Search Results (2,245)

Background/Objectives: Infections remain a leading cause of morbidity and mortality following liver transplantation, with bloodstream infections (BSIs) representing one of the most critical complications. This study aimed to identify factors associated with mortality in liver transplant recipients who developed BSIs over a 10-year period. Methods: This retrospective study was conducted at a tertiary university hospital between 1 April 2014 and 31 December 2024. A total of 467 adult patients underwent liver transplantation during the study period. Among 467 patients, a total of 210 bloodstream infection episodes occurring in 136 patients were included in the study. Results: BSIs occurred in 29.1% (136/467) of patients, with a total of 210 episodes. The median age was 55 years (IQR: 45–63). Most transplants (95.2%) were from living donors. Hepatitis B virus infection (27.1%) was the most common underlying etiology of cirrhosis. The majority of BSIs (61.2%) occurred within the first three months post-transplant. A total of 242 pathogens were isolated, with ESBL-producing Enterobacterales identified in 72.6% and carbapenem-resistant Enterobacterales (CRE) in 30.1% of cases. Notably, carbapenem resistance among Klebsiella spp. was high at 51.78%. The overall mortality rate was 14.28%. Multivariate analysis identified that a high Pitt Bacteremia Score (hazard ratio [HR] 1.502, 95% confidence interval [CI] 1.361–1.657, p < 0.001) and CRE infection (HR 3.644, 95% CI 1.380–9.620, p = 0.009) were independent predictors of mortality. Conclusions: BSIs are a significant post-transplant complication with high antimicrobial resistance. The Pitt bacteremia score is a strong predictor of mortality and may guide early risk stratification and clinical management in liver transplant recipients. Full article

Background: Large language models (LLMs) are increasingly used in clinical medicine, yet their ability to interpret advanced intraoperative hemodynamic monitoring—particularly in the context of liver transplantation—remains largely unexplored. In this proof-of-concept study, we evaluated ChatGPT’s capacity to interpret multimodal hemodynamic data derived from both standard anesthesia monitoring and the PiCCO system. The study also employed a structured assessment instrument (ARQuAT), adapted through a Delphi-based process to evaluate LLM-generated clinical interpretations. Methods: Ten key surgical–hemodynamic phases of liver transplantation were identified using a modified Delphi approach to capture the major physiological transitions of the procedure. Sequential screenshots representing these phases were obtained from five liver transplant recipients, yielding a total of 50 images. Each screenshot, along with standardized clinical background information, was submitted to ChatGPT. Five expert anesthesiologists independently assessed the model’s responses using the modified ARQuAT tool, which includes six content-quality domains (Accuracy, Up-to-dateness, Contextual Consistency, Clinical Usability, Trustworthiness, Clarity) and a separate catastrophic Risk item. Descriptive statistics were calculated for domain-level performance. Inter-rater reliability (Kendall’s W) and internal consistency (Cronbach’s alpha, McDonald’s omega) were also analyzed. All statistical analyses and visualizations were performed using NumIQO. Results: ChatGPT demonstrated consistently high performance across all content-quality domains, with median scores ranging from 4.6 to 4.8 and more than 90% of all ratings classified as satisfactory. Lower scores appeared only in a small subset of frames associated with abrupt hemodynamic changes and did not indicate a recurring weakness in any specific domain. Catastrophic Risk exhibited a pronounced floor effect, with 86% of ratings scored as 0 and only three isolated high-risk assessments across the dataset. Internal consistency of the six ARQuAT content domains was excellent, while inter-rater agreement was modest, reflecting ceiling effects and tied ratings among evaluators. Conclusions: ChatGPT generated clinically acceptable, contextually aligned interpretations of complex intraoperative hemodynamic data in liver transplant recipients, with minimal evidence of unsafe recommendations. These findings suggest preliminary promise for LLM-assisted interpretation of advanced monitoring, while underscoring the need for future studies involving larger datasets, dynamic physiological inputs, and expanded evaluator groups. The reliability characteristics observed also provide initial support for further refinement and broader validation of the Delphi-derived ARQuAT framework. Full article

Vancomycin-resistant Enterococci (VRE) are established nosocomial pathogens; however, vancomycin-dependent Enterococci (VDE) represent a rare and underrecognized phenomenon. These organisms paradoxically require vancomycin for growth due to mutations in cell wall precursor synthesis. Limited awareness and significant diagnostic challenges associated with VDE can lead to delayed recognition and treatment failure. We report a case of vancomycin-dependent Enterococcus faecium isolated from a liver transplant recipient receiving oral vancomycin prophylaxis for recurrent Clostridioides difficile infection. The isolate failed to grow on standard media but exhibited robust growth on vancomycin-supplemented agar, confirmed by vancomycin disc diffusion testing and PCR detection of the vanB gene. Additionally, we reviewed four further VDE cases identified over a two-year period in our tertiary care microbiology laboratory. All patients originated from complex care settings, had significant comorbidities, and had received prolonged glycopeptide therapy. We summarize the clinical features, diagnostic findings, and microbiological challenges encountered across this case series. This series documents the first reported Canadian case of VDE and highlights the critical need for clinical vigilance and diagnostic suspicion in high-risk patients with prior enterococcal colonization and ongoing glycopeptide exposure. Laboratory findings such as failure to grow on blood agar coupled with growth around vancomycin discs should prompt specific evaluation for VDE. Our findings reinforce the necessity for targeted antimicrobial stewardship and infection prevention strategies and underscore the remarkable evolutionary adaptability of Enterococci under sustained antimicrobial pressure. Full article

Hepatic ischemia–reperfusion injury (IRI) is a critical clinical condition associated with liver transplantation and acute liver injury. This study investigated the role of sulfide quinone oxidoreductase (SQOR) and its downstream product, supersulfides, in hepatic IRI. C57BL/6NJ mice were subjected to 45 min of partial hepatic ischemia, followed by reperfusion lasting 4 h. Control of shRNA mediated knockdown of SQOR expressing adeno-associated viral vectors were administered 3 weeks prior to liver ischemia. In the shRNA-mediated knockdown of SQOR group, the hydro-trisulfide donor sodium trisulfide was administered daily for 1 week prior to the induction of liver ischemia. SQOR played a crucial protective role during hepatic IRI by facilitating electron transport to the mitochondrial respiratory chain and maintaining the oxidized and reduced nicotinamide adenine dinucleotide ratio. Administration of sodium trisulfide, exhibited protective effects against hepatic IRI. Sodium trisulfide restored the oxidized and reduced nicotinamide adenine dinucleotide ratio, reduced oxidative stress, and preserved the expression of key enzymes involved in the sulfide oxidation pathway. SQOR and supersulfides contribute to hepatic protection against IRI, likely through their potent antioxidative and redox-regulating functions, and highlight sodium trisulfide as a potential therapeutic agent. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer and cancer-related death worldwide. Beyond the well-known factors influencing the risk of HCC, experimental data from animal models and observational human studies support a significant role of the gut microbiota (GM) in HCC initiation and progression. Dysbiosis and increased intestinal permeability synergistically disrupt the ‘gut–liver axis,’ exposing the liver to bacterial metabolites and microbial-associated molecular patterns, thereby contributing to hepatocarcinogenesis. While these findings have expanded our understanding of HCC pathogenesis, a critical translational gap persists as most data derive from preclinical settings, with limited validation in large-scale clinical studies. Methods: This narrative review aimed to contextualise the current evidence on the GM-HCC axis and its clinical translatability. A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science up to July 2025 using Medical Subject Headings and related keywords, including HCC, GM, dysbiosis, intestinal permeability, gut–liver axis, microbial metabolites, inflammation/immune modulation, and microbiota-targeted interventions (probiotics, antibiotics, and faecal microbiota transplantation). Reference lists of relevant articles were also screened to identify additional studies. Results: Preclinical models consistently indicate that dysbiosis and impaired gut barrier function can promote hepatic inflammation, immune dysregulation, and pro-tumorigenic signalling through microbe-derived products and metabolite perturbations, supporting a contributory role of the GM in hepatocarcinogenesis. In humans, HCC and advanced chronic liver disease are associated with altered microbial composition and function, increased markers of intestinal permeability, and changes in bile acid and other metabolite profiles; however, reported signatures are heterogeneous across cohorts and analytical platforms. Conclusions: The GM is a biologically plausible and experimentally supported contributor to HCC initiation and progression, with potential for biomarker development and therapeutic targeting. However, clinical translation is limited by predominantly preclinical/associative evidence, interindividual variability, and non-standardised microbiome methods. Large longitudinal studies and adequately powered randomised trials are needed to establish causality, validate biomarkers, and determine whether GM modulation improves HCC prevention, detection, stratification, or outcomes. Full article

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Transarterial radioembolization (TARE) has emerged as a locoregional therapy to downstage tumors and expand surgical eligibility. Methods: This retrospective study included patients with HCC who underwent TARE as a bridging treatment. The primary outcomes assessed were the efficacy of TARE in facilitating curative surgery and long-term oncological outcomes, specifically overall survival (OS) and disease-free survival (DFS). Results: This study included 25 patients. 17 patients subsequently underwent surgical resection and eight underwent living-donor liver transplantation (LDLT). At a median follow-up of 33.4 months, the median disease-free survival (DFS) was 11.2 months. Patients with recurrence had a median DFS of 3.65 months, and those without recurrence had a median DFS of 27.1 months. The median overall survival (OS) for the cohort was 33.4 months. At the last follow-up, 76% of patients were alive and disease-free. Kaplan–Meier analysis demonstrated sustained OS in the LDLT group, while resection patients gradually declined within the first two years. Conclusions: TARE is an effective bridging strategy that enables curative-intent surgery in selected patients with HCC and supports favorable long-term oncological outcomes. Careful patient selection and multidisciplinary management remain essential to optimize survival benefits. Full article

Liver function plays a pivotal role in the management of hepatocellular carcinoma (HCC). Consequently, managing HCC requires a dual focus on both tumour staging and liver function assessment to guide therapeutic decisions. Comprehensive liver function evaluation involves clinical tools such as the Child–Pugh classification and the Model for End-Stage Liver Disease (MELD) score. This is supplemented by newer metrics, including the MELD-Na score, the albumin–bilirubin (ALBI) grade and liver stiffness measurements. These assessments are integral to tailoring treatments, ranging from curative approaches such as surgical resection and liver transplantation to locoregional options (percutaneous ablation, transarterial chemoembolisation and radioembolisation), and systemic therapies. This review explores strategies for balancing the aggressiveness of cancer therapy with the need to preserve hepatic function, particularly in patients with advanced liver dysfunction. A multidisciplinary approach, incorporating expertise from hepatology, oncology, radiology and surgery, is essential for optimising outcomes. Advanced imaging techniques and biochemical markers also improve decision-making and ensure individualised care. Full article

Background: Solid organ transplant recipients (SOTRs) are highly vulnerable to severe COVID-19 infection, yet initial vaccine trials provided limited data on efficacy and safety in this immunocompromised population. Heterogeneous seroconversion rates and conflicting safety reports complicate the formulation of clear clinical guidelines. This systematic review and meta-analysis aim to aggregate existing evidence to determine the precise seroconversion and safety profiles of COVID-19 vaccines and identify key factors influencing immune response in SOTRs. Methods: A comprehensive literature search was conducted identifying 125 studies evaluating WHO/FDA-authorized vaccines in SOTRs. Outcomes were the pooled seroconversion proportion and safety profile. Subgroup analyses were performed based on vaccine type, transplanted organ, number of doses, and prior SARS-CoV-2 infection status, confirmed by leave-one-out sensitivity analysis and bootstrap methods. Results: Most studies assessed mRNA-based vaccines (123/125, 98.4%). The overall pooled seroconversion proportion across all SOTRs was significantly blunted at 0.49 (95% CI, 0.43 to 0.55), demonstrating high heterogeneity (I² = 94.2%). Seroconversion showed a clear positive dose–response relationship, increasing from 27% after one dose to 84% after four doses. Prior COVID-19 infection was the strongest predictor of a response, resulting in a pooled seroconversion of 0.90 (95% CI, 0.82 to 0.94; I² = 0%). Organ-specific analyses revealed the highest response in Liver recipients (0.80) and the lowest in Lung recipients (0.29). Vaccine platform analysis showed that the highest response was with mRNA-1273 (0.55) and the lowest with CoronaVac (0.29). The safety profile was limited. Conclusions: SOTRs exhibit profound hypo responsiveness to COVID-19 vaccines; however, the extreme heterogeneity observed across studies necessitates a cautious interpretation of pooled seroconversion estimates. While the data indicates a significant dose–response relationship favoring an aggressive, multi-dose strategy, the apparent safety profile may reflect under-reporting and limited follow-up rather than confirmed safety equivalence. Rare but clinically critical outcomes, such as acute allograft rejection, remain inadequately characterized in the current literature. Consequently, while the prioritization of multi-dose regimens and hybrid immunity is supported to maximize protection, clinicians must recognize that individual responses remain highly variable, and the long-term immunological impact of repeated stimulation requires further standardized investigation. Full article

Background: This study seeks to evaluate the 23 year experience of the İnonu University Liver Transplantation Institute from a public health perspective by examining demographic patterns, etiological factors, and transplantation trends between 2002 and 2025. Aims: This analysis aims to provide insights into the epidemiological landscape of liver transplantation in Türkiye from a public health perspective. Methods: In this retrospective cross sectional study, we analyzed 4011 liver transplant procedures performed between March 2002 and March 2025. Recipient demographics, disease etiologies, donor characteristics, and patients geographic distribution were assessed to delineate regional health needs and service utilization patterns. Results: A total of 4011 patients were included. The cohort comprised 2618 males (65.3%) and 1393 females (34.7%). Recipients were classified as adult (n = 3232, 80.9%) or pediatric (n = 779, 19.1%). Among adults, infectious etiologies were the most prevalent (35.5%), followed by cryptogenic liver cirrhosis (24.7%). In contrast, pediatric patients most commonly presented with toxic etiologies (29.4%), metabolic disorders (22.6%) and bile duct diseases (15.9%). Most liver transplantations were performed using living donors (n = 3481, 86.8%), while deceased donors accounted for 530 procedures (13.2%). Additionally, 244 living donor liver transplantations were performed via liver paired exchange (LPE). Conclusions: These findings may inform resource allocation, health policy development, and the optimization of transplantation services. This center-based model offers a useful framework for characterizing regional health needs and strengthening community health, particularly through prevention, screening, and early intervention strategies for liver diseases. Full article

Liver fibrosis is a common pathological result of chronic hepatic injury caused by various factors, such as viral hepatitis, alcohol-induced liver disease, and metabolic dysfunction-associated steatohepatitis (MASH). It is characterized by an excessive deposition of extracellular matrix, which disrupts the architecture of the liver and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Globally, nearly 10% of the population has significant fibrosis, with its prevalence increasing with age, obesity, and metabolic syndrome. Despite its significant clinical impact, early detection of liver fibrosis is still limited due to insufficient diagnostic technologies and low public awareness. The increasing burden of MASH emphasizes the urgent need for scalable therapeutic strategies. Currently, liver transplantation is the only definitive treatment, but it is limited by donor shortages and the need for lifelong immunosuppression. However, fibrosis is now recognized as a dynamic and potentially reversible process if the underlying cause is addressed. This shift in understanding has prompted efforts to develop pharmacological agents that target hepatic stellate cell activation, immune system interactions, and metabolic dysfunction. Advances in organoid platforms, multi-omics, and non-invasive diagnostics are accelerating translational research in this area. This review aims to synthesize current knowledge about the molecular drivers of fibrosis, bottlenecks in the current anti-fibrotic drug discovery process, and emerging therapeutic approaches to inform precision medicine strategies and reduce the global burden of chronic liver disease. Full article

The global burden of acute and chronic liver diseases warrants safe and effective regenerative therapies that can complement or defer liver transplantation. Mesenchymal stromal/stem cells (MSCs) have been recognized as versatile biologics that modulate inflammation, reverse fibrosis, and promote hepatic repair predominantly through paracrine signaling. In hepatic milieu, MSCs act on hepatocytes, hepatic stellate cells, endothelial cells, and immune cell subsets through trophic factors and extracellular vesicles (EVs). Despite demonstrating hepatocyte-like differentiation of MSCs, their in vivo efficacy is primarily attributed to micro-environmental reprogramming rather than durable engraftment. This review covers MSC biology, liver regeneration, and cell-based versus EV therapies, including administration, dosing, quality, and safety. Future directions focus on biomarkers, multi-center trials, and engineered MSC/EV platforms for scalable personalized liver regeneration. Full article

Liver graft shortage remains a major limiting factor in contemporary liver transplantation, particularly in the setting of increasing waiting list pressure and constrained donor availability. While the biological quality of donor organs cannot be modified surgically, several operative strategies have been developed to optimize liver utilization and compensate for insufficient graft volume. These include split liver transplantation (SLT), dual-graft living donor liver transplantation (DGLT), auxiliary procedures, and selected multi-graft or hybrid configurations. This review provides an updated and structured overview of surgical concepts aimed at maximizing effective liver mass for transplantation. We discuss indications, technical considerations, and reported outcomes of split, dual, and combined graft approaches, with particular emphasis on graft-to-recipient weight ratio (GRWR), portal inflow modulation, and prevention of small-for-size syndrome. The role of machine perfusion technologies—including normothermic and hypothermic approaches—as enabling tools for graft assessment and safer utilization of partial grafts is also examined. Finally, we address ethical and logistical challenges associated with complex graft strategies and outline future directions in which advances in perfusion, graft assessment, and staged transplantation concepts may further refine patient selection and procedural safety. Collectively, these strategies represent complementary solutions for extending liver transplantation beyond conventional single-graft paradigms in highly selected settings. Full article

Background: Cirrhosis represents the final common pathway of chronic liver injury, arising from diverse etiologies such as metabolic, viral, autoimmune, and alcohol-related liver diseases. Despite similar exposures, disease progression varies considerably among individuals, suggesting a genetic contribution to susceptibility and outcome. Objective: This narrative review examines how specific genetic variants influence the risk, progression, and phenotypic expression of cirrhosis. It provides a structured synthesis of established and emerging gene associations, emphasizing their biological mechanisms and potential clinical relevance. Methods: This narrative review synthesizes evidence from all major biomedical and scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar, as well as reference lists of relevant articles, covering literature published between 2005 and 2025 on genetic polymorphisms associated with cirrhosis and its etiological subtypes. Content: Variants are categorized into four mechanistic domains—metabolic regulation, immune modulation, liver enzyme activity, and ancestry-linked expression patterns—representing a novel integrative framework for understanding genetic risk in cirrhosis. Well-characterized variants such as PNPLA3, TM6SF2, HSD17B13, and MBOAT7, along with less commonly studied loci and chromosomal alterations, are discussed in relation to major etiologies, including MASLD/MASH, viral hepatitis, alcohol-related liver disease, and autoimmune conditions. Conclusions: Genetic insights into cirrhosis offer pathways toward early risk stratification and personalized disease management. While polygenic risk scores and multi-omic integration show promise, their clinical translation remains exploratory and requires further validation through large-scale prospective studies. Full article

A 25-year-old woman with decompensated liver cirrhosis and complete inferior vena cava (IVC) occlusion was referred to our department for liver transplantation. The etiology of cirrhosis was Budd-Chiari syndrome (BCS) related to systemic lupus erythematosus, autoimmune hepatitis, and primary biliary cholangitis (AIH-PBC) overlap syndrome. Transplantation was feasible due to an extensive collateral circulation of pre-vertebral veins that drained blood from the lower extremities and both kidneys to the azygos-hemiazygos veins. This venous anomaly enabled the excision of the obstructed retrohepatic IVC, followed by an alternative anastomosis of the suprahepatic IVC to the right atrium without reconstruction of the infrahepatic IVC. Despite good venous patency and normalization of liver graft function, the patient developed cecum perforation, cardiovascular and respiratory insufficiency, which led to the patient’s death two months after transplantation. This case report supports an individual approach and highlights the feasibility of liver transplantation despite an extensive IVC thrombosis. To our knowledge, it is the first description of the application of a deceased donor liver transplantation in patients with AIH-PBC overlap syndrome and lupus-related BCS. A concise review of published literature on IVC-atrial anastomosis in adult liver transplant recipients is provided, and the technique is discussed based on our recent experience. Full article

The liver is the primary site of synthesis for most coagulation factors and the central organ responsible for maintaining hemostatic equilibrium. In individuals with advanced liver disease, significant disruptions in coagulation homeostasis occur and consequently predispose patients to both thrombotic and bleeding complications. This review summarizes the pathophysiologic basics of liver cirrhosis-associated coagulopathies and discusses the diagnosis and treatment of common procoagulant conditions such as portal vein thrombosis and post-transplant hepatic artery thrombosis. The review also systematically addresses the most common bleeding complications, including spontaneous, portal hypertension-related, and periprocedural bleeding. The proper pre-procedural assessment of the bleeding risk is often required due to the great number of invasive procedures to which these patients are frequently subjected. The viscoelastic testing (thromboelastogram and thromboelastometry) seems to emerge as the most appropriate diagnostic method. Specific treatment recommendations for the correction of coagulation abnormalities and the management of severe thrombocytopenia are hereby presented. Full article