Abstract A subset of deceased liver donors have a history of heavy alcohol intake. We evaluated whether donor heavy alcohol history is associated with graft failure after liver transplantation (LT) and whether associations differ by donor sex and macrosteatosis. We conducted a retrospective cohort study using the OPTN/UNOS registry, including 29,170 adult LT recipients (2000–2023). The exposure was heavy alcohol intake (> 2 drinks/day). The primary outcome was graft failure. Associations were estimated using Cox proportional hazards models adjusted for donor, recipient, and transplant covariates. The proportion of donors with heavy alcohol history increased over time (2000–2007, 19.0%; 2008–2015, 20.3%; 2016–2023, 22.3%). In multivariable analyses, donor heavy alcohol history was not associated with graft failure overall (HR = 0.96 [0.90–1.03], P = 0.249). Donor macrosteatosis was independently associated with higher risk (HR = 1.07 [1.01–1.13], P = 0.020). Associations differed by donor sex: among female donors, heavy alcohol history was associated with lower graft failure risk (HR = 0.87 [0.77–0.98], P = 0.010), whereas no association was observed among male donors (P = 0.802). The lower risk seen with female donors was not present when donor livers had macrosteatosis (P = 0.271). In conclusion, donor heavy alcohol history was not associated with increased graft failure risk overall. Notably, grafts from female donors with a heavy alcohol history were associated with lower failure risk, an apparent advantage that was not observed in the presence of macrosteatosis. No association was observed among male donors. These findings suggest sex- and liver-quality–dependent heterogeneity in the relationship between donor alcohol history and post-transplant outcomes.

BACKGROUND:Donor safety is paramount in living donor liver transplantation. The safety of intermittent hepatic inflow occlusion (IHIO) during laparoscopic donor hepatectomy (LDH) remains uncertain due to concerns that pneumoperitoneum may impair hepatic venous backflow during inflow occlusion and exacerbate ischemia-reperfusion (IR) injury. This study aimed to compare the tolerance to IHIO-induced hepatic IR injury and clinical outcomes between LDH and open donor hepatectomy (ODH). MATERIALS AND METHODS:This retrospective, single-center cohort study included 914 adult living liver donors who underwent right hemi-hepatectomy from 2010 to 2024. After propensity score matching, 819 donors were analyzed. The exposure of interest was IHIO during either LDH or ODH. The primary outcome was tolerance to hepatic IR injury, defined as the increase in alanine transaminase (ALT) and aspartate transaminase (AST) per minute of IHIO. Secondary outcomes included postoperative complications. Quantile regression at the 50th percentile (median regression) was used for analysis. RESULTS:IHIO was performed in 87.2% of ODHs and 74.7% of LDHs. In ODH, each minute of IHIO increased median ALT and AST by 2.4 (1.7-3.2) U/L and 1.9 (1.2-2.6) U/L, respectively, vs. 1.2 (0.9-1.6) U/L and 0.8 (0.5-1.2) U/L in LDH. Tolerance to IHIO was significantly greater in LDH than in ODH (ALT: P = 0.007; AST, P = 0.003). Biliary complication rates increased with IHIO duration in ODH (0 min, 5%; >0‒30 min, 14.3%; >30 min, 12%), but not in LDH (4.2%, 3.9%, and 3.7%). When IHIO was used, biliary complication risk was significantly lower in LDH than ODH (>0-30 min, P = 0.028; >30 min, P = 0.004). CONCLUSIONS:We found no evidence that laparoscopic IHIO increases donor risk compared with open IHIO. Instead, LDH was associated with greater tolerance to IHIO-induced hepatic IR injury and lower biliary complication risk. These findings suggest IHIO can be used safely in LDH without added risk to open IHIO.

SummaryBackgroundWhile evidence from preclinical and observational cohort studies have suggested potential disparities in tumour behaviour associated with the choice of intra‐operative anaesthetics, clinical evidence of tumour recurrence and metastasis remains inconclusive. We aimed to compare the impact of intra‐operative anaesthesia on oncologic outcomes following hepatectomy for hepatocellular carcinoma.MethodsAdult patients scheduled for elective hepatectomy for hepatocellular carcinoma were assigned randomly (1:1) to either propofol‐based total intravenous anaesthesia or sevoflurane‐based inhalational anaesthesia. For recurrence‐free survival, overall survival, intrahepatic recurrence‐free survival and extrahepatic recurrence‐free survival, the survival curves of the two groups were estimated using the Kaplan–Meier method and compared with the log‐rank test. The primary outcome was one‐year recurrence‐free survival.ResultsAmong the 536 patients enrolled, primary analysis comprised 228 and 226 patients in the total intravenous anaesthesia and sevoflurane‐based inhalational anaesthesia groups, respectively. The probability of recurrence‐free survival at one year was 79.1% (47 events) and 77.7% (50 events) in the total intravenous anaesthesia and sevoflurane‐based inhalational anaesthesia groups, respectively (adjusted hazard ratio 1.04, 95%CI 0.72–1.52). The probability of intrahepatic and extrahepatic recurrence‐free survival, as well as overall survival at one year, was not significantly different between total intravenous anaesthesia and sevoflurane‐based inhalational anaesthesia: 81.3% (42 events) vs. 81.7% (41 events); 91.5% (19 events) vs. 88.8% (25 events); 99.1% (2 events) vs. 100.0% (no event), respectively. Subgroup analyses revealed that in patients undergoing open hepatectomy, total intravenous anaesthesia was associated with a significantly lower hazard of tumour recurrence or death (hazard ratio 0.49, 95%CI 0.25–0.95, p = 0.034), while in patients undergoing laparoscopic surgery, no significant difference was observed (hazard ratio 1.14, 95%CI 0.73–1.80, p = 0.558).DiscussionIntra‐operative anaesthesia technique did not affect postoperative recurrence and overall survival in patients with hepatocellular carcinoma undergoing hepatectomy.

Background Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. Methods In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000–2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Results Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16–1.76], p < 0.001; vs. male-to-female, HR = 1.46 [1.18–1.81], p < 0.001; vs. male-to-male, HR = 1.26 [1.16–1.49], p = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, p = 0.907; vs. male-to-female, p = 0.781; vs. male-to-male, p = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. Conclusions In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor–recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y.

Background: Acute kidney injury (AKI) is one of the most common complications after living-donor liver transplantation (LDLT) that has great impact on recipient and graft outcomes. Dexmedetomidine is reported to decrease the incidence of AKI. In the current study, we investigated whether intraoperative dexmedetomidine infusion would reduce the AKI following LDLT. Material and Methods: In total, 205 adult patients undergoing elective LDLT were randomly assigned to the dexmedetomidine group (n=103) or the control group (n=102). Dexmedetomidine group received continuous dexmedetomidine infusion at a rate of 0.4 mcgּ/kg/hr after the anesthesia induction until 2 hours after graft reperfusion. The primary outcome was to compare the incidence of AKI. Secondary outcomes included serial lactate levels during surgery, chronic kidney disease, major adverse cardiovascular events, early allograft dysfunction, graft failure, overall mortality, duration of mechanical ventilation, ICU and hospital length of stay. Intraoperative hemodynamic parameters were also collected. Results: Of 205 recipients, 42.4% (n=87) developed AKI. The incidence of AKI was lower in the dexmedetomidine group (35.0%, n=36/103) compared with the control (50.0%, n=51/102) (P=0.042). There were significantly lower lactate levels in the dexmedetomidine group after reperfusion (4.39 [3.99-4.8] vs 5.02 [4.62-5.42], P=0.031) until the end of surgery (4.23 [3.73-4.73] vs 5.35 [4.84-5.85], P=0.002). There were no significant differences in the other secondary outcomes besides lactate. Also, intraoperative mean blood pressure, cardiac output, and systemic vascular resistance did not show any difference. Conclusion: Our study suggests that intraoperative dexmedetomidine administration was associated with significantly decreased AKI incidence and lower intraoperative serum lactate levels in LDLT recipients, without untoward hemodynamic effects.

To the editor, We read with great interest a recent randomized controlled trial by Kim et al1 in which the authors studied the correlation between serum albumin and neutrophil gelatinase–associated lipocalin (NGAL) levels to predict post-liver transplantation (LT)-acute kidney injury (AKI). In this proof of concept study, 20% albumin infusion during the reperfusion phase was neither associated with a decrease in plasma NGAL levels nor a decrease in the incidence of post-transplant AKI. This study is mainly based on 3 hypotheses: (1) hepatic ischemia-reperfusion-injury (IRI) is associated with post-LT-AKI. (2) Serum NGAL can detect post-LT-AKI 1 hour after graft reperfusion. (3) Intraoperative hypertonic albumin therapy decreases plasma NGAL level 1 hour after the graft reperfusion. We have specific essential points to note: First, in LT surgery, several preoperative and perioperative factors have been linked to the development of AKI, including IRI. IRI is an unavoidable consequence of the preservation process in deceased-donor liver transplantation due to longer cold-ischemia time. In living-donor liver transplantation, a partial liver graft is usually transplanted after a brief cold-ischemia time, leading to minimal IRI. In this study, only 21% of 136 adult recipients underwent deceased-donor LT. Thus, this study’s negative results are unsurprising and need better generalizability. The pathophysiology of post-LT-AKI in living-donor liver transplantation versus deceased-donor liver transplantation setting and the impact of IRI on AKI in living-donor liver transplantation settings should be studied. Second, although NGAL is a surrogate marker for perioperative AKI,2 there are a few concerns regarding its use as the marker of post-LT-AKI. There is new evidence from a preclinical study pointing toward the liver as the primary site of NGAL production in ischemic AKI. Increased plasma IL-6 was associated with increased hepatic NGAL mRNA and plasma NGAL levels. In mice with hepatic-specific NGAL deletion and ischemic AKI, plasma and urinary NGAL levels were reduced.3 Hepatic IRI is associated with an increase in IL-6, which may increase the level of NGAL in the blood. Thus, higher NGAL may not truly represent the development of AKI following graft reperfusion. It would be interesting to know if the NGAL levels are elevated in the living donors, as most living donors have a normal renal function posthepatectomy, which will further clarify if the source of NGAL is the liver. Third, the association of low serum albumin levels with a higher incidence of AKI and the protective antioxidant effects of albumin against IRI has been suggested. However, in this study, albumin infusion and increasing serum albumin levels are not protective against AKI. The association of low serum albumin levels with post-LT-AKI is not equivalent to causation. Thus, this idea that intraoperative hypertonic albumin therapy might decrease post-LT-AKI is too simplistic for this essentially complex and multifactorial entity. In conclusion, the novel idea of albumin infusion to decrease the effects of ischemia-reperfusion injury–related AKI is commendable. However, NGAL may not be the best marker to identify the risk of AKI immediately after LT. Further studies are required to address the need for better markers and interventions to mitigate the risk of ischemia-reperfusion injury-related AKI.

BACKGROUND:With the rise of metabolic diseases and aging in liver transplant (LT) candidates, mitral annular calcification (MAC) is more recognizable. Despite cardiovascular risk becoming a leading cause of mortality in LT recipients, the influence of MAC remains unexamined. This study investigates the prevalence, related factors, and impact of MAC on LT outcomes. METHODS:We explored 4148 consecutive LT patients who underwent routine pretransplant echocardiography from 2008 to 2019. Multivariate logistic analysis and the tree-based Shapley additive explanation scores in machine learning were used to evaluate the significant and important related factors. The primary outcome was 30-d major adverse cardiac events (MACE), and the secondary outcome was a median of 5-y cumulative all-cause mortality. RESULTS:MAC was found in 123 (3.0%) patients. Significant and important related factors included age, alcoholic liver disease, chronic kidney disease, hyperuricemia, hypertension, and coronary artery disease. The MACE rate was higher in patients with MAC compared with those without MAC at 30 d ( P < 0.001, adjusted hazard ratio 1.67; 95% confidence interval, 1.08-2.57). Patients with MAC had poorer cumulative overall survival probability compared with those without MAC ( P = 0.0016; adjusted hazard ratio 1.47; 95% confidence interval, 1.01-2.15). Specifically, women with MAC had a poorer survival probability compared with men without MAC (65.0% versus 80.7%, P < 0.001) >10 y post-LT. CONCLUSIONS:The presence of MAC before LT was linked to increased 30-d MACE and lower long-term survival rates, especially in women. Identification and management of MAC and potential risk factors are crucial for improving post-LT survival.

Decompensated cirrhotic patients experience severely increased intestinal permeability and bacterial translocation. Thus, autologous blood salvaged during deceased donor liver transplantation (DDLT) may be contaminated with enteric bacteria. We aimed to evaluate bacterial contamination of autologous blood salvaged during DDLT and its association with post-transplant bacteremia. In 30 patients undergoing DDLT, bacterial culture was performed in salvaged autologous blood samples: one before graft reperfusion (non-leukoreduced) and two after graft reperfusion (non-leukoreduced and leukoreduced). The primary outcome was bacterial contamination of salvaged autologous blood. Seven of 30 patients (23.3%) were positive for bacteria (3 enteric/4 non-enteric) before graft reperfusion while 11 patients (36.7%) were positive (5 enteric/6 non-enteric) after graft reperfusion. Six of 7 patients who were positive for bacteria before graft reperfusion were positive after graft reperfusion with the same bacteria. Only 4 of 11 contaminated blood samples were converted to negative after leukoreduction. Post-transplant bacteremia risk was insignificantly greater in patients who received autologous blood with bacteria than in patients without bacteria (30.0% vs. 5.0%, P = 0.06). We found contamination of salvaged autologous blood with enteric bacteria throughout DDLT and incomplete performance of leukoreduction, indicating high bacterial load. The potential association between contaminated autotransfusion and post-transplant bacteremia warrants further validation in a larger prospective study. Clinical trial notation: This study was registered at the Clinical Research Information Service (CRiS; https://cris.nih.go.kr ; No. KCT0007223; principal registration investigator: Sangbin Han, date of registration: April 25, 2022).

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

Accurately analyzing the functional activities of natural killer (NK) cells in clinical diagnosis remains challenging due to their coupling with other immune effectors. To address this, an integrated immune cell separator is required, which necessitates a streamlined sample preparation workflow including immunological cell isolation, removal of excess red blood cells (RBCs), and buffer exchange for downstream analysis. Here, a self-powered integrated magneto-microfluidic cell separation (SMS) chip is presented, which outputs high-purity target immune cells by simply inputting whole blood. The SMS chip intensifies the magnetic field gradient using an iron sphere-filled inlet reservoir for high-performance immuno-magnetic cell selection and separates target cells size-selectively using a microfluidic lattice for RBC removal and buffer exchange. In addition, the chip incorporates self-powered microfluidic pumping through a degassed polydimethylsiloxane chip, enabling the rapid isolation of NK cells at the place of blood collection within 40 min. This chip is used to isolate NK cells from whole blood samples of hepatocellular cancer patients and healthy volunteers and examined their functional activities to identify potential abnormalities in NK cell function. The SMS chip is simple to use, rapid to sort, and requires small blood volumes, thus facilitating the use of immune cell subtypes for cell-based diagnosis.

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 (< 36.0 °C). The secondary outcomes included plasma lactate concentration. Intraoperative hypothermia risk was significantly lower in prewarming group than in non-prewarming group (60.0% vs. 95.0%, P = 0.020). The difference in hypothermia incidence between groups was greater in the post-induction phase (20.0% vs. 85.0%, P < 0.001) than in the anhepatic or post-reperfusion phase, suggesting that prewarming mainly acts on preventing post-induction core-to-peripheral heat redistribution. Hypothermia duration was significantly shorter in prewarming group (60 [0–221] min vs. 383 [108–426] min, 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.

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.

BACKGROUND:The relationship between intraoperative anesthetic management and postoperative pulmonary complications (PPCs) after liver transplantation is not fully understood. We aimed to determine the intraoperative contributors to PPC. METHODS:The retrospectively collected cohort included 605 patients who underwent living donor liver transplantation. PPCs comprised respiratory failure, respiratory infection, pulmonary edema, atelectasis (at least moderate degree), pneumothorax, and pleural effusion (at least moderate degree). The presence and type of PPC were evaluated by 2 pulmonary physicians. Logistic regression analysis was performed to determine the association between perioperative variables and PPC risk. RESULTS:Of the 605 patients, 318 patients (52.6%) developed 486 PPCs. Multivariable analysis demonstrated that PPC risk decreased with low tidal volume ventilation (odds ratio [OR] 0.62 [0.41-0.94], P  = 0.023) and increased with greater driving pressure at the end of surgery (OR 1.08 [1.01-1.14], P  = 0.018), prolonged hypotension (OR 1.85 [1.27-2.70], P  = 0.001), and blood albumin level ≤3.0 g/dL at the end of surgery (OR 2.43 [1.51-3.92], P  < 0.001). Survival probability at 3, 6, and 12 mo after transplantation was 91.2%, 89.6%, and 86.5%, respectively, in patients with PPCs and 98.3%, 96.5%, and 93.4%, respectively, in patients without PPCs (hazard ratio 2.2 [1.3-3.6], P  = 0.004). Graft survival probability at 3, 6, and 12 mo after transplantation was 89.3%, 87.1%, and 84.3%, respectively, in patients with PPCs and 97.6%, 95.8%, and 92.7%, respectively, in patients without PPCs (hazard ratio 2.3 [1.4-3.7], P  = 0.001). CONCLUSIONS:We found that tidal volume, driving pressure, hypotension, and albumin level during living donor liver transplantation were significantly associated with PPC risk. These data may help determine patients at risk of PPC or develop an intraoperative lung-protective strategy for liver transplant recipients.

Background:Days alive and out of hospital (DAOH) is a simple metric representing the number of days not in hospital within a defined postoperative period. In a case of mortality within the defined period, the DAOH is considered zero. DAOH has been validated in various surgical procedures, but not in living donor liver transplantation (LDLT). This study aimed to demonstrate correlation between DAOH and graft failure after LDLT.Methods:In this cohort study, we identified 1,335 adult-to-adult LDLT performed from June 1997 to April 2019 in our institution. We calculated DAOH at 30, 60, and 90 days among survivors and divided the recipients according to the estimated threshold of each defined period.Results:The median duration of hospital stay after LDLT in the entire population was 25 (interquartile 22-41) days. Mean DAOH of survivors at 30, 60, and 90 days were 3.3 (±3.9), 19.7 (±15.9), and 40.3 (±26.3) days, respectively. We estimated the thresholds associated with three-year graft failure for DAOH at 30, 60, and 90 days and they were 1, 12, and 42 days, respectively. The incidence of graft failure was higher in recipients with short DAOH than long DAOH (10.9% vs. 23.6%, 10.3% vs. 24.3%, and 9.3% vs. 22.2% for DAOH at 30, 60, and 90 days, respectively). Among survivors at 60 days, recipients with short DAOH showed significantly higher incidence of three-year graft failure [hazard ratio (HR), 2.49; 95% confidence interval (CI): 1.86-3.34; P<0.001].Conclusions:Considering clinical situations after LDLT, DAOH at 60 days may be a valid outcome measure.

Greater graft-failure-risk of female-to-male liver transplantation (LT) is thought to be due to acute decrease in hepatic-estrogen-signaling. Our previous research found evidence that female hepatic-estrogen-signaling decreases after 40 years or with macrosteatosis. Thus, we hypothesized that inferiority of female-to-male LT changes according to donor-age and macrosteatosis. We stratified 780 recipients of grafts from living-donors into four subgroups by donor-age and macrosteatosis and compared graft-failure-risk between female-to-male LT and other LTs within each subgroup using Cox model. In recipients with ≤ 40 years non-macrosteatotic donors, graft-failure-risk was significantly greater in female-to-male LT than others (HR 2.03 [1.18–3.49], P = 0.011). Within the subgroup of recipients without hepatocellular carcinoma, the inferiority of female-to-male LT became greater (HR 4.75 [2.02–11.21], P < 0.001). Despite good graft quality, 1y-graft-failure-probability was 37.9% (23.1%–57.9%) in female-to-male LT within this subgroup while such exceptionally high probability was not shown in any other subgroups even with worse graft quality. When donor was > 40 years or macrosteatotic, graft-failure-risk was not significantly different between female-to-male LT and others ( P > 0.60). These results were in agreement with the estrogen receptor immunohistochemistry evaluation of donor liver. In conclusion, we found that the inferiority of female-to-male LT was only found when donor was ≤ 40 years and non-macrosteatotic. Abrogation of the inferiority when donor was > 40 years or macrosteatotic suggests the presence of dominant contributors for post-transplant graft-failure other than graft quality/quantity and supports the role of hepatic-estrogen-signaling mismatch on graft-failure after female-to-male LT.

Laparoscopic donor hepatectomy is being increasingly adopted in transplant programs due to its numerous advantages. However, the role of intrathecal morphine (ITM) in laparoscopic donor hepatectomy has not been thoroughly investigated. This study aimed to compare the analgesic effects and safety of ITM between laparoscopic and open donor hepatectomy. This retrospective study included 742 donors who underwent hepatectomy with ITM between April 2007 and June 2019. Among them, 168 and 574 donors underwent laparoscopic hepatectomy (LH) and open hepatectomy (OH), respectively. Propensity score matching yielded two comparable groups of 168 donors each. The primary endpoint was the incidence of moderate-to-severe pain (maximum numerical rating scale [NRS] pain score >= 4) within 24 postoperative hours. The LH group had a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours than the OH group (16.1% vs 64.3%, P < .001). Moreover, the cumulative rescue intravenous opioids (in morphine-equivalent dose) on postoperative day (POD) 1 was lower in the LH group than in the OH group (3.3 [0-8.3] mg vs 10 [3.3-17.3] mg; P < .001). There were no significant between-group differences in the incidence of respiratory depression (2.4% vs 0.6%; P = .371) and prescriptions for pruritus (14.3% vs 15.5%; P = .878). However, the prescriptions for postoperative nausea and vomiting (PONV) was significantly higher in the LH group than in the OH group (64.9% vs 41.7%; P < .001). The predictors of antiemetic agent prescription included the use of laparoscopic procedure (adjusted odds ratio [OR], 2.05; 95% confidence interval [CI], 1.11-3.79; P = .021) and female sex (adjusted OR, 5.63; 95% CI, 3.19-9.92; P < .001). Preoperative ITM administration resulted in a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours after laparoscopic donor hepatectomy than after open donor hepatectomy.

Background The Portland intensive insulin therapy effectively controls acute hyperglycemic change after graft reperfusion during liver transplantation. However, the time-consuming sophistication acts as a barrier leading to misinterpretation and decreasing compliance to the protocol; thus, we newly introduced an application software “Insulin protocol calculator” which automatically calculates therapeutic bolus/continuous insulin doses based on the Portland protocol. Methods Of 144 patients who underwent liver transplantation, 74 patients were treated before the introduction of "Insulin protocol calculator" by using a paper manual, and 70 patients were treated by using the application. Compliance was defined as the proportion of patients treated with exact bolus/continuous insulin dose according to the Portland protocol. Results Compliance was significantly greater in app group than in paper group regarding bolus dose (94.5% and 86.9%, P < 0.001), continuous dose (88.9% and 77.3%, P = 0.001), and both doses (86.6% and 73.8%, P < 0.001). Blood glucose concentration was significantly lower in app group at 3 h (125 ± 17 mg/dl vs. 136 ± 19 mg/dl, P = 0.014) and 4 h (135 ± 22 mg/dl vs. 115 ± 15 mg/dl, P = 0.029) after graft reperfusion. Acute hyperglycemic change during 30 min was more prominent in app group while hyperglycemia incidence was 71.4% vs. 54.1% (P = 0.031). However, hyperglycemia risk was comparable at 2 h (31.4% vs. 31.1%, P = 0.964), and even insignificantly lower in app group at 3 h (7.1% vs. 19.5%, P = 0.184). Conclusions Compliance to the Portland protocol was significantly improved after introducing the application software; post-reperfusion hyperglycemia was better controlled. “Insulin protocol calculator” is cost-effective and time-saving with potential clinical benefits.

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.

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.

Objective: The aim of this study was 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 of 129 without autotransfusion were matched with 74 of 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 nonautotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the 2 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)]. Conclusions: 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.