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Background: Acute-on-chronic liver failure (ACLF) is a life-threatening disease that requires urgent liver transplantation (LT). Accurate identification of high-risk patients is essential for predicting post-LT survival. The chronic liver failure consortium ACLF score is a widely accepted risk-stratification score that includes total white blood cell (WBC) counts as a component. This study aimed to evaluate the predictive value of total and differential WBC counts for short-term mortality following LT in patients with ACLF., Methods: A total of 685 patients with ACLF who underwent LT between January 2008 and February 2019 were analyzed. Total and differential WBC counts were examined as a function of the model for end-stage liver disease for sodium (MELD-Na) score. The association between total and differential WBC counts and 90-day post-LT mortality was assessed using multivariable Cox proportional hazards regression analysis., Results: The total WBC counts and neutrophil ratio were higher in patients with ACLF than in those without ACLF. The neutrophil ratio was significantly associated with 90-day post-LT mortality after adjustment (hazard ratio [HR], 1.04; P = 0.001), whereas total WBC counts were not significantly associated with 90-day post-LT mortality in either univariate or multivariate Cox analyses. The neutrophil ratio demonstrated a relatively linear trend with an increasing MELD-Na score and HR for 90-day post-LT mortality, whereas the total WBC counts exhibited a plateaued pattern., Conclusions: Neutrophilia, rather than total WBC counts, is a better prognostic indicator for short-term post-LT mortality in patients with ACLF.

Background: High B-type natriuretic peptide (BNP) levels within the first 3 postoperative days (postBNPPOD3) after liver transplantation (LT) are greatly predictive of the 30-day mortality. We evaluated clinical impact of transient decrease in postBNPPOD3 compared to pretransplant BNP (preBNP) level on mortality and major adverse cardiac event (MACE) within 30 days after LT., Methods: We retrospectively evaluated 3,811 LT patients who measured delta BNP (deltaBNP), defined by serial postBNPPOD3 minus preBNP. Thirty-day all-cause mortality and MACE were estimated in patients with deltaBNP < 0 (n = 594, 15.6%) and > 0 (n = 3,217, 84.4%), respectively. Kaplan-Meier survival and multivariable Cox regression analysis were used., Results: Within 30 days, 100 (2.6%) of all patients died. Unexpectedly, 30-day mortality rate (6.1% [95% CI: 4.2-8.4%] vs. 2.0% [95% CI: 1.5-2.5%], P < 0.001) and MACE (24.2% [95% CI: 20.4-28.5%] vs. 15.3% [95% CI: 14.0-16.7%], P < 0.001) were higher in patients with deltaBNP < 0 compared to those with deltaBNP > 0, respectively. Patients with deltaBNP < 0 had higher preBNP level (median [interquartile range], 251 [118, 586] vs. 43 [21, 92] pg/ml, P < 0.001) and model for end-stage liver disease score (26 [14, 37] vs. 14 [9, 23], P < 0.001) and more transfused intraoperatively. DeltaBNP < 0 remained significant after adjustments for potential confounders in multivariable analysis of 30-day mortality and MACE., Conclusions: DeltaBNP < 0 within the first 3 postoperative days is mainly attributed to pre-LT severe liver and cardiac disease status, therefore, transient decrease in BNP level after LT does not ensure favorable post-LT 30-day outcomes.

Background: Considering the importance of the inflammatory status of recipients on outcomes following liver transplantation (LT), we investigated the association between C-reactive protein-to-albumin ratio (CAR) and one-year mortality following LT and compared it with other parameters reflecting patients' underlying inflammatory status., Methods: A total of 3,614 consecutive adult LT recipients were retrospectively evaluated. Prognostic parameters were analyzed using area under the receiver operating characteristic curve (AUROC) analysis, and subsequent cutoffs were derived. For survival analysis, Cox proportional hazards and Kaplan-Meier analyses were performed., Results: The AUROC for CAR to predict one-year mortality after LT was 0.68 (0.65-0.72), which was the highest compared with other inflammatory parameters, with the best cutoff of 0.34. A CAR ≥ 0.34 was associated with a significantly higher one-year mortality rate (13.3% vs. 5.8 %, log-rank P < 0.001) and overall mortality rate (24.5% vs. 12.9%, log-rank P = 0.039). A CAR ≥ 0.34 was an independent predictor of one-year mortality (hazard ratio, 1.40 [1.03-1.90], P = 0.031) and overall mortality (hazard ratio 1.39 [1.13-1.71], P = 0.002) after multivariable adjustment., Conclusions: Preoperative CAR (≥ 0.34) was independently associated with a higher risk of one-year and overall mortality after LT. This may suggest that CAR, a simple and readily available biomarker, maybe a practical index that may assist in the risk stratification of liver transplantation outcomes.

Background: Patients with acute-on-chronic liver failure (ACLF) are critically ill and have high waiting-list mortality. Although studies demonstrated that appropriately treated coronary artery disease (CAD) should not be regarded as a contraindication to liver transplant (LT), data regarding long-term outcomes in critically ill liver LT recipients are lacking. The aim of this study was to compare the rates of all-cause death at 5 years following LT in patients with ACLF with or without CAD., Methods: Between 2010 and 2020, we evaluated 921 consecutive LT patients (MELD score, 32 ± 9) and ACLF classified by CLIF-C ACLF score. Up to 5-year all-cause death according to the CAD status was examined. CAD was defined as a preoperative history of coronary artery bypass graft or a percutaneous intervention and old myocardial infarction. Kaplan-Meier survival analysis was used., Results: Up to 5 years, 212 (23.0%) of all ACLF patients (n = 921) in whom 17 (29.3%) of 58 CAD patients died. In patients with CAD (6.3%, 58/921), the Kaplan-Meier cumulative mortality rate at 5 years was numerically higher but was not statistically significant when compared with those without CAD (32.9% vs. 23.5%, log-rank, P = 0.25). In subgr oup analysis, there were comparable risks of cumulative mortalities at 5 years across the stratification of ACLF grade 1, 2, and 3 (log-rank P = 0.062, P = 0.72, and P = 0.999, respectively)., Conclusions: All-cause mortality is high in patients with ACLF after LT but is not related to the presence of revascularized or treated CAD, across the stratification of ACLF grades.

Background: Coronary artery disease (CAD) is increasing worldwide due to the aging population and cardiometabolic syndrome. However, the extent of postoperative myocardial injury, the most common cause of death during the 30 days after noncardiac surgery, remains unclear with respect to liver transplant (LT) patients with CAD. We examined the link between post-LT high sensitivity cardiac troponin I (hs&#95;cTnI) and long-term survival according to liver disease severity., Methods: Consecutive patients who underwent LT (n = 3,220) from 2010 to 2020 were evaluated retrospectively. CAD was defined as a history of coronary artery bypass surgery or percutaneous intervention, or previous myocardial infarction. Peak hs&#95;cTnI levels within 30 days post-transplant were compared in patients with and without CAD. The primary endpoint was defined as an all-cause mortality at 12 years following LT. Secondary endpoints include peak hs&#95;cTnI level within post-transplant 30 days and 30-day mortality. Survival analysis was performed using the Kaplan-Meier method., Results: CAD patients (n = 264, 8.2%) had higher peak hs&#95;cTnI levels within 30 days post-LT than those without CAD (median [interquartile]: 0.068 [0.030-0.154] vs. 0.087 [0.037-0.203] ng/ml, respectively; P = 0.004); however, the mortality rate was comparable (14.7% vs. 14.8%, respectively, P = 0.999), at 12 years, and 1.9% vs. 1.1% (P = 0.522) at 30 days, respectively, at 30 days. Subgroup analysis with stratified liver disease severity identified a similar risk of long-term mortality., Conclusions: Although the peak hs&#95;cTnI level within 30 days was higher in revascularized or treated CAD patients after LT compared those without CAD, long-term mortality rates at 12 years and 30-day mortality rate were comparable.

Background: We aimed to explore the distribution of intraoperative lactic acid (LA) level during liver transplantation (LT) and determine the optimal cutoff values to predict post-LT 30-day and 90-day mortality., Methods: Intraoperative LA data from 3,338 patients were collected between 2008 to 2019 and all-cause mortalities within 30 and 90 days were retrospectively reviewed. Of the three LA levels measured during preanhepatic, anhepatic, and neohepatic phase of LT, the peak LA level was selected to explore the distribution and predict early post-LT mortality. To determine the best cutoff values of LA, we used a classification and regression tree algorithm and maximally selected rank statistics with the smallest P value., Results: The median intraoperative LA level was 4.4 mmol/L (range: 0.5-34.7, interquartile range: 3.0-6.2 mmol/L). Of the 3,338 patients, 1,884 (56.4%) had LA levels > 4.0 mmol/L and 188 (5.6%) had LA levels > 10 mmol/L. Patients with LA levels > 16.7 mmol/L and 13.5-16.7 mmol/L showed significantly higher 30-day mortality rates of 58.3% and 21.2%, respectively. For the prediction of the 90-day mortality, 8.4 mmol/L of intraoperative LA was the best cutoff value., Conclusions: Approximately 6% of the LT recipients showed intraoperative hyperlactatemia of > 10 mmol/L during LT, and those with LA > 8.4 mmol/L were associated with significantly higher early post-LT mortality.

Background: Generally, lactate levels > 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is often defined as lactate > 4 mmol/L. Although hyperlactatemia is common finding in liver transplant (LT) candidates, association between lactate and organ failures with Acute-on-chronic Liver Failure (ACLF) is poorly studied. We searched the important variables for pre-LT hyperlactatemia and examined the impact of preoperative hyperlactatemia on early mortality after LT., Methods: A total of 2,002 patients from LT registry between January 2008 and February 2019 were analyzed. Six organ failures (liver, kidney, brain, coagulation, circulation, and lung) were defined by criteria of EASL-CLIF ACLF Consortium. Variable importance of preoperative hyperlactatemia was examined by machine learning using random survival forest (RSF). Kaplan-Meier Survival curve analysis was performed to assess 90-day mortality., Results: Median lactate level was 1.9 mmol/L (interquartile range: 1.4, 2.4 mmol/L) and 107 (5.3%) patients showed > 4.0 mmol/L. RSF analysis revealed that the four most important variables for hyperlactatemia were MELD score, circulatory failure, hemoglobin, and respiratory failure. The 30-day and 90-day mortality rates were 2.7% and 5.1%, whereas patients with lactate > 4.0 mmol/L showed increased rate of 15.0% and 19.6%, respectively., Conclusions: About 50% and 5% of LT candidates showed pre-LT hyperlactatemia of > 2.0 mmol/L and > 4.0 mmol/L, respectively. Pre-LT lactate > 4.0 mmol/L was associated with increased early post-LT mortality. Our results suggest that future study of correcting modifiable risk factors may play a role in preventing hyperlactatemia and lowering early mortality after LT.

Background: Although systolic anterior motion (SAM) of the mitral valve anterior leaflet is well-known to cause hemodynamic perturbation in many anesthetic situations, the prevalence and clinical implication of SAM of mitral chordae tendineae (chordal SAM) in liver transplantation (LT) has not been evaluated. We aimed to assess the impact of chordal SAM on intraoperative postreperfusion syndrome and short and long-term all-cause mortality., Methods: We retrospectively evaluated 1751 LT recipients from January 2011 to June 2017 who had preoperative echocardiography. Echocardiography-derived parameters and the prevalence of post-reperfusion syndrome between those with chordal SAM and without chordal SAM were compared. The cumulative mortality rate according to the presence of chordal SAM was evaluated by the Kaplan-Meier survival curve., Results: Of the enrolled recipients, 21 (1.2%) had chordal SAM in preoperative echocardiography. Compared to those without chordal SAM, patients with chordal SAM had a smaller end-systolic volume index (median 18 ml/m 2 vs. 22 ml/m 2 , P = 0.015) and end-diastolic volume index (median 52 ml/m 2 vs. 63 ml/m 2 , P = 0.011). However, there was no difference in systolic and diastolic function in echocardiography. The prevalence of intraoperative post-reperfusion syndrome did not show any difference (42.9% vs. 45.3%, P = 1.000). Over the mean 4.8-year follow-up, cumulative 90-day and overall mortality also did not show a difference (Log rank P > 0.05, both)., Conclusions: Preoperative screening of echocardiography in LT recipients detects 1.2% of chordal SAM. It is found with small left ventricular volume, but is not related with intraoperative post-reperfusion syndrome and short- and long-term postoperative all-cause mortality in LT., Competing Interests: CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © the Korean Society of Anesthesiologists, 2020.)

Background: Diabetes mellitus (DM) increases risk of heart failure. It has been shown that diabetes leads to DM-cardiomyopathy, characterized by systolic and diastolic dysfunction. Pre-transplant diastolic dysfunction, has been associated with poor graft outcome and mortality. We assessed the hypothesis that end-stage liver disease (ESLD) patients with diabetes (DM-ESLD), have more advanced cardiac systolic and diastolic dysfunction, compared to ESLD patients without diabetes (Non DM-ESLD)., Methods: We retrospectively evaluated preoperative echocardiography of 1,319 consecutive liver transplant recipients (1,007 Non DM-ESLD vs. 312 DM-ESLD [23.7%]) January 2012-May 2016. Systolic and diastolic indices, such as left ventricular ejection fraction, transmital E/A ratio, tissue doppler s', e' velocity, and E/e' ratio (index of left ventricular end-diastolic pressure), were compared using 1:2 propensity-score matching., Results: DM-ESLD patients showed no differences in systolic indices of left ventricular ejection fraction and s' velocity, whereas diastolic indices of E/A ratio ≤ 1 (49.0% vs. 40.2% P = 0.014), e' velocity (median = 7.0 vs. 7.4 cm/s, P < 0.001) and E/e' ratio (10.9 ± 3.2 vs. 10.1 ± 3.0, P < 0.001), showed worse diastolic function compare with Non DM-ESLD patients, respectively., Conclusions: DM-ESLD patients suffer higher degree of diastolic dysfunction compared with Non DM-ESLD patients. Based on this, careful preoperative screening for diastolic dysfunction in DM-ESLD patients is encouraged, because poor transplant outcomes have been noted in patients with preoperative diastolic dysfunction., Competing Interests: CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright: © Anesthesia and Pain Medicine.)