Search Results (162)

Background: Patient survival after liver transplantation is lower in donor–recipient race mismatched patients for indications other than primary sclerosing cholangitis. Objectives: To determine if survival is lower after liver transplantation in donor–recipient race mismatched recipients with primary sclerosing cholangitis. Methods: The Organ Procurement and Transplantation Network database was analyzed for deceased donor adult liver transplant recipients with primary sclerosing cholangitis. Graft and patient survival by donor–recipient race were estimated using Kaplan–Meier survival method and compared using the log-rank test. Multivariable analysis was performed using Cox regression. Results: From 2002 to 2018, 5-year patient survival in White (n = 2223) and Black recipients (n = 491), was 89.8% and 87.1%, respectively. Five-year patient survival for the donor–recipient pairs, White–White (n = 1622), Black–Black (n = 110), Black–White (n = 335), and White–Black (n = 314) was 90.8%, 91.1%, 87.1%, and 86.0%, respectively, p = 0.026. In multivariable analysis, 5-year patient mortality was higher in Black recipients of White donors [HR 1.69, 95% CI 1.16, 2.45], compared to White recipients of White donors. Conclusions: Five-year patient mortality after deceased donor liver transplantation for primary sclerosing cholangitis is higher in Black recipients who received livers from White donors compared to matched White donors and recipients. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article

Background: Primary sclerosing cholangitis (PSC) accounts for 10–15% of liver transplants but is the leading cause of retransplant. This study evaluates whether PSC patients have different survival and graft outcomes when receiving grafts from donors after brain death (DBD) versus circulatory (DCD) death. Methods: Using the SRTR database (2004–2024), we compared PSC patients receiving DCD vs. DBD grafts. Demographics and outcomes including graft loss, mortality, and retransplant were analyzed using multivariable logistic and Cox regression, along with propensity-matched analysis. Results: Among 5762 PSC patients, 391 (6.8%) received DCD grafts. Patients receiving DCD grafts were older but had lower MELD scores (19 vs. 22; p < 0.001) and were less often functionally dependent (11.3% vs. 24.4%; p < 0.001). Multivariable Cox regression demonstrated that receipt of a DCD graft was independently associated with time to graft loss (HR 1.59; CI 1.10–2.31; p = 0.013. Similarly, DCD graft receipt significantly increased the likelihood of requiring retransplant (HR 3.25; CI: 1.93–5.46; p < 0.001) but did not increase the likelihood of mortality. Propensity matched analysis further supported these finding with significantly higher graft loss with DCD grafts at one and two years and higher retransplant rates at all time points including 5-years (+7.9%, CI 4.4 to 11.4%; p < 0.001). Conclusions: DCD grafts in PSC patients are linked to worse graft survival and higher retransplant rates. They may be best suited for older, lower-MELD patients, but further studies on perfusion strategies are needed. Full article

Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: This retrospective study analyzed outcomes from 62 liver transplant recipients between 2016 and 2025, comparing 8 grafts preserved by HMP using the Liver Assist^® system and 54 grafts preserved by SCS. Parameters assessed included postoperative complications, hemodynamic stability, ischemia times, and survival outcomes. Results: HMP significantly reduced surgical (0% vs. 75.9%, p = 0.01) and biliary complications (0% vs. 34.4%, p = 0.004), improved hemodynamic stability post-reperfusion (∆MAP%: 1 vs. 21, p = 0.006), and achieved superior one-year survival rates (100% vs. 84.4%). Despite longer ischemia periods, grafts treated with HMP exhibited fewer adverse effects from ischemia-reperfusion injury. Discussion: These findings highlight the substantial benefits of HMP, particularly in improving graft quality from marginal donors and reducing postoperative morbidity. Further adoption of this technology could significantly impact liver transplantation outcomes by expanding the viable donor pool. Conclusions: The study underscores the effectiveness of hypothermic machine perfusion (HMP) as a superior preservation method compared to traditional static cold storage (SCS), HMP appears to be associated with improved short-term outcomes in liver transplantation. By substantially reducing postoperative complications and enhancing graft viability, HMP emerges as a pivotal strategy for maximizing the use of marginal donor organs. Further research and broader clinical implementation are recommended to validate these promising results and to fully harness the potential of HMP in liver transplantation. Full article

Background/Objectives: Hepatic artery thrombosis (HAT) is a serious vascular complication in patients undergoing orthotopic liver transplantation (OLT). It is associated with a high risk of graft loss, re-transplantation (re-OLT), and mortality. This study aimed to evaluate the incidence and management of HAT, analyzing potential risk factors. The secondary objectives included quantifying 90-day postoperative morbidity and mortality rates. Methods: In this retrospective, observational, single-center study, data from liver transplant donors and recipients who underwent OLT between 2004 and 2024 were analyzed. HAT was classified as early (e-HAT, ≤30 days) or late (l-HAT, >30 days). Univariate statistical analysis was performed to identify the risk factors associated with HAT occurrence. Multivariate analysis was not performed due to the small number of HAT events, which would increase the risk of model overfitting. Results: In the 20 year study period, a total of 532 OLTs were performed, including 37 re-OLTs. The rates of major morbidity, reoperation, and mortality within 90 days were 44.5%, 22.3%, and 7.1%, respectively. HAT occurred in 2.4% of cases (e-HAT: 1.6%; l-HAT: 0.7%). Among e-HAT cases, 66.6% were asymptomatic and identified through routine postoperative Doppler ultrasound. All e-HAT cases were surgically treated, with a re-OLT rate of 33.3%. Three l-HAT cases required re-OLT. Overall, the HAT-related mortality and re-OLT rates were 7.6% and 46.1%, respectively. At a follow-up of 86 months, the rate of graft loss was 9.2%, and the rate of post-OLT survival was 77%. Patients who developed HAT had a higher donor-to-recipient body weight ratio and longer warm ischemia times (WITs). Additionally, patients undergoing re-OLT had a higher risk of developing HAT. Conclusions: Although the incidence of HAT is low, its clinical consequences are severe. Early Doppler ultrasound surveillance is crucial for detecting e-HAT and preventing graft loss. A high donor-to-recipient body weight ratio, a prolonged warm ischemia time, and re-OLT seem to be associated with a high risk of HAT. Full article

Background/Objectives: Salvage liver transplantation (SLT) is a well-established option for hepatocellular carcinoma (HCC) recurrence after liver resection. Laparoscopic microwave ablation (L-MWA) represents another curative strategy for early-stage HCC. However, its role within this therapeutic framework remains unexplored. Methods: Between 2014 and 2023, we treated 1341 patients with HCC using L-MWA. From this cohort, patients with Child-Pugh class A liver function, HCC within the Milan criteria, no contraindications to transplantation, and ≥12 months of follow-up were selected. SLT failure was defined as non-transplantable recurrence or death, resulting in the loss of a potentially curative therapeutic opportunity. The primary endpoint was overall survival (OS); secondary endpoints included predictors of survival and SLT failure. Results: A total of 341 patients met the inclusion criteria. Five-year OS was 62%. Independent predictors of poorer survival included the presence of cardiac disease or oesophageal varices, a Child-Pugh score of 6, tumour size, and elevated alpha-fetoprotein (AFP) levels. Treatment was successful in 255 patients (74.8%): 102 (29.9%) underwent SLT, 67 (19.6%) received alternative therapies, and 93 (27.3%) remained recurrence-free. Treatment failure occurred in 86 patients (25.2%) due to non-transplantable recurrence or death. Independent predictors of failure included older age, non-HBV aetiology, and elevated AFP levels. Five-year OS rates were 79% in the success group and 22% in the failure group (p < 0.001). Conclusions: A combined L-MWA and SLT strategy is safe and effective, yielding a 62% 5-year OS rate. This approach supports more efficient graft use with a consequent increase in the population transplant benefit. Improved selection may further reduce failure rates. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) have significantly improved the management of diabetes mellitus (DM). In the general population, these drugs have additional benefits, such as weight loss, improvement of liver steatosis, and a cardiorenal protective effect. However, data regarding the effects of GLP-1RAs or SGLT-2Is in the treatment of posttransplant diabetes mellitus (PTDM), obesity, and their potential cardiorenal protective effects in liver transplant (LT) recipients remain limited. PTDM increases the risk of developing graft steatosis, experiencing major cardiovascular events (MACEs), and developing chronic kidney disease and reduces long-term survival in LT recipients. The aim of this systematic review was to evaluate the efficacy and safety of GLP-1RAs and SGLT-2Is in the treatment of PTDM in LT recipients. Methods: Twelve retrospective studies (five specifically conducted in LT recipients and seven in mixed solid organ transplant cohorts, including LT recipients) that collectively enrolled 402 LT recipients treated with GLP-1RAs and/or SGLT-2Is for PTDM were selected. Results: GLP-1Ras and SGLT-2Is reduced serum glycated hemoglobin levels, body weight, and insulin requirements in LT recipients. Some studies reported benefits in reducing graft steatosis, improving renal function, and in reducing the occurrence of MACEs. Common adverse events included gastrointestinal symptoms, which rarely required treatment discontinuation. Conclusions: GLP-1RAs and SGLT-2Is represent promising treatment options for PTDM in LT recipients, offering metabolic benefits with manageable side effects. However, further prospective studies are needed to establish the long-term safety and efficacy, as well as the favorable impact on patient survival, of these drugs in LT recipients. Full article

Liver transplantation faces significant challenges, primarily due to the severe shortage of organs—aggravated by the increasing prevalence of liver diseases—and graft loss due to the consequences of ischemia/reperfusion injury (I/RI) and rejection. A recent study highlights the critical role of autophagy, a cellular breakdown and recycling mechanism, in addressing these issues. This article examines the role of autophagy in liver transplantation, focusing on organ preservation and recovery after surgery, as well as its potential to regulate immune responses and increase graft survival. Additionally, it will cover the role of autophagy in xenotransplantation, a prospective solution to the organ scarcity crisis. Ultimately, it assesses the importance of precisely timing autophagy modulation—whether induction or inhibition—to enhance transplantation outcomes, while identifying key knowledge gaps and future research directions. Full article

Hepatocellular carcinoma (HCC) is one of the leading causes of liver transplant worldwide. While liver transplantation offers a survival advantage for early-stage HCC patients, post-transplant recurrence remains a significant concern, affecting up to 15% of recipients. We sought to conduct a comprehensive review related to HCC recurrence after liver transplant. Tumor-related factors such as poor differentiation, vascular invasion, and elevated tumor biomarkers like alpha-fetoprotein are key predictors of recurrence. Donor-related factors, including graft type and surgical procedures, can also influence outcomes, though their effects are less conclusive. Advancements in patient selection criteria and scoring systems, such as the Milan Criteria and RETREAT score, have improved risk stratification by incorporating tumor size, biomarkers, and response to pre-transplant treatment. Despite these measures, recurrent HCC after transplantation poses treatment challenges. Curative approaches such as resection are feasible for localized or oligometastatic recurrence and offer the best outcomes when applicable. Locoregional treatments, including ablation and transarterial chemoembolization, provide options for unresectable cases but have limited long-term efficacy. Systemic therapies, including targeted agents like sorafenib, regorafenib, and lenvatinib, have shown modest benefits in managing advanced recurrent HCC. Emerging immunotherapy approaches hold promise but face unique challenges due to the required immunosuppression in transplant recipients. Multidisciplinary evaluation remains essential for tailoring treatment plans. Future efforts should focus on refining predictive tools and exploring novel therapies to improve survival outcomes for patients with recurrent HCC after liver transplantation. Full article

Background/Objectives: Biliary atresia (BA) is the most common etiology for pediatric liver transplantation (LT). However, whether a previous Kasai hepatoportoenterostomy (KP) and its timing influence the outcomes of BA patients who undergo LT remains controversial. Methods: Pediatric patients with BA who underwent LT at Beijing Friendship Hospital, Capital Medical University, between June 2013 and November 2022 were recruited. The patients were divided into non-KP, early-KP (before 90 days of life), and late-KP subgroups. The clinical data were compared among the groups. A nomogram to predict the 1-, 3-, and 5-year graft survival probabilities based on a multivariate Cox model was constructed and validated. Results: Among the 475 BA patients, the no-KP group accounted for 31.8%, the early KP for 60.4%, and the late KP for 7.8%, respectively. The incidences of LT complications were comparable among the groups. From the multivariate Cox analyses, an intensive care unit (ICU) stay and bleeding were identified as the independent risk factors for postoperative patient survival, and the LT type, graft type, vascular complications, and biliary complications were those for graft survival. A nomogram for graft survival was constructed, with a C-index of 0.82, and areas under the curves (AUCs) of 0.829, 0.824, and 0.824 for the 1-, 3-, and 5-year survival nomograms, respectively. The calibration and decision curve analysis (DCA) curves showed good discrimination ability and clinical applicability. A risk classification system was further developed, and the Kaplan–Meier curves demonstrated high discrimination between the high- and low-risk groups (p < 0.0001). Conclusions: A previous KP has no impact on patients or graft survival after LT in BA patients. The established nomogram may be helpful for counseling BA patients about their clinical prognosis after LT. Full article

Introduction: Acute kidney injury (AKI) and chronic kidney disease (CKD) are common complications following liver transplantation (LT), significantly impacting graft and patient survival. AKI affects more than 50% of LT recipients, with a subset requiring renal replacement therapy (RRT), while CKD develops in up to 60% of cases, increasing long-term morbidity and mortality. This study aimed to determine the incidence of AKI and CKD post-LT and to identify risk factors associated with CKD development. Methods: All adult cirrhotic patients without concurrent CKD submitted to LT between January 2001 and December 2017 at the main transplant center in Salvador, Bahia, Brazil, with more than 6-month survival were included in the study. AKI was defined by KDIGO criteria within the first 7 days post-LT. CKD was diagnosed in the presence of the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² and/or proteinuria ≥ 200 mg/g 1 and 5 years after LT. Clinical and biochemical parameters were analyzed using multivariate logistic regression to identify independent predictors of CKD. Results: A total of 177 LT recipients (72.9% male; mean age 53.6 ± 12.6 years) were studied. AKI occurred in 51.4% of them in the first 7 days after LT, and 10 (11%) required RRT. CKD was diagnosed in 30% of LT recipients at 1 year and in 42.9% at 5 years. The majority displayed CKD stage G3 (72.4% at 5 years). Multivariate analysis identified pre-LT serum creatinine (OR 7.74, 95% CI 1.99–30.02) and AKI within 7 days after LT (OR 2.72, 95% CI 1.22–6.06) as independent predictors of CKD development. Conclusions: AKI is highly prevalent in the early post-LT period and is a major determinant of CKD progression. Pre-LT renal function and perioperative AKI were significantly associated with worse long-term nephrological outcomes. Optimized perioperative management and renal monitoring strategies are crucial to minimize progression to end-stage kidney disease in LT recipients. Full article

Background: Living donor liver transplantation (LDLT) has become a widely accepted alternative to deceased donor liver transplantation (DDLT). Nevertheless, the available meta-analyses shed light on a perplexing issue regarding which transplant is better. Therefore, we performed an umbrella review to summarize and evaluate the evidence from current meta-analyses. Methods: Two independent reviewers conducted a search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception to 1 June 2024. The methodological quality of each included meta-analysis was evaluated using AMSTAR2 (A Measurement Tool to Assess Systematic Reviews). Results: The search identified 10 meta-analyses from 486 individual articles, including cohort studies and observational studies. Regrettably, the quality of these meta-analyses ranged from critically low to moderate. Receipt of LDLT offers a survival advantage to the patients with HCC compared with DDLT but with a higher complication rate. However, high-quality studies are required in the future to validate our assertions owing to the low certainty of the evidence. Conclusions: Despite the complication risks, LDLT remains a cost-effective option without compromising patient and graft survival, especially for HCC patients. Extensive, well-designed studies are essential to validate these conclusions. Full article

Background/Objectives: Liver transplantation is a life-saving procedure for patients with end-stage liver disease. In recent years, the demand for liver transplantation has surpassed the supply of available donor organs. Utilizing extended-criteria donors (ECDs) alleviates the scarcity of suitable donor livers for transplantation. One of the ECD was donors with a history of alcohol abuse. Liver grafts from donors with a history of chronic and active alcohol abuse are typically promptly excluded, diminishing the available organ pool. This highlights the need to re-evaluate the donor exclusion criteria and expand the organ pool to address the ongoing shortage. Methods: We examined adult (>18 years) liver transplant recipients who received deceased donor livers and had a documented history of alcohol abuse between 2011 and 2024. Liver transplant indications were conventional and included hepatitis C virus (HCV), non-alcoholic steatohepatitis, alcoholic liver disease, alcoholic liver disease coexisting with HCV, cryptogenic cirrhosis, chronic cholestatic liver disease, primary biliary cholangitis, primary sclerosing cholangitis, metabolic liver disease, hepatocellular carcinoma, and alcoholic hepatitis. We compared the 1-year, 5-year, and 9-year survival rates with those of liver recipients from non-alcohol-consuming donors. Results: In total, 370 liver recipients from deceased donors with a documented history of alcohol abuse were included. At 1 year post-transplant, survival was comparable between the two groups. Conclusions: Liver transplantation from deceased donors with a history of alcohol abuse yielded survival rates and liver function outcomes comparable to those from non-alcohol-using donors. By expanding the criteria to include carefully screened alcohol-using donors, transplant programs can improve access to life-saving transplantations. Full article

Chronic liver disease (CLD) in children poses significant challenges, necessitating timely management to mitigate morbidity and mortality. Liver transplantation (LT) has emerged as a transformative intervention, offering improved long-term survival for paediatric patients with CLD. This review explores the evolving landscape of liver transplantation, focusing on indications and timing considerations. The aetiology of CLD is diverse, encompassing intrahepatic, extrahepatic cholestatic conditions, metabolic diseases, malignancy, and drug-induced liver injury. LT is indicated when children exhibit signs of hepatic decompensation, necessitating a comprehensive evaluation to assess transplant suitability. Indications for LT include biliary atresia, inborn errors of metabolism, hepatocellular carcinoma, and emerging indications such as mitochondrial hepatopathies and acute on chronic liver failure. The timing of transplantation is critical, emphasizing the need for early recognition of decompensation signs to optimise outcomes. Advancements in LT techniques and immunosuppressive therapies have enhanced patient and graft survival rates. Various transplant modalities, including reduced-size LT and living-related LT, offer tailored solutions to address the unique needs of paediatric patients. While LT represents a cornerstone in the management of paediatric CLD, careful patient selection, multidisciplinary collaboration, and ongoing refinements in transplant protocols are imperative for optimizing outcomes and addressing the evolving landscape of paediatric liver disease management. Full article

Background/Objectives: Ischemic time plays a crucial role in graft function and survival during kidney transplantation. Cooling methods, including cold perfusion and ice slush, are predominantly applied to preserve the kidney, but they may cause uneven cooling and complications. The Organ Pocket^®, an insulated gel bag, has been introduced as an alternative cooling method. However, no studies have compared renal temperature changes between the Organ Pocket^® and conventional cooling methods. Methods: We retrospectively analyzed 49 cases of living-donor kidney transplantation. Among these, 33 received kidney grafts preserved with the Organ Pocket^® (OP group), and 16 underwent conventional cooling (control group). Renal surface temperatures were recorded at 5 min intervals during vascular anastomosis using thermography. Postoperative renal function was assessed with estimated glomerular filtration rate (eGFR), serum creatinine (sCr), and liver-type fatty acid-binding protein (L-FABP) levels. Results: The OP group demonstrated significantly higher renal surface temperatures than the control group during vascular anastomosis (p < 0.05). Renal surface temperature before reperfusion was 20.4 °C ± 2.5 °C and 17.2 °C ± 2.5 °C in the OP and control groups, respectively. No significant differences in postoperative eGFR, sCr, and L-FABP levels; delayed graft function (DGF); or acute rejection rates were observed between the groups. Conclusions: The Organ Pocket^® effectively stabilized renal temperatures during vascular anastomosis without direct cooling, thereby reducing continuous manual cooling requirements. Short-term renal function outcomes were comparable between groups; however, the Organ Pocket^® may improve surgical efficiency and be particularly beneficial in robot-assisted kidney transplantation. Further studies are warranted to investigate its long-term benefits. Full article