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Hepatic estrogen signaling, which is important in liver injury/recovery, is determined by the level of systemic estrogen and hepatic estrogen receptor. We aimed to evaluate whether females' advantage in the tolerance of hepatic ischemia-reperfusion injury decreases according to the age of 40 y (systemic estrogen decrease) and macrosteatosis (hepatic estrogen receptor decrease).We included 358 living liver donors (128 female and 230 male individuals). The tolerance of hepatic ischemia-reperfusion injury was determined by the slope of the linear regression line modeling the relationship between the duration of intraoperative hepatic ischemia and the peak postoperative transaminase level. Estrogen receptor content was measured in the biopsied liver samples using immunohistochemistry.In the whole cohort, the regression slope for aspartate transaminase was comparable between female and male individuals (P = 0.940). Within the subgroup of donors aged ≤40 y, the regression slope was significantly smaller in female individuals (P = 0.031), whereas it was comparable within donors aged40 y (P = 0.867). Within the subgroup of nonmacrosteatotic donors aged ≤40 y, the regression slope was significantly smaller in female individuals in univariable (P = 0.002) and multivariable analysis (P = 0.006), whereas the sex difference was not found within macrosteatotic donors aged ≤40 y (P = 0.685). Estrogen receptor content was significantly greater in female individuals within nonmacrosteatotic donors aged ≤40 y (P = 0.021), whereas it was not different in others of age40 y or with macrosteatosis (P = 0.450).The tolerance of hepatic ischemia-reperfusion injury was greater in female individuals than in male individuals only when they were40 y and without macrosteatosis. The results were in agreement with the hepatic estrogen receptor immunohistochemistry study.

Background Enhancing postoperative recovery of the donor is important to encourage living kidney donation. We investigated the effects of anesthetic agents (intravenous [IV] propofol versus inhaled [IH] sevoflurane) on the quality of early recovery of healthy living kidney donors after hand-assisted laparoscopic nephrectomy (HALN) under analgesic intrathecal morphine injection. Methods This single-center, prospective randomized controlled study enrolled 80 living donors undergoing HALN from October 2019 to June 2020 at Seoul St. Mary’s Hospital. Donors were randomly assigned to the IV propofol group or IH sevoflurane group. To measure the quality of recovery, we used the Korean version of the Quality of Recovery-40 questionnaire (QoR-40 K) on postoperative day (POD) 1, and ambulation (success rate, number of footsteps) 6–12 h after surgery and on POD 1. The pain score for the wound site, IV opioid requirement, postoperative complications including incidences of nausea/vomiting, and length of in-hospital stay were also assessed. Results The global QoR-40 K score and all subscale scores (physical comfort, emotional state, physical independence, psychological support, and pain) were significantly higher in the IV propofol group than in the IH sevoflurane group. The numbers of footsteps at all time points were also higher in the IV propofol group. Donors in the IV propofol group had a lower incidence of nausea/vomiting, and a shorter hospitalization period. Conclusions Total IV anesthesia with propofol led to better early postoperative recovery than that associated with IH sevoflurane. Trial registration Clinical Research Information Service, Republic of Korea (approval number: KCT0004351) on October 18, 2019.

Introduction We evaluated whether second-generation laryngeal mask airway (LMA) could provide an adequate pulmonary gas exchange during prolonged abdominal surgery compared to endotracheal tube (ETT) using propensity score matching. Methods Of the 257 recipients who underwent living donor kidney transplantation (LDKT), the LMA group and ETT group were matched: 87 of 101 recipients who inserted second-generation LMA were matched with 87 of 156 recipients who inserted ETT. Arterial partial pressure of carbon dioxide (PaCO2) and ratio of arterial partial pressure of oxygen to fractional inspired oxygen (PFR) and intraoperative ventilator parameters were compared between the 2 groups. In addition, we compared incidences of postoperative pulmonary and nonpulmonary complications including hoarseness, vocal cord palsy, nausea, vomiting, arrhythmia, and delirium between the 2 groups. Results Median anesthesia time was 357 minutes. PaCO2 and PFR were comparable between the 2 groups and did not show group and time interaction. Ventilator parameters during surgery were comparable, and incidences of both postoperative pulmonary and nonpulmonary complications were also comparable between the 2 groups. Conclusion Second-generation LMA could provide an adequate pulmonary gas exchange compared with ETT during LDKT. In terms of pulmonary gas exchange, second-generation LMA could be considered as a suitable alternative to ETT during prolonged abdominal surgery.

BACKGROUND Prestorage leukoreduction has the advantage over poststorage leukoreduction in reducing leukocyte-derived molecules in red blood cells (RBC) unit, which induce immunomodulation. Our institution newly introduced prestorage leukoreduction, instead of conventional poststorage leukoreduction, for liver transplant recipients since March 2012. In this study, we aimed to evaluate the risk of posttransplant hepatocellular carcinoma (HCC) recurrence after the conversion of poststorage leukoreduction into prestorage leukoreduction for transfused allogeneic RBCs. METHODS Among 220 patients who underwent living-donor liver transplantation for HCC, 83 of 113 who received only poststorage-leukoreduced RBCs were matched with 83 of 107 who received only prestorage-leukoreduced RBCs using 1:1 propensity score matching based on factors like tumor biology. The primary outcome was overall HCC recurrence. Survival analysis was performed with death as a competing risk event. RESULTS In the matched cohort, recurrence probability at 1, 2, and 5 years posttransplant was 9.6%, 15.6%, and 18.1% in prestorage group and 15.6%, 21.6%, and 33.7% in poststorage group (hazard ratio [HR], 0.52; 0.28-0.97; P = 0.040). Multivariable analysis confirmed a significance of prestorage leukoreduction (HR, 0.29; 0.15-0.59; P < 0.001). Overall death risk was also lower with prestorage leukoreduction (HR, 0.51; 0.26-0.99; P = 0.049). In subgroup analysis for the unmatched cohort, recurrence risk was significantly lower in prestorage group within the patients who underwent surgery 2 years (HR, 0.24; 0.10-0.61; P = 0.002), 1 year (HR, 0.16; 0.03-0.92; P = 0.040), and 6 months (HR, 0.13; 0.02-0.85; P = 0.034), respectively, before and after the conversion to prestorage leukoreduction. CONCLUSIONS Our findings suggest a potential benefit of prestorage leukoreduction in reducing the risk of HCC recurrence in liver transplant recipients who received allogeneic RBCs during the perioperative period.

Objective To determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). Background Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. Methods Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74/129 without autotransfusion were matched with 74/220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. Results Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/38.3%/39.7% for non-autotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the two groups in overall recurrence (hazard ratio [HR] = 0.72 [0.43-1.21]), intrahepatic recurrence (HR = 0.70 [0.35-1.40]), and extrahepatic recurrence (HR = 0.82 [0.46-1.47]). Also, there were no significant differences in overall death (HR = 0.57 [0.29-1.12]), HCC-related death (HR = 0.59 [0.29-1.20]), and HCC-unrelated death (HR = 0.48 [0.09-2.65]). Conclusion When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.

Preoperative neutrophil–lymphocyte ratio (NLR), has shown a predictive value in living donor liver transplantation (LDLT). However, the change in the NLR during LDLT has not been fully investigated. We aimed to compare graft survival between the NLR increase and decrease during LDLT. From June 1997 to April 2019, we identified 1292 adult LDLT recipients with intraoperative NLR change. The recipients were divided according to NLR change: 103 (8.0%) in the decrease group and 1189 (92.0%) in the increase group. The primary outcome was graft failure in the first year. In addition, variables associated with NLR change during LDLT were evaluated. During 1-year follow-up, graft failure was significantly higher in the decrease group (22.3% vs. 9.1%; hazard ratio 1.87; 95% confidence interval 1.10–3.18; p = 0.02), but postoperative complications did not differ between two groups. This finding was consistent for the overall follow-up. Variables associated with NLR decrease included preoperative NLR > 4, model for end-stage liver disease score, intraoperative inotropic infusion and red blood cell transfusion, and operative duration. The least absolute shrinkage and selection operator model yielded similar results. NLR decrease during LDLT appeared to be independently associated with graft survival. Further studies are needed to confirm our findings.

This study sought to evaluate the association between newly-developed significant hypercholesterolemia within one year following living donor liver transplantation (LDLT) and long term outcomes in light of cardiovascular events and graft failure. From October 2003 to July 2017, 877 LDLT recipients were stratified according to development of significant hypercholesterolemia within one year following LDLT. The primary outcome was occurrence of a major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction, and coronary revascularization after LDLT. The incidence of graft failure, defined as all-cause death or retransplantation, was also compared. A total of 113 (12.9%) recipients developed significant hypercholesterolemia within one year. The differences in incidences of cardiac related events and graft related events began emerging significantly higher in the hypercholesterolemia group after 24 months and 60 months since the LDLT, respectively. After adjustment using the inverse probability of weighting, the hazard ratio (HR) for MACE was 2.77 (95% confidence interval (CI) 1.16–6.61; p = 0.02), while that for graft failure was 3.76 (95% CI 1.97–7.17, p

Background: Measurement of natural killer (NK) cell function has important clinical utility in several diseases. Although the flow cytometry (FC)-based 4-h NK cytotoxicity assay using peripheral blood mononuclear cells (PBMCs) in the clinical laboratory has been used for this purpose, this assay requires large amounts of blood and a rapid PBMC isolation step. Here, we developed an FC-based overnight NK cytotoxicity assay using whole blood (WB), and applied it to patients with liver diseases. Methods: Peripheral blood of healthy volunteers (n = 28) and patients with liver diseases, including hepatocellular carcinoma (n = 19) and liver cirrhosis (n = 7), was analyzed for complete blood count, absolute NK cell count, and NK cell activity (NKA). NKA was evaluated in three assay types: an FC-based overnight WB NK cytotoxicity assay using carboxyfluorescein diacetate succinimidyl ester-labeled K562 cells in the presence of various cytokine combinations [including interleukin (IL)-2, IL-18, and IL-21], an FC-based 4-h PBMC NK cytotoxicity assay, and an FC-based CD107a degranulation assay using WB and PBMCs. Results: Optimal cytokine combinations for NK cell activation in WB were determined (IL-2/IL-18, IL-2/IL-21, and IL-2/IL-18/IL-21). A good correlation was observed between WB and PBMC NK cytotoxicity assays; absolute NK cell counts were better correlated with the WB NK cytotoxicity assay than with the PBMC NK cytotoxicity assay. This WB NK cytotoxicity assay showed that patients with liver diseases had significantly lower NK cytotoxicity than healthy volunteers, under stimulation with various cytokines (p < 0.001). Conclusion: The proposed FC-based overnight WB NK cytotoxicity assay correlates well with the conventional 4-h PBMC NK cytotoxicity assay, demonstrating future potential as a supportive assay for clinical laboratory research and observational studies.

BACKGROUND: The characteristics of red blood cell (RBC) products change after 2 weeks of cold storage. It is unclear whether older RBCs affect mortality after liver transplantation. This retrospective cohort study aimed to evaluate the association between the age of transfused RBCs and death after living donor liver transplantation (LDLT). STUDY DESIGN AND METHODS: Of 200 recipients who underwent LDLT, 118 who received RBCs with a mean storage duration of less than 10 days (shorter storage group) were compared with 82 with an RBC mean storage duration of more than 14 days (longer storage group). Key exclusion criteria were transfusion of very fresh RBCs stored for less than 4 days and transfusion of old RBCs in recipients of the shorter storage group. The primary outcome was posttransplant overall death. Survival analysis was performed using the Cox model. RESULTS: Mean RBC storage duration was 7 days in the shorter storage group and 17 days in the longer storage group. Death probability at 1, 2, and 5 years posttransplant was 5.1%, 7.6%, and 13.6% in the shorter storage group, respectively, and 6.1%, 8.5%, and 13.5% in the longer storage group. Death risk was comparable between the two groups in univariable (hazard ratio [HR] 1.00, 95% confidence interval [CI], 0.47-2.16, p = 0.991) and multivariable (HR 1.07, 95% CI, 0.46-2.50, p = 0.882) analyses. Graft failure risk was also comparable (HR 1.04, 95% CI, 0.50-2.18, p = 0.916). Hepatocellular carcinoma recurrence probability at 1, 2, and 5 years was 10.8%, 15.4%, and 23.1%, respectively, in the shorter storage group and 11.4%, 15.9%, and 20.7% in the longer storage group (HR 0.84, 95% CI, 0.37-1.89, p = 0.670). No significant differences were observed regarding graft regeneration/function, vascular/biliary complications, acute kidney injury, surgical site infection, or rejection (p > 0.05). CONCLUSIONS: No evidence was found that transfusion of old RBCs contributes to death after LDLT.

Pure laparoscopic donor right hepatectomy (PLDRH) is not a standard procedure for living donor liver transplantation but is safe and reproducible in the hands of experienced surgeons. However, the perioperative outcomes of PLDRH have not been fully evaluated yet. We used propensity score matching to compare the perioperative complications and postoperative short-term outcomes of donors undergoing PLDRH and open donor right hepatectomy (ODRH). A total of 325 consecutive donors who underwent elective, adult-to-adult right hepatectomy were initially screened. After propensity score matching, all patients were divided into two groups: PLDRH (n = 123) and ODRH (n = 123) groups. Perioperative complications and postoperative outcomes were compared between the two groups. Postoperative pulmonary complications were significantly more common in the ODRH than in the PLDRH group (54.5 vs. 31.7%, P P = 0.167). Overall, surgical complication rates were similar between the two groups (P = 0.730). The opioid requirement during the first 7 postoperative days was higher in the ODRH group (686 vs. 568 mg, P P = 0.003 and P

Background Posttransplant liver graft failure occurs most often in male recipients of livers from female donors. The respective role of donor sex itself and the size disparity in graft vessels/bile ducts according to donor sex are unclear. Thus, we aimed to evaluate the importance of donor sex with adjustment for anastomotic size disparity between female and male donor grafts. Methods A total of 309 male patients without hepatic tumors who underwent living donor liver transplantation were analyzed (109 female donors and 200 male donors). The primary outcome was posttransplant graft failure (ie, retransplantation or death). Survival analysis was performed using the Cox model. Analyzed anastomosis-related factors comprised graft weight, number and size of hepatic vessels/bile ducts, and anastomosis techniques. Results Graft failure probabilities at 1, 6, 12, 24, and 60 months posttransplantation were 9.1%, 19.5%, 20.2%, 23.0%, and 27.0%, respectively, with female donors and 2.0%, 5.5%, 8.1%, 10.1%, and 13.5% with male donors (hazards ratio [HR], 2.29; 95% confidence interval [CI], 1.35-3.88; P = 0.002). Multivariable analysis confirmed the significance of donor sex (HR, 2.30; 95% CI, 1.14-4.67; P = 0.021) after adjustment for anastomosis-related factors. All analyzed anastomosis-related factors showed no significant association with graft failure, although size of the graft hepatic artery showed marginal significance (HR, 0.50; 95% CI, 0.25-1.01; P = 0.053). The significance of donor sex was lost when donor was older than 36 to 40 years (age of poor ovarian reserve and the end of female fertility). Our institutional pediatric recipient cohort validated the inferiority of female-to-male donation. Conclusions Donor sex appears to be an independent factor modulating graft failure risk in male liver transplant recipients.

We recently showed that platelet counts and the amount of platelet transfusion during liver transplantation are positively associated with early graft regeneration. It was hypothesized that platelet-derived serotonin mediates liver regeneration.This study aimed to evaluate the association between intraoperative platelet count, platelet transfusion, and serum serotonin level.Thirty-two recipients undergoing living-donor liver transplantation were enrolled into this prospective observational study. Serum platelet counts and serotonin levels were measured at the following times: anesthetic induction, start of the anhepatic phase, before graft reperfusion, 5 minutes/1 hour/3 hours/5 hours after graft reperfusion, and before/after platelet transfusion. Serotonin was measured by using a liquid chromatography tandem mass spectrometry.Serotonin level at the anesthetic induction was 24.5 μg/mL (interquartile range, 14.6 to 38.1 μg/mL). During surgery, serial changes in platelet counts and serotonin levels showed a similar trend: they decreased during the anhepatic phase, increased during the first hour after graft reperfusion, and thereafter gradually decreased. Serotonin level was positively correlated with platelet counts (correlation coefficient = 0.620, P .001). Allogeneic platelet transfusion significantly increased platelet count from 22 (19-31) × 10Our findings indicate that allogeneic platelets could act as effector cells deriving serotonins. Also, our findings support the hypothesis that the association between platelets and post-transplantation graft regeneration is mediated by serotonin. Further studies are warranted regarding the respective role of serotonin and other platelet-derived molecules mediating liver regeneration.

To evaluate the association between sarcopenia and tumor recurrence after living donor liver transplantation (LDLT) in patients with advanced hepatocellular carcinoma (HCC), we analyzed 92 males who underwent LDLT for treating HCC beyond the Milan criteria. Sarcopenia was defined when the height-normalized psoas muscle thickness was

This study aimed to evaluate risk factors and postoperative clinical outcome associated with myocardial injury detected by an elevated high-sensitivity cardiac troponin I (hs-cTnI) immediately after living donor liver transplantation (LDLT).Between January 2011 and December 2016, 313 adult recipients undergoing LDLT, with normal preoperative hs-cTnI were selected. Hs-cTnI level above 0.04 ng/mL according to 99th percentile reference limit was defined as myocardial injury. The recipients were divided into 2 groups according to postoperative hs-cTnI measured immediately after LDLT and postoperative clinical outcome was compared.The primary outcome was composite of death or graft failure during hospital stay. Risk factors associated with myocardial injury during LDLT was also evaluated. Of the 313 recipients with normal preoperative hs-cTnI level, 159 (50.8%) had elevated hs-cTnI level and 154 (49.2%) had normal level after LDLT. The incidence of all-cause death or graft failure during hospital stay was significantly higher in recipients with myocardial injury (1.9% vs 7.6%; hazard ratio, 4.15; 95% confidence interval, 1.01-17.14; P = 0.049). The same result was shown in propensity-matched population (0.9% vs 9.0%; hazard ratio, 9.08; 95% confidence interval, 1.16-71.01; P = 0.04). The results during 1-year follow-up were not consistent. Female sex, ischemia time, and presence of postreperfusion syndrome were independent predictors of myocardial injury during LDLT.Myocardial injury detected by elevation of hs-cTnI level immediately after LDLT was independently associated with adverse outcome during hospital stay.

Objective The aim of this study is to evaluate the association between fresh red blood cell (RBC) transfusion and recipient survival after liver transplantation. Background Fresh RBC products contain many viable leukocytes. Allogeneic leukocytes are responsible for adverse transfusion reactions in the immunocompromised host. Methods Among 343 liver transplant recipients who underwent perioperative RBC transfusion, 91 of 226 who did not receive fresh RBCs were matched with 91 of 117 who received fresh RBCs with 1:1 matching ratio using the propensity score based on the amount of transfused blood products and others. Survival analysis was performed using the Cox model. Results All transfused 3230 RBCs were leukoreduced and irradiated. Before matching, recipients in fresh RBC group received 3 U (2-6 U) of fresh RBCs. After a median follow-up of 60 months, 60 of 343 recipients (17.5%) died. Survival probability at 1/2/5 years after transplantation was 94.7%/92.0%/85.8% for nonfresh RBC group and 82.9%/76.0%/72.0% for fresh RBC group [death hazard ratio (HR) = 2.37 (1.43-3.94), P = 0.001]. In multivariable analysis, fresh RBC transfusion was significantly associated with increased death risk [HR = 2.33 (1.35-4.01), P = 0.002]. After matching, recipients in fresh RBC group received 3 U (2-5 U) of fresh RBCs. After a median follow-up of 56 months, 35 of 182 recipients (19.2%) died. Survival probability at 1/2/5 years was 95.6%/93.2%/86.0% for nonfresh RBC group and 85.7%/78.0%/73.0% for fresh RBC group [HR = 2.23 (1.43-3.94), P = 0.028]. Multivariable analysis confirmed a significance of fresh RBC transfusion [HR = 3.20 (1.51-6.78), P = 0.002]. Conclusion Our findings suggest a potential negative impact of fresh RBC transfusion on the survival of patients undergoing liver transplantation.

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75 × 109 /L were matched with 97 of 119 patients who had preoperative PLT >75 × 109 /L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 109 /L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow-up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio [HR] = 3.09; 95% confidence interval [CI], 1.86-5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23-3.60; P = 0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR = 2.33; 95% CI, 1.36-4.01; P = 0.002) and multivariate analyses (HR = 1.90; 95% CI, 1.02-3.54; P = 0.04). Preoperative PLT had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation-based scores including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the inflammation-based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation. Liver Transplantation 24 44-55 2018 AASLD.

BackgroundTransfusion-associated graft-versus-host disease (TA-GvHD) is caused by leukocytes, specifically T cells within a transfused blood product. Currently, the prevention of transfusion-associated graft-versus-host disease is performed by irradiation of blood products. With a sufficient reduction of leukocytes, the risk for TA-GvHD can be decreased. With consistent advances in current state-of-the-art blood filters, we herein propose that double filtration can sufficiently reduce leukocytes to reduce the risk for TA-GvHD.MaterialsThirty RBC concentrates were filtered with leukocyte filters, followed by storage at 1-6 oC for 72 hours, and then a second filtration was performed. Residual leukocytes in the double-filtered RBC units (n = 30) were assessed with flow cytometric methods, and an additional assay with isolated peripheral blood mononuclear cells (PBMCs) (n = 6) was done by both flow cytometric methods and an automated hematology analyzer. Quality of the RBCs after filtration was evaluated by hematological and biochemical tests. In vitro T cell expansion was performed using anti-CD3/CD28-coated Dynabeads or anti-CD3 (OKT3). In vivo experiment for GvHD was performed by using NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice.ResultsDouble-filtered blood products showed residual leukocyte levels below detection limits, which calculated to be below 1200-2500 cells per blood unit. In vitro expansion rate of T cells showed that 6x103 and 1x103 cell-seeded specimens showed 60.8±10.6 fold and 10.2±9.7-fold expansion, respectively. Cell expansion was not sufficiently observed in wells planted with 1x102 or 10 cells. In vivo experiments showed that mice injected with 1x105 or more cells cause fatal GvHD. GvHD induced inflammation was observed in mice injected with 1x104 or more cells. No evidence of GvHD was found in mice injected with 103 cells.ConclusionsOur study suggests that additional removal of contaminating lymphocytes by a second leukodepletion step may further reduce the risk for TA-GvHD.

The aim of the study was to evaluate the association between postoperative hyperglycemia and CMV infection. We analyzed 741 CMV seropositive recipients, of livers from seropositive living donors, who underwent preemptive CMV treatment without CMV prophylaxis. The primary outcome was early CMV infection within 1 month after surgery. Hyperglycemia was defined when mean postoperative blood glucose concentration was >180 mg/dl based on previous research and guidelines. Survival analysis was performed using the Fine and Gray model by accounting for the competing risk of CMV infection-unrelated death. Of the 741 recipients (hyperglycemic group, n = 287; nonhyperglycemic group, n = 454), 372 (50.2%) recipients developed cytomegalovirus (CMV) infection within 1 month after surgery. CMV infection risk was significantly higher in hyperglycemic group than in nonhyperglycemic group in univariable analysis [hazard ratio (HR) 1.34, 95% confidence interval (CI), 1.08-1.66; P = 0.007] and in multivariable analysis (HR 1.25, 95% CI 1.0-1.54; P = 0.038). CMV infection risk was also significantly associated with recipient age, graft ischemia time, model for end-stage liver disease score, and preoperative neutrophil-to-lymphocyte ratio (P < 0.05). In conclusion, preventing postoperative hyperglycemia appears to be an important factor decreasing the risk of CMV infection in seropositive liver transplant recipients undergoing preemptive CMV treatment.

Serum bilirubin level, which may reflect the host defense against increased oxidative stress, is inversely associated with the risk of cancer development. In liver transplantation, the intrinsic bilirubin metabolism of donor liver is subsequently translated into recipient. Thus, we hypothesized that liver transplantation conducted with living donors with higher serum bilirubin reduces hepatocellular carcinoma (HCC) recurrence.Two hundred fifty recipients who underwent liver transplantation for treating HCC within the Milan criteria were included in the study. The association between donor preoperative total bilirubin concentration and the risk of HCC recurrence was analyzed using the Fine and Gray regression model with posttransplant death as a competing risk event with adjustment for tumor biology including α-fetoprotein, histological differentiation, and microvascular invasion.All donors were confirmed to have no underlying hepatobiliary diseases or hematological disorders. Donor preoperative total bilirubin concentration was 0.7 mg/dL in median and ranged from 0.2 to 2.7 mg/dL. Thirty-five (14.0%) recipients developed HCC recurrence. Multivariable analysis demonstrated that donor preoperative total bilirubin concentration was inversely associated with the recurrence risk (hazard ratio, 0.22; 95% confidence interval, 0.07-0.72; P = 0.013). The highest (≥1.0 mg/dL) versus lowest (≤0.6 mg/dL) tertile of donor preoperative total bilirubin showed a significant reduction of the recurrence risk (hazard ratio, 0.28; 95% confidence interval, 0.11-0.70; P = 0.006).Hepatocellular carcinoma recurrence risk decreases in relation to the increase in total serum bilirubin level of healthy living donors without underlying hepatobiliary or hematological disorders. Further validation of bilirubin as a potent anticancer substance against HCC is warranted.

Patients with chronic obstructive pulmonary disease (COPD) exhibit airflow limitation and suboptimal lung function, and they are at high risk of developing postoperative pulmonary complications (PPCs). We aimed to determine the factors that would decrease PPC risk in patients with COPD. We retrospectively analyzed 419 patients with COPD who were registered in our institutional PPC database and had undergone an abdominal surgery under general anesthesia. PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm, the presence or type of PPC was diagnosed by respiratory physicians and recorded in the database before this study. Binary logistic regression was used for statistical analysis. Of the 419 patients, 121 patients (28.8%) experienced 200 PPCs. Multivariable analysis showed three modifiable anesthetic factors that could decrease PPC risk: low tidal volume ventilation, restricted fluid infusion, and sugammadex-induced neuromuscular blockade reversal. We found that the 90-day mortality risk was significantly greater in patients with PPC than in those without PPC (5.8% vs. 1.3%, p = 0.016). Therefore, PPC risk in patients with COPD can be decreased if low tidal volume ventilation, restricted fluid infusion, and sugammadex-induced reversal during abdominal surgery are efficiently managed, as these factors result in decreased postoperative mortality.

Rationale: Hepatectomy is a treatment to increase survival and curability of patients with intrahepatic lesions or malignant tumors. However, posthepatectomy liver failure (PHLF) can occur. This case is a patient showing acute mental change in postanesthetic care unit (PACU) as an uncommon symptom of PHLF after extended right hepatectomy. Patient concerns: A 68-year-old male patient was admitted for surgery of Klatskin tumor. He had hypertension and atrial fibrillation. His model for end-stage liver disease score was 16 pts. His serum bilirubin and ammonia levels were 4.75 mg/dL and 132.8 mcg/dL, respectively. Other laboratory data were nonspecific. He underwent extended right hepatic lobectomy including segments IV-VIII for 9 hours. Weight of liver specimen was 1028 g which was about 58% of total liver volume based on computed tomographic volumetry. The patient was extubated and moved to the PACU with stable vital sign and regular self-breathing. He could obey verbal commands. Fifteen minutes after admission to the PACU, the patient showed abruptly decreasing mental status and self-breathing. Diagnoses: Brain computed tomography, blood culture, and sputum culture were performed to diagnose brain lesions and sepsis for evaluating the sudden onset comatous mental status. Results showed nonspecific finding. Interventions: He was intubated for securing airway and applying ventilatory care. The patient was moved to the intensive care unit. He received intensive conservative therapy including continuous renal replacement therapy and broad-spectrum antibiotics. Outcomes: The patient's condition was worsened. He expired on postoperative day 3. Lessons: Acute mental change is uncommon and rare as initial symptoms of PHLF. Therefore, clinician may overlook the diagnosis of PHLF in patients with acute mental change after hepatectomy. Thus, clinician should plan an aggressive treatment for PHLF including liver transplantation by recognizing any suspicious symptom, although such symptom is rare.

Despite technical difficulties, right lobe liver grafting is preferred in living donor liver transplantation because of the graft size. Re-exploration after living donor right lobe liver transplantation (LRLT) has never been separately analyzed. We aimed to analyze the incidence, causes, outcomes, and risk factors of re-exploration after LRLT. We reviewed medical records of 1016 LRLT recipients from October 2003 to July 2017 and identified recipients who underwent re-exploration within hospital stay. Separate analyses were also performed according to cause of re-exploration. The overall incidence of re-exploration was 17.0% (173/1016). The most common cause of re-exploration was bleeding (50%). Overall re-exploration was associated with clinical outcome, but different results were shown on analyses according to cause of re-exploration. Risk factors of re-exploration were underlying hepatocellular carcinoma and operative duration [Odds ratio (OR), 1.49; 95% confidence interval (CI), 1.05-2.12; P = 0.03, and OR, 1.002; 95% CI, 1.001-1.004; P = 0.0023, respectively]. Re-exploration after LRLT is relatively common, and is strongly associated with mortality and graft failure.

Background ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. This study compares hepatocellular carcinoma (HCC) recurrence in ABO-I LDLT with that in ABO-compatible (ABO-C) LDLT and explores the effects of rituximab prophylaxis and total plasma exchange on HCC recurrence after LDLT. Methods Two hundred forty patients with a diagnosis of HCC underwent LDLT between 2010 and 2015. Fifty-nine patients underwent ABO-I LDLT. Results Baseline, perioperative, and tumor characteristics did not vary between the 2 groups. The 1-, 2-, and 3-year disease-free survival rates in the ABO-I LDLT and ABO-C LDLT groups were 90.3%, 79.7%, and 73.3% and 86.7%, 79.0%, and 75.3%, respectively (P = 0.96). The overall patient survival rates for the same period in the ABO-I LDLT and ABO-C LDLT groups were 90.6%, 85.0%, and 81.9% and 88.0%, 83.5%, and 82.5%, respectively (P = 0.77). Hepatocellular carcinoma recurrence after LDLT was associated with preoperative α-fetoprotein greater than 35 ng/mL, increased tumor size, encapsulation, and microvascular invasion. ABO incompatibility was not related to HCC recurrence after LDLT. Conclusions Hepatocellular carcinoma recurrence and patient survival in the ABO-I LDLT group are comparable to those in the ABO-C LDLT group. Rituximab prophylaxis and total plasma exchange do not increase HCC recurrence after LT.

Many liver transplant recipients experience intraoperative hyperglycemia after graft reperfusion. Accordingly, we introduced the Portland intensive insulin therapy (PoIIT) in our practice to better control blood glucose concentration (BGC). We evaluated the effects of PoIIT by comparing with our conventional insulin therapy (CoIT). Of 128 patients who underwent living donor liver transplantation (LDLT) during the phaseout period of CoIT, 89 were treated with the PoIIT and 39 were treated with CoIT. The primary outcome was hyperglycemia (BGC > 180 mg/dL) during the intraoperative postreperfusion phase. The secondary outcomes were postoperative complications such as infection. The incidence of hyperglycemia (22.5% vs. 53.8%, p = 0.001) and prolonged hyperglycemia for >2 hours (7.9% vs. 30.8%, p = 0.002) was significantly lower in PoIIT group than in CoIT group. A mixed linear model further demonstrated that repeatedly measured BGCs were lower in PoIIT group (p

Purpose This study aimed to report intraoperative abortion of adult living donor liver transplantation (LDLT). Methods From June 1997 to December 2016, 1,179 adult LDLT cases were performed. 15 cases (1.3%) of intraoperative abortions in LDLT were described. Results Among 15 cases, 5 intraoperative abortions were donor-related, and remaining 10 cases were recipient-related. All donor-related abortions were due to unexpected steatohepatitis. Among remaining 10 recipient-related intraoperative abortions, unexpected extension of hepatocellular carcinoma was related in 5 cases. Two cases of intraoperative abortions were related to bowel inflammation, and 2 cases were associated with severe adhesion related to previous treatment. One recipient with severe pulmonary hypertension was also aborted. Conclusion Complete prevention of aborted LDLT is still not feasible. In this regard, further efforts to minimize intraoperative abortion are required.

Intermittent hepatic inflow occlusion (IHIO) during liver graft procurement is known to confer protection against graft ischemia/reperfusion injury and thus may benefit the recipient's outcome. We evaluated whether the protective effect of IHIO differs with the presence of macrosteatosis (MaS) and with an increase or decrease in the cumulative occlusion time. The subgroup of 188 recipients who received grafts with MaS was divided into 3 groups according to the number of total IHIO rounds during graft procurement: no IHIO, n = 70; 1 to 2 rounds of IHIO, n = 50; and ≥3 rounds of IHIO, n = 68. Likewise, the subgroup of 200 recipients who received grafts without MaS was divided into 3 groups: no IHIO, n = 108; 1 to 2 rounds of IHIO, n = 40; and ≥3 rounds of IHIO, n = 52. The Cox model was applied to evaluate the association between the number of total IHIO rounds and recipient survival separately in the subgroup of MaS recipients and the subgroup of non-MaS recipients. Analyzed covariables included the etiology, Milan criteria, transfusion, immunosuppression, and others. In the subgroup of MaS recipients, 1 to 2 rounds of IHIO were favorably associated with recipient survival [hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.10-0.80; P = 0.03 after Bonferroni correction], whereas ≥3 rounds of IHIO were not associated with recipient survival (HR, 0.56; 95% CI, 0.25-1.23). In the subgroup of non-MaS recipients, neither 1 to 2 rounds of IHIO (HR, 0.69; 95% CI, 0.30-1.61) nor ≥3 rounds of IHIO (HR, 0.91; 95% CI, 0.42-1.96) were associated with recipient survival. In conclusion, 1 to 2 rounds of IHIO may be used for the procurement of MaS grafts with potential benefit for recipient survival, whereas IHIO has a limited impact on recipient survival regardless of the cumulative occlusion time when it is used for non-MaS grafts. Liver Transpl 21:644–651, 2015. © 2015 AASLD.

Background & Aims The insignificance of pure microsteatosis (MiS) was reported in living donor liver transplantation (LDLT). However, since steatosis is mostly found in a mixed form of microsteatosis (MiS) and macrosteatosis (MaS), we aimed to determine the importance of MiS mixed with MaS in LDLT. Methods Donor matching and recipient matching were independently performed with unfixed matching ratios. In donor matching, 51 donors with high (⩾30%) MiS mixed with MaS (H-MiS) were matched with 160 donors with low (⩽10%) MiS mixed with MaS (L-MiS), based on MaS degree, remnant liver volume, and others. In recipient matching, 50 recipients who received H-MiS grafts were matched with 176 recipients who received L-MiS grafts, based on MaS degree, graft volume, MELD score, and others. Results The median MiS degree was 10% (range 0%–10%) vs. 35% (range 30%–80%) in L-MiS livers vs. H-MiS livers after both matching. L-MiS and H-MiS donors were not significantly different regarding postoperative biochemical liver function (e.g. peak AST 232 vs. 246IU/L, p =0.931). L-MiS and H-MiS recipients were not significantly different regarding 2-week graft regeneration (51% for both) and 5-year survival (HR 0.87, 95% CI 0.43–1.76, p =0.699). Post-transplant donor/recipient complication rates were not significantly different, either. Conclusions There were no evidences of a significant impact of MiS mixed with MaS on post-LDLT outcomes. The results suggest less importance of MiS, and further indicate that there is no interaction between MiS and MaS. Thus, the risk of steatosis may be determined by the relative composition of MiS and MaS, rather than the total quantitative degree.

Objective To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. Background HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. Methods Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. Results The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15-3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20-3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05-3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05-3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05-3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11-3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. Conclusions Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

This study was aimed to evaluate the association between preoperative high-sensitivity cardiac troponin I (hs-cTnI) level and mortality in patients undergoing liver transplantation (LT). From January 2011 to May 2016, preoperative hs-cTnI level was measured in consecutive 487 patients scheduled for LT. Patients with elevated preoperative hs-cTnI were compared with those who had normal level. The primary outcome was all-cause death in follow-up period of 30 days to 1 year after operation. Of the 487 patients, 58 (11.9%) had elevated preoperative hs-cTnI and 429 (88.1%) had normal preoperative hs-cTnI. In multivariate analysis, the rate of 1-year mortality and 30-day mortality were higher in elevated preoperative hs-cTnI group (hazard ratio [HR], 3.69; confidence interval [CI] 95%, 1.83-7.42; p < 0.001, HR, 6.61; CI, 1.91-22.82; p = 0.003, respectively). After adjustment with inverse probability weighting (IPW), the incidence of 1-year mortality and 30-day mortality were higher in elevated group (HR, 4.66; CI, 3.56-6.1; p < 0.001, HR, 10.31; CI, 6.39-16.66; p < 0.001, respectively). In conclusion, this study showed that in patients who underwent LT, elevation of preoperative hs-cTnI level was associated with 1-year mortality and 30-day mortality.

Background Rapid fluid warming has been a cardinal measure to maintain normothermia during fluid resuscitation of hypovolemic patients. A previous laboratory simulation study with different fluid infusion rates showed that a fluid warmer using magnetic induction is superior to a warmer using countercurrent heat exchange. We tested whether the simulation-based result is translated into the clinical liver transplantation. Methods Two hundred twenty recipients who underwent living donor liver transplantation between April 2009 and October 2011 were initially screened. Seventeen recipients given a magnetic induction warmer (FMS2000) were matched 1 : 1 with those given a countercurrent heat exchange warmer (Level-1 H-1000) based on propensity score. Matched variables included age, gender, body mass index, model for end-stage liver disease score, graft size and time under anesthesia. Core temperatures were taken at predetermined time points. Results Level-1 and FMS groups had comparable core temperature throughout the surgery from skin incision, the beginning/end of the anhepatic phase to skin closure. (P = 0.165, repeated measures ANOVA). The degree of core temperature changes within the dissection, anhepatic and postreperfusion phase were also comparable between the two groups. The minimum intraoperative core temperature was also comparable (Level 1, 35.6℃ vs. FMS, 35.4℃, P = 0.122). Conclusions A countercurrent heat exchange warmer and magnetic induction warmer displayed comparable function regarding the maintenance of core temperature and prevention of hypothermia during living donor liver transplantation. The applicability of the two devices in liver transplantation needs to be evaluated in various populations and clinical settings.

A safe use of intermittent hepatic inflow occlusion (IHIO) has been reported for living donor hepatectomy. However, it remains unclear whether the maneuver is safe in steatotic donors. In addition, the respective importance of macrosteatosis (MaS) and microsteatosis (MiS) is an important issue. Thus, we compared MiS and MaS with respect to the tolerance of hepatic ischemia/reperfusion (IR) injury induced by IHIO. One hundred forty-four donors who underwent a right hepatectomy were grouped according to the presence of MaS and MiS: a non-MaS group (n = 68) versus an MaS group (n = 76) and a non-MiS group (n = 51) versus an MiS group (n = 93). The coefficients of the regression lines between the cumulative IHIO time and the peak postoperative transaminase concentrations were used as surrogate parameters indicating the tolerance of hepatic IR injury. The coefficients were significantly greater for the MaS group versus the non-MaS group (4.12 ± 0.59 versus 2.22 ± 0.46 for alanine aminotransferase, P = 0.01). Conversely, the MiS and non-MiS groups were comparable. A subgroup analysis of donors who underwent IHIO for >30 minutes showed that MaS significantly increased the transaminase concentrations, whereas MiS had no impact. Also, IHIO for >30 minutes significantly increased the biliary complication rate for MaS donors (12.1% for ≤ 30 minutes versus 32.6% for >30 minutes, P = 0.04), whereas MiS donors were not affected. In conclusion, the tolerance of hepatic IR injury might differ between MaS livers and MiS livers. It would be rational to assign more clinical importance to MaS versus MiS. We further recommend limiting the cumulative IHIO time to 30 minutes or less for MaS donors undergoing right hepatectomy.

Hypothermia (core temperature 35°C) causes multiple physiologic disturbances, including coagulopathy and cardiac dysfunction. Patients undergoing liver transplantation are at risk of inadvertent hypothermia and might be more vulnerable to its adverse effects. We sought to identify the factors contributing to hypothermia during living-donor liver transplantation (LDLT), which have not yet been studied in depth.Medical records of 134 recipients who underwent adult-to-adult LDLT were reviewed. Core temperature at the following time points were taken: anesthetic induction, skin incision, start and end of the anhepatic phase, and hourly after hepatic reperfusion.Of 134 recipients, 29 (21.6%) developed hypothermia during surgery. Four independent risk factors for hypothermia were identified: small body weight-to-body surface area ratio, acute hepatic failure, high Model for End-Stage Liver Disease (MELD) score, and low graft-to-recipient weight ratio. The amount of core temperature drop was positively correlated with the number of involved risk factors. Each risk factor had a respective contribution according to the operative phases: body weight-to-body surface area ratio and the MELD score for the preanhepatic phase, acute deterioration of hepatic failure for the anhepatic phase, and graft-to-recipient weight ratio was for the postreperfusion phase.Hypothermia was independently associated with the recipient's morphometric characteristics, emergency of end-stage liver disease, MELD score, and graft volume. These factors showed a cumulative effect, and the role of each factor was different according to the operative phase. These results should aid in the development of an optimal thermal strategy during LDLT.

Liver steatosis mostly exists in a mixed form of macrosteatosis (MaS) and microsteatosis (MiS). This coexistence is responsible for previous conflicting results regarding the importance of MiS in liver transplantation. We aimed to evaluate the independent effect of MiS on posttransplant outcomes with the exclusion of the confounding effect of MaS. Seventy-one living donors who had pure MiS (defined as an MiS degree > 5% without MaS) were matched 1:1 with control donors, and 66 recipients who received pure MiS grafts were matched 1:1 with control recipients on the basis of propensity scores. Matched variables included the donor age, remnant liver volume, cold ischemia time, graft-to-recipient weight ratio and Model for End-Stage Liver Disease score. The degree of pure MiS ranged from 5% to 50%. Donors in the control and pure MiS groups were comparable with respect to peak postoperative transaminase concentrations [alanine aminotransferase (ALT): 194 versus 176 IU/L, P = 0.61] and postoperative complications. Recipients in the control and pure MiS groups were comparable with respect to recipient (P = 0.15) and graft survival rates (P = 0.56) as well as peak postoperative transaminase concentrations (ALT: 266 versus 281 IU/L, P = 0.88), and graft regeneration rates at 2 weeks (61% versus 59%, P = 0.73). The 2 groups were also comparable with respect to major complications, primary graft dysfunction/nonfunction, intensive care unit/hospital stays, and metabolic diseases. In conclusion, MiS alone does not seem to impair the posttransplant outcomes of living donors and their recipients. The interaction between MiS and MaS, and the effect of a greater degree of MiS are the next important topics to be further evaluated in the mixed steatosis population.