Sumeet K. Asrani M.D.

Weiss, E., Saner, F., Asrani, S.K., Biancofiore, G., Blasi, A., Lerut, J., Durand, F., Fernandez, J., Findlay, J.Y., Fondevila, C., Francoz, C., Gustot, T., Jaber, S., Karvellas, C., Kronish, K., Laleman, W., Laterre, P.F., Levesque, E., Mandell, M.S., Mc Phail, M., Muiesan, P., Olson, J.C., Olthoff, K., Daniele Pinna, A., Reiberger, T., Reyntjens, K., Saliba, F., Scatton, O., Simpson, K.J., Soubrane, O., Subramanian, R.M., Tacke, F., Tomescu, D., Xia, V., Wagener, G. and Paugam-Burtz, C. (2021). “When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.” Transplantation 105(3): 561-568.

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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 <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 mm Hg, a norepinephrine dose >1 μg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: 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.

Fallahzadeh, M.A., Hansen, D.J., Trotter, J.F., Everson, G.T., Saracino, G., Rahimi, R.S., Helmke, S., Boutte, J. and Asrani, S.K. (2021). “Predicting clinical decompensation in patients with cirrhosis using the Hepquant-SHUNT test.” Aliment Pharmacol Ther Feb 8. [Epub ahead of print].

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BACKGROUND: Early identification of risk for decompensation in clinically stable cirrhotic patients helps specialists target early interventions and supports effective referrals from primary care providers to specialty centres. AIMS: To examine whether the HepQuant-SHUNT test (HepQuant LLC, Greenwood Village, Colorado, USA) predicts decompensation and the need for liver transplantation, hospitalisation or liver-related death. METHODS: Thirty-five compensated and 35 subjects with a previous episode of decompensation underwent the SHUNT Test and were followed for a median of 4.2 years. The disease severity index (DSI) (range 0-50) was examined for association with decompensation in compensated patients; and liver transplantation, liver-related death, and the number and days of liver related hospitalisations in all. DSI prediction of decompensation was also evaluated in 84 subjects with compensated cirrhosis from the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial (HALT-C) followed for a median of 5.8 years. RESULTS: At baseline, subjects with prior decompensation had significantly higher DSI than compensated subjects (32.6 vs 20.9, P < 0.001). DSI ≥24 distinguished the decompensated from the compensated patients and independently predicted adverse clinical outcomes (hazard ratio: 4.92, 95% confidence interval: 1.42-17.06). In the HALT-C cohort, 65% with baseline DSI ≥24 vs 19% with DSI <24 experienced adverse clinical outcomes (relative risk 3.45, P < 0.0001). CONCLUSIONS: The SHUNT test is a novel, noninvasive test that predicts risk of decompensation in previously compensated patients. DSI ≥24 is independently associated with risk for clinical decompensation, liver transplantation, death and hospitalisation.

Karnam, R.S., Mitsakakis, N., Saracino, G., Lilly, L., Asrani, S.K. and Bhat, M. (2021). “Predicting Long-Term Survival After Liver Transplantation in Patients With NASH Cirrhosis.” Clin Gastroenterol Hepatol Jan 16;S1542-3565(21)00071-9. [Epub ahead of print].

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Nonalcoholic steatohepatitis (NASH) cirrhosis is the second most common indication for liver transplantation (LT) in the United States.(1) Patients are increasingly older at presentation, with higher rates of metabolic syndrome, obesity, hyperlipidemia, diabetes mellitus, and renal failure.(2) They are also at higher risk of cardiovascular events and mortality while on the waiting list(1) and in the post-transplant period.(3)(,)(4) We sought to identify predictors of long-term benefit based on 5-year survival post-LT in NASH cirrhosis, thereby delineating those patients that derive a clear benefit from LT versus those in whom LT may be futile.

Abdallah, M.A., Kuo, Y.F., Asrani, S., Wong, R.J., Ahmed, A., Kwo, P., Terrault, N., Kamath, P.S., Jalan, R. and Singal, A.K. (2020). “Validating a novel score based on interaction between ACLF grade and MELD score to predict waitlist mortality.” J Hepatol Dec 13;S0168-8278(20)33840-X. [Epub ahead of print].

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BACKGROUND AND AIM: Among candidates listed for liver transplant (LT), MELD score may not capture acute on chronic liver failure (ACLF) severity. Data on interaction between ACLF and MELD score in predicting waitlist (WL) mortality are scanty. METHODS: UNOS database (01/2002 to 06/2018) on LT listings for adults with cirrhosis and ACLF (without HCC) was analyzed. ACLF grades 1, 2, 3a, and 3b- were defined using modified EASL-CLIF criteria. RESULTS: Of 18,416 candidates with ACLF at listing (mean age 54 years, 69% males, 63% Caucasians), 90-d WL mortality (patient death or being too sick for LT) was 21.6% (18%, 20%, 25%, and 39% for ACLF grades 1, 2, 3a, and 3b respectively). Fine and Gray regression model identified interaction between MELD and ACLF grade, with higher impact of ACLF at lower MELD score. Other variables included candidate’s age, gender, liver disease etiology, listing MELD, ACLF grade, obesity, and performance status. A score developed using parameter estimates from the interaction model on the derivation cohort (N=9181) stratified the validation cohort (N=9235) to four quartiles Q1 (score <10.42), Q2 (10.42-12.81), Q3 (12.82-15.50), and Q4 (>15.50). WL mortality increased with each quartile from 13%, 18%, 23%, and 36% respectively. Observed versus expected deciles on WL mortality in validation cohort showed good calibration (goodness of fit P=0.98) and correlation (R=0.99). CONCLUSION: Among selected candidates who are in ACLF at listing, MELD score and ACLF interact in predicting cumulative risk of 90-d WL mortality, with higher impact of ACLF grade at lower listing MELD score. Validating these findings in large prospective studies will support to factor in both MELD and ACLF in prioritizing transplant candidates and allocation of liver grafts.E

Sarmast, N., Ogola, G.O., Kouznetsova, M., Leise, M.D., Bahirwani, R., Maiwall, R., Tapper, E., Trotter, J., Bajaj, J.S., Thacker, L.R., Tandon, P., Wong, F., Reddy, K.R., O’Leary, J.G., Masica, A., Modrykamien, A.M., Kamath, P.S. and Asrani, S.K. (2020). “Model for End-Stage Liver Disease-Lactate and Prediction of Inpatient Mortality in Patients With Chronic Liver Disease.” Hepatology 72(5): 1747-1757.

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BACKGROUND AND AIMS: Compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased LA clearance. We hypothesized that a parsimonious model consisting of Model for End-Stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD. APPROACH AND RESULTS: We examined all patients with CLD in two large and diverse health care systems in Texas (North Texas [NTX] and Central Texas [CTX]) between 2010 and 2015. We developed (n = 3,588) and validated (n = 1,804) a model containing MELD and LA measured at the time of hospitalization. We further validated the model in a second cohort of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 726). MELD-LA was an excellent predictor of inpatient mortality in development (concordance statistic [C-statistic] = 0.81, 95% confidence interval [CI] 0.79-0.82) and both validation cohorts (CTX cohort, C-statistic = 0.85, 95% CI 0.78-0.87; multicenter cohort C-statistic = 0.82, 95% CI 0.74-0.88). MELD-LA performed especially well in patients with specific cirrhosis diagnoses (C-statistic = 0.84, 95% CI 0.81-0.86) or sepsis (C-statistic = 0.80, 95% CI 0.78-0.82). For MELD score 25, inpatient mortality rates were 11.2% (LA = 1 mmol/L), 19.4% (LA = 3 mmol/L), 34.3% (LA = 5 mmol/L), and >50% (LA > 8 mmol/L). A linear increase (P < 0.01) was seen in MELD-LA and increasing number of organ failures. Overall, use of MELD-LA improved the risk prediction in 23.5% of patients compared to MELD alone. CONCLUSIONS: MELD-LA (bswh.md/meldla) is an early and objective predictor of inpatient mortality and may serve as a model for risk assessment and guide therapeutic options.