Benefits of liver transplant in critically ill patients with acute-on chronic liver failure: implementation of an urgent living-donor program.

We evaluated the liver transplantation (LT) criteria in acute-on-chronic liver failure (ACLF), incorporating an urgent living-donor LT (LDLT) program. Critically ill patients with a Chronic Liver Failure-Consortium-ACLF score (CLIF-C_ACLF_score)≥65, previously considered unsuitable for LT, were included to explore the mortality threshold of the CLIF-C_ACLF_score (CLIF-C_ACLF_score_threshold). We followed 854 consecutive patients with ACLF (276 ACLF-2 and 215 ACLF-3) over 10 years among 4432 LT recipients between 2008 and 2019. For advanced ACLF patients without immediate deceased-donor (DD) allocation, an urgent LDLT program was expedited. The CLIF-C_ACLF_score_threshold was determined by the metrics of transplant survival benefit: >60% 1-year and >50% 5-year survival rate. In predicting post-LT mortality, the CLIF-C_ACLF_score outperformed the MELD-Na and MELD-3.0 scores but was comparable to the Sundaram ACLF-LT-mortality (SALT-M) score. A CLIF-C_ACLF_score≥65 (n=54) demonstrated post-transplant survival benefits, with 1-year and 5-year survival rates of 66.7% and 50.4% (P<0.001). Novel CLIF-C_ACLF_score_threshold for 1-year and 5-year mortalities was 70 and 69, respectively. A CLIF-C_ACLF_score-based nomogram for predicting survival probabilities, integrating cardiovascular disease, diabetes, and donor type (LDLT vs. DDLT), was generated. This study suggests reconsidering the criteria for unsuitable LT with a CLIF-C_ACLF_score≥65. Implementing a timely salvage LT strategy, incorporating urgent LDLT, can enhance survival rates.

Impact of preoperative nonselective beta-blocker use on acute kidney injury after living donor liver transplantation: Propensity score analysis.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is prevalent and has deleterious effects on postoperative outcomes following liver transplantation (LT). The impact of nonselective beta-blockers (NSBBs) in patients with liver cirrhosis remains controversial. This study investigated the association between preoperative NSBB use and AKI after living donor LT (LDLT). PATIENTS AND METHODS: We evaluated 2,972 adult LDLT recipients between January 2012 and July 2022. The patients were divided into two groups based on the preoperative NSBB use. Propensity score matched (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate the association between preoperative NSBB use and postoperative AKI. Multiple logistic regression analyses were also used to identify the risk factors for AKI. RESULTS: The overall incidence of AKI was 1,721 (57.9%) cases. The NSBB group showed a higher incidence of AKI than the non-NSBB group (62.4% vs. 56.7%; P = 0.011). After PSM and IPTW analyses, no significant difference in the incidence of AKI was found between the two groups (Odds ratio, OR 1.13, 95% confidence interval, CI 0.93-1.37, P = 0.230, PSM analysis; OR 1.20, 95% CI 0.99-1.44, P = 0.059, IPTW analysis). In addition, preoperative NSBB use was not associated with AKI after multivariate logistic regression analysis (OR 1.16, 95% CI 0.96-1.40, P = 0.118). CONCLUSIONS: Preoperative NSBB use was not associated with AKI after LDLT. Further studies are needed to validate our results.

Left ventricular remodeling in end-stage liver disease and post-transplant mortality assessed using end-diastolic pressure-volume relation analysis: Observational retrospective study.

BACKGROUND: Diastolic dysfunction is regarded as an important predictor of outcome after liver transplantation (LT). We investigated the influence of liver disease severity on left ventricular diastolic properties using end-diastolic pressure-volume relationship (EDPVR) analysis in patients with end-stage liver disease (ESLD). Association between alterations of the EDPVR and mortality after LT was evaluated. METHODS: In this observational retrospective cohort study, 3,211 patients who underwent LT for ESLD were included in analysis. Variables derived from single-beat EDPVR (diastolic stiffness-coefficient [ß] and end-diastolic volume at an end-diastolic pressure of 20 mmHg [EDVI20] indicating ventricular capacitance) were estimated using preoperative echocardiographic data. Alterations in EDPVR with increased stiffness (ß > 6.16) were categorized into 3 groups; leftward-shifted (EDVI20 <51 mL/m2), rightward-shifted (EDVI20 > 69.7 mL/m2), and intermediate (EDVI20 51-69.7 mL/m2). RESULTS: As the model for ESLD score increases, both EDVI20 and ß gradually increased, which indicated ventricular remodeling with larger capacitance and higher diastolic stiffness. Among patients with increased stiffness (ß > 6.16, n = 1,090), survival rates after LT were lower in leftward-shifted EDPVR than in rightward-shifted EDPVR (73.7% vs 82.9%; log-rank P = 0.002). In the adjusted Cox proportional hazard model, risk of cumulative all-cause mortality at 11 years was the highest in leftward-shifted EDPVR (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.27-2.92), followed by intermediate EDPVR (HR: 1.55; 95% CI: 1.12-2.26), compared with rightward-shifted EDPVR. The SHapley Additive exPlanation model revealed that the variables associated with leftward-shifted EDPVR were diabetes, female sex, old age, and hypertension. CONCLUSIONS: As ESLD advances, diastolic ventricular properties are characterized by increased EDVI20 and ß on rightward-shifted EDPVR, indicating larger capacitance and higher stiffness. However, leftward-shifted EDPVR with left ventricle remodeling failure is associated with poor post-LT survival.

Association between visceral obesity and tumor recurrence in hepatocellular carcinoma recipients undergoing liver transplantation.

BACKGROUND: Excessive visceral obesity in recipients of living donor liver transplantation (LDLT) is associated with mortality, and a recent study reported the correlation between visceral adiposity of male LDLT recipients and hepatocellular carcinoma (HCC) recurrence. However, there is no study on the relationship between the donor's visceral adiposity and surgical outcomes in LDLT recipients. We investigated the association of the visceral-to-subcutaneous fat area ratio (VSR) in donors and recipients with HCC recurrence and mortality in LDLT. METHODS: We analyzed 1386 sets of donors and recipients who underwent LDLT between January 2008 and January 2018. The maximal chi-square method was used to determine the optimal cutoff values for VSR for predicting overall HCC recurrence and mortality. Cox regression analyses were performed to evaluate the association of donor VSR and recipient VSR with overall HCC recurrence and mortality in recipients. RESULTS: The cutoff values of VSR was determined as 0.73 in males and 0.31 in females. High donor VSR was significantly associated with overall HCC recurrence (adjusted hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.06-1.93, p = 0.019) and mortality (HR: 1.35, 95% CI: 1.03-1.76, p = 0.030). High recipient VSR was significantly associated with overall HCC recurrence (HR: 1.40, 95% CI: 1.04-1.88, p = 0.027) and mortality (HR: 1.50, 95% CI: 1.14-1.96, p = 0.003). CONCLUSIONS: Both recipient VSR and donor VSR were significant risk factors for HCC recurrence and mortality in LDLT recipients. Preoperative donor VSR and recipient VSR may be strong predictors of the surgical outcomes of LDLT recipients with HCC.

Association of sex-specific donor skeletal muscle index with surgical outcomes in living donor liver transplantation recipients.

BACKGROUND: A recent study reported a correlation between the muscle mass of male donors and graft failure in living donor liver transplantation (LDLT) recipients. We investigated the association of sex-specific donor skeletal muscle index (SMI) with mortality and graft failure in LDLT recipients. METHODS: We retrospectively analysed 2750 sets of donors and recipients between January 2008 and January 2018. The recipient outcomes were analysed by dividing the data according to donor sex. Cox regression analyses were performed to evaluate the association between donor SMI by sex and 1-year mortality and graft failure in recipients. RESULTS: In the male donor group, robust donor (increased SMI) was significantly associated with higher risks for mortality (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.00-1.06, p = .023) and graft failure (HR: 1.04, 95% CI: 1.01-1.06, p = .007) at 1 year. In the female donor group, the robust donor was significantly associated with lower risks for mortality (HR: 0.92, 95% CI: 0.87-0.97, p = .003) and graft failure (HR: 0.95, 95% CI: 0.90-1.00, p = .032) at 1 year. CONCLUSIONS: Donor SMI was associated with surgical outcomes in recipients. Robust male and female donors were a significant negative and protective factor for grafts respectively.

Associations of sarcopenia with graft failure and mortality in patients undergoing living donor liver transplantation.

Recent studies have reported that sarcopenia influences morbidity and mortality in surgical patients. However, few studies have investigated the associations of sarcopenia with short-term and long-term graft failure in recipients after living donor liver transplantation (LDLT). In this study, we investigated the associations between sarcopenia and graft failure/mortality in patients undergoing LDLT. We retrospectively examined 2816 recipients who underwent LDLT between January 2008 and January 2018. Cox regression analysis was performed to evaluate the associations between sarcopenia and graft failure/mortality in recipients at 60 days, 180 days, and 1 year and overall. Sarcopenia in the recipient was significantly associated with 60-day graft failure (adjusted hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.09-3.61; p = 0.03), 180-day graft failure (HR, 1.85; 95% CI, 1.19-2.88; p = 0.01), 1-year graft failure (HR, 1.45; 95% CI, 1.01-2.17; p = 0.05), and overall graft failure (HR, 1.42; 95% CI, 1.08-1.87; p = 0.01). In addition, recipient sarcopenia was associated with 180-day mortality (HR, 1.88; 95% CI, 1.17-3.01; p = 0.01), 1-year mortality (HR, 1.53; 95% CI, 1.01-2.29; p = 0.04), and overall mortality (HR, 1.43; 95% CI, 1.08-1.90; p = 0.01). Preoperative sarcopenia was associated with high rates of graft failure and mortality in LDLT recipients. Therefore, preoperative sarcopenia may be a strong predictor of the surgical prognosis in LDLT recipients.

Prognostic Value of B-Type Natriuretic Peptide in Liver Transplant Patients: Implication in Posttransplant Mortality.

BACKGROUND AND AIMS: Despite frequent cirrhotic cardiomyopathy or subclinical heart failure (HF), the prognostic value of peri-liver transplant (LT) B-type natriuretic peptide (BNP) has been poorly studied in advanced liver disease. We examined the association between BNP and mortality in a large cohort of LT patients and identified risk factors for peri-LT BNP increase. APPROACH AND RESULTS: Using prospectively collected data from the Asan LT Registry between 2008 and 2019, 3,811 patients who measured serial pretransplant BNP (preBNP) and peak BNP levels within the first 3 posttransplant days (postBNPPOD3 ) were analyzed. Thirty-day all-cause mortality predicted by adding preBNP and/or postBNPPOD3 to the traditional Revised Cardiac Risk Index (RCRI) was evaluated. PreBNP > 400 pg/mL (known cutoff of acute HF) was found in 298 (7.8%); however, postBNPPOD3  > 400 pg/mL was identified in 961 (25.2%) patients, specifically in 40.4% (531/1,315) of those with a Model for End-Liver Disease score (MELDs) > 20. Strong predictors of postBNPPOD3  > 400 pg/mL were preBNP, hyponatremia, and MELDs, whereas those of preBNP > 400 pg/mL were MELDs, kidney failure, and respiratory failure. Among 100 (2.6%) post-LT patients who died within 30 days, patients with postBNPPOD3  ≤ 150 pg/mL (43.1%, reference group), 150-400 pg/mL (31.7%), 400-1,000 pg/mL (18.5%), 1,000-2,000 pg/mL (4.7%), and >2,000 pg/mL (2.0%) had 30-day mortalities of 0.9%, 2.2%, 4.0%, 7.7%, and 22.4%, respectively. Adding preBNP, postBNPPOD3 , and both BNP to RCRI improved net reclassification index to 22.5%, 29.5%, and 33.1% of 30-day mortality, respectively. CONCLUSIONS: PostBNPPOD3  > 400 pg/mL after LT was markedly prevalent in advanced liver disease and mainly linked to elevated preBNP. Routine monitoring of peri-LT BNP provides incremental prognostic information; therefore, it could help risk stratification for mortality as a practical and useful biomarker in LT.

Association of skeletal muscle index with postoperative acute kidney injury in living donor hepatectomy: A retrospective single-centre cohort study.

BACKGROUND: Although living donor liver transplantation (LDLT) is the standard treatment option for patients with end-stage liver disease, it always entails ethical concerns about the risk of living donors. Recent studies have reported a correlation between sarcopenia and surgical prognosis in recipients. However, there are few studies of donor sarcopenia and the surgical prognosis of donors. This study investigated the association between sarcopenia and postoperative acute kidney injury in liver donors. METHODS: This retrospective study analysed 2892 donors who underwent donor hepatectomy for LDLT between January 2008 and January 2018. Sarcopenia was classified into pre-sarcopenia and severe sarcopenia, which were determined to be -1 standard deviation (SD), and -2 SD from the mean baseline of the skeletal muscle index, respectively. Multivariate regression analysis was performed to evaluate the association between donor sarcopenia and postoperative AKI. Additionally, we assessed the association between donor sarcopenia and delayed recovery of liver function (DRHF). RESULTS: In the multivariate analysis, donor sarcopenia was significantly associated a higher incidence of postoperative AKI (adjusted odds ratio [OR]: 2.65, 95% confidence interval [CI]: 1.15-6.11, P = .022 in pre-sarcopenia, OR: 5.59, 95% CI: 1.11-28.15, P = .037 in severe sarcopenia, respectively). Additionally, hypertension and synthetic colloid use were significantly associated with postoperative AKI. In the multivariate analysis, risk factors of DRHF were male gender, indocyanine green retention rate at 15 minutes, and graft type, however, donor sarcopenia was not a risk factor. CONCLUSIONS: Donor sarcopenia is associated with postoperative AKI following donor hepatectomy.

Perioperative management of adult living donor liver transplantation: Part 1 - recipients.

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation option has become an established and widely practiced transplantation method for adult patients suffering from end-stage liver disease. It has successfully addressed the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplant Anesthesia jointly reviewed published studies on the perioperative management of live donor liver transplant recipients. The review aims to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live liver transplantation recipients. We feature the status, outcomes, surgical procedure, portal venous decompression, anesthetic management, prevention of acute kidney injury, avoidance of blood transfusion, monitoring and therapeutic strategies of hemodynamic derangements, and Enhanced Recovery After Surgery protocols for liver transplant recipients.

Appraisal of Cardiac Ejection Fraction With Liver Disease Severity: Implication in Post-Liver Transplantation Mortality.

BACKGROUND AND AIMS: Enhanced sympathetic nervous activation and peripheral vasodilation in end-stage liver disease (ESLD) may limit the importance of left ventricular ejection fraction (LVEF) as an influential prognosticator. We sought to understand the LVEF and cardiac dimensions in ESLD patients in order to define the LVEF threshold to predict all-cause mortality after liver transplantation (LT). APPROACH AND RESULTS: Data were collected prospectively from the Asan LT Registry between 2008 and 2016, and outcomes were retrospectively reviewed. LVEF, end-diastolic volume index (EDVI), and end-diastolic elastance (Eed) were measured by preoperative echocardiography. Of 2,799 patients, 452 (16.2%) had LVEF ≤ 60%, with 29 (1.0%) having LVEF < 55% and 269 (9.6%) had LVEF ≥ 70%. Over a median of 5.4-year follow-up, 329 (11.8%) patients died: 104 (3.7%) died within 90 days. LVEF (range, 30%-81%) was directly proportionate to Model for End-stage Liver Disease (MELD) scores, an index of liver disease severity, in survivors but showed a fixed flat-line pattern in nonsurvivors (interaction P = 0.004 between groups), with lower EDVI (P = 0.013) and higher Eed (P = 0.001) in the MELD ≥ 20 group. Patients with LVEF ≤ 60% had higher 90-day (13% vs. 7.4%; log rank, P = 0.03) and median 5.4-year (26.7% vs. 16.2%; log rank, P = 0.003) mortality rates in the MELD ≥ 20 group, respectively, compared to those with LVEF > 60%. Specifically, in the MELD > 35 group, median 5.4-year mortality rate was 53.3% in patients with LVEF ≤ 60% versus 24% in those with LVEF > 60% (log rank P < 0.001). By contrast, mortality rates of LVEF ≤ 60% and > 60% were similar in the MELD < 20 group (log rank P = 0.817). CONCLUSIONS: LVEF ≤ 60% is strongly associated with higher post-LT mortality rates in the MELD ≥ 20 group, indicating the need to appraise both LVEF and liver disease severity simultaneously. Enhanced diastolic elastance with low EDVI provides insights into pathogenesis of low LVEF in nonsurvivors with MELD ≥ 20.

Clinical impact of mild to moderate pulmonary hypertension in living-donor liver transplantation.

Severe pulmonary hypertension (PHT) is a contraindication to liver transplantation (LT); however, the prognostic implication of mild to moderate PHT in living-donor LT (LDLT) is unknown. The study cohort retrospectively included 1307 patients with liver cirrhosis who underwent LDLT. PHT was defined as a mean pulmonary artery pressure (PAP) of ≥25 mmHg, measured intraoperatively just before surgery. The primary endpoint was graft failure within 1 year after LDLT, including retransplantation or death from any cause. The secondary endpoints were in-hospital adverse events. In the overall cohort, the median Model for End-stage Liver Disease-Sodium (MELD-Na) score was 19, and 100 patients (7.7%) showed PHT. During 1-year follow-up, graft failure occurred in 94 patients (7.2%). Patients with PHT had lower 1-year graft survival (86% vs. 93.4%, P = 0.005) and survival rates (87% vs. 93.6%, P = 0.011). Mean PAP was associated with a high risk of in-hospital adverse events and 1-year graft failure. Adding the mean PAP to the clinical risk model improved the risk prediction. In conclusion, mild to moderate PHT was associated with higher risks of 1-year graft failure and in-hospital events, including mortality after LDLT in patients with liver cirrhosis. Intraoperative mean PAP can help predict the early clinical outcomes after LDLT.

Markedly prolonged QTc interval in end-stage liver disease and risk of 30-day cardiovascular event after liver transplant.

BACKGROUND AND AIM: The proportional increase of corrected QT interval (QTc) along end-stage liver disease (ESLD) severity may lead to inconsistent outcome reporting if based on conventional threshold of prolonged QTc. We investigated the comprehensive QTc distribution among ESLD patients and assessed the association between QTc > 500 ms, a criterion for diagnosing severe long-QT syndrome, and the 30-day major adverse cardiovascular event (MACE) after liver transplantation (LT) and identified the risk factors for developing QTc > 500 ms. METHODS: Data were collected prospectively from the Asan LT Registry between 2011 and 2018, and outcomes were retrospectively reviewed. Multivariable analysis and propensity score-weighted adjusted odds ratios (ORs) were calculated. Thirty-day MACEs were defined as the composite of cardiovascular mortality, arrhythmias, myocardial infarction, pulmonary thromboembolism, and/or stroke. RESULTS: Of 2579 patients, 194 (7.5%) had QTc > 500 ms (QTc500_Group), and 1105 (42.8%) had prolonged QTc (QTcP_Group), defined as QTc > 470 ms for women and >450 ms for men. The 30-day MACE occurred in 336 (13%) patients. QTc500_Group showed higher 30-day MACE than did those without (20.1% vs 12.5%, P = 0.003), with corresponding adjusted OR of 1.24 (95% CI: 1.06-1.46, P = 0.007). However, QTcP_Group showed comparable 30-day MACE (13.3% vs 12.8% without prolonged QTc, P = 0.764). Significant risk factors for QTc > 500 ms development were advanced liver disease, female sex, hypokalemia, hypocalcemia, high left ventricular end-diastolic volume, and tachycardia. CONCLUSION: Our results revealed that, among ESLD patients, a novel threshold of QTc > 500 ms was associated with post-LT 30-day MACE but not with conventional threshold, indicating that a longer QTc threshold should be considered for this unique patient population.

Effect of Remote Ischemic Preconditioning Conducted in Living Liver Donors on Postoperative Liver Function in Donors and Recipients Following Liver Transplantation: A Randomized Clinical Trial.

OBJECTIVE: This study aimed to assess the effects of remote ischemic preconditioning (RIPC) on liver function in donors and recipients after living donor liver transplantation (LDLT). BACKGROUND: Ischemia reperfusion injury (IRI) is known to be associated with graft dysfunction after liver transplantation. RIPC is used to lessen the harmful effects of IRI. METHODS: A total of 148 donors were randomly assigned to RIPC (n = 75) and control (n = 73) groups. RIPC involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to the upper arm, followed by 5-minute reperfusion with cuff deflation. The primary aim was to assess postoperative liver function in donors and recipients and the incidence of early allograft dysfunction and graft failure in recipients. RESULTS: RIPC was not associated with any differences in postoperative aspartate aminotransferase (AST) and alanine aminotransferase levels after living donor hepatectomy, and it did not decrease the incidence of delayed graft hepatic function (6.7% vs 0.0%, P = 0.074) in donors. AST level on postoperative day 1 [217.0 (158.0, 288.0) vs 259.5 (182.0, 340.0), P = 0.033] and maximal AST level within 7 postoperative days [244.0 (167.0, 334.0) vs 296.0 (206.0, 395.5), P = 0.029) were significantly lower in recipients who received a preconditioned graft. No differences were found in the incidence of early allograft dysfunction (4.1% vs 5.6%, P = 0.955) or graft failure (1.4% vs 5.6%, P = 0.346) among recipients. CONCLUSIONS: RIPC did not improve liver function in living donor hepatectomy. However, RIPC performed in liver donors may be beneficial for postoperative liver function in recipients after living donor liver transplantation.

Risk stratification of myocardial injury after liver transplantation in patients with computed tomographic coronary angiography-diagnosed coronary artery disease.

We aimed to determine if the severity of computed tomographic coronary angiography (CTCA)-diagnosed coronary artery disease (CAD) is associated with postliver transplantation (LT) myocardial infarction (MI) within 30 days and early mortality. We retrospectively evaluated 2118 consecutive patients who underwent CAD screening using CTCA. Post-LT type-2 MI, elicited by oxygen supply-and-demand mismatch within a month after LT, was assessed according to the severity of CTCA-diagnosed CAD. Obstructive CAD (>50% narrowing, 9.2% prevalence) was identified in 21.7% of patients with 3 or more known CAD risk factors of the American Heart Association. Post-LT MI occurred in 60 (2.8%) of total patients in whom 90-day mortality rate was 16.7%. Rates of post-LT MI were 2.1%, 3.1%, 3.4%, 4.3%, and 21.4% for normal, nonobstructive CAD, and 1-, 2-, and 3-vessel obstructive CAD, respectively. Two-vessel or 3-vessel obstructive CAD showed a 4.9-fold higher post-LT MI risk compared to normal coronary vessels. The sensitivity and negative predictive value of obstructive CAD in detecting post-LT MI were, respectively, 20% and 97.5%. In conclusion, negative CTCA finding in suspected patients can successfully exclude post-LT MI, whereas proceeding with invasive angiography is needed to further risk-stratify in patients with significant CTCA-diagnosed CAD. Prognostic role of CTCA in predicting post-LT MI needs further research.

Neutrophil-to-lymphocyte ratio is a predictor of early graft dysfunction following living donor liver transplantation.

BACKGROUND & AIMS: Early allograft dysfunction (EAD) is predictive of poor graft and patient survival following living donor liver transplantation (LDLT). Considering the impact of the inflammatory response on graft injury extent following LDLT, we investigated the association between neutrophil-to-lymphocyte ratio (NLR) and EAD, 1-year graft failure, and mortality following LDLT, and compared it to C-reactive protein (CRP), procalcitonin, platelet-to-lymphocyte ratio and the Glasgow prognostic score. METHODS: A total of 1960 consecutive adult LDLT recipients (1531/429 as development/validation cohort) were retrospectively evaluated. Cut-offs were derived using the area under the receiver operating characteristic curve (AUROC), and multivariable regression and Cox proportional hazard analyses were performed. RESULTS: The risk of EAD increased proportionally with increasing NLR, and the NLR AUROC was 0.73, similar to CRP and procalcitonin and higher than the rest. NLR ≥ 2.85 (best cut-off) showed a significantly higher EAD occurrence (20.5% vs 5.8%, P < 0.001), higher 1-year graft failure (8.2% vs 4.9%, log-rank P = 0.009) and higher 1-year mortality (7% vs 4.5%, log-rank P = 0.039). NLR ≥ 2.85 was an independent predictor of EAD (odds ratio, 1.89 [1.26-2.84], P = 0.002) after multivariable adjustment, whereas CRP and procalcitonin were not. Increasing NLR was independently associated with higher 1-year graft failure and mortality (both P < 0.001). Consistent results in the validation cohort strengthened the prognostic value of NLR. CONCLUSIONS: Preoperative NLR ≥ 2.85 predicted higher risk of EAD, 1-year graft failure and 1-year mortality following LDLT, and NLR was superior to other parameters, suggesting that preoperative NLR may be a practical index for predicting graft function following LDLT.

Remote Ischemic Preconditioning and Diazoxide Protect from Hepatic Ischemic Reperfusion Injury by Inhibiting HMGB1-Induced TLR4/MyD88/NF-κB Signaling.

Remote ischemic preconditioning (RIPC) is known to have a protective effect against hepatic ischemia-reperfusion (IR) injury in animal models. However, the underlying mechanism of action is not clearly understood. This study examined the effectiveness of RIPC in a mouse model of hepatic IR and aimed to clarify the mechanism and relationship of the ATP-sensitive potassium channel (KATP) and HMGB1-induced TLR4/MyD88/NF-κB signaling. C57BL/6 male mice were separated into six groups: (i) sham-operated control, (ii) IR, (iii) RIPC+IR, (iv) RIPC+IR+glyburide (KATP blocker), (v) RIPC+IR+diazoxide (KATP opener), and (vi) RIPC+IR+diazoxide+glyburide groups. Histological changes, including hepatic ischemia injury, were assessed. The levels of circulating liver enzymes and inflammatory cytokines were measured. Levels of apoptotic proteins, proinflammatory factors (TLR4, HMGB1, MyD88, and NF-κB), and IκBα were measured by Western blot and mRNA levels of proinflammatory cytokine factors were determined by RT-PCR. RIPC significantly decreased hepatic ischemic injury, inflammatory cytokine levels, and liver enzymes compared to the corresponding values observed in the IR mouse model. The KATP opener diazoxide + RIPC significantly reduced hepatic IR injury demonstrating an additive effect on protection against hepatic IR injury. The protective effect appeared to be related to the opening of KATP, which inhibited HMGB1-induced TRL4/MyD88/NF-kB signaling.

The Impact of Postreperfusion Syndrome on Acute Kidney Injury in Living Donor Liver Transplantation: A Propensity Score Analysis.

BACKGROUND: Postreperfusion syndrome (PRS) has been shown to be related to postoperative morbidity and graft failure in orthotopic liver transplantation. To date, little is known about the impact of PRS on the prevalence of postoperative acute kidney injury (AKI) and the postoperative outcomes after living donor liver transplantation (LDLT). The purpose of our study was to determine the impact of PRS on AKI and postoperative outcomes after LDLT surgery. METHODS: Between January 2008 and October 2015, we retrospectively collected and evaluated the records of 1865 patients who underwent LDLT surgery. We divided the patients into 2 groups according to the development of PRS: PRS group (n = 715) versus no PRS group (n = 1150). Risk factors for AKI and mortality were investigated by multivariable logistic and Cox proportional hazards regression model analysis. Propensity score (PS) analysis (PS matching and inverse probability of treatment weighting analysis) was designed to compare the outcomes between the 2 groups. RESULTS: The prevalence of PRS and the mortality rate were 38% and 7%, respectively. In unadjusted analyses, the PRS group showed more frequent development of AKI (P < .001), longer hospital stay (P = .010), and higher incidence of intensive care unit stay over 7 days (P < .001) than the no PRS group. After PS matching and inverse probability of treatment weighting analysis, the PRS group showed a higher prevalence of postoperative AKI (P = .023 and P = .017, respectively) and renal dysfunction 3 months after LDLT (P = .036 and P = .006, respectively), and a higher incidence of intensive care unit stay over 7 days (P = .014 and P = .032, respectively). CONCLUSIONS: We demonstrated that the magnitude and duration of hypotension caused by PRS is a factor contributing to the development of AKI and residual renal dysfunction 3 months after LDLT.

Impact of Inhalational Anesthetics on Liver Regeneration After Living Donor Hepatectomy: A Propensity Score-Matched Analysis.

BACKGROUND: Although desflurane and sevoflurane, the most commonly used inhalational anesthetics, have been linked to postoperative liver injury, their impact on liver regeneration remains unclear. We compared the influence of these anesthetics on the postoperative liver regeneration index (LRI) after living donor hepatectomy (LDH). METHODS: We conducted a retrospective chart review of 1629 living donors who underwent right hepatectomy for LDH between January 2008 and August 2016. The patients were divided into sevoflurane (n = 1206) and desflurane (n = 423) groups. Factors associated with LRI were investigated using multivariable logistic regression analysis. Propensity score matching analysis compared early (1 postoperative week) and late (within 1-2 months) LRIs and delayed recovery of hepatic function between the 2 groups. RESULTS: The mean early and late LRIs in the 1629 patients were 63.3% ± 41.5% and 93.7% ± 48.1%, respectively. After propensity score matching (n = 403 pairs), there were no significant differences in early and late LRIs between the sevoflurane and desflurane groups (early LRI: 61.2% ± 41.5% vs 58.9% ± 42.4%, P = .438; late LRI: 88.3% ± 44.3% vs 94.6% ± 52.4%, P = .168). Male sex (regression coefficient [ß], 4.6; confidence interval, 1.6-7.6; P = .003) and remnant liver volume (ß, -4.92; confidence interval, -5.2 to -4.7; P < .001) were associated with LRI. The incidence of delayed recovery of hepatic function was 3.6% (n = 29) with no significant difference between the 2 groups (3.0% vs 4.2%, P = .375) after LDH. CONCLUSIONS: Both sevoflurane and desflurane can be safely used without affecting liver regeneration and delaying liver function recovery after LDH.

Effect of ventriculo-arterial coupling on transplant outcomes in cirrhotics: Analysis of pressure-volume curve relations.

BACKGROUND & AIMS: Ventriculo-arterial coupling (VAC) reflects the interaction between ventricular performance and effective arterial load. Current criteria for cirrhotic cardiomyopathy focus only on cardiac function without addressing the effect of hyperdynamic, low-resistance circulation. We investigated alterations in VAC in cirrhotic patients and their associations with post-liver transplant all-cause mortality. METHODS: In this single institution cohort study, cirrhotic patients who underwent liver transplantation (LT) (n=914) were retrospectively compared with healthy matched controls using noninvasively measured end-systolic ventricular elastance (Ees), arterial elastance (Ea), and VAC (Ea/Ees). All-cause mortality based on VAC values were investigated using a Cox hazard model with the inverse probability treatment weighting (IPTW) of propensity score. RESULTS: Cirrhotic patients had significantly lower Ees, Ea and VAC values than controls. Over a median of 30months, 96 patients died after LT. In patients with a high model for end-stage liver disease score (⩾25), VAC of >0.61 (highest tertile) had poorer survival outcomes than patients with VAC of ⩽0.50 (lowest tertile) (66.0% vs. 91.8%; Log-rank p=0.001), and was independently associated with risk of mortality (hazard ratio, 2.44; 95% CI, 1.10-5.39; p=0.028) compared with VAC of ⩽0.61 after IPTW adjustment. CONCLUSIONS: In cirrhotic patients, ventricular elastance and VAC values are lower than those in controls. However, in advanced cirrhotic patients, an increase in VAC value is associated with all-cause mortality after LT, suggesting that this non-invasive estimation of ventriculo-arterial uncoupling is an additional novel prognosticator in cirrhotic cardiovascular disorders. LAY SUMMARY: In cirrhotic patients, cardiac dysfunction is latent and only manifests under stressful conditions because of arterial vasodilation. In this study, based on the pressure-volume curve of cardiac function, we investigated characteristics of the ventricular-arterial coupling in cirrhotic patients and further found that disparities in the ventriculo-arterial relationship are associated with graft failure and all-cause mortality after liver transplantation.