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Bile duct surgeries are conventionally considered to promote bacterial contamination of the surgical field. However, liver transplantation recipients' bile produced by the newly implanted liver graft from healthy living donors may be sterile. We tested bacterial contamination of autologous blood salvaged before and after bile duct anastomosis (BDA) during living donor liver transplantation (LDLT). In 29 patients undergoing LDLT, bacterial culture was performed for four blood samples and one bile sample: two from autologous blood salvaged before BDA (one was nonleukoreduced and another was leukoreduced), two from autologous blood salvaged after BDA (one was nonleukoreduced and another was leukoreduced), and one from bile produced in the newly implanted liver graft. The primary outcome was bacterial contamination. The risk of bacterial contamination was not significantly different between nonleukoreduced autologous blood salvaged before BDA and nonleukoreduced autologous blood salvaged after BDA (44.8% and 31.0%; odds ratio 0.33, 95% confidence interval 0.03-1.86; p = 0.228). No bacteria were found after leukoreduction in all 58 autologous blood samples. All bile samples were negative for bacteria. None of the 29 patients, including 13 patients who received salvaged autologous blood positive for bacteria, developed postoperative bacteremia. We found that bile from the newly implanted liver graft is sterile in LDLT and BDA does not increase the risk of bacterial contamination of salvaged blood, supporting the use of blood salvage during LDLT even after BDA. Leukoreduction converted all autologous blood samples positive for bacteria to negative. The clinical benefit of leukoreduction for salvaged autologous blood on post-LDLT bacteremia needs further research.

There is a lack of convincing data concerning the safety of iron therapy in patients with advanced liver cirrhosis (LC). This study investigated the hepatic effects of ferric carboxymaltose, an intravenous iron supplement, in a rat model of cirrhosis.In total, 45 Sprague-Dawley rats were allocated into three groups: normal rats (control group, n=15), cirrhotic rats receiving intravenous normal saline (LC group, n=15), and cirrhotic rats receiving 20 mg/kg intravenous ferric carboxymaltose (LC-iron group, n=15). LC was induced by twice-weekly intraperitoneal injection of carbon tetrachloride. Biochemical parameters were compared at 0, 2, 14, and 28 days. Additionally, liver tissue samples were extracted from five rats in each group at 2, 14, and 28 days for evaluation of the degrees of hepatic fibrosis and iron deposition. Inflammatory and oxidative stress markers were also compared among groups.Serum alanine transferase levels did not significantly differ between the LC and LC-iron groups at 0 (443±110 vs. 444±117 IU/L, P0.99), 2 (453±117 vs. 479±136 IU/L, P=0.84), 14 (1,535±1,058 vs. 1,578±711 IU/L, P=0.55), or 28 days (2,067±641 vs. 2,533±914 IU/L, P=0.15). The degree of hepatic fibrosis was comparable between the groups, although hepatic iron accumulation was greater in the LC-iron group than in the LC group. The levels of inflammatory and oxidative stress markers were significantly lower in the LC-iron group than in the LC group.In our rat model of cirrhosis, the administration of intravenous iron appears safe. However, further preclinical and clinical studies are warranted to confirm the safety and efficacy of intravenous iron in patients with LC or end-stage liver disease.

The radial artery is commonly used as the site measuring pulse pressure variation (PPV) during surgery. Accurate measurement of circulating blood volume and timely interventions to maintain optimal circulating blood volume is important to deliver sufficient oxygen to tissues and organs. It has not rather than never studied in patients undergoing liver transplantation whether PPV measured at peripheral sites, such as the radial artery, do represent central PPV for evaluating blood volume. In this retrospective study, 51 liver transplant recipients were enrolled. The two PPVs had been automatically recorded every minute in electrical medical records. A total 1878 pairs of the two PPVs were collected. The interchangeability of PPV measured at the radial and the femoral artery was analyzed by using the Bland–Altman plot, four-quadrant plot, Cohen’s kappa (k), and receiver operating curve. The bias and limits of agreement of the two PPVs were −1.3% and −8.8% to 6.2%, respectively. The percentage error was 75%. The concordance rate was 65%. The Kappa of PPV-radial determining whether PPV-femoral was >13% or ≤13% was 0.64. We found that PPV-radial is not interchangeable with PPV-femoral during liver transplantation. Additionally, PPV-radial failed to reliably track changes of PPV-femoral. Lastly, the clinical decision regarding blood volume status (depletion or not) is significantly different between the two PPVs. Therefore, PPV-femoral may help maintain blood volume circulating to major organs including the newly transplanted liver graft for liver transplant recipients.

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.

Despite various intraoperative thermal strategies, core heat loss is considerable during liver transplantation and hypothermia is common. We tested whether forced-air prewarming prevents hypothermia during liver transplantation. Adult patients undergoing living donor liver transplantation were randomly assigned to non-prewarming group (n = 20) or prewarming group (n = 20). Patients in prewarming group underwent 30-min forced-air warming before anesthetic induction. During surgery, core temperature was measured in the pulmonary artery. The primary outcome was intraoperative hypothermia (P = 0.020). The difference in hypothermia incidence between groups was greater in the post-induction phase (20.0% vs. 85.0%, P P = 0.001). Lactate concentration decreased during 3 h after graft reperfusion in prewarming group, whereas it continuously increased in non-prewarming group (− 0.19 [− 0.48 to 0.13] mmol/L vs. 1.17 [3.31–0.77] mmol/L, P = 0.034). In conclusion, forced-air prewarming decreases the incidence and duration of intraoperative hypothermia with potential clinical benefit while mainly acting by preventing the core-to-peripheral heat redistribution.Clinical trial registration: Registered at the Clinical Research Information Service (https://cris.nih.go.kr, [KCT0003230]) on 01/10/2018.

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: 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-40K) on postoperative day (POD) 1, and ambulation (success rate, number of footsteps) 6–12 hours after surgery and on POD 1. The pain score for the wound site, IV opioid requirement, postoperative complications including incidence of nausea/vomiting, length of in-hospital stay were also assessed.Results: The global QoR-40K 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 timepoints were also higher in the IV propofol group. The 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.https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15768&sLeft=2&ltype=my&rtype=my

Additional file 1: Supplemental file 1. Summary of our study protocol.

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.

Recipient's immune responses are an important factor in allograft survival in transplantation. Cytokines are reflected with immune responses. In the present study, we aimed to evaluate potential affecting factors of liver allograft survival and their possible correlation with seroum cytokine levels in living donor liver transplantation (LDLT). One hundred and seventy-one adult patients' data were collected retrospectively. Five cytokines were collected: interferon (IFN)-γ, interleukin (IL)-2, IL-10, IL-6, and IL-17. Ischemic time of liver grafts was divided into two periods: cold and warm ischemic times (CIT and WIT, respectively). CIT had no statically significant correlation, but WIT showed a significant correlation with IFN-γ, IL-2, and IL-17 serum levels (r = 0.0252, 0.282, 0.178, respectively; P 0.05). WIT was dichotomized as T1 (22 min), T2 (22-70 min), and T3 (70 min). IFN-γ was significantly increased in T2 and T3 as compared to T1. IL-6 was in T3 compared to T1 and T2. IL-17 was in T3 compared to T1. For the Th1-to-Th2 ratio, IFN-γ/IL-10, IFN-γ/IL-6, and IL-2/IL-10 were significantly different in T2 and T3 as compared to T1, and also in T3 as compared to T2. Th1 cell activities were enhanced with increased WIT. In conclusion, the longer WIT (70 min) in LDLT is more likely to induce immunological reactions of recipients by leading to a deleterious cytokine balances in favor of an reinforced production of Th1 cytokines.

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.