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The risk of acute kidney injury (AKI) after liver transplantation was lower in patients with serum albumin levels ≥3.0 mg/dL during surgery. We tested whether intraoperative infusion of 20% albumin affects neutrophil gelatinase-associated lipocalin (NGAL) level, a reliable indicator of AKI. We randomly assigned 134 patients undergoing liver transplantation into albumin group (n=70, 20% albumin 200 mL) and the control group (n=66, crystalloid solution 200 mL). The 2 study fluids were infused at 100 mL/h from the start of the anhepatic phase. The primary outcome was plasma NGAL level at 1 hour after graft reperfusion. Albumin level at the start of graft reperfusion was significantly greater in albumin group than in the control group [2.9 (2.4-3.3) g/dL vs. 2.3 (2.0-2.7) g/dL, p <0.001]. The NGAL level at 1 hour after graft reperfusion was not significantly different between the 2 groups [100.2 (66.7-138.8) ng/mL vs. 92.9 (70.8-120.6) ng/mL, p =0.46], and the AKI risk was not either (63.9% vs. 67.8%, adjusted p =0.73). There were no significant differences between the 2 groups regarding hospital readmission within 30 days/90 days after transplantation (32.6% vs. 41.5%, adjusted p =0.19 and 55.0% vs. 55.7%, adjusted p =0.87). Graft survival probability at 30 days/90 days/1 year after transplantation was 90.0%/84.3%/78.6% in albumin group and 97.0%/90.9%/89.4% in the control group [HR=1.6 (0.6-4.0), adjusted p =0.31]. In conclusion, intraoperative infusion of 20% albumin 200 mL increased the albumin level but failed to maintain serum albumin ≥3.0 mg/dL during surgery. The hypertonic albumin therapy did not significantly affect plasma NGAL level and clinical outcomes including AKI., (Copyright © 2023 American Association for the Study of Liver Diseases.)

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., (© 2022 American Association for the Study of Liver Diseases.)

Donor safety and graft results of pure laparoscopic living donor right hepatectomy (LLDRH) have previously been compared with those of open living donor right hepatectomy (OLDRH). However, the clinical outcomes of recipients at 1-year follow-up have never been accurately compared. We aimed to compare 1-year outcomes of recipients of living donor right liver transplantation (LRLT) using pure LLDRH and OLDRH. From May 2013 to May 2017, 197 consecutive recipients underwent LRLT. Donor hepatectomies were performed either by OLDRH (n = 127) or pure LLDRH (n = 70). After propensity score matching, 53 recipients were included in each group for analysis. The clinical outcomes at 1-year follow-up were compared between the 2 groups. The primary outcome was recipient death or graft failure during the 1-year follow-up period. In the propensity-matched analysis, the incidence of death or graft failure during the 1-year follow-up period was not different between the 2 groups (3.8% versus 5.7%; odds ratio [OR], 1.45; 95% confidence interval [CI], 0.24-8.95; P = 0.69). However, the composite of Clavien-Dindo 3b-5 complications was more frequent in the pure LLDRH group (OR, 2.62; 95% CI, 1.15-5.96; P = 0.02). In conclusion, although pure LLDRH affords a comparable incidence of fatal complications in recipients, operative complications may increase at the beginning of the program. The safety of the recipients should be confirmed to accept pure LLDRH as a feasible option., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

We aimed to evaluate the association between intraoperative pulmonary vascular resistance (PVR) and clinical outcome of liver transplantation (LT). Cardiovascular involvement of end-stage liver disease is relatively common, and hemodynamic instability during LT can be fatal to recipients. However, the clinical impact of intraoperative PVR in LT remains undetermined. A total of 363 adult recipients with intraoperative right heart catheterization from January 2011 to May 2016 were analyzed. Patients were divided into 2 groups according to PVR. Two separate analyses were performed according to the time point of measurement: at the beginning and at the end of LT. The primary outcome was all-cause death or graft failure during the follow-up period. Increased PVR was observed in 11.8% (43/363) of recipients at the beginning and 12.7% (46/363) of recipients at the end of LT. PVR at the beginning of LT had no significant effect on the rate of death or graft failure in the multivariate analysis (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.64-2.38; P = 0.52). In contrast, PVR at the end of LT was significantly associated with death or graft failure during the overall follow-up period (HR, 2.00; 95% CI, 1.13-3.54; P = 0.02). In conclusion, PVR at the end of LT, rather than the beginning, is associated with clinical outcome. Larger trials are needed to support this finding., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

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 × 10 9 /L were matched with 97 of 119 patients who had preoperative PLT >75 × 10 9 /L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 10 9 /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., (© 2017 by the American Association for the Study of Liver Diseases.)

The aim of this study was to evaluate the protective effect of remote ischemic postconditioning (RIPostC) on graft function and acute kidney injury (AKI) after living donor liver transplantation (LT). Recipients undergoing elective living donor LT were randomly assigned to either the RIPostC group or the control group. Immediately after reperfusion, 4 cycles of ischemia and reperfusion lasting for 5 minutes each were performed on 1 upper limb in the RIPostC group. Graft function was assessed through evaluations of the serum levels of total bilirubin and liver enzymes and the prothrombin time for 28 days after surgery. The incidence of AKI, as defined by the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease classification, was evaluated within 28 days of the operation. In addition, the incidences of graft dysfunction, acute cellular rejection, and major complications; the 1-, 3-, and 6-month mortality rates; the length of stay in the intensive care unit; and the length of hospital stay were also investigated. In all, 78 patients were enrolled in the analysis (n = 39 in each group). No differences in graft function or clinical outcomes were observed between the groups. The incidences of postoperative AKI were 38% (n = 15) in the RIPostC group and 72% (n = 28) in the control group (P = 0.006). Despite no improvements in postoperative graft function, RIPostC decreased the incidence of postoperative AKI after living donor LT in this study. However, no other clinical benefits with respect to the complication rate, length of hospital stay, or short-term mortality rate were observed. Thus, further studies will be needed to evaluate the clinical efficacy of RIPostC in LT fully., (© 2014 American Association for the Study of Liver Diseases.)

Postoperative analgesia and care for living liver donors have become particular interests for clinicians as the use of living donor liver transplantation has increased. Local anesthetic-based analgesia has been known to provide effective pain control. In this prospective, randomized study, we compared the postoperative analgesic efficacy of local anesthetic-based analgesia (PainBuster) with the efficacy of opioid-based analgesia [intrathecal morphine (ITM) with intravenous (IV) fentanyl] in liver donors. Forty adult donors were randomly allocated to 1 of 2 groups: an ITM/IV fentanyl group (n = 21) and a PainBuster group (n = 19). Donors in the PainBuster group received 0.5% ropivacaine via a multi-orifice catheter (ON-Q PainBuster) placed at the wound. Donors in the ITM/IV fentanyl group received ITM sulfate (400 μg) preoperatively and a continuous IV fentanyl infusion postoperatively. A visual analogue scale (VAS) at rest and with coughing and rescue IV fentanyl and meperidine consumption were assessed for 72 hours after the operation. Side effects, including sedation, dizziness, nausea, vomiting, pruritus, respiratory depression, wound seroma or hematoma, and the first time to flatus, were recorded. The VAS score at rest during the first 12 postoperative hours was significantly lower for the ITM/IV fentanyl group. At other times, the VAS scores were comparable between the groups. In the PainBuster group, rescue IV fentanyl and meperidine use was significantly reduced 24 to 48 hours and 48 to 72 hours after surgery in comparison with the first 24 postoperative hours. The time to first flatus was significantly reduced in the PainBuster group. There were no differences in side effects. In conclusion, analgesia was more satisfactory with ITM/IV fentanyl versus PainBuster during the first 12 hours after surgery, but they became comparable thereafter, with a shortened bowel recovery time in the PainBuster group. The concurrent use of ITM with PainBuster may be considered in a future investigation., (© 2013 American Association for the Study of Liver Diseases.)

Cytomegalovirus (CMV) infections contracted after liver transplantation put patients at an increased risk of morbidity and mortality. We analyzed the effects of CMV infection by time of onset, mortality, and graft failure risk factors in liver recipients who were CMV donor-positive/recipient-positive (D+/R+). We reviewed 618 medical records for consecutive adult liver transplant cases. CMV pp65 antigenemia assays to determine patient CMV status were administered monthly. The incidences of CMV infection and disease were 55.7% (344 of 618 records) and 5.5% (34 of 618 records), respectively. The differences in patient survival and graft failure rates for CMV-infected and CMV-uninfected patients were not significant (P = 0.707 and P = 0.973), but the rates were lower in patients with CMV disease than in CMV-uninfected patients (P = 0.005 and P = 0.030, respectively). The recurrence of hepatitis B virus and hepatocellular carcinoma, hepatic dysfunction, infection, numerous pp65-staining cells, and CMV disease were found to be the risk factors for mortality and graft failure in CMV D+/R+ adult liver transplant patients. In conclusion, the occurrence of CMV disease, and not asymptomatic CMV infection, was a risk factor for mortality and graft failure in adult liver transplant recipients with CMV D+/R+., (Copyright © 2011 American Association for the Study of Liver Diseases.)

We evaluated the value of the stroke volume variation (SVV) calculated with the Vigileo monitor, which recently has been increasingly advocated for fluid management, as a predictor of fluid responsiveness during the anhepatic phase of liver transplantation (LT). We also compared SVV to the central venous pressure (CVP) and pulmonary arterial occlusion pressure (PAOP) in patients. Thirty-three adult recipients scheduled for elective living donor LT were enrolled in this study. Twenty minutes after the start of the anhepatic phase, the CVP, PAOP, approximate inferior vena caval pressure, femoral SVV, and cardiac output values were measured before and 12 minutes after fluid loading. Fluid loading was performed with a 6% hydroxyethyl starch solution (10 mL/kg). The responders were defined as patients whose cardiac index increased ≥ 15% after fluid loading. Receiver operating characteristic (ROC) analysis showed that only femoral SVV (area under the curve = 0.894, P = 0.0001) could be used to predict fluid responsiveness during the anhepatic phase of LT. The area under the ROC curve for femoral SVV was 0.894 (P = 0.0001), and it was significantly larger than those for CVP (area under the curve = 0.576, P = 0.004) and PAOP (area under the curve = 0.670, P = 0.021). Femoral SVV >8% identified the responders with a sensitivity of 89% and a specificity of 80%. Our results suggest that femoral SVV derived with the Vigileo monitor would be useful for fluid management during the anhepatic phase in LT recipients., (Copyright © 2011 American Association for the Study of Liver Diseases.)

The healthy condition of living donors makes their tolerance to pain particularly low, and clinicians are often challenged to come up with an analgesic technique that is effective yet ensures donor safety. This study compared, in donor right hepatectomy, the efficacy and safety of preoperative intrathecal morphine (ITM) combined with intravenous patient-controlled analgesia (IV-PCA) with IV-PCA alone. Forty adult patients were randomly allocated into 2 groups: ITM+IV-PCA group (n = 20) and IV-PCA-only group (n = 20). Patients in the ITM+IV-PCA group received morphine sulfate (400 microg). The visual analog scale (VAS) at rest and when coughing and supplementary meperidine and IV-PCA (fentanyl) consumption were assessed at 2, 4, 6, 8, 10, 12, 18, 24, 30, 36, 42, 48 56, 64, and 72 hours after surgery. Also, side effects such as sedation, dizziness, nausea, vomiting, pruritus, and respiratory depression were evaluated. The ITM+IV-PCA group showed significantly less pain at rest and when coughing for up to 30 hours and 24 hours, respectively. Cumulative postoperative consumption of meperidine and IV-PCA (fentanyl) were significantly less in the ITM+IV-PCA group. The incidence of side effects were comparable between the 2 groups except for pruritus; its incidence was significantly higher in the ITM+IV-PCA group during the first 24 hours, but no treatment was required due to its mild severity. The results of our study suggest that preoperative ITM combined with IV-PCA may be considered as an effective and safe pain management regimen in living liver donors who have characteristics of low tolerance to pain and postoperative coagulation derangement., (Copyright 2009 AASLD.)

Various volatile anesthetics have been used in hepatectomy in living donors, and their effects on major organs have been extensively evaluated. However, the impact of total intravenous anesthesia (TIVA) on postoperative liver and renal functions after large liver resections has been less extensively investigated than that of volatile agents. The aim of this study was to compare the postoperative hepatic and renal functions between volatile anesthesia with desflurane and TIVA with propofol-remifentanil in living donors undergoing right hepatectomy. Seventy adult patients were randomly allocated into 2 groups: the desflurane group (n = 35) and TIVA group (n = 35). Aspartate aminotransferase, alanine aminotransferase, prothrombin time (PT), albumin, total bilirubin (TB), blood urea nitrogen (BUN), creatinine (Cr), BUN/Cr ratio, estimated glomerular filtration rate (GFR), platelet count, and hemoglobin levels were analyzed in the preoperative period, immediately after the operation, and on the first, second, third, fifth, seventh, and thirtieth postoperative days (PODs). Most of the liver function test results were not significantly different between the 2 groups. However, PT (international normalized ratio) and TB were significantly greater on POD 5 in the TIVA group. Among the renal function tests, Cr was significantly higher and estimated GFR was significantly lower on POD 1 in the TIVA group. The platelet counts and hemoglobin levels were similar between the 2 groups. In conclusion, the results of our study suggest that living related donors for liver transplant may have a better outcome following anesthesia with desflurane. However, further testing will be necessary to prove this hypothesis.

Liver allograft recipients may develop a hyperdynamic circulation and cardiac electrophysiologic abnormalities. The incidence of severe ventricular arrhythmias in liver allograft recipients during pulmonary artery (PA) catheterization was determined. One hundred five liver allograft recipients were studied prospectively; 5 of the patients with preexisting valvular heart disease, ischemic heart disease, or arrhythmias were excluded. Severe ventricular arrhythmia, defined as 3 or more consecutive ventricular premature beats occurring at a rate of >100 per minute, was observed in 37.0% of the patients during insertion of the catheter and in 25.0% of the patients during removal of the catheter. Two patients developed ventricular tachycardia, and 2 developed ventricular fibrillation; the arrhythmias in these 4 patients did not respond to appropriate pharmacological treatment but resolved promptly after removal of the PA catheter. The catheter transit time from the right ventricle to the pulmonary capillary wedge position was longer in patients with severe ventricular arrhythmia than in those without this arrhythmia (91.6+/-103.6 s versus 53.3+/-18.4 s, P<0.05). In conclusion, patients undergoing liver transplantation have a high risk of developing a ventricular arrhythmia during PA catheterization., (Copyright (c) 2007 AASLD.)

The safety of living donors is a matter of cardinal importance in addition to obtaining optimal liver grafts to be transplanted. Central venous pressure (CVP) is known to have significant correlation with the amount of bleeding during parenchymal transection and many centers have adopted CVP monitoring for right hepatectomy. However, central line cannulation can induce some serious complications. Peripheral venous pressure (PVP) has been suggested as a comparable alternative to CVP. The aim of this study was to determine whether a clinically acceptable agreement or a reliable correlation between CVP and PVP exist and if CVP can be replaced by PVP in living liver donors. A central venous catheter was placed through the right internal jugular vein and a peripheral venous catheter was inserted at antecubital fossa in the right arm. CVP and PVP were recorded in 15-minute intervals in 50 adult living donors. The paired data were divided into 3 stages: preparenchymal transection, parenchymal transection, and postparenchymal transection. A total of 1,430 simultaneous measurements of CVP and PVP were recorded. Overall, the PVP, CVP, and bias were 7.0+/-2.46, 5.9+/-2.32, and 1.16+/-1.12 mmHg, respectively. A total of 88.9% of all measurements were clinically within acceptable limits of bias (+/-2 mmHg). Regression analysis showed a high correlation coefficient between PVP and CVP (r=0.893; P<0.001) and the limits of agreement were -1.03 to 3.34 overall. In conclusion, frequencies of differences, bias, correlation coefficient, and limits of agreement between PVP and CVP remained relatively constant throughout the operation. Therefore, PVP measurement in the arm can be an alternative to predict CVP and further, obviate central venous catheter-related complications in living liver donors., (Copyright (c) 2007 AASLD.)

The use of epidural catheters has been a subject of active debate in living liver donors because of the possible postoperative coagulation derangement and the subsequent risk of epidural hematoma. The aim of this study was to evaluate the safety of epidural catheters in relation to the changes in coagulation profile based on a review of previously published literature and the results of our 360 donors. In both the literature and in our cases, platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT) in cases of heparin administration showed significant changes (P < 0.05), especially after right lobectomy. Platelet count reached its nadir on postoperative day (POD) 2-3, while PT and aPTT reached their peaks on POD 1-2 and at the end of the operation, respectively. In our donors, the ranges of platelet count, PT, and aPTT for the first 3 PODs were 54-359 x10/microL, 0.99-2.38 international normalized ratio (INR), and 25.9-300 seconds, respectively, and of note, 5 donors (1.4%) had a platelet count of <80 x 10/microL and 9 donors (2.5%) had a PT of >2.0 INR. Epidural catheterizations were performed in 242 donors, and the catheters were removed on POD 3-4 in 177 donors (73.1%). Mean (range) of platelet count, PT, and aPTT on the day of catheter removal were 168.4 +/- 42.9 (82-307) x 10/microL, 1.33 +/- 0.18 (0.99-1.93) INR, and 40.9 +/- 4.8 (32.0-70.6) seconds, respectively. No epidural hematoma was observed in this study. In conclusion, the discreet use of epidural catheters in live liver donors, in spite of postoperative coagulation derangements, appears to be safe regardless of the type of hepatectomy performed., ((c) 2006 AASLD.)

During liver transplantation for hepatocellular carcinoma (HCC) patients, HCC could theoretically be introduced into the systemic circulation when salvaged blood is used with an autotransfusion device. Several reports have shown that some types of leukocyte depletion filters (LDFs) could completely reduce the risk for reintroducing some types of tumor cells. In this study, we tested the ability of the LDF (RCEZ1T, Pall Biomedical Co, NY, USA) to reduce the risk for reintroducing HCC cells in vitro by using a very sensitive detection method. We divided the test group into 6 groups: group I was 10 cells, group II was 20 cells, group III was 2 x 10(3) cells, group IV was 2 x 10(5) cells, group V was 2 x 10(6) cells, and group VI was 2 x 10(7) cells. The counted cells in 200 mL saline were passed through the RCEZ1T using the force of gravity. To identify the presence of cells, the pellet was resuspended, and polymerase chain reaction (PCR) was performed. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene, was used as a primer. In groups I and II, the HCC cells were completely filtered in all experiments. However, in groups III, IV, and V, the HCC cells were not completely filtered in a few of the repeated experiments, with the unfiltered rate of tumor cells being between 8% and 20%. In group VI, the HCC cells were not completely filtered in all the repeated experiments. In conclusion, the RCEZ1T filter markedly reduced the risk for reintroduction of HCC cells. However, at high HCC cell load the filter cannot completely remove all the tumor cells. Further studies are required to assess the impact in clinical settings.