Long-term outcome following liver transplantation of patients with ACLF grade 3.

BACKGROUND AND AIMS: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included the three-center retrospective French experience published in 2017. METHOD: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors. RESULTS: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients' survival. Long-term grafts' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years. CONCLUSION: 5- and 10-year patients' and grafts' survivals in ACLF-3 patients were not different from their controls. 5-year patients' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death. IMPACT AND IMPLICATIONS: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time.

Clinical Implications and Management of Spontaneous Portosystemic Shunts in Liver Cirrhosis.

Portal hypertension from chronic liver disease leads to the formation of collateral blood vessels called spontaneous portosystemic shunts (SPSS). These shunts may form from existing vessels or through neo-angiogenesis. Their location affects clinical outcomes due to varying risks and complications. This review summarizes current knowledge on SPSS, covering their clinical impact and management strategies. Recent data suggest that SPSS increases the risk of variceal bleeding, regardless of shunt size. The size of the shunt is crucial in the rising incidence of hepatic encephalopathy (HE) linked to SPSS. It also increases the risk of portopulmonary hypertension and portal vein thrombosis. Detecting and assessing SPSS rely on computed tomography (CT) and magnetic resonance imaging. CT enables precise measurements and the prediction of cirrhosis progression. Management focuses on liver disease progression and SPSS-related complications, like HE, variceal bleeding, and portopulmonary hypertension. Interventional radiology techniques such as balloon-occluded, plug-assisted, and coil-assisted retrograde transvenous obliteration play a pivotal role. Surgical options are rare but are considered when other methods fail. Liver transplantation (LT) often resolves SPSS. Intraoperative SPSS ligation is still recommended in patients at high risk for developing HE or graft hypoperfusion.

The Negative Impact of Sarcopenia on Hepatocellular Carcinoma Treatment Outcomes.

INTRODUCTION: Hepatocellular carcinoma (HCC) represents a major global health concern, characterized by evolving etiological patterns and a range of treatment options. Among various prognostic factors, sarcopenia, characterized by loss of skeletal muscle mass, strength, and function, has emerged as a pivotal contributor to HCC outcomes. Focusing on liver transplantation, surgical resection, locoregional treatments, and systemic therapies, this review aims to analyze the impact of sarcopenia on HCC treatment outcomes, shedding light on an underexplored subject in the pursuit of more personalized management. METHODS: A comprehensive literature review was conducted by searching peer-reviewed articles on sarcopenia and treatment outcomes in patients with HCC from inception up to October 2023. RESULTS: Sarcopenia was found to be prevalent among HCC patients, exhibiting different occurrence, possibly attributable to diverse diagnostic criteria. Notably, despite variations in studies utilizing skeletal muscle indices, sarcopenia independently correlated with lower overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) across surgical (both transplantation and resection), locoregional, and systemic therapies, including tyrosine-kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs). Moreover, a link between sarcopenia and increased rate and severity of adverse events, particularly in surgery and TKIs recipients, and larger tumor size at diagnosis was observed. While baseline sarcopenia negatively influenced treatment outcomes, alterations in muscle mass post-treatment emerged as primary determinants of reduced OS. CONCLUSIONS: Sarcopenia, either present before or after HCC treatment, negatively correlates with response to it, across all etiologies and therapeutic strategies. Although only a few studies have evaluated the impact of supervised physical activity training on muscle mass and OS after HCC treatment, it is crucial to evaluate the presence of sarcopenia before treatment initiation, to better stratify patients' prognosis, thus performing a more tailored approach, and identify therapies able to restore muscle mass in HCC patients. Conversely, the impact of sarcopenia on HCC recurrence and extrahepatic spread remains inadequately explored.

Liver Transplantation for Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors.

Hepatocellular carcinoma (HCC) remains the leading oncological indication for liver transplantation (LT), with evolving and broadened inclusion criteria. Immune checkpoint inhibitors (ICIs) gained a central role in systemic HCC treatment and showed potential in the peri-transplant setting as downstaging/bridging therapy before LT or as a treatment for HCC recurrence following LT. However, the antagonistic mechanisms of action between ICIs and immunosuppressive drugs pose significant challenges, particularly regarding the risk of acute rejection (AR). This review analyzes the main signaling pathways targeted by ICI therapies and summarizes current studies on ICI therapy before and after LT. The literature on this topic is limited and highly heterogeneous, precluding definitive evidence-based conclusions. The use of ICIs before LT appears promising, provided that a sufficient wash-out period is implemented. In contrast, the results of post-LT ICI therapy do not support its wide clinical application due to high AR rates and overall poor response to treatment. In the future, modern graft preservation techniques might support the selection of good ICI responders, but data from high-level studies are urgently needed.

Systemic Treatment of Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Multicenter Trial.

INTRODUCTION: The tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib represent the first-line systemic therapy of choice for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Under sorafenib and lenvatinib, HCC patients have shown increasingly improved overall survival in clinical studies over the years. In contrast, data on overall survival for patients with HCC recurrence after LT under TKIs are scarce and limited to small retrospective series. In this retrospective, multicenter study, we investigated the efficacy of TKI therapy and the influence of immunosuppression in patients with HCC recurrence after LT. METHODS: Retrospective data were collected from four transplant centers from Germany and Austria. We included patients with HCC recurrence after LT between 2007 and 2020 who were treated with a TKI. RESULTS: In total, we analyzed data from 46 patients with HCC recurrence after LT. The most common underlying liver disease was hepatitis C, accounting for 52.2%. The median time to relapse was 11.8 months (range 0-117.7 months). The liver graft was affected in 21 patients (45.7%), and 36 patients (78.3%) had extrahepatic metastases at initial diagnosis of recurrence, with the lung being the most commonly affected (n = 25, 54.3%). Of the total, 54.3% (n = 25) of the patients were initially treated locally; 39 (85.8%) and 7 (15.2%) patients received sorafenib and lenvatinib, respectively, as first-line systemic therapy. Median overall survival of the whole cohort was 10.9 months (95% confidence interval (95% CI) 6.9-14.9 months) and median progression free survival was 5.7 months (95% CI 2.0-9.4 months) from treatment initiation. CONCLUSION: Since history of liver transplantation is considered a contraindication for immunotherapy, prognosis of patients with HCC recurrence after LT remains poor.

Clinical application of infrared spectroscopy in liver transplantation for rapid assessment of lipid content in liver graft.

Liver transplantation (LT) is a major treatment for patients with end-stage liver diseases. Steatosis is a significant risk factor for primary graft non-function and is associated with poor long-term graft outcomes. Traditionally, the evaluation of steatosis is based on frozen section examination to estimate the percentage of hepatocytes containing lipid vesicles. However, this visual evaluation correlates poorly with the true lipid content. This study aimed to address the potential of infrared (IR) microspectroscopy for rapidly estimating lipid content in the context of LT and assessing its impact on survival. Clinical data were collected over 20 months from 58 patients who underwent transplantation. For each liver graft, macrovacuolar and microvesicular steatosis were evaluated through histological examination on frozen tissue section. Triglycerides (TG) were further quantified using gas-phase chromatography coupled with a flame ionization detector (GC-FID) as well as estimated by IR microspectroscopy. A linear relationship and significant correlation were observed between the TG measured by GC-FID and those estimated by IR microspectroscopy (R2 = 0.86). In some cases, microvesicular steatosis was related to high lipid content despite low levels of macrovacuolar steatosis. Seven patients experienced post-transplantation liver failure, including 5 deceased patients. All patients underwent transplantation with grafts containing significantly high TG levels. A concentration of 250 nmol/mg was identified as the threshold above which the risk of failure after LT significantly increased, affecting 35% of patients. Our study established a strong correlation between LT outcomes and lipid content. IR microspectroscopy proved to be a rapid and reliable approach for assessing the lipid content in clinical settings.

The Spread Pattern of New Practice in Liver Transplantation in the United States.

BACKGROUND: Introducing new liver transplantation (LT) practices, like unconventional donor use, incurs higher costs, making evaluation of their prognostic justification crucial. This study reexamines the spread pattern of new LT practices and its prognosis across the United States. METHODS: The study investigated the spread pattern of new practices using the UNOS database (2014-2023). Practices included LT for hepatitis B/C (HBV/HCV) nonviremic recipients with viremic donors, LT for COVID-19-positive recipients, and LT using onsite machine perfusion (OMP). One year post-LT patient and graft survival were also evaluated. RESULTS: LTs using HBV/HCV donors were common in the East, while LTs for COVID-19 recipients and those using OMP started predominantly in California, Arizona, Texas, and the Northeast. K-means cluster analysis identified three adoption groups: facilities with rapid, slow, and minimal adoption rates. Rapid adoption occurred mainly in high-volume centers, followed by a gradual increase in middle-volume centers, with little increase in low-volume centers. The current spread patterns did not significantly affect patient survival. Specifically, for LTs with HCV donors or COVID-19 recipients, patient and graft survivals in the rapid-increasing group was comparable to others. In LTs involving OMP, the rapid- or slow-increasing groups tended to have better patient survival (p = 0.05) and significantly improved graft survival rates (p = 0.02). Facilities adopting new practices often overlap across different practices. DISCUSSION: Our analysis revealed three distinct adoption groups across all practices, correlating the adoption aggressiveness with LT volume in centers. Aggressive adoption of new practices did not compromise patient and graft survivals, supporting the current strategy. Understanding historical trends could predict the rise in future LT cases with new practices, aiding in resource distribution.

Defining Surgical Difficulty During Open Right Lobe Donor Hepatectomy and its Prediction Using Preoperative Donor Computed Tomography Morphometry.

Background: There is no accepted way to define difficult donor hepatectomy (DiffDH) during open right live donor hepatectomy (ORLDH). There are also no studies exploring association between DiffDH and early donor outcomes or reliable pre-operative predictors of DiffDH. Methods: Consecutive ORLDH performed over 18 months at a single center were included. Intraoperative parameters were used to develop an objective definition of DiffDH. The impact of DiffDH on early postoperative outcomes and achievement of textbook outcome (TO) was evaluated. Donor morphometry data on axial and coronal sections of donor computed tomography (CT) at the level of portal bifurcation were collected. Donor and graft factors predictive of DiffDH were evaluated using univariate and multivariate logistic regression. Results: One-hundred-eleven donors (male: 40.5%, age: 34 ± 9.5 years) underwent ORLDH during the study period. The difficulty score was constructed using five intraoperative parameters, i.e., operating time, transection time, estimated blood loss, need for intraoperative vasopressors, and need for Pringle maneuver. Donors were classified as DiffDH (score ≥ 2) or standard donor hepatectomy (StDH) (score <2). Twenty-nine donors (26%) were classified as DiffDH. DiffDH donors suffered greater all-cause morbidity (P = 0.004) but not major morbidity (Clavien-Dindo score >2; P = 0.651), more perioperative transfusion (P = 0.013), increased postoperative systemic inflammatory response syndrome (P = 0.034), delay in achieving full oral diet (P = 0.047), and a 70% reduced chance of achieving TO as compared to StDH (P = 0.007). On logistic regression analysis, increasing right lobe anteroposterior depth (RLdepth) was identified as an independent predictor of DiffDH (Odds ratio: 2.0 (95% confidence interval = 1.2, 3.3), P < 0.006). Receiver operating characteristic curve analysis identified an RLdepth of >14 cm as the best predictor of DiffDH (sensitivity:79%, specificity: 66%, area under curve = 0.803, P < 0.001). Conclusion: We report a novel definition of DiffDH and show that it is associated with worse postoperative outcomes, including a lesser chance of achieving TO. We also report that DiffDH can be predicted from readily available donor CT parameters.

First Report of Two-stage Living Donor Liver Transplantation to Avoid Futility and Ensure Double Equipoise in Acute Liver Failure Complicated by Toxic Liver Syndrome.

Acute hepatic failure may occasionally be complicated by toxic liver syndrome. Emergency hepatectomy for stabilization followed by delayed graft implantation is a recognized strategy in such cases in the setting of deceased donor liver transplantation. Living donor liver transplantation adds additional complexity to this scenario as the donor liver is a directed donation and failure to stabilize the patient after emergency hepatectomy can lead to a futile live donor hepatectomy, hepar-divisum, or an orphan graft. We report a case where the two-stage strategy was utilized to circumvent this situation. A patient with toxic liver syndrome underwent emergency hepatectomy and was closely monitored in the operating theater. A live donor hepatectomy was started after the recipient demonstrated cardiovascular and neurological stabilization. Graft implantation was completed after an anhepatic period of 9.45 h. To our knowledge, this is the first reported instance of using the two-stage strategy in living-donor-liver-transplantation for toxic liver syndrome to prevent futile donor surgery and achieve double equipoise.

Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation.

In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from Streptomyces tsukubaensis, is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.

Portal vein arterialization in 25 liver transplant recipients: A Latin American single-center experience.

BACKGROUND: Portal vein arterialization (PVA) has been used in liver transplantation (LT) to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis (PVT). The effect of PVA on portal perfusion and primary graft dysfunction (PGD) has not been assessed. AIM: To examine the outcomes of patients who required PVA in correlation with their LT procedure. METHODS: All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed. To account for the time-sensitive effects of graft perfusion, patients were classified into two groups: prereperfusion (pre-PVA), if the arterioportal anastomosis was performed before graft revascularization, and postreperfusion (post-PVA), if PVA was performed afterward. The pre-PVA rationale contemplated poor portal hemodynamics, severe vascular steal, or PVT. Post-PVA was considered if graft hypoperfusion became evident. Conservative interventions were attempted before PVA. RESULTS: A total of 25 cases were identified: 15 before and 10 after graft reperfusion. Pre-PVA patients were more affected by diabetes, decompensated cirrhosis, impaired portal vein (PV) hemodynamics, and PVT. PGD was less common after pre-PVA (20.0% vs 60.0%) (P = 0.041). Those who developed PGD had a smaller increase in PV velocity (25.00 cm/s vs 73.42 cm/s) (P = 0.036) and flow (1.31 L/min vs 3.34 L/min) (P = 0.136) after arterialization. Nine patients required PVA closure (median time: 62 d). Pre-PVA and non-PGD cases had better survival rates than their counterparts (56.09 months vs 22.77 months and 54.15 months vs 31.91 months, respectively). CONCLUSION: This is the largest report presenting PVA in LT. Results suggest that pre-PVA provides better graft perfusion than post-PVA. Graft hyperperfusion could play a protective role against PGD.

Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures.

BACKGROUND: Endoscopic management is the first-line therapy for post-liver-transplant anastomotic strictures. Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months, data on safety and duration for metal stents in this setting is scarce. Due to limited access to endoscopic retrograde cholangiopancreatography (ERCP) during the coronavirus disease 2019 pandemic in our centre, there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy. This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents. AIM: To compare the safety and efficacy profile of different stenting durations using Kaffes stents. METHODS: Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query. Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records. The main outcome was the incidence of complications when stents were left indwelling for 3 months vs 6 months. Stent efficacy was calculated via rates of stricture recurrence between patients that had stenting courses for ≤ 120 d or > 120 d. RESULTS: During the study period, a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course. In 33 ERCPs, the stent was removed or exchanged on a 3-month interval. No pancreatitis, perforations or deaths occurred. Minor post-ERCP complications were similar between the 3-month (abdominal pain and intraductal migration) and 6-month (abdominal pain, septic shower and embedded stent) groups - 6.1% vs 9.1% respectively, P = 0.40. All strictures resolved at the end of the stenting course, but the stenting course was variable from 3 to 22 months. The recurrence rate for stenting courses lasting for up to 120 d was 71.4% and 21.4% for stenting courses of 121 d or over (P = 0.03). There were 28 patients that were treated with a single ERCP with Kaffes, 21 with removal after 120 d and 7 within 120 d. There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course (71.0% vs 10.0%, P = 0.01). CONCLUSION: Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that requires liver transplantation (LT). Despite patients with HCC being prioritized by most organ allocation systems worldwide, they still have to wait for long periods. Locoregional therapies (LRTs) are employed as bridging therapies in patients with HCC awaiting LT. Although largely used in the past, transarterial embolization (TAE) has been replaced by transarterial chemoembolization (TACE). However, the superiority of TACE over TAE has not been consistently shown in the literature. AIM: To compare the outcomes of TACE and TAE in patients with HCC awaiting LT. METHODS: All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included. All patients underwent LRT with either TACE or TAE. Some patients also underwent percutaneous ethanol injection (PEI), concomitantly or in different treatment sessions. The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus. The primary outcome was waitlist dropout due to tumor progression, and the secondary outcome was the occurrence of adverse events. In the subset of patients who underwent LT, complete pathological response and post-transplant recurrence-free survival were also assessed. RESULTS: Twelve (18.5%) patients in the TACE group (only TACE and TACE + PEI; n = 65) and 3 (7.9%) patients in the TAE group (only TAE and TAE + PEI; n = 38) dropped out of the waitlist due to tumor progression (P log-rank test = 0.29). Adverse events occurred in 8 (12.3%) and 2 (5.3%) patients in the TACE and TAE groups, respectively (P = 0.316). Forty-eight (73.8%) of the 65 patients in the TACE group and 29 (76.3%) of the 38 patients in the TAE group underwent LT (P = 0.818). Among these patients, complete pathological response was detected in 7 (14.6%) and 9 (31%) patients in the TACE and TAE groups, respectively (P = 0.145). Post-LT, HCC recurred in 9 (18.8%) and 4 (13.8%) patients in the TACE and TAE groups, respectively (P = 0.756). Posttransplant recurrence-free survival was similar between the groups (P log-rank test = 0.71). CONCLUSION: Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC. Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Identification of the Anti-ischemia-reperfusion Injury Effect of Baicalein from Scutellaria Baicalensis Georgi in Liver Transplantation.

BACKGROUND: The complex etiology of Ischemia-Reperfusion Injury (IRI) induced by liver transplantation (LT) and the "one-target-focused" method limit the development of effective therapeutic interventions. We aimed to reveal the specific active ingredients and mechanisms involved in the Chinese herb Scutellaria baicalensis Georgi (SBG) in alleviating IRI in LT. METHODS: The active ingredients and potential macromolecular targets of SBG were screened through related databases. The differentially expressed genes of LT were obtained from GSE151648. The protein-protein interaction network was constructed by the STRING database, and Cytoscape 3.7.1 was used to construct a compound-target-disease network. GO and KEGG enrichment analyses were performed on the DAVID database. Finally, the main active components of SBG and the corresponding mechanisms were verified in a donation after circulatory death (DCD) rat LT model. RESULTS: Thirty-two active ingredients of SBG and their targets were identified, and a total of 38 intersection targets were obtained. GO function and KEGG pathway enrichment analyses demonstrated that the plasma membrane and its components play an important role. Molecular docking showed baicalein, the core component of SBG, had a strong binding ability to all hub targets. Next, in DCD rats, baicalein was proven to improve liver function, alleviate pathological injury and apoptosis, and increase the survival rate. Baicalein also significantly affected the expression of 7 hub genes. Furthermore, baicalein could inhibit ferroptosis by inhibiting phospholipid peroxidation. CONCLUSION: Baicalein, the main component of SBG, could alleviate IRI, affect the expression of hub genes, and inhibit ferroptosis in LT.

How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach.

BACKGROUND: Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients. AIM: To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT. METHODS: A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ²-test. RESULTS: In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis (n = 1) and pulmonary infections (n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality (n = 1), postoperative pulmonary infections (n = 8), abdominal infection (n = 1), hepatic artery thromboses (n = 3), portal vein thrombosis (n = 1), and intra-abdominal bleeding (n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups (P > 0.05). CONCLUSION: Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors.

BACKGROUND: Hepatic artery occlusion (HAO) after liver transplantation (LT) is a devastating complication, resulting in early graft loss and reduced overall survival. Ultrasound is an established assessment method for HAO in patients following LT, especially those with complex hepatic artery reconstruction. AIM: To investigate the ultrasound characteristics and analyze the risk factors associated with HAO in patients after LT. METHODS: We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022. Fourteen patients diagnosed with acute HAO (A-HAO) by surgery and fifteen diagnosed with chronic HAO (C-HAO) were included. A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table. All patients underwent an ultrasonography examination. Parameters including resistance index (RI), peak systolic velocity (PSV), and portal vein velocity (PVV) were compared across the groups. Additionally, basic clinical data were collected for all patients, including gender, age, primary diagnosis, D-dimer concentration, total operation time, cold ischemia time, hot ischemia time, intraoperative blood loss and transfusion, intraoperative urine volume, infusion, model for end-stage liver disease (MELD) score, and whether complex hepatic artery reconstructions were performed. Furthermore, risk factors influencing HAO formation after LT were analyzed. RESULTS: Compared to the non-HAO group, PVV and RI were higher in the A-HAO group, while PSV was lower. Conversely, both PSV and RI were lower in the C-HAO group compared to the non-HAO group. The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase (GGT) level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group. However, there were no distinct differences between the two groups in D-dimer, MELD score, pre-occlusion alanine transaminase and aspartate transaminase levels, or intraoperative conditions. CONCLUSION: Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development. Additionally, complex hepatic artery reconstructions, defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries, constitute a risk factor for A-HAO. Besides, abnormal pre-occlusion GGT elevation is an important biochemical indicator. Therefore, ultrasound examination serves as an important tool for screening HAO, especially in patients with the identified risk factors.

The impact of socioeconomic deprivation on liver transplantation.

Despite global expansion, social disparities impact all phases of liver transplantation, from patient referral to post-transplant care. In pediatric populations, socioeconomic deprivation is associated with delayed referral, higher waitlist mortality, and reduced access to living donor transplantation. Children from socially deprived communities are twice as much less adherent to immunosuppression and have up to a 32% increased incidence of graft failure. Similarly, adult patients from deprived areas and racial minorities have a higher risk of not initiating the transplant evaluation, lower rates of waitlisting, and a 6% higher risk of not being transplanted. Social deprivation is racially segregated, and Black recipients have an increased risk of post-transplant mortality by up to 21%. The mechanisms linking social deprivation to inferior outcomes are not entirely elucidated, and powered studies are still lacking. We offer a review of the most recent evidence linking social deprivation and post-liver transplant outcomes in pediatric and adult populations, as well as a literature-derived theoretical background model for future research on this topic.

A narrative review: predicting liver transplant graft survival using artificial intelligence modeling.

Liver transplantation is the only treatment for patients with liver failure. As demand for liver transplantation grows, it remains a challenge to predict the short- and long-term survival of the liver graft. Recently, artificial intelligence models have been used to evaluate the short- and long-term survival of the liver transplant. To make the models more accurate, suitable liver transplantation characteristics must be used as input to train them. In this narrative review, we reviewed studies concerning liver transplantations published in the PubMed, Web of Science, and Cochrane databases between 2017 and 2022. We picked out 17 studies using our selection criteria and analyzed them, evaluating which medical characteristics were used as input for creation of artificial intelligence models. In eight studies, models estimating only short-term liver graft survival were created, while in five of the studies, models for the prediction of only long-term liver graft survival were built. In four of the studies, artificial intelligence algorithms evaluating both the short- and long-term liver graft survival were created. Medical characteristics that were used as input in reviewed studies and had the biggest impact on the accuracy of the model were the recipient's age, recipient's body mass index, creatinine levels in the recipient's serum, recipient's international normalized ratio, diabetes mellitus, and recipient's model of end-stage liver disease score. To conclude, in order to define important liver transplantation characteristics that could be used as an input for artificial intelligence algorithms when predicting liver graft survival, more models need to be created and analyzed, in order to fully support the results of this review.

Potential for organ donation after controlled circulatory death: a retrospective analysis.

Objectives: Despite the discrepancy between demand and availability of organs for transplantation, controlled circulatory death donation has not been implemented in Portugal. This study aimed to estimate the potential increase in organ donation from implementing such a program. Material and Methods: All deceased patients within the intensive care medicine department at Centro Hospitalar Universitário de São João, throughout the year 2019, were subjected to retrospective analysis. Potential gain was estimated comparing the results with the number of donors and organs collected during the same period at this hospital center. Differences in variables between groups were assessed using t tests for independent samples or Mann-Whitney U tests for continuous variables, and chi-squared tests were used for categorical variables. Results: During 2019, 152 deaths occurred after withdrawal of life-sustaining therapies, 10 of which would have been potentially eligible for donation after controlled circulatory death. We can anticipate a potential increase of 10 prospective donors, a maximum 21% growth in yearly transplantation activity, with a greater impact on kidney transplantation. For most patients, the time between withdrawal of organ support and death surpassed 120 minutes, an outcome explained by variations in withdrawal of life-sustaining measures and insufficient clinical records, underestimating the potential for controlled circulatory arrest donation. Conclusion: This study effectively highlights public health benefits of controlled circulatory arrest donation. Legislation allowing donation through this method represents a social gain and enables patients who will never meet brain death criteria to donate organs as part of the end-of-life process in intensive care medicine, within a framework of complete ethical alignment.