Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2023? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registered delegates from 54 countries representing 5 continents, with the 10 countries comprising the bulk of the delegates. Of the 647 abstracts initially submitted, 542 were eventually presented at the meeting, coming from 38 countries (mainly North America, Europe, and Asia) and 85% of them (462 abstracts) came from only 10 countries. Fifty-three (9.8%) abstracts, originated from 17 countries, were submitted under the Basic/Translational Scientific Research category, a similar percentage as in 2022. Abstracts presented at the meeting were classified as (1) ischemia and reperfusion injury, (2) machine perfusion, (3) bioengineering and liver regeneration, (4) transplant oncology, (5) novel biomarkers in liver transplantation, (6) liver immunology (rejection and tolerance), and (7) artificial intelligence and machine learning. Finally, we evaluated the number of abstracts commented in the Basic and Translational Research Committee-International Liver Transplantation Society annual reports over the past 5 y that resulted in publications in peer-reviewed journals to measure their scientific impact in the field of liver transplantation.

Concomitant training in robotic and laparoscopic liver resections of low-to-intermediate difficulty score: a retrospective analysis of the learning curve.

In the setting of minimally invasive liver surgery (MILS), training in robotic liver resections (RLR) usually follows previous experience in laparoscopic liver resections (LLR). The aim of our study was to assess the learning curve of RLR in case of concomitant training with LLR. We analyzed consecutive RLRs and LLRs by a surgeon trained simultaneously in both techniques (Surg1); while a second surgeon trained only in LLRs was used as control (Surg2). A regression model was used to adjust for confounders and a Cumulative Sum (CUSUM) analysis was carried out to assess the learning phases according to operative time and difficulty of the procedures (IWATE score). Two-hundred-forty-five procedures were identified (RobSurg1, n = 75, LapSurg1, n = 102, LapSurg2, n = 68). Mean IWATE was 4.0, 4.3 and 5.8 (p < 0.001) in each group. The CUSUM analysis of the adjusted operative times estimated the learning phase in 40 cases (RobSurg1), 40 cases (LapSurg1), 48 cases (LapSurg2); for IWATE score it was 38 cases (RobSurg1), 33 cases (LapSurg1), 38 cases (LapSurg2) respectively. Our preliminary experience showed a similar learning curve of 40 cases for low and intermediate difficulty RLR and LLR. Concomitant training in both techniques was safe and may be a practical option for starting a MILS program.

First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.

Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience.

BACKGROUND: The advantages of the robotic approach in minimally invasive liver surgery (MILS) are still debated. This study compares the short-term outcomes between laparoscopic (LLR) and robotic (RLR) liver resections in propensity score matched cohorts. METHODS: Data regarding minimally invasive liver resections in two liver surgery units were retrospectively reviewed. A propensity score matched analysis (1:1 ratio) identified two groups of patients with similar characteristics. Intra- and post-operative outcomes were then compared. The difficulty of MILS was based on the IWATE criteria. RESULTS: Two hundred sixty-nine patients underwent MILS between January 2014 and December 2021 (LLR = 192; RLR = 77). Propensity score matching identified 148 cases (LLR = 74; RLR = 74) consisting of compensated cirrhotic patients (100%) underwent non-anatomic resection of IWATE 1-2 class (90.5%) for a solitary tumor < 5 cm in diameter (93.2%). In such patients, RLRs had shorter operative time (227 vs. 250 min, p = 0.002), shorter Pringle's cumulative time (12 vs. 28 min, p < 0.0001), and less blood loss (137 vs. 209 cc, p = 0.006) vs. LLRs. Conversion rate was nihil (both groups). In RLRs compared to LLRs, R0 rate (93 vs. 96%, p > 0.71) and major morbidity (4.1 vs. 5.4%, p > 0.999) were similar, without post-operative mortality. Hospital stay was shorter in the robotic group (6.2 vs. 6.6, p = 0.0001). CONCLUSION: This study supports the non-inferiority of RLR over LLR. In compensated cirrhotic patients underwent resection of low-to-intermediate difficulty for a solitary nodule < 5 cm, RLR was faster, with less blood loss despite the shorter hilar clamping, and required shorter hospitalization compared to LLR.

A narrative review of intrahepatic cholangiocarcinoma: a surgical curative option.

BACKGROUND AND OBJECTIVE: Cholangiocarcinoma (CCA) is the second commonest primary liver malignancy. Nowadays, the only available treatment with curative intent of intrahepatic cholangiocarcinoma (iCCA) is surgical resection, with a 5-year overall survival (OS) of 25-40%. However, recurrence rate remains high. In this comprehensive review, we describe the newest surgical strategies for iCCA management, including vascular resection, the role of mini-invasive surgery, liver transplant, strategies for future liver remnant augmentation, and the role of neoadjuvant therapies. METHODS: A review of medical databases (PubMed, Scopus and Cochrane Database) was conducted selecting most relevant articles in English language without a specific timeframe. KEY CONTENT AND FINDINGS: Multifocal presentation, vascular, perineural invasion, and lymph nodes involvement are associated with poor outcome. Prognostic factors are being investigated to improve therapeutic approach and outcomes. The role of lymph nodes dissection remains debated. Harvesting at least 6 lymph nodes is recommended to ensure accurate nodal staging. Liver transplantation (LT) recently represented a treatment option only in patients with unresectable early disease (≤2 cm). CONCLUSIONS: Surgical resection remains the only potentially curative treatment for patients with CCA, but continue understanding in diagnosis, operative technique and chemotherapies are changing the landscape in the prognosis. Multicentric and randomized studies are necessaries in the future research with the intent to personalize the treatments, improve patient selection for the resection and reduce recurrence rate.

New Insights in the Setting of Transplant Oncology.

Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT's impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required.

Outcome of liver transplantation in elderly patients: an Italian multicenter case-control study.

Despite the controversial results of liver transplantation (LT) in elderly recipients, the proportion of patients continues to increase. This study investigated the outcome of LT in elderly patients (≥ 65 years) in an Italian, multicenter cohort. Between January 2014 and December 2019, 693 eligible patients were transplanted, and two groups were compared: recipients ≥ 65 years (n = 174, 25.1%) versus 50-59 years (n = 519, 74.9%). Confounders were balanced using a stabilized inverse probability therapy weighting (IPTW). Elderly patients showed more frequent early allograft dysfunction (23.9 versus 16.8%, p = 0.04). Control patients had longer posttransplant hospital stays (median: 14 versus 13 days; p = 0.02), while no difference was observed for posttransplant complications (p = 0.20). At multivariable analysis, recipient age ≥ 65 years was an independent risk factor for patient death (HR 1.76; p = 0.002) and graft loss (HR 1.63; p = 0.005). The 3-month, 1-year, and 5-year patient survival rates were 82.6, 79.8, and 66.4% versus 91.1, 88.5, and 82.0% in the elderly and control group, respectively (log-rank p = 0.001). The 3-month, 1-year, and 5-year graft survival rates were 81.5, 78.7, and 66.0% versus 90.2, 87.2, and 79.9% in the elderly and control group, respectively (log-rank p = 0.003). Elderly patients with CIT > 420 min showed 3-month, 1-year, and 5-year patient survival rates of 75.7%, 72.8%, and 58.5% versus 90.4%, 86.5%, and 79.4% for controls (log-rank p = 0.001). LT in elderly (≥ 65 years) recipients provides favorable results, but inferior to those achieved in younger patients (50-59), especially when CIT > 7 h. Containment of cold ischemia time seems pivotal for favorable outcomes in this class of patients.

The role of sequential normothermic regional perfusion and end-ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death.

The use of pre-procurement normothermic regional perfusion (NRP) allowed us to implement controlled DCD liver transplantation with results comparable to brain death donors, but the use of uncontrolled DCD is declining due to logistic challenges and the high incidence of post-transplant complications. In Italy, the mandatory stand-off period of 20 min for DCD donors has driven the combined use of NRP and ex-situ machine perfusion with the intent to counterbalance the negative impact of prolonged warm ischemia. Organ viability during NRP is based on duration of warm ischemia, regional perfusion flow, lactate, transaminases values and histology, and those used in Italy are the widest worldwide. However, this evaluation can be difficult, especially when the acute damage is particularly severe. The use of ex-situ NRP could provide a safe organ evaluation. In the period from 06/2020 to 06/2022, all DCD grafts exceeding NRP viability criteria at a single center were eventually evaluated using ex-situ normothermic machine perfusion. Machine perfusion viability criteria were based on lactate clearance, irrespectively to bile production, unless 1-h transaminases perfusate level were not exceeding 5000 IU/L. Three cases of uncontrolled DCD grafts in excess of NRP viability criteria underwent ex-situ graft evaluation. Two matched ex-situ normothermic machine perfusion viability criteria and were successfully transplanted. Both recipients are doing well after 26 and 5 months after surgery with no signs of ischemic cholangiopathy. This experience suggests that the sequential use of NRP and normothermic machine perfusion may further expand the boundaries of organ viability in uncontrolled DCD liver transplantation.

Proposal and validation of a liver graft discard score for liver transplantation from deceased donors: a multicenter Italian study.

Several studies have explored the risk of graft dysfunction after liver transplantation (LT) in recent years. Conversely, risk factors for graft discard before or at procurement have poorly been investigated. The study aimed at identifying a score to predict the risk of liver-related graft discard before transplantation. Secondary aims were to test the score for prediction of biopsy-related negative features and post-LT early graft loss. A total of 4207 donors evaluated during the period January 2004-Decemeber 2018 were retrospectively analyzed. The group was split into a training set (n = 3,156; 75.0%) and a validation set (n = 1,051; 25.0%). The Donor Rejected Organ Pre-transplantation (DROP) Score was proposed: - 2.68 + (2.14 if Regional Share) + (0.03*age) + (0.04*weight)-(0.03*height) + (0.29 if diabetes) + (1.65 if anti-HCV-positive) + (0.27 if HBV core) - (0.69 if hypotension) + (0.09*creatinine) + (0.38*log10AST) + (0.34*log10ALT) + (0.06*total bilirubin). At validation, the DROP Score showed the best AUCs for the prediction of liver-related graft discard (0.82; p < 0.001) and macrovesicular steatosis ≥ 30% (0.71; p < 0.001). Patients exceeding the DROP 90th centile had the worse post-LT results (3-month graft loss: 82.8%; log-rank P = 0.024).The DROP score represents a valuable tool to predict the risk of liver function-related graft discard, steatosis, and early post-LT graft survival rates. Studies focused on the validation of this score in other geographical settings are required.

Implementing a robotic liver resection program does not always require prior laparoscopic experience.

BACKGROUND: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program. METHODS: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs. 67; p = 0.74), male sex (62.5% vs. 59.6%; p = 0.96), incidence of chronic liver disease (97.5% vs.98.1%; p = 0.85), median model for end-stage liver disease (MELD) score (8 vs. 9; p = 0.92), and median largest nodule size (22 vs. 24 mm) were similar between RLR and LLR. In the LLR group, there was a numerically higher incidence of nodules located in segment 4 (20.0% vs. 16.6%; p = 0.79); a numerically higher use of Pringle's maneuver (32.7% vs. 20%; p = 0.23), and a shorter duration of surgery (median of 165.5 vs. 217.5 min; p = 0.04). Incidence of complications (25% vs.32.7%; p = 0.49), blood transfusions (2.5% vs.9.6%; p = 0.21), and median length of stay (6 vs. 5; p = 0.54) were similar between RLR and LLR. The overall (OS) and recurrence-free (RFS) survival rates at 1 and 5 years were 100 and 79 and 95 and 26% for RLR versus 96.2 and 76.9 and 84.6 and 26.9% for LLR (log-rank p = 0.65 for OS and 0.72 for RFS). CONCLUSIONS: Based on our results, concurrent implementation of a robotic and laparoscopic liver resection program appears feasible and safe, and is associated with similar oncologic long-term outcomes.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

The impact of hepatitis C virus direct acting agents in liver transplant using very old donor grafts: a real-world single-center analysis.

The correct timing of use of direct acting agents (DAAs) among transplanted patients remains unknown. The aim of this paperwork is to evaluate the impact of DAAs treatment in pre- or peri-operative period in liver transplantation when grafts ≥ 70 years are used. This is a retrospective analysis comparing adult liver transplant performed for HCV-related cirrhosis and/or hepatocarcinoma using a graft ≥ 70 in the period 2015-2018 (Group DAA-HCV-OLD, study group) to three different groups: (a) anti-HCV-Ab-negative patients receiving graft ≥ 70 (no-HCV-OLD), (b) anti-HCV-Ab-negative patients receiving a graft aged 18-69 years (no-HCV-YOUNG), and (c) anti-HCV-Ab-positive patients receiving a donor graft ≥ 70 in the period 2007-2011 (no-DAA-HCV-OLD). Totally, 528 liver transplants were considered: 164 in DAA-HCV-OLD, 143 in no-HCV-OLD, 120 in no-HCV-YOUNG and 101 in no-DAA-HCV-OLD Group. Graft survival rates at 1 and 3 years were 88% and 81% in DAA-HCV-OLD Group, 82% and 68% in no-DAA-HCV-OLD (p = 0.007), 89% and 84% in no-HCV-OLD (p = 0.76), and 94% and 92% in no-HCV-YOUNG (p = 0.02). No differences were observed among groups in the incidence of primary non-function, primary dysfunction, vascular or biliary complications. DAAs were able to zero HCV-related graft loss, with a 3-year graft survival > 80%. The outcomes of older graft recipients became equal irrespectively of their HCV serological status.

Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation.

Liver transplantation (LT) is the first-line treatment for patients diagnosed with unresectable early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. It is well known that HCC patients within the Milan criteria (solitary tumour ≤ 5 cm or ≤3 tumours, each <3 cm) could undergo LT with excellent results. However, there is a growing tendency to enlarge inclusion criteria since the Milan criteria are nowadays considered too restrictive and may exclude patients who would benefit from LT. On the other hand, there is a persistent shortage of donor organs. In this scenario, there is consensus about the role of loco-regional therapy (LRT) during the waiting list to select patients who would benefit more from LT, reducing the risk of drop off from the waiting list as well as decreasing tumour dimension to meet acceptable criteria for LT. In this review, current evidence on the safety, efficacy and utility of LRTs as neoadjuvant therapies before LT are summarized.

Morbidity and mortality of iatrogenic hemothorax occurring in a cohort of liver transplantation recipients: a multicenter observational study.

Hemothorax (HT) is a life-threatening condition, mainly iatrogenic and poorly explored in Liver Transplantation (LT) recipients. The aim of this study is to report and analyze for the first time incidence and outcomes of HT in LT recipients, as well as to suggest a management strategy. Data concerning 7130 consecutive adult liver and liver-kidney transplant recipients were retrospectively collected from ten Transplantation Centers' institutional databases, over a 10-year period. Clinical parameters, management strategies and survival data about post-operative HT were analyzed and reported. Thirty patients developed HT during hospitalization (0.42%). Thoracentesis was found to be the most common cause of HT (16 patients). A non-surgical management was performed in 17 patients, while 13 patients underwent surgery. 19 patients developed thoracic complications after HT treatment, with an overall mortality rate of 50%. The median length of stay in Intensive Care Units was 22 days (IQR25-75 5-66.5). Postoperative hemothorax is mainly due to iatrogenic causes in LT recipients. Despite rare, it represents a serious complication with a high mortality rate and a challenging medical and surgical management. Its occurrence should always be prevented.

Microwave Ablation of Very-Early- and Early-Stage HCC: Efficacy Evaluation by Correlation with Histology after Liver Transplantation.

Microwave (MW) ablation is a worldwide-diffused technique for the percutaneous ablation of hepatocellular carcinoma (HCC). Nevertheless, the efficacy of this technique still needs to be confirmed in pathological specimens. The purpose of this study was to evaluate the efficacy of MW ablation by correlation with histology in excised liver samples at the time of liver transplantation (LT). All patients with MW-ablated HCC who subsequently underwent LT between 2012 and 2020 were retrospectively evaluated. In the explanted livers, the treated lesions were evaluated at pathology, and the necrosis was classified as complete or partial. Thirty-six HCCs were ablated in 30 patients (20.9 ± 6.1 mm, a range of 10-30 mm). Ablations were performed with a single insertion of a MW antenna under ultrasound or CT guidance. A complete radiological response was demonstrated in 30/36 nodules (83.3%) in 24/30 patients (80%) at imaging performed one-month after MW ablation. At pathology, of the 36 treated nodules, 28 (77.8%) showed a complete necrosis, and 8 (22.2%) showed a pathological partial necrosis. Good agreement was found between the imaging performed one-month after treatment and the complete pathological response (Cohen's k = 0.65). The imaging accuracy in detecting a complete response to treatment was 88.9%. All lesions with complete necrosis did not show recurrence at follow-up imaging until transplantation. The rad-path correlation in the explanted livers showed that MW ablation achieved a high rate of complete necrosis if a macroscopical complete ablation was obtained.

Comparison between galectin-3 and YKL-40 levels for the assessment of liver fibrosis in cirrhotic patients.

BACKGROUND AND STUDY AIMS: The circulatory levels of Galectin-3 and YKL-40 are considered as candidate biomarkers for the noninvasive assessment of liver fibrosis. This study aimed to evaluate the plasma protein profiles of Galectin-3 and YKL-40 in patients with cirrhosis (with and without hepatocellular carcinoma [HCC]) who underwent deceased-donor liver transplantation (LT), before and after surgery. PATIENTS AND METHODS: The plasma levels of Galectin-3 and YKL-40 were assessed in 46 subjects, including 24 liver graft recipients (before, 1 day after, and 1 month after LT) and 22 healthy controls using enzyme-linked immunosorbent assays. RESULTS: The levels of Galectin-3 and YKL-40 in the LT recipients before the transplant were significantly higher than those in the healthy controls (p < 0.001 and p < 0.01, respectively). YKL-40 levels returned to normal within 1 day after LT, whereas those of Galectin-3 decreased 1 day after LT and returned to normal levels after 1 month. The levels of both proteins did not differ between patients with and without HCC. Unlike YKL-40, the pre-transplant levels of Galectin-3 were directly correlated to that of aspartate aminotransferase (AST; r = 0.473, p = 0.01), alanine aminotransferase (r = 0.395, p = 0.04), total bilirubin (r = 0.545, p = 0.003), and lactate dehydrogenase (r = 0.452, p = 0.02) and to the AST to platelet ratio index (APRI; r = 0.411, p = 0.03) and Child-Pugh score (r = 0.601, p < 0.001). Galectin-3 levels increased significantly according to the severity of cirrhosis (25.9 ± 2.7; 57.4 ± 29.6; and 81 ± 27 ng/mL in Class A, B, and C cirrhosis, respectively), whereas those of YKL-40 tended to be higher in the Class C patients compared to the Class A patients (8.9 ± 2.6 vs. 7.4 ± 0.8 ng/mL). CONCLUSION: Circulating levels of Galectin-3 could be an indicator of liver damage and inflammation that are correlated with fibrosis.

Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.