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Background: Prone position has been proven to improve ventilation and oxygenation in infants. Currently, there are few reports of early prone position ventilation after pediatric liver transplantation. Here, we present our experience with prone position in an infant following living donor liver transplantation, in an attempt to improve oxygenation., Case Presentation: An 8-month-old boy, 7.5 kg, experienced two failed extubations that presented with Type II respiratory failure due to dyspnea, potentially caused by consolidation and airway secretions. To prevent the third failure of extubation, prone position ventilation was implemented after the third extubation on the 11th postoperative day. Oxygenation increased after each prone position session with no signs of transplant liver ischemia or other adverse outcomes. Following two days of continuous prone position, airway secretions decreased, and the infant was discharged from the ICU. The third extubation procedure was successful., Conclusions: Prone position ventilation may be effective in this infant without adverse events, indicating that early prone position is not absolutely contraindicated after pediatric liver transplantation. Therefore, more reasonable prone position strategies should be sought in infants undergoing liver transplantation., (© 2024. The Author(s).)

Background: Hypothermic Oxygenated machine PErfusion (HOPE) can reduce ischemic reperfusion injury and improve outcomes for liver transplant recipients. However, the effect of HOPE on high-risk extended criteria donor (ECD) and donation after circulatory death determination (DCDD) grafts is incomplete, despite the expectation that this cohort benefit maximally from HOPE. Accordingly, this paper aims to characterize the effect of HOPE on ECD and DCDD grafts., Methods: This study includes all papers comparing HOPE to static cold storage for high-risk ECD and DCDD grafts. Systematic searches of Medline, Embase, and Scopus were completed using the terms "HOPE" OR "hypothermic oxygenated machine perfusion" AND "liver transplantation". Data were extracted and analyzed using IBM SPSS to perform the meta-analysis., Results: A total of 2286 records were identified, with 10 meeting the inclusion criteria. Overall, the quality of evidence is heterogenous with many papers relying on retrospective controls. However, pooled analysis demonstrates HOPE to significantly reduce the rate of early allograft dysfunction, 12-month graft failure, re-transplantation, total biliary complications, and non-anastomotic strictures for high-risk grafts., Conclusions: There is good evidence that HOPE improves outcomes following liver transplantation across a number of biochemical and clinical endpoints for high-risk grafts. Of note, the reduction in biliary complications and re-transplantation is particularly significant given the morbidity associated with these endpoints. However, further, high-quality prospective trials with contemporary controls and clinically relevant primary endpoints are needed to better define the impact of HOPE for this cohort of grafts., (© 2024 The Author(s). Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Immunotherapy has revolutionised the treatment of advanced hepatocellular carcinoma (HCC). In addition, several phase III trials of immunotherapy in combination with surgical or locoregional therapies for early-to intermediate-stage HCC have recently reported positive results, and other phase III trials in the same patient population are currently in progress. As the application of immunotherapy is shifting to include patients with earlier stages of HCC, one looming question now emerges: What is the role of immunotherapy in the pre-liver transplant population? Liver transplantation is a potentially curative therapy for HCC and confers the additional advantage of restoring a normal, healthy liver. In pre-transplant patients, immunotherapy may improve downstaging success and tumour control at the cost of some immunologic risks. These include immune-related toxicities, which are particularly relevant in a uniquely vulnerable population with chronic liver disease, and the possibility of acute rejection after transplantation. Ultimately, the goal of immunotherapy in this population will be to effectively expand access to liver transplantation while preserving pre- and post-transplant outcomes. In this review, we discuss the mechanisms supporting combination immunotherapy, summarise key recent clinical data from major immunotherapy trials, and explore how immunotherapy can be applied in the neoadjuvant setting prior to liver transplantation in selected high-risk patients., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare no funding or conflicts of interest.

Background: Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are organ procurement and transport techniques that can improve organ quality, facilitate longer transport, and reduce postoperative complications, increasing organ availability and improving outcomes. NRP and NMP often require allogeneic red blood cells (RBCs). Our academic transfusion service began providing RBCs to support NRP and NMP for adult heart transplant (HT), orthotopic liver transplant (OLT), and multiorgan transplant (MOT) in August 2020., Methods: This single-center, retrospective study describes the implementation process and analyzes the characteristics of RBC support during the first 3 years of the perfusion programs. Timing and quantity of units issued and used, organ recipient demographics, and transplant outcomes were obtained from transfusion service and electronic medical records., Results: From 2020 to 2023, the transfusion service received 233 requests to support NRP and NMP perfusion cases. Of these, 105 cases resulted in RBC use, and units were returned or discarded in 112 cases. A total of 131 patients received perfusion-facilitated transplants (92 HT, 27 OLT, and 12 MOT). The majority of perfusion-facilitated HTs utilized NRP (81/92, 88%), whereas most perfusion-facilitated OLTs utilized NMP (21/27, 78%). Across all 233 requests, a total of 381 RBC units were used to facilitate 131 transplants, averaging 2.91 units/transplant., Discussion: Provision of RBCs for NRP and NMP techniques represents a novel method for transfusion services to support and facilitate life-saving organ transplants with only modest product use, about three RBC units per organ transplant in this single-center study., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

In the United States, the discrepancy between organ availability and need has persisted despite changes in allocation, innovations in preservation, and policy initiatives. Living donor liver transplant remains an underutilized means of improving access to timely liver transplantation and decreasing waitlist mortality. Liver paired exchange (LPE) represents an opportunity to overcome living donor liver transplant pair incompatibility due to size, anatomy, or blood type. LPE was adopted as a strategy to augment access to liver transplantation at our institution. Specific educational materials, consent forms, and selection processes were developed to facilitate LPE. From 2019 through October 2023, our center performed 11 LPEs, resulting in 23 living donor liver transplant pairs. The series included several types of LPE: those combining complementary incompatible pairs, the inclusion of compatible pairs to overcome incompatibility, and the use of altruistic nondirected donors to initiate chains. These exchanges facilitated transplantation for 23 recipients, including 1 pediatric patient. LPE improved access to liver transplantation at our institution. The ethical application of LPE includes tailored patient education, assessment and disclosure of exchange balance, mitigation of risk, and maximization of benefit for donors and recipients., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss., Methods: In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively., Results: We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78-184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg (p < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m 2 to 23.8 ± 3.1 kg/m 2 (p < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p = 0.3185). The graft and recipient survival rates were comparable between the groups (p = 1.000)., Conclusion: Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background: Three-dimensional reconstruction of the liver offers several advantages to the surgeon before and during liver resection. This review discusses the factors behind the use of liver 3-D reconstruction., Methods: Systematic electronic search, according to PRISMA criteria, was performed. A literature search of scientific papers was performed until October 2023. Articles were chosen based on reference to 3-D liver reconstruction and their use in liver surgery. GRADE methodology and the modified Newcastle-Ottawa scale were used to assess the quality of the studies., Results: The research included 47 articles and 7724 patients were analyzed. Preoperative planning was performed with 3-D liver reconstruction in the 87.2% of the studies. Most of preoperative 3-D liver reconstructions were performed in the planning of complex or major hepatectomies. Complex hepatectomies were performed in 64.3% patients. The 55.3% of the studies reported an improved navigation and accuracy during liver resection. Four studies (8.6%) on living donor liver transplant (LDLT) concluded that 3-D liver reconstruction is useful for graft selection and vascular preservation. Nine papers (19.1%) reported an accurate measurement of future liver remnant., Conclusion: Liver 3-D reconstruction helps surgeons in the planning of liver surgery, especially in liver graft and complex liver resections, increasing the accuracy of the surgical resection., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Surgical resection and liver transplantation (LT) are the most effective curative options for hepatocellular carcinoma (HCC). However, few patients with huge HCC (> 10 cm in diameter), especially those with portal vein tumor thrombus (PVTT), can receive these treatments. Selective internal radiation therapy (SIRT) can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume. However, in patients with huge HCC, high lung absorbed dose often prevents them from receiving SIRT., Case Summary: A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month. The computed tomography scan showed a 20.2 cm × 19.8 cm tumor located in the right lobe-left medial lobes with right portal vein and right hepatic vein invasion. After the pathological type of HCC was confirmed by biopsy, two conversions were presented. The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab, converted to SIRT, and the second one was sequential SIRT with continued systemic treatment. The tumor size significantly decreased from 20.2 cm × 19.8 cm to 16.2 cm × 13.8 cm, then sequentially to 7.8 cm × 6.8 cm. In the meantime, the ratio of spared volume to total liver volume increased gradually from 34.4% to 55.7%, then to 62.9%. Furthermore, there was visualization of the portal vein, indicating regression of the tumor thrombus. Finally, owing to the new tumor in the left lateral lobe, the patient underwent LT instead of resection without major complications., Conclusion: Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially., Competing Interests: Conflict-of-interest statement: All the authors have no relevant conflicts of interest to declare for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Pure laparoscopic donor hepatectomy (PLDH) has become a standard practice for living donor liver transplantation in expert centers. Accurate understanding of biliary structures is crucial during PLDH to minimize the risk of complications. This study aims to develop a deep learning-based segmentation model for real-time identification of biliary structures, assisting surgeons in determining the optimal transection site during PLDH. A single-institution retrospective feasibility analysis was conducted on 30 intraoperative videos of PLDH. All videos were selected for their use of the indocyanine green near-infrared fluorescence technique to identify biliary structure. From the analysis, 10 representative frames were extracted from each video specifically during the bile duct division phase, resulting in 300 frames. These frames underwent pixel-wise annotation to identify biliary structures and the transection site. A segmentation task was then performed using a DeepLabV3+ algorithm, equipped with a ResNet50 encoder, focusing on the bile duct (BD) and anterior wall (AW) for transection. The model's performance was evaluated using the dice similarity coefficient (DSC). The model predicted biliary structures with a mean DSC of 0.728 ± 0.01 for BD and 0.429 ± 0.06 for AW. Inference was performed at a speed of 15.3 frames per second, demonstrating the feasibility of real-time recognition of anatomical structures during surgery. The deep learning-based semantic segmentation model exhibited promising performance in identifying biliary structures during PLDH. Future studies should focus on validating the clinical utility and generalizability of the model and comparing its efficacy with current gold standard practices to better evaluate its potential clinical applications., (© 2024. The Author(s).)

Despite being the standard treatment for end-stage liver disease, liver transplantation has limitations like donor scarcity, high surgical costs, and immune rejection risks. Mesenchymal stem cells (MSCs) and their derivatives offer potential for liver regeneration and transplantation. MSCs, known for their multipotency, low immunogenicity, and ease of obtainability, can differentiate into hepatocyte-like cells and secrete bioactive factors that promote liver repair and reduce immune rejection. However, the clinical application of MSCs is limited by risks such as aberrant differentiation and low engraftment rates. As a safer alternative, MSC-derived secretomes and extracellular vesicles (EVs) offer promising therapeutic benefits, including enhanced graft survival, immunomodulation, and reduced ischemia-reperfusion injury. Current research highlights the efficacy of MSC-derived therapies in improving liver transplant outcomes, but further studies are necessary to standardize clinical applications. This review highlights the potential of MSCs and EVs to address key challenges in liver transplantation, paving the way for innovative therapeutic strategies.

BACKGROUND End-stage hepatic alveolar echinococcosis (AE) can result in cavernous transformation of the portal vein (CTPV) due to extensive invasion of the portal vein. Ex vivo liver resection and autotransplantation (ELRA) is a new treatment option for patients with end-stage hepatic AE combined with CTPV. ELRA can achieve radical resection of HAE lesions and vascular reconstruction, and also effectively controls bleeding, particularly in cases involving multiple tortuous PV collaterals. Unfortunately, postoperative complications related to the portal vein can impede liver blood flow, thereby increasing the risk of portal hypertension and eventual failure of the transplanted liver if not promptly treated through appropriate medical interventions. CASE REPORT We report the case of a 31-year-old woman who underwent ELRA for end-stage hepatic AE combined with CTPV, and early postoperative portal vein anastomotic stenosis occurred. Stenting of the portal vein was performed after clarification of the stenotic segment by portal venography, followed by anticoagulation therapy and close ultrasound follow-up. After the operation, the patient's portal vein anastomosis widened and the blood flow into the liver returned to normal, avoiding graft liver failure. At 3-year follow-up, the portal vein stent was patent and no serious portal vein complications such as thrombosis had occurred. CONCLUSIONS ELRA provides a new therapeutic approach for patients with HAE combined with CTPV, and intraoperative portal vein reconstruction is one of the key procedures. For CTPV patients with early postoperative portal vein stenosis, interventional therapy (IVR) offers fresh perspectives and avoids acute liver failure caused by liver hypoperfusion.

Percutaneous transhepatic biliary drainage (PTBD) is commonly used in the treatment of malign and benign biliary pathologies. Certain complications after PTBD may occur, such as biliary fistula, biliary leakage, bilioma, and hematoma. The purpose of this study was to evaluate the safety and effectiveness of using a sterile gelatin sponge to seal the biliary tract after PTBD in patients with liver transplants to prevent complications. A total of 131 biliary drainages were introduced in 97 patients, and a sterile gelatin sponge was used to seal the biliary tract after removal of the biliary drainage catheter. The patients were immediately examined for complications using ultrasound and then followed up clinically unless imaging was required. Five fluid collections within the liver with a diameter <2 cm, consistent with hematoma or bilioma, were resolved spontaneously. No hematoma or bilioma required treatment, and no biliary leakage or fistula was detected. No compli¬cations related to the use of the sponge were observed. The use of a sterile gelatin sponge is a safe and effec-tive method for sealing the biliary tract to prevent complications after PTBD in patients with liver transplants.

Pioneer studies suggested that liver transplantation (LT) has the potential to provide long-term survival in patients with liver-limited metastatic colorectal cancer (mCRC) not amenable for surgery of metastases. Evidence, however, was limited to single-arm studies with few patients enrolled and suboptimal selection criteria, with concerns over access to organ availability overcoming the potential efficacy of LT in this setting. Recently, 5-year survival rates with chemotherapy followed by LT (73%) compared with chemotherapy alone (9%) have been demonstrated by the randomized TransMet trial, enrolling 94 definitively unresectable strictly selected liver-limited mCRC patients. These findings should now prompt clinical oncologists to reconsider LT as a valuable option for unresectable liver-limited mCRC patients meeting TransMet criteria, and transplantation agencies to adapt their policies of access to organ donation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: To review the impact of the operating microscope (OM) for reconstruction of the hepatic artery (HA) by comparing the outcomes with standard loupe reconstruction (SL) in pediatric liver transplantation (LT)., Methods: Studies comparing the application of OM and SL for the reconstruction of the HA in primary pediatric LT were included from a systematic search of MEDLINE, Cochrane Library and EMBASE from inception to June 2022. Re-transplantation, dual grafts and auxiliary transplants were excluded. Primary outcome was the rate of HA thrombosis (HAT). Secondary outcomes were graft loss and mortality., Results: There were 1261 liver recipients from 9 included studies published until June 2022. There were 484 patients in the OM group and 777 patients in the SL group. HAT incidence with OM was significantly lower with OR = 0.18 (95% CI: 0.07-0.48). The 1-year graft survival was significantly better in the OM group with OR = 2.77 (95% CI: 1.13-6.80). 1-year overall mortality was also significantly lower with OM with OR = 0.39 (0.18-0.86). The use of OM did not significantly impact the incidence of HAT in the living donor liver transplant subgroup. Differences in time for hepatic HA reconstruction, total operating time and length of hospital stay did not reach statistical significance., Conclusion: The use of OM has reduced the risk of HAT, graft loss and mortality in pediatric liver transplantation. Adoption of microsurgical principles in general may have contributed to the improved outcomes with SL reconstruction of HA in pediatric LT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Compared with young liver donors, aged liver donors are more susceptible to ischemia-reperfusion injury (IRI) following transplantation, which may be related to excessive inflammatory response and macrophage dysfunction, but the specific mechanism is unclear. Macrophage scavenger receptor 1 (MSR1) is a member of the scavenger receptor family, and plays an important regulatory role in inflammation response and macrophage function regulation. But its role in IRI following aged-donor liver transplantation is still unclear. This study demonstrates that MSR1 expression is decreased in macrophages from aged donor livers, inhibiting their efferocytosis and pro-resolving polarisation. Decreased MSR1 is responsible for the more severe IRI suffered by aged donor livers. Overexpression of MSR1 using F4/80-labelled AAV 9 improved intrahepatic macrophage efferocytosis and promoted pro-resolving polarisation, ultimately ameliorating IRI following aged-donor liver transplantation. In vitro co-culture experiments further showed that overexpression of MSR1 promoted an increase in calcium concentration, which further activated the PI3K-AKT-GSK3β pathway, and induced the upregulation of β-catenin. Overall, MSR1-dependent efferocytosis promoted the pro-resolving polarisation of macrophages through the PI3K-AKT-GSK3β pathway-induced up-regulating of β-catenin leading to improved IRI following aged-donor liver transplantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Laparoscopic liver resection (LLR) has been associated with improved patient recovery as well as reduced postoperative adhesions compared to open LR (OLR) and could therefore facilitate redo liver surgery. LLR prior to liver transplantation (LT) is increasingly performed, LT being saved for HCC recurrence. LT is still performed by open surgery due to vascular reconstructions and underlying liver chronic disease. We evaluated the impact of laparoscopic approach for LR prior to LT in terms of intraoperative transfusions, adhesions severity and outcome., Methods: Data from all patients who underwent a LT after LR in two French high-volume tertiary centers were retrospectively reviewed. The impact of LLR on per operative and postoperative outcome was assessed using logistic regression., Results: 170 patients were included, 43 patients in the LLR group and 127 in the OLR group. Preoperative characteristics were comparable between both groups, except LLR group included more patients with "very early-stage" BCLC tumors than OLR group (51% vs. 33%, p = 0.02) and less anatomical resections (54% vs. 75%, p = 0.015). During LT, the transfusion rate was significantly higher in the OLR group (71.4% vs 44.2%, p = 0.002) as well as the proportion of type III adhesions according to OLSG classification (p < 0.001). Multivariate analysis found LLR to be an independent protective factor for adhesions and transfusion (p = 0.001 and p = 0.03 respectively)., Conclusion: Laparoscopic liver resection was associated with reduced postoperative adhesions and transfusion requirements during subsequent liver transplantation., Competing Interests: Conflicts of interest None to declare., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

There is no recent update on the clinical course of retransplantation (re-LT) after living donor liver transplantation (LDLT) in the US using recent national data. The UNOS database (2002-2023) was used to explore patient characteristics in initial LT, comparing deceased donor liver transplantation (DDLT) and LDLT for graft survival (GS), reasons for graft failure, and GS after re-LT. It assesses waitlist dropout and re-LT likelihood, categorizing re-LT cohort based on time to re-listing as acute or chronic (≤ or > 1 mo). Of 132,323 DDLT and 5955 LDLT initial transplants, 3848 DDLT and 302 LDLT recipients underwent re-LT. Of the 302 re-LT following LDLT, 156 were acute and 146 chronic. Primary nonfunction (PNF) was more common in DDLT, although the difference was not statistically significant (17.4% vs. 14.8% for LDLT; p = 0.52). Vascular complications were significantly higher in LDLT (12.5% vs. 8.3% for DDLT; p < 0.01). Acute re-LT showed a larger difference in primary nonfunction between DDLT and LDLT (49.7% vs. 32.0%; p < 0.01). Status 1 patients were more common in DDLT (51.3% vs. 34.0% in LDLT; p < 0.01). In the acute cohort, Kaplan-Meier curves indicated superior GS after re-LT for initial LDLT recipients in both short-term and long-term ( p = 0.02 and < 0.01, respectively), with no significant difference in the chronic cohort. No significant differences in waitlist dropout were observed, but the initial LDLT group had a higher re-LT likelihood in the acute cohort (sHR 1.40, p < 0.01). A sensitivity analysis focusing on the most recent 10-year cohort revealed trends consistent with the overall study findings. LDLT recipients had better GS in re-LT than DDLT. Despite a higher severity of illness, the DDLT cohort was less likely to undergo re-LT., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: The aim of the present study was to compare the outcomes of pediatric LT with left liver grafts, obtained either from a living donor (LD) or a split deceased donor (sDD)., Methods: Retrospective single-center study from 2002 to 2022. All pediatric LT with left liver grafts (not including middle hepatic vein) from LD or sDD were included. Reduced grafts were not included., Results: A total of 112 pediatric LT were performed: 58 with LD grafts and 54 with sDD grafts (17 split ex situ and 37 in situ). Donor characteristics were similar, apart from donor age (33 years in LD vs. 30 years in sDD, p = 0.03). Indications were similar with 55% biliary atresia in each group. Retransplantation was more frequently performed in the sDD group (2% vs. 15%, p = 0.01). Recipient age, weight, and PELD score at transplant were not significantly different between groups. Cold ischemia time was longer for sDD (158 min in LD vs. 390 min in sDD; p < 0.0001). Posttransplant peak ALT was higher with sDD grafts (1470 vs. 1063, p = 0.018), and hospital stay was longer with sDD grafts (27 vs. 21 days, p = 0.005). However, there was no difference between groups in terms of major morbidity (Dindo-Clavien grade ≥3), vascular and biliary complications, and 90-day mortality. Patient survival at 10 years was 93.1% for LD and 92.8% for sDD (p = 0.807). Graft survival at 10 years was 89.7% for LD and 83.1% for sDD (p = 0.813)., Conclusions: Technically similar LD and sDD grafts achieve very similar postoperative and long-term outcomes with excellent patient and graft survival., (© 2024 The Author(s). Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Pediatric liver transplantation for small recipients presents significant challenges, particularly in securing suitably sized donor organs. This case report illustrates the feasibility of performing an in situ split procurement in an 18.5-kg toddler, the smallest recorded case in the OPTN database to date, for a critically ill 8-week-old infant recipient., Case Presentation: An 8-week-old infant with severe hepatitis of unknown etiology was urgently listed as Status 1A. An organ offer from a 3.5-year-old donor, requiring a reduction procedure, became available 1939 nautical miles away. Instead of a back-table reduction procedure, we performed an in situ split to reduce cold ischemic time given the distance. The recipient surgery was started ahead of the organ's arrival, and the recipient was ready for graft implantation upon the organ's arrival, resulting in a total of 510 min of cold ischemic time. Post-operatively, the graft did not show signs of significant injury or dysfunction, which expedited recovery from her other medical conditions., Conclusions: In situ split liver procurement is an invaluable tool for pediatric centers as it effectively provides more graft options for pediatric patients on the waitlist. Additionally, in situ split can offer significant benefits in optimizing recipient surgery, especially when the donor is located at an extreme distance. Despite these benefits, in situ split is not currently widely utilized across transplant centers. Addressing the logistical challenges associated with this technique is crucial for broader implementation and improved patient outcomes., (© 2024 Wiley Periodicals LLC.)

Liver transplantation is lifesaving for patients with end-stage liver disease. Similar to the role of transplantation for patients with end-stage liver disease, gender-affirming hormone therapy (GAHT) can be lifesaving for transgender and gender diverse (TGGD) patients who experience gender dysphoria. However, management of such hormone therapy during the perioperative period is unknown and without clear guidelines. Profound strides can be made in improving care for TGGD patients through gender-affirming care and appropriate management of GAHT in liver transplantation. In this article, we call for the transplant community to acknowledge the integral role of GAHT in the care of TGGD liver transplant candidates and recipients. We review the current literature and describe how the transplant community is ethically obligated to address this health care gap. We suggest tangible steps that clinicians may take to improve health outcomes for this minoritized patient population., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. The authors here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis., Methods: Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5 cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets., Results: The median operation time was 495 (range 420-630). The median time of explant hepatectomy and inferior vena cava anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than 12 months follow-up., Conclusion: LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers., Methods: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis., Results: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP., Conclusion: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development., (© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background & Aims: The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to offer livers from deceased donors to patients on the national waiting list based, for most patients, on calculated transplant benefit. Before NLOS, livers were offered to transplant centres by geographic donor zones and, within centres, by estimated recipient need for a transplant., Methods: UK Transplant Registry data on patient registrations and transplants were analysed to build statistical models for survival on the list (M1) and survival post-transplantation (M2). A separate cohort of registrations - not seen by the models before - was analysed to simulate what liver allocation would have been under M1, M2 and a transplant benefit score (TBS) model (combining both M1 and M2), and to compare these allocations to what had been recorded in the UK Transplant Registry. The number of deaths on the waiting list and patient life years were used to compare the different simulation scenarios and to select the optimal allocation model. Registry data were monitored, pre- and post-NLOS, to understand the performance of the scheme., Results: The TBS was identified as the optimal model to offer donation after brain death (DBD) livers to adult and large paediatric elective recipients. In the first 2 years of NLOS, 68% of DBD livers were offered using the TBS to this type of recipient. Monitoring data indicate that mortality on the waiting list post-NLOS significantly decreased compared with pre-NLOS (p <0.0001), and that patient survival post-listing was significantly greater post- compared to pre-NLOS (p = 0.005)., Conclusions: In the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, delivering on the scheme's objectives., Impact and Implications: The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to increase transparency of the deceased donor liver offering process, maximise the overall survival of the waiting list population, and improve equity of access to liver transplantation. To our knowledge, it is the first scheme that offers organs based on statistical prediction of transplant benefit: the transplant benefit score. The results are important to the transplant community - from healthcare practitioners to patients - and demonstrate that, in the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, thus delivering on the scheme's objectives. The scheme continues to be monitored to ensure that the transplant benefit score remains up-to-date and that signals that suggest the possible disadvantage of some patients are investigated., (Copyright © 2024 NHS Blood and Transplant. Published by Elsevier B.V. All rights reserved.)

Over the last 50 years, liver transplantation has evolved into a procedure routinely performed in many countries worldwide. Those able to access this therapy frequently experience a miraculous risk-benefit ratio, particularly if they face the imminently life-threatening disease. Over the decades, the success of liver transplantation, with dramatic improvements in early posttransplant survival, has aggressively driven demand. However, despite the emergence of living donors to augment deceased donors as a source of organs, supply has lagged far behind demand. As a result, rationing has been an unfortunate focus in recent decades. Recent shifts in the epidemiology of liver disease combined with transformative innovations in liver preservation suggest that the underlying premise of organ shortage may erode in the foreseeable future. The focus will sharpen on improving equitable access while mitigating constraints related to workforce training, infrastructure for organ recovery and rehabilitation, and their associated costs. Research efforts in liver preservation will undoubtedly blossom with the aim of optimizing both the timing and conditions of transplantation. Coupled with advances in genetic engineering, regenerative biology, and cellular therapies, the portfolio of innovation, both broad and deep, offers the promise that, in the future, liver transplantation will not only be broadly available to those in need but also represent a highly durable life-saving therapy., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Competing Interests: Declaration of Competing Interest None.

Background: Currently, graft options for pediatric liver transplantation (PLT) include whole (WL) and partial (P) grafts, in the form of either deceased donor transplantation (DD) or living donor liver transplantation (LD). WL transplants from LD are commonly referred to as domino LT. The objective of this manuscript is to compare the outcomes of PLT performed with each of the available graft options., Methods: Retrospective cohort study from Jan. 2010 to Dec. 2022. The variables included data on the recipients' preoperative clinical status, intraoperative technical aspects, post-operative complications, and survival studies. There were 4 groups: SPLIT (17), DD-WL (55), LD-WL (824), and LD-P (22)., Results: The median age and BW of the recipients was smaller in SPLIT, LD-P, and LD-WL compared to DDT-WL groups. HVOO (HR 15.87, 95% CI 1.89-133.06, P = 0.01), retransplantation (HR 7.94, 95% CI 2.63-24.02, P < 0.01), and malignancies (HR 3.08, 95% CI 1.29-7.37, P = 0.01) were independently associated with decreased patient survival. HAT (HR 27.54, 95% CI 10.44-72.68, P < 0.01) and malignancies (HR 2.42, 95% CI 1.10-5.34, P = 0.03) increased the risk of graft loss. The overall survival in this series was 91.4% (mean follow-up of 74.3 months). Patient and graft survival were not different among groups., Conclusion: HAT and malignancies were associated with reduced graft survival. Whole liver from living donors with MSUD presented 100% patient survival at 120 months. Even without statistical differences in survival among the studied groups, LD-P and LD-WL recipients presented a trend towards better outcomes., Level of Evidence: LEVEL III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion., Methods: Liver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high)., Results: An increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients' model for end-stage liver disease scores showed a significant association with both overall patient and graft survival., Conclusion: The use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In 1984, 21 years after the first liver transplantation, Thomas Starzl achieved a milestone by performing the world's first combined heart-liver transplantation. While still uncommon, the practice of combined heart-liver transplants is on the rise globally. In this review, the authors delve into the current literature on this procedure, highlighting the evolving landscape and key considerations for anesthesiologists. Over the years, there has been a remarkable increase in the number of combined heart-liver transplantations conducted worldwide. This surge is largely attributed to the growing population of adult survivors with single-ventricle physiology, palliated with a Fontan procedure, who later present with late Fontan failure and Fontan-associated liver disease. Research indicates that combined heart-liver transplantation is an effective treatment option, with reported outcomes comparable with isolated heart or liver transplants. Managing anesthesia during a combined heart-liver transplant procedure is challenging, especially in the context of underlying Fontan physiology. International experience in this field remains somewhat limited, with most techniques derived from expert opinions or experiences with single-organ heart and liver transplants. These procedures are highly complex and performed infrequently. As the number of combined heart-liver transplants continues to rise globally, there is a growing need for clear guidance on periprocedural surgical and anesthetic management. Anesthesiologists overseeing these patients must consider multiple factors, balancing various comorbidities with significant hemodynamic and metabolic shifts. An increase in (multicenter) studies focusing on specific interventions to enhance patient and organ outcomes is anticipated in the coming years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Normothermic machine perfusion (NMP) allows for the assessment and resuscitation of ex-vivo human livers prior to transplantation. Commercially available NMP systems are closed circuits that accumulate metabolic waste and cytokines over time, potentially limiting organ preservation times. Dialysis has been proposed as a method to remove waste and excess fluid from such systems. This study aimed to demonstrate the utility of integrating dialysis into a commercially available system by quantifying solute removal., Methods: A dialysis filter was attached in parallel to a commercially available liver perfusion system. Three livers declined for transplantation were split before undergoing long-term NMP with blood using the modified system. During perfusion, dialysate flow rates were set in the range of 100-600 mL/h for short periods of time. At each flow rate, perfusate and spent dialysate samples were collected and analyzed for solute clearance., Results: The addition of dialysis to a commercial NMP system removed water-soluble waste and helped regulate electrolyte concentrations. Interleukin-6 was successfully removed from the perfusate. Solute clearance was proportional to dialysate flow rate. A guide for our perfusion setup was created for the appropriate selection of dialysis flow rates and duration based on real-time perfusate composition., Conclusions: Dialysis circuits can efficiently remove waste and regulate perfusate composition, and can be easily incorporated to improve the performance of commercially available systems. Quantification of the effect of dialysis on perfusate composition enables refined dialysis control to optimize electrolyte profiles and avoid the over- or under-correction of key solutes., (© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Situs inversus totalis is a rare congenital anomaly characterized by a mirror-image orientation of abdominal, and in some cases, thoracic organs. Here, we report our situs inversus totalis transplantation experience and further review liver transplantations in adult recipients and donors with situs inversus totalis., Case Presentation: We describe three cases with situs inversus totalis. The first case was liver transplantation in a recipient (a 61-year-old Iranian man) with situs inversus totalis, the second was a liver transplantation from a donor (a 52-year-old Iranian woman) with situs inversus totalis, and finally, for the first time, a simultaneous pancreas and kidney transplantation in a recipient (a 26-year-old Iranian man) with situs inversus totalis. In patient one, hepatectomy could be performed according to the standard method and on the basis of preoperative studies. Hepatic vein and arterial anastomosis were performed as in every other patient without situs inversus totalis. To prevent biliary complications, a Roux-en-Y hepaticojejunostomy was performed. In patient two, implantation time, suprahepatic vein, portal vein, arterial, and biliary reconstruction could be done as in any other case without situs inversus totalis. Plication of the right-sided diaphragm and fixation of the falciform ligament was done for our patient. In patient three, systemic drainage was preferred to portal flow for establishing the outflow drainage of the pancreas compared with otherwise normal patients., Conclusion: Although situs inversus totalis is a rare condition, our reported techniques are suitable, considering advantages such as easier accessibility, more acceptable placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs., (© 2024. The Author(s).)

Transplant oncology is an expanding area of cancer therapy that specifically emphasizes the use of liver transplantation (LT) as the preferred treatment for patients with manageable, but unresectable, tumors. The management and optimization of overall survival strategies, accompanied by an arguably decent quality of life, have been at the forefront of liver oncology treatment, as a plurality of all primary liver cancers are identified as either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA), which are classified as highly aggressive malignancies and frequently remain asymptomatic until they progress to advanced stages, rendering curative procedures, such as resection, impractical. This has led to an increase in utilization of neoadjuvant interventions conducted prior to surgery, which has yielded favorable outcomes. Though this treatment modality has prompted further investigations into the efficacy of immune checkpoint inhibitors (ICPIs) as standalone treatments and in combination with locoregional treatments (LRTs) to bridge more patients into curative eligibility. This multidisciplinary methodology and treatment planning has seen multiple successful trials of immunotherapy regimes and combinate treatments, setting the groundwork for increasing eligibility through downstaging and "bridging" previously ineligible patients within stringent LT criteria. Surveillance after LT is a crucial component of transplant oncology. The emergence of circulating tumor DNA (ctDNA) has provided a novel approach to identifying the recurrence of cancer in its early stages. Recent research has focused on liquid biopsy, a technique that effectively identifies the dynamics of cancer. This is another innovation to demonstrate the rate at which transplant oncology is rapidly advancing, making the focus of care feel disorienting. Modalities of care are constantly evolving, but when a field is changing as rapidly as this one, it is imperative to reorient to the data and the needs of the patients. In this commentary, we reflect on the update's utilization of ICPIs in neoadjuvant settings as well as the updates on the utilization of liquid biopsy in post-LT follow-up surveillance.

Since the first published report of experimental kidney transplantation in dogs in 1902, there were many experimental and clinical trials of organ transplantation, with many sacrifices. After the establishment of the surgical technique and the discovery of immunosuppressive drugs, transplantation became the definitive treatment strategy for patients with terminal organ failure. However, this is not a common therapy method due to the difficulty of solving the fundamental issues behind organ transplantation, including the shortage of donor graft, potential risks of transplant surgery and economic capability. The pre- and post-transplant management of recipients is another critical issue that may affect transplant outcome. Most liver transplant recipients experience post-transplant complications, including infection, acute/chronic rejection, metabolic syndrome and the recurrence of hepatocellular carcinoma. Therefore, the early prediction and diagnosis of these complications may improve overall and disease-free survival. Furthermore, how to induce operational tolerance is the key to achieving the ultimate goal of transplantation. In this review, we focus on liver transplantation, which is known to achieve operational tolerance in some circumstances, and the mechanical similarities and differences between liver transplant immunology and fetomaternal tolerance, autoimmunity or tumor immunity are discussed.

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.

Fontan surgery is vital for infants born with a single-ventricle heart. This intervention establishes a new blood flow circuit bypassing the single ventricle, thereby the separating pulmonary and systemic circulation to preserve single ventricular function. However, it carries risks of hepatic complications, collectively termed Fontan-associated liver disease (FALD), characterized by progressive hepatic congestion and fibrosis potentially leading to an equivalent of cirrhosis. Diagnosis and staging of FALD are complex, requiring multidisciplinary management. In advanced FALD, consideration is given to heart transplantation alone or combined heart-liver transplantation, underscoring the importance of an integrated approach to optimize care for these increasingly more common patients., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.