Background Stress-induced hyperglycemia (SIH) frequently occurs after liver transplantation, leading to impaired graft recovery and increased morbidity. This study aimed to identify independent intraoperative predictors of SIH and establish a simplified predictive model for early clinical application in non-diabetic transplant recipients. Methods Clinical data from 56 non-diabetic patients undergoing first-time liver transplantation (December 2019–November 2023) were retrospectively analyzed. Logistic regression identified independent predictors of postoperative SIH. A predictive model was developed, validated via receiver operating characteristic (ROC) curve analysis, and visualized with a clinical nomogram. Results The incidence of SIH was 46.4%. Multivariate analysis identified donor age (OR = 1.06, P = 0.033), anhepatic phase duration (OR = 1.16, P = 0.018), and pre-incision blood glucose (OR = 3.41, P = 0.009) as independent SIH predictors. The combined predictive model showed strong discriminative ability (AUC = 0.922; sensitivity = 84.6%, specificity = 90.0%), surpassing individual predictors. A nomogram was developed for rapid clinical risk assessment. Conclusions Donor age, anhepatic phase duration, and pre-incision blood glucose independently predict postoperative SIH. This simplified predictive model provides clinicians a practical tool for early identification and targeted management of high-risk patients to mitigate hyperglycemia-related complications.

Biliary stricture, primarily caused by inflammation, hepatobiliary and pancreatic malignancies and other pathological factors, often leads to impaired bile drainage and subsequent poor clinical outcomes. While biliary stent implantation has become a standard palliative and therapeutic intervention, conventional plastic and metal stents are limited by issues such as biofilm formation, epithelial hyperplasia, and the necessity for secondary removal surgery. The emergence of biodegradable stents offers a promising alternative by providing temporary mechanical support and controlled in vivo degradation, thereby eliminating the need for retrieval procedures. However, single-material stents often fail to address the complex and varied clinical demands, particularly in cases involving biliary fibrosis, infection, or malignancy. This review comprehensively summarizes recent advances in functionalized biodegradable biliary stents, referring to additional capabilities beyond their primary mechanical function, with a focus on material innovations and their enhanced functionalities such as anti-fibrotic, anti-tumor, antimicrobial, anti-corrosion, and visualizable properties. We also discuss integrated therapeutic strategies, such as drug-eluting systems and tissue-engineered scaffolds, alongside manufacturing breakthroughs like 3D printing. Furthermore, we also highlight the persistent translational challenges and preclinical limitations of current biodegradable stent technologies, while outlining promising directions for future research to bridge the gap between experimental development and clinical application.

Organ transplantation is the most effective treatment for endu2010stage organ disease. One of the major challenges in organ transplantation is organ shortage. For this reason, more and more extended criteria donor organs, including those from donation after circulatory determination of death (DCDD), are used in clinical practice. However, DCDD organs suffer from additional warm ischemic damage, which seriously affects transplant outcomes and organ utilization. Recent studies at home and abroad have shown that the application of normothermic regional perfusion (NRP) is able to improve the quality of organs and transplantation outcomes. At present, an expert consensus on the clinical application of NRP in DCDD is lacking in China, which limits the standardization and highu2010quality development of DCDD in our country. We summarized the results of clinical studies and conducted inu2010depth discussions based on the principles of evidenceu2010based medicine to form this consensus on the application of NRP in DCDD. This consensus focuses on the executive specification and corresponding research evidence of applying NRP technology in DCDD, aiming to provide reference opinions and guidance for the standardization of NRP in organ transplantation and to promote the rapid development of NRP technology and DCDD organ transplantation in China.

Hepatic fibrosis is a progressive liver disease characterized by excessive accumulation of extracellular matrix (ECM) proteins, primarily collagen, in response to chronic liver injury. Despite the availability of treatment options, current therapies face significant challenges, including poor drug targeting and systemic toxicity. In this study, we developed a nanodrug delivery system, Rosiglitazone (RGZ)-loaded perfluoropropane (PFP)-based lipid nanoparticles (LNPs) functionalized with Arg-Gly-Asp (RGD) peptides (RGZ/PFP@LNP-RGD), for ultrasound-assisted targeted therapy of liver fibrosis. RGZ, a selective PPARγ agonist, was encapsulated in LNPs functionalized with RGD peptides, allowing for targeted delivery to activated hepatic stellate cells (aHSCs), the central cells involved in fibrosis progression. PFP, incorporated into the nanoparticle core, serves as an ultrasound-responsive agent, enabling controlled drug release upon ultrasound irradiation. In vitro, RGZ/PFP@LNP-RGD treatment led to a reduction in the expression of key fibrosis markers such as Col Iα1, α-SMA, and TGF-β1 at both the protein and mRNA levels. Ultrasound treatment further enhanced RGZ release from the nanocarriers, improving the inhibition of HSC activation. In vivo, RGZ/PFP@LNP-RGD combined with ultrasound treatment resulted in a marked reduction in liver fibrosis and improved liver function compared to free RGZ treatment. Histological and biochemical assessments confirmed reduced fibrosis marker expression and liver damage. These results suggest that RGZ/PFP@LNP-RGD, especially when combined with ultrasound, offers a promising noninvasive therapeutic strategy for liver fibrosis, with enhanced targeting, controlled drug release, and reduced systemic toxicity.

BACKGROUND:Calciphylaxis, also called calcific uremic arteriolopathy, is characterized by microvascular calcification and occlusion, which is commonly seen in patients with end-stage renal disease (ESRD). Although several studies have demonstrated an association of calciphylaxis with ESRD, reports linking calciphylaxis to LT (LT) are scarce. This report presents a rare case of calciphylaxis in a patient who underwent LT, leading to microvascular occlusion and hyperbilirubinemia. CASE SUMMARY:A 34-year-old man presented with a 7-day history of jaundice and severe bilateral leg pain. The patient had undergone LT and was put on hemodialysis for one year due to calcineurin inhibitor-induced ESRD. Physical examination revealed jaundice, leathery skin changes, severe muscle pain in both legs, and penile induration. Laboratory tests identified elevated bilirubin levels, gamma-glutamyltransferase, and alkaline phosphatase, while alanine aminotransferase and aspartate aminotransferase concentrations were within normal limits. Computed tomography (CT) revealed extensive calcifications in the subcutaneous tissue. Three-dimensional CT reconstruction indicated significantly reduced blood flow in the hepatic artery, primarily in the small to medium-sized branches. Contrast-enhanced ultrasonography confirmed hepatic ischemia, with no enhancement seen in hepatic artery branches. Liver biopsy specimen revealed no signs of rejection. The patient decided to receive conservative treatment and succumbed to the illness after six months. CONCLUSION:This case indicates that calciphylaxis should be suspected in patients who have undergone LT with ESRD presenting with hyperbilirubinemia and skin lesions.

Polycystic liver disease is a hereditary disease, which is characterized by the presence of multiple cysts within the liver. In this case, we report a patient with multiple cysts in the kidneys and liver, who underwent kidney transplantation in 2019 and then liver transplantation 4 years later. The complexities of performing liver transplantation in a patient with a prior kidney transplant were significant, particularly due to the enlarged liver obscuring critical vascular structures and necessitating careful intraoperative strategies, such as the side-to-side anastomosis or piggyback techniques to ensure venous return and protect the renal graft. One year post-transplant, the patient exhibited stable liver and kidney functions, demonstrating the feasibility of liver transplantation after kidney transplantation from different donor grafts. The surgical technique and perioperative management require careful consideration.

Objective This study aimed to investigate the role of microRNA-34a (miR-34a) in regulating liver regeneration (LR) and the development of liver cancer in rats by targeting Notch signaling pathway. Methods Thirty male Sprague-Dawley (SD) rats were randomly assigned into partial hepatectomy (PH) group and sham hepatectomy (SH) group. Hematoxylin and eosin (HE) staining was used to observe the histological change in liver tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels. Dual-luciferase reporter gene assay was performed to examine whether miR-34a targeted Notch1 gene. Human liver cancer Huh7 cells were transfected and divided into blank, negative control (NC), miR-34a mimics and miR-34a inhibitors groups. MTT and flow cytometry were used to detect cell growth, and cell cycle and apoptosis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied detect to the expressions of miR-34a and Notch receptor mRNA. Western blotting was performed to detect the protein expressions of Notch receptors, P21, Bax, Bcl-2 and Bcl-xL. Tumor xenograft in nude mice was done to observe tumor formation in different groups. Results Compared to the SH group, miR-34a expression in liver tissues in the PH group decreased first and then increased to the normal level during LR. In early stage of LR, the expressions of Notch receptors and miR-34a were negatively correlated. Compared to the blank and NC groups, the cell growth was inhibited, cell cycle was mainly arrested in the G2/M phase and cell apoptosis rate increased in the miR-34a mimics group. Moreover, the expressions of miR-34a, P21 and Bax were up-regulated, while the expressions of Notch receptors, and Bcl-2 and Bcl-xL were down-regulated in this group. Additionally, the tumor growth in the miR-34a mimics group was reduced. The miR-34a inhibitors group showed contrary tendencies. Conclusion Our study demonstrates that miR-34a regulated LR and the development of liver cancer by inhibiting Notch signaling pathway.

www.transplantjournal.com 1855 First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China: 5-year Experience at a High-volume Donor and Recipient Liver Transplant Center Zhitao Chen, MD, Ming Han, MD, Yuqi Dong, MA, Ping Zeng, MA, Yuan Liao, MA, Tielong Wang, MD, Qiang Zhao, MD, Dongping Wang, MD, Yi Ma, MD, Yinhua Chen, MD, Anbin Hu, MD, Xiaofeng Zhu, MD, Zhiyong Guo, MD, Yunhua Tang, MD, Maogen Chen, MD, Weiqiang Ju, MD, and Xiaoshun He, MD, PhD

Background & Aims: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.Methods: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. Results: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to - 1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference - 11.66; 95% CI -21.81 to -1.51; p = 0.025).Conclusions: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.Clinical trial registration: chictr.org. ChiCTR1900021158.

Objective:To establish donor liver quality related risk factors for the loss of function of transplanted liver.Methods:The data of donors and recipients of liver transplantation at the Organ Donation and Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University from Nov 2011 to Dec 2018 were analyzed retrospectively. Propensity score matching (PSM) was performed to evaluate and screen the data of donors and recipients, in order to balance the covariates.Results:Of the organ donation, there were 70 males and 20 females , aging (40.6±16.3) years. Of the liver transplantation recipients, there were 70 males and 20 females , aging (41.8±20.3) years. Liver dysfunction after transplantation was significantly correlated with the following variables: the donor's CPR time( t=0.429, P=0.000), 15-minute retention rate of indocyanine green ( χ2=67.151, P=0.000), liver function grading ( χ2=54.154, P=0.000), bullae fatty liver grading ( χ2=8.120, P=0.017), vesicular fatty liver grading ( χ2=16.000, P=0.001), ICU stay time ( χ2=14.900, P=0.001)and serum creatinine level ( χ2=44.685, P=0.000). The donor scoring system was established in our studying. For the 90 organ donation cases, the donated liver quality were classified into four levels,which were of good correspondence to the prognosis of the recipients. Conclusion:This donor scoring system and grading standards established by analyzing the high-risk factors of liver dysfunction after transplantation helps evaluate the quality of donor liver in China.

The occurrence of fungal infection seriously affects the survival and life quality of transplanted patients. The accurate diagnosis is of particular importance in the early stage of infection. To develop a novel diagnostic method for this kind of patient, we established a post-transplant immunosuppressed mice model with fungus inoculation and collected their peripheral blood at specific time points after infection. After screening by microarray, differentially expressed miRNAs and lncRNAs were selected and homologously analyzed with those of human beings from the gene database. These miRNAs and lncRNAs candidates were validated by qRT-PCR in peripheral blood samples from transplanted patients. We found that, compared with normal transplanted patients, the levels of miR-215 and miR-let-7 c were up-regulated in the plasma of patients with fungal infection (P < 0.01), while levels of miR-154, miR-193a, NR_027669.1, and NR_036506.1 were down-regulated in their peripheral blood mononuclear cells (P < 0.01). Principal component analysis shows that the expression pattern of the above RNAs was different between the two groups. A 6-noncoding-RNA detection panel was established by the support vector machine analysis, whose area under the ROC curve was 0.927. The accuracy, precision, sensitivity, and specificity of this model were 0.928, 0.919, 0.944, and 0.910, respectively. Though our detection panel has excellent diagnostic efficacy, its clinical application value still needs to be further confirmed by multi-center prospective clinical trials.

器官短缺是全球移植界共同面临的难题,寻找多渠道的供者器官来源成为器官移植界的当务之急.近日,关于"扩大可控型经循环标准确定死亡后器官捐献(cDCDD)实践的联合声明"受到学术界的广泛关注,该声明旨在推广cDCDD,以提高器官捐献率,以期实现移植自给自足的最终目标.本文将整理声明提及的重点内容,阐述经循环标准确定死亡后器官捐献(DCDD)的学术名称更新及相关讨论、DCDD的发展趋势、构成cDCDD临床路径的基本部分及影响实施cDCDD的关键因素,思考该声明对我国器官捐献事业可持续发展的启示.

In order to safely carry out organ donation transplants during the outbreak of coronavirus disease 2019 (COVID-19), we have formulated strict procedures in place for organ donation and transplantation. We retrospectively analyzed our transplantation work from January 20 to May 5, 2020, to discuss whether organ transplantation can be carried out safely during the epidemic period. From January 20 to May 5, 43 cases of donation were carried out in our hospital, and the utilization rate of liver, kidney, heart, lung, and pancreas donations was more than 90%. Forty-one cases of liver transplantation and 84 cases of kidney transplantation were performed. No graft loss or recipient death occurred within one month after kidney transplantation, and one patient (2.4%) died after liver transplantation. There was no significant difference in the length of hospital stay compared with that during the same period in the previous three years. More importantly, COVID-19 infection did not occur among healthcare providers, donors, patients, or their accompanying families in our center. Under the premise of correct protection, it is safe and feasible to carry out organ transplantation during the epidemic period. Our experience during the outbreak might provide a clinical reference for countries facing COVID-19 worldwide.

Abstract BackgroundLiver transplantation (LT) is considered the only curative treatment for end-stage liver disease (ESLD), and the surgical techniques of LT have continually evolved and have been modified. In this study, we prospectively analyzed a single-center case series in our center and compared the advantages and disadvantages of each method.MethodsIn total, 1,029 patients with OLT at our department were enrolled in this study. The recipient perioperative data were assessed and analyzed. Three types of LT techniques were utilized: modified classic, modified piggy-back (MPB) and classic piggy-back (PB) orthotopic LT, corresponding to groups A, B and C.ResultsCirrhosis was the most prevalent condition in group B, while tumors tended to be more common in group A. Patients in group C were in poorer general condition with higher creatinine, total bilirubin and PT-INR (P = 0.029, 0.011 and 0.026, respectively). Two hundred ninety-five patients had previous abdominal surgery, and the proportion was higher in group B (P = 0.017). The cold ischemia time in group B was longer than those in the other two groups (P<0.001). The mortality rate was 7.9% within 30 days and 11.7% within 90 days. Most of the deaths were not technique-related.ConclusionThe advantages and disadvantages are different for these three surgical techniques. A reasonable operation technique should be adopted considering the patient's unique condition to ensure the stability of hemodynamics.

Background: Normothermic machine perfusion (NMP) can provide access to evaluate and resuscitate high-risk donor livers before transplantation. The purpose of this study was to determine the efficacy of NMP in preservation and assessment of extended-criteria donor (ECD) livers in China. Case Reports: From September 2018 to March 2019, 4 liver grafts from 3 transplant center defined as ECD were subjected to NMP, and then were transplanted successfully. During perfusion, perfusion parameters such as vascular flow, glucose level, lactate clearance, and bile production/composition were recorded to assess graft viability. All recipients were followed up 6 months after transplantation. Conclusions: NMP provides a potential tool for preservation and assessment of ECD livers in China.

Aim: To explore molecular mechanisms underlying liver ischemia-reperfusion injury (IRI). Materials & methods: Four Gene Expression Omnibus datasets comprising liver transplantation data were collected for a comprehensive analysis. A proteomic analysis was performed and used for correlations analysis with transcriptomic. Results & conclusion: Ten differentially expressed genes were co-upregulated in four Gene Expression Omnibus datasets, including ATF3, CCL4, DNAJB1, DUSP5, JUND, KLF6, NFKBIA, PLAUR, PPP1R15A and TNFAIP3. The combined analysis demonstrated ten coregulated genes/proteins, including HBB, HBG2, CA1, SLC4A1, PLIN2, JUNB, HBA1, MMP9, SLC2A1 and PADI4. The coregulated differentially expressed genes and coregulated genes/proteins formed a tight interaction network and could serve as the core factors underlying IRI. Comprehensive and combined omics analyses revealed key factors underlying liver IRI, and thus having potential clinical significance.

Background: Ischemia-reperfusion injury (IRI) has been considered an inevitable event in organ transplantation since the first successful kidney transplant was performed in 1954. To avoid IRI, we have established a novel procedure called ischemia-free organ transplantation. Here, we describe the first case of ischemia-free kidney transplantation (IFKT). Materials and Methods: The kidney graft was donated by a 19-year-old brain-dead donor. The recipient was a 47-year-old man with end-stage diabetic nephropathy. The graft was procured, preserved, and implanted without cessation of blood supply using normothermic machine perfusion. Results: The graft appearance, perfusion flow, and urine production suggested that the kidney was functioning well-during the whole procedure. The creatinine dropped rapidly to normal range within 3 days post-transplantation. The levels of serum renal injury markers were low post-transplantation. No rejection or vascular or infectious complications occurred. The patient had an uneventful recovery. Conclusion: This paper marks the first case of IFKT in humans. This innovation may offer a unique solution to optimizing transplant outcomes in kidney transplantation.