n = 321) of grafts in the study cohort (79% in DCD grafts and 40% in DBD grafts). EAD grafts had higher donor risk index (DRI) scores (1.9 vs. 1.6, p < 0.0001), were more likely to come from DCD donors (48% vs. 13.8%, p < 0.0001), were regionally allocated (p = 0.003), and had higher cold ischemia times (median 6.0 vs. 5.5 h, p = 0.001). Primary nonfunction events were rare in both groups (1.3% vs. 0.3%, p = 0.22). Post-LT acute kidney injury occurred at a similar frequency in recipients with and without EAD (43.6% vs. 30.3%, p = 0.41), and there were no differences in ICU (median 2 vs. 1 day, p = 0.60) or hospital (6 vs. 5 days, p = 0.24) length of stay. For DCD grafts, the rate of ischemic cholangiopathy was similar in the two groups (14.9% EAD vs. 17.5% no EAD, p = 0.69). One-year patient survival for grafts with and without EAD was 96.0% and 94.1% (HR 1.2, 95% CI 0.7–1.8; p = 0.54); one-year graft survival was 92.5% and 92.1% (HR 1.0, 95% CI 0.7–1.5; p = 0.88). Conclusions: In this cohort, EAD occurred in 52% of grafts. The occurrence of EAD, however, did not portend inferior outcomes. Compared to those without EAD, recipients with EAD had similar post-operative outcomes, as well as one-year patient and graft survival. EAD should be managed supportively and should not be viewed as a deterrent to utilization of non-ideal grafts.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Decreasing Significance of Early Allograft Dysfunction with Rising Use of Nonconventional Donors

et al. 2022

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“…Indeed, postoperative levels of transaminases are influenced by the perfusion itself and the large volume of perfusate (wash-out) ( 72 ). Additionally, bilirubin and INR seem to have a stronger predictive capacity for patient and graft survival compared to AST, indicating that hepatocyte injury with little involvement of the biliary tree has a more benign course ( 86 ). The usefulness of the current definition of early allograft dysfunction (using peak transaminases in the first week, total bilirubin and INR levels) ( 55 ) in case of livers transplanted after perfusion is unclear and the definition might need revisiting ( 86 , 87 ).…”

Section: Livermentioning

confidence: 99%

Sense and Sensibilities of Organ Perfusion as a Kidney and Liver Viability Assessment Platform

Verstraeten¹,

Jochmans

2022

Transpl Int

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Predicting organ viability before transplantation remains one of the most challenging and ambitious objectives in transplant surgery. Waitlist mortality is high while transplantable organs are discarded. Currently, around 20% of deceased donor kidneys and livers are discarded because of “poor organ quality”, Decisions to discard are still mainly a subjective judgement since there are only limited reliable tools predictive of outcome available. Organ perfusion technology has been posed as a platform for pre-transplant organ viability assessment. Markers of graft injury and function as well as perfusion parameters have been investigated as possible viability markers during ex-situ hypothermic and normothermic perfusion. We provide an overview of the available evidence for the use of kidney and liver perfusion as a tool to predict posttransplant outcomes. Although evidence shows post-transplant outcomes can be predicted by both injury markers and perfusion parameters during hypothermic kidney perfusion, the predictive accuracy is too low to warrant clinical decision making based upon these parameters alone. In liver, further evidence on the usefulness of hypothermic perfusion as a predictive tool is needed. Normothermic perfusion, during which the organ remains fully metabolically active, seems a more promising platform for true viability assessment. Although we do not yet fully understand “on-pump” organ behaviour at normothermia, initial data in kidney and liver are promising. Besides the need for well-designed (registry) studies to advance the field, the catch-22 of selection bias in clinical studies needs addressing.

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“…Further to this, innovative liver graft viability and injury markers have been applied. However, whether they are acceptable predictors of the outcomes after LT remains to be proven ( 2 , 4 , 11 , 12 ). Novel non-invasive methods for the estimation of organ quality during NMP are necessitated.…”

Section: Introductionmentioning

confidence: 99%

Hyperspectral Imaging as a Tool for Viability Assessment During Normothermic Machine Perfusion of Human Livers: A Proof of Concept Pilot Study

Fodor¹,

Lanser²,

Hofmann³

et al. 2022

Transpl Int

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Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 (p < 0.001), THI (p < 0.001) and NIR (p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped (p = 0.005) during the observational period. At 12–24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers (p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = −0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP.

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Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality

Cited by 9 publications

References 29 publications

Decreasing Significance of Early Allograft Dysfunction with Rising Use of Nonconventional Donors

Decreasing Significance of Early Allograft Dysfunction with Rising Use of Nonconventional Donors

Sense and Sensibilities of Organ Perfusion as a Kidney and Liver Viability Assessment Platform

Hyperspectral Imaging as a Tool for Viability Assessment During Normothermic Machine Perfusion of Human Livers: A Proof of Concept Pilot Study

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