Sumeet K. Asrani M.D.

Weiss, E., F. Saner, S. K. Asrani, G. Biancofiore, A. Blasi, J. Lerut, F. Durand, J. Fernandez, J. Y. Findlay, C. Fondevila, C. Francoz, T. Gustot, S. Jaber, C. Karvellas, K. Kronish, W. Laleman, P. F. Laterre, E. Levesque, S. M. Mandell, M. McPhail, P. Muiesan, J. C. Olson, K. Olthoff, A. D. Pinna, T. Reiberger, K. Reyntjens, F. Saliba, O. Scatton, K. J. Simpson, O. Soubrane, R. M. Subramanian, F. Tacke, D. Tomescu, V. Xia, G. Wagener and C. Paugam-Burtz (2020). “When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.” Transplantation. Jun 15. [Epub ahead of print].

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BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT).Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty, and persistent fever or less than 72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a PaO2/FiO2 ratio<150 mmHg, a norepinephrine dose >1μg/kg/min and a serum lactate level >9 mmol/l. CONCLUSION: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.

Tapper, E. B. and S. K. Asrani (2020). “The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care.” J Hepatol Apr 13. pii: S0168-8278(20)30217-8. [Epub ahead of print].

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The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging ‘return to normal’ following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed.

Mahmud, N. and S. K. Asrani (2020). “Defining (and refining) the role of the Model for End Stage Liver Disease-Lactate (MELD-LA) score in cirrhosis.” Hepatology Apr 20. [Epub ahead of print].

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We appreciate the interest in our manuscript which details the derivation and external validation of the MELD-lactate (MELD-LA) score (bswh.md/meldla). Among patients with cirrhosis admitted to the hospital for liver-related indications, we found MELD-LA to significantly improve in-hospital mortality predictions versus MELD and MELD-Na. Singh and colleagues note that in the development cohort (n=14,733), only 38% of patients had admission lactate levels measured, which could indicate selection bias.

Levitsky, J., S. K. Asrani, T. Schiano, A. Moss, K. Chavin, C. Miller, K. Guo, L. Zhao, M. Kandpal, N. Bridges, M. Brown, B. Armstrong, S. Kurian, A. J. Demetris and M. Abecassis (2020). “Discovery and Validation of a Novel Blood-Based Molecular Biomarker of Rejection following Liver Transplantation.” Am J Transplant Apr 30. [Epub ahead of print].

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Non-invasive biomarker profiles of acute rejection (AR) could impact the management of liver transplant (LT) recipients. Peripheral blood was collected following LT for discovery (Northwestern University (NU)) and validation (NIAID CTOT-14 study). Blood gene profiling was paired with biopsies showing AR or ADNR (acute dysfunction no rejection) as well as stable graft function samples (Transplant eXcellent – TX). CTOT-14 subjects had serial collections prior to AR, ADNR, TX, and after AR treatment. NU cohort gene expression (46 AR, 45 TX) was analyzed using random forest models to generate a classifier training set (36 gene probe) distinguishing AR vs. TX (AUC 0.92). The algorithm and threshold were locked and tested on the CTOT-14 validation cohort (14 AR, 50 TX), yielding an accuracy of 0.77, sensitivity 0.57, specificity 0.82, PPV 0.47, and NPV 0.87 for AR vs. TX. The probability score line slopes were positive preceding AR, and negative preceding TX and non-AR (TX + ADNR) (p=<0.001) and following AR treatment. In conclusion, we have developed a blood biomarker diagnostic for AR that can be detected prior to AR-associated graft injury as well a normal graft function (non-AR). Further studies are needed to evaluate its utility in precision-guided immunosuppression optimization following LT.

Asrani, S. K., L. W. Jennings, W. R. Kim, P. S. Kamath, J. Levitsky, M. K. Nadim, G. Testa, M. D. Leise, J. F. Trotter and G. Klintmalm (2020). “MELD-GRAIL-Na: Glomerular Filtration Rate and Mortality on Liver-Transplant Waiting List.” Hepatology 71(5): 1766-1774.

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BACKGROUND AND AIMS: Among patients with cirrhosis awaiting liver transplantation, prediction of wait-list (WL) mortality is adjudicated by the Model for End Stage Liver Disease-Sodium (MELD-Na) score. Replacing serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) in the MELD-Na score may improve prediction of WL mortality, especially for women and highest disease severity. APPROACH AND RESULTS: We developed (2014) and validated (2015) a model incorporating eGFR using national data (n = 17,095) to predict WL mortality. Glomerular filtration rate (GFR) was estimated using the GFR assessment in liver disease (GRAIL) developed among patients with cirrhosis. Multivariate Cox proportional hazard analysis models were used to compare the predicted 90-day WL mortality between MELD-GRAIL-Na (re-estimated bilirubin, international normalized ratio [INR], sodium, and GRAIL) versus MELD-Na. Within 3 months, 27.8% were transplanted, 4.3% died on the WL, and 4.7% were delisted for other reasons. GFR as estimated by GRAIL (hazard ratio [HR] 0.382, 95% confidence interval [CI] 0.344-0.424) and the re-estimated model MELD-GRAIL-Na (HR 1.212, 95% CI 1.199-1.224) were significant predictors of mortality or being delisted on the WL within 3 months. MELD-GRAIL-Na was a better predictor of observed mortality at highest deciles of disease severity (>/= 27-40). For a score of 32 or higher (observed mortality 0.68), predicted mortality was 0.67 (MELD-GRAIL-Na) and 0.51 (MELD-Na). For women, a score of 32 or higher (observed mortality 0.67), the predicted mortality was 0.69 (MELD-GRAIL-Na) and 0.55 (MELD-Na). In 2015, use of MELD-GRAIL-Na as compared with MELD-Na resulted in reclassification of 16.7% (n = 672) of patients on the WL. CONCLUSION: Incorporation of eGFR likely captures true GFR better than SCr, especially among women. Incorporation of MELD-GRAIL-Na instead of MELD-Na may affect outcomes for 12%-17% awaiting transplant and affect organ allocation.