Endoscopic Hyperspectral Imaging System to Discriminate Tissue Characteristics in Tissue Phantom and Orthotopic Mouse Pancreatic Tumor Model.

In this study, we developed an endoscopic hyperspectral imaging (eHSI) system and evaluated its performance in analyzing tissues within tissue phantoms and orthotopic mouse pancreatic tumor models. Our custom-built eHSI system incorporated a liquid crystal tunable filter. To assess its tissue discrimination capabilities, we acquired images of tissue phantoms, distinguishing between fat and muscle regions. The system underwent supervised training using labeled samples, and this classification model was then applied to other tissue phantom images for evaluation. In the tissue phantom experiment, the eHSI effectively differentiated muscle from fat and background tissues. The precision scores regarding fat tissue classification were 98.3% for the support vector machine, 97.7% for the neural network, and 96.0% with a light gradient-boosting machine algorithm, respectively. Furthermore, we applied the eHSI system to identify tumors within an orthotopic mouse pancreatic tumor model. The F-score of each pancreatic tumor-bearing model reached 73.1% for the KPC tumor model and 63.1% for the Pan02 tumor models. The refined imaging conditions and optimization of the fine-tuning of classification algorithms enhance the versatility and diagnostic efficacy of eHSI in biomedical applications.

Postoperative alterations in ventriculoarterial coupling are an indicator of cardiovascular outcomes in liver transplant recipients.

BACKGROUND: Liver transplantation (LT) increases the heart and vessel workload in patients with cirrhotic cardiomyopathy. While the interaction of the left ventricle (LV) with the arterial system (ventriculoarterial coupling, VAC) is a key determinant of cardiovascular performance, little is known about changes in VAC after LT. Therefore, we evaluated the relationship between VAC after LT and cardiovascular outcomes. METHODS: 344 consecutive patients underwent echocardiographic assessments before and within 30 days after LT. Non-invasive arterial elastance (Ea), LV end-systolic elastance (Ees), and LV end-diastolic elastance (Eed) were calculated. The postoperative outcomes included the development of major adverse cardiovascular events (MACE) and the length of stay in the intensive care unit and hospital. RESULTS: A total of 240 patients were included in the analyses. After LT, Ea increased by 16% (P < 0.001), and Ees and contractility index of systolic velocity (S') increased by 18% (P < 0.001) and 7% (P < 0.001), respectively. The Eed increased by 6% (P < 0.001). The VAC remained unchanged (0.56 to 0.56, P = 0.912). Of these patients, 29 had MACE, and those with MACE had significantly higher postoperative VAC. Additionally, a higher postoperative VAC was an independent risk factor for a longer postoperative hospital stay (P = 0.038). CONCLUSIONS: These data suggest that ventriculoarterial decoupling is associated with poor postoperative outcomes after LT.

Korean clinical practice guidelines for diagnostic and procedural sedation.

Safe and effective sedation depends on various factors, such as the choice of sedatives, sedation techniques used, experience of the sedation provider, degree of sedation-related education and training, equipment and healthcare worker availability, the patient's underlying diseases, and the procedure being performed. The purpose of these evidence-based multidisciplinary clinical practice guidelines is to ensure the safety and efficacy of sedation, thereby contributing to patient safety and ultimately improving public health. These clinical practice guidelines comprise 15 key questions covering various topics related to the following: the sedation providers; medications and equipment available; appropriate patient selection; anesthesiologist referrals for high-risk patients; pre-sedation fasting; comparison of representative drugs used in adult and pediatric patients; respiratory system, cardiovascular system, and sedation depth monitoring during sedation; management of respiratory complications during pediatric sedation; and discharge criteria. The recommendations in these clinical practice guidelines were systematically developed to assist providers and patients in sedation-related decision making for diagnostic and therapeutic examinations or procedures. Depending on the characteristics of primary, secondary, and tertiary care institutions as well as the clinical needs and limitations, sedation providers at each medical institution may choose to apply the recommendations as they are, modify them appropriately, or reject them completely.

Neutrophilia is more predictive than increased white blood cell counts for short-term mortality after liver transplantation in patients with acute-on-chronic liver failure.

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.

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.

Characterizing Heart Failure With Preserved Ejection Fraction in End-Stage Liver Disease and Liver Transplant Outcomes.

Background: Heart failure with preserved ejection fraction (HFpEF) and its risk factors are increasingly recognized in patients with end-stage liver disease (ESLD). Objectives: The aim of this study was to characterize HFpEF and identify relevant risk factors in patients with ESLD. Additionally, the prognostic impact of high-probability HFpEF on post-liver transplantation (LT) mortality was investigated. Methods: Patients with ESLD prospectively enrolled from the Asan LT Registry between 2008 and 2019 were divided into groups with low (scores of 0 and 1), intermediate (scores of 2-4), and high (scores of 5 and 6) probability using the Heart Failure Association-PEFF diagnostic score for HFpEF. Gradient-boosted modeling in machine learning was further used to appraise the apparent importance of risk factors. Finally, post-LT all-cause mortality was followed for 12.8 years (median 5.3 years); there were 498 deaths after LT. Results: Among the 3,244 patients, 215 belonged to the high-probability group, commonly those with advanced age, female sex, anemia, dyslipidemia, renal dysfunction, and hypertension. The highest risk factors for the high-probability group, according to gradient-boosted modeling, were female sex, anemia, hypertension, dyslipidemia, and age >65 years. Among patients with Model for End-Stage Liver Disease scores of >30, those with high, intermediate, and low probability had cumulative overall survival rates of 71.6%, 82.2%, and 88.9% at 1 year and 54.8%, 72.1%, and 88.9% at 12 years after LT (log-rank P = 0.026), respectively. Conclusions: High-probability HFpEF was found in 6.6% of patients with ESLD with poorer long-term post-LT survival, especially those with advanced stages of liver disease. Therefore, identifying HFpEF using the Heart Failure Association-PEFF score and addressing modifiable risk factors can improve post-LT survival.

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 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.

A look into hemostatic characteristics during pediatric liver transplantation using the thromboelastometry (ROTEM® ) test.

There is a paucity of evidence about the coagulation profile regarding the complexity of children undergoing liver transplantation (LT). This study aimed to investigate intraoperative hemostatic changes during pediatric LT according to the etiology for LT and examine the ability of rotational thromboelastometry (ROTEM® , TEM International GmbH, Munich, Germany) as a point-of-care monitoring method. We evaluated 106 patients aged 3 months to 17 years undergoing LT for acute liver failure (ALF) and chronic liver disease, which consists of patients with cholestatic disease, metabolic/genetic disease, and cancer. A total of 731 ROTEM® measurements, including 301 ellagic acid to initiate clotting via the intrinsic pathway, 172 tissue factor to initiate the extrinsic clotting cascade (EXTEM), and 258 cytochalasin D to inhibit platelet activity reflecting fibrinogen (FIBTEM), were analyzed at predetermined time points (the preanhepatic, anhepatic, and postreperfusion phases). We simultaneously conducted conventional coagulation tests. In children with ALF, preanhepatic measurements of conventional coagulation tests and ROTEM® showed a more hypocoagulable state than other diseases. During LT, the coagulation profile was deranged, with a prolonged clotting time and reduced clot firmness, changes that were more profound in the cholestatic disease group. Maximum clot firmness (MCF) on EXTEM and FIBTEM were well correlated with the platelet count and fibrinogen concentration (r = 0.830, p < 0.001 and r = 0.739, p < 0.001, respectively). On the EXTEM, MCF with 30 mm predicted a platelet count <30,000/mm3 (area under the curve, 0.985), and 6 mm predicted a fibrinogen concentration <100 mg/dl on the FIBTEM (area under the curve, 0.876). However, the activated partial thromboplastin time and prothrombin time were significant but only weakly correlated with the clotting time on the ROTEM® . In children undergoing LT, coagulation profiles depend on the etiology for LT. During LT, ROTEM® parameters could help detect thrombocytopenia and hypofibrinogenemia and guide transfusion therapy as a point-of-care monitoring method.

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.

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.

Low Preoperative Antithrombin III Level Is Associated with Postoperative Acute Kidney Injury after Liver Transplantation.

We aimed to determine the association between the preoperative antithrombin III (ATIII) level and postoperative acute kidney injury (AKI) after LT (post-LT AKI). We retrospectively evaluated 2395 LT recipients between 2010 and 2018 whose data of perioperative ATIII levels were available. Patients were divided into two groups based on the preoperative level of ATIII (ATIII < 50% vs. ATIII ≥ 50%). Multivariable regression analysis was performed to assess the risk factors for post-LT AKI. The mean preoperative ATIII levels were 30.2 ± 11.8% in the ATIII < 50% group and 67.2 ± 13.2% in the ATIII ≥ 50% group. The incidence of post-LT AKI was significantly lower in the ATIII ≥ 50% group compared to that in the ATIII < 50% group (54.7% vs. 75.5%, p < 0.001); odds ratio (OR, per 10% increase in ATIII level) 0.86, 95% confidence interval (CI) 0.81-0.92; p < 0.001. After a backward stepwise regression model, female sex, high body mass index, low albumin, deceased donor LT, longer duration of surgery, and high red blood cell transfusion remained significantly associated with post-LT AKI. A low preoperative ATIII level is associated with post-LT AKI, suggesting that preoperative ATIII might be a prognostic factor for predicting post-LT AKI.

Association between Neutrophil-Lymphocyte Ratio and Herpes Zoster Infection in 1688 Living Donor Liver Transplantation Recipients at a Large Single Center.

Liver transplantation (LT) is closely associated with decreased immune function, a contributor to herpes zoster (HZ). However, risk factors for HZ in living donor LT (LDLT) remain unknown. Neutrophil-lymphocyte ratio (NLR) and immune system function are reportedly correlated. This study investigated the association between NLR and HZ in 1688 patients who underwent LDLT between January 2010 and July 2020 and evaluated risk factors for HZ and postherpetic neuralgia (PHN). The predictive power of NLR was assessed through the concordance index and an integrated discrimination improvement (IDI) analysis. Of the total cohort, 138 (8.2%) had HZ. The incidence of HZ after LT was 11.2 per 1000 person-years and 0.1%, 1.3%, 2.9%, and 13.5% at 1, 3, 5, and 10 years, respectively. In the Cox regression analysis, preoperative NLR was significantly associated with HZ (adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.09; p = 0.005) and PHN (HR, 1.08; 95% CI, 1.03-1.13; p = 0.001). Age, sex, mycophenolate mofetil use, and hepatitis B virus infection were risk factors for HZ versus age and sex for PHN. In the IDI analysis, NLR was discriminative for HZ and PHN (p = 0.020 and p = 0.047, respectively). Preoperative NLR might predict HZ and PHN in LDLT recipients.

Changes in Left Ventricular Ejection Fraction after Mitral Valve Repair for Primary Mitral Regurgitation.

This study sought to identify the short- and long-term changes in left ventricular ejection fraction (LVEF) after mitral valve repair (MVr) in patients with chronic primary mitral regurgitation according to preoperative LVEF (pre-LVEF) and preoperative left ventricular end-systolic diameter (pre-LVESD). This study evaluated 461 patients. Restricted cubic spline regression models were constructed to demonstrate the long-term changes in postoperative LVEF (post-LVEF). The patients were divided into four groups according to pre-LVEF (<50%, 50-60%, 60-70%, and ≥70%). The higher the pre-LVEF was, the greater was the decrease in LVEF immediately after MVr. In the same pre-LVEF range, immediate post-LVEF was lower in patients with pre-LVESD ≥ 40 mm than in those with pre-LVESD < 40 mm. The patterns of long-term changes in post-LVEF differed according to pre-LVEF (p for interaction < 0.001). The long-term post-LVEF reached a plateau of approximately 60% when the pre-LVEF was ≥50%, but it seemed to show a downward trend after reaching a peak at approximately 3-4 years after MVr when the pre-LVEF was ≥70%. The patterns of short- and long-term changes in post-LVEF differed according to pre-LVEF and pre-LVESD values in patients with chronic primary mitral regurgitation after MVr.

Association of Preoperative Prognostic Nutritional Index and Postoperative Acute Kidney Injury in Patients Who Underwent Hepatectomy for Hepatocellular Carcinoma.

Various biological indicators are reportedly associated with postoperative acute kidney injury (AKI) in the surgical treatment of hepatocellular carcinoma (HCC). However, only a few studies have evaluated the association between the preoperative prognostic nutritional index (PNI) and postoperative AKI. This study evaluated the association of the preoperative PNI and postoperative AKI in HCC patients. We retrospectively analyzed 817 patients who underwent open hepatectomy between December 2007 and December 2015. Multivariate regression analysis was performed to evaluate the association between the PNI and postoperative AKI. Additionally, we evaluated the association between the PNI and outcomes such as postoperative renal replacement therapy (RRT) and mortality. Cox regression analysis was performed to assess the risk factors for one-year and five-year mortality. In the multivariate analysis, high preoperative PNI was significantly associated with a lower incidence of postoperative AKI (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.85 to 0.99, p = 0.021). Additionally, diabetes mellitus and the use of synthetic colloids were significantly associated with postoperative AKI. PNI was associated with postoperative RRT (OR: 0.76, 95% CI: 0.60 to 0.98, p = 0.032) even after adjusting for other potential confounding variables. In the Cox regression analysis, high PNI was significantly associated with low one-year mortality (Hazard ratio (HR): 0.87, 95% CI: 0.81 to 0.94, p < 0.001), and five-year mortality (HR: 0.93, 95% CI: 0.90-0.97, p < 0.001). High preoperative PNI was significantly associated with a lower incidence of postoperative AKI and low mortality. These results suggest that the preoperative PNI might be a predictor of postoperative AKI and surgical prognosis in HCC patients undergoing open hepatectomy.

Rupture Risk of Intracranial Aneurysm and Prediction of Hemorrhagic Stroke after Liver Transplant.

Postoperative hemorrhagic stroke (HS) is a rare yet devastating complication after liver transplantation (LT). Unruptured intracranial aneurysm (UIA) may contribute to HS; however, related data are limited. We investigated UIA prevalence and aneurysmal subarachnoid hemorrhage (SAH) and HS incidence post-LT. We identified risk factors for 1-year HS and constructed a prediction model. This study included 3544 patients who underwent LT from January 2008 to February 2019. Primary outcomes were incidence of SAH, HS, and mortality within 1-year post-LT. Propensity score matching (PSM) analysis and Cox proportional hazard analysis were performed. The prevalence of UIAs was 4.63% (n = 164; 95% confidence interval (CI), 3.95-5.39%). The 1-year SAH incidence was 0.68% (95% CI, 0.02-3.79%) in patients with UIA. SAH and HS incidence and mortality were not different between those with and without UIA before and after PSM. Cirrhosis severity, thrombocytopenia, inflammation, and history of SAH were identified as risk factors for 1-year HS. UIA presence was not a risk factor for SAH, HS, or mortality in cirrhotic patients post-LT. Given the fatal impact of HS, a simple scoring system was constructed to predict 1-year HS risk. These results enable clinical risk stratification of LT recipients with UIA and help assess perioperative HS risk before LT.

Over 500 Liver Transplants Including More Than 400 Living-Donor Liver Transplants in 2019 at Asan Medical Center.

BACKGROUND: More than 400 liver transplants were performed at Asan Medical Center (AMC) in 2011, and over 500 liver transplants including 420 living-donor liver transplants (LDLTs) were performed in 2019. Herein, we report the methodology of these procedures. METHODS: Since the first adult LDLTs at AMC using the left and right lobes were successfully performed, various innovative techniques and approaches have been developed: modified right lobe, dual graft, donor exchange for ABO incompatibility, expansion of indications and no-touch techniques for hepatocellular carcinoma, intraoperative cine-portogram and additional intervention for large collaterals, management of portal vein thrombosis (PVT) and stenosis, salvage LDLT after major hepatectomy, and timely LDLT for patients with acute-on-chronic liver failure. RESULTS: Four hundred twenty LDLTs in 403 adult and 17 pediatric patients and 85 deceased-donor liver transplants in 74 adult and 11 pediatric patients were performed. The number of deceased-donor liver transplants remained constant since 2011, but the number of LDLTs increased steadily. One hundred thirty patients (25.7%) required urgent liver transplantations and 24 patients with acute-on-chronic liver failure underwent LDLT. PVT including grade 1,2,3, and 4 was reported in 91 patients (18.0%), and Yerdel's grade 2, 3, and 4 PVT was reported in 47 patients (51.6%); all patients with PVT were successfully treated. Adult LDLTs for hepatocellular carcinoma and ABO incompatibility accounted for 52.6% and 24.3% of the cases, respectively. In-hospital mortality in 2019 was 2.97%. CONCLUSION: Continual efforts to overcome challenging problems in LDLT with various innovations and dedication of the team members during the perioperative period to improve patient outcomes were crucial in increasing the number of liver transplantations at Asan Medical Center.

Preoperative high-sensitivity troponin I and B-type natriuretic peptide, alone and in combination, for risk stratification of mortality after liver transplantation.

BACKGROUND: Given the severe shortage of donor liver grafts, coupled with growing proportion of cardiovascular death after liver transplantation (LT), precise cardiovascular risk assessment is pivotal for selecting recipients who gain the greatest survival benefit from LT surgery. We aimed to determine the prognostic value of pre-LT combined measurement of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI) in predicting early post-LT mortality. METHODS: We retrospectively evaluated 2,490 consecutive adult LT patients between 2010 and 2018. Cut-off values of BNP and hsTnI for predicting post-LT 90-day mortality were calculated. According to the derived cut-off values of two cardiac biomarkers, alone and in combination, adjusted hazard ratios (aHR) of post-LT 90-day mortality were determined using multivariate Cox regression analysis. RESULTS: Mortality rate after 90 days was 2.9% (72/2,490). Rounded cut-off values for post-LT 90-day mortality were 400 pg/ml for BNP (aHR 2.02 [1.15, 3.52], P = 0.014) and 60 ng/L for hsTnI (aHR 2.65 [1.48, 4.74], P = 0.001), respectively. Among 273 patients with BNP ≥ 400 pg/ml, 50.9% of patients were further stratified into having hsTnI ≥ 60 ng/L. Combined use of pre-LT cardiac biomarkers predicted post-LT 90-day mortality rate; both non-elevated: 1.0% (21/2,084), either one is elevated: 9.0% (24/267), and both elevated: 19.4% (27/139, log-rank P < 0.001; aHR vs non-elevated 4.23 [1.98, 9.03], P < 0.001). CONCLUSIONS: Concomitant elevation of both cardiac biomarkers posed significantly higher risk of 90-day mortality after LT. Pre-LT assessment cardiac strain and myocardial injury, represented by BNP and hsTnI values, would contribute to prioritization of LT candidates and help administer target therapies that could modify early mortality.

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.

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.