Annals of Transplantation最新文献

BACKGROUND Immune checkpoint inhibitors (ICIs) are widely used as first-line combination therapies for many cancers. However, ICIs are associated with an increased risk of graft rejection in patients requiring liver transplants, and the tumor response rate has yet to be determined. MATERIAL AND METHODS This retrospective study included liver transplant recipients who received ICIs for recurrent hepatocellular carcinoma. During ICI therapy, baseline immunosuppressant doses were maintained, with low-dose steroid treatments added when clinically indicated. RESULTS A total of 25 patients were included, with 12 receiving ICIs as first-line therapy, and 13 as second-line therapy. The median progression-free survival (PFS) was 4.93 months (95% CI, 2.33-28.63) and 7.20 months (3.80-32.47), respectively. One patient (4.0%) developed grade 2 hepatitis, and 2 (8%) experienced grade 3 gastrointestinal bleeding. Concurrent steroid use was associated with fewer immune-related adverse events (0% vs 30%, P=0.052) but showed a trend toward shorter PFS (HR=2.30, P=0.071). Two patients (8%) achieved complete remission, and 4 (16%) maintained disease control for more than 1 year. In multivariable analysis, recurrence within 1 year after transplantation was the only significant prognostic factor for PFS (HR=2.98, P=0.043). CONCLUSIONS Our findings suggest that ICIs can be administered after liver transplantation without reducing baseline immunosuppressant doses, potentially minimizing the risk of fatal allograft rejection while still allowing antitumor activity. These results should be interpreted cautiously, and larger studies are needed to define the safe and appropriate use of ICIs in this population.

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection in kidney transplant recipients (KTRs). Early identification of patients liable to progress to severe disease is critical for improving prognosis. This study aimed to construct and validate a machine learning-based nomogram for predicting the risk of severe PJP in KTRs using routine clinical indicators. MATERIAL AND METHODS A retrospective cohort of 169 KTRs diagnosed with PJP was analyzed. Severe PJP was defined as cases requiring intensive care unit (ICU) admission or death. The cohort was randomized into training (n=120) and testing (n=49) sets. Three machine learning algorithms (Boruta, RFE, and LASSO) were utilized for feature selection. A multivariate logistic regression model was established and visualized as a nomogram. Model performance was evaluated via area under the ROC curve (AUC), calibration plots, and decision curve analysis (DCA). Kaplan-Meier analysis was performed to assess risk stratification. RESULTS Four key predictors were identified: procalcitonin (PCT), (1→3)-ß-D-glucan (G_test), C-reactive protein (CRP), and the time from kidney transplantation to PJP onset (Time KT to PJP). Notably, shorter post-transplant time and elevated biomarkers were associated with greater severity. The nomogram demonstrated robust discrimination with AUCs of 0.935 (training) and 0.886 (testing), alongside excellent calibration. DCA confirmed a significant clinical net benefit. Furthermore, Kaplan-Meier analysis revealed that patients stratified as high-risk by the model had significantly lower survival rates compared to the low-risk group (P<0.0001). CONCLUSIONS We developed a practical nomogram incorporating 4 accessible indicators to accurately predict severe PJP in KTRs. This tool facilitates the early identification of high-risk patients, enabling timely, individualized interventions and the rational allocation of medical resources.

BACKGROUND Achieving alcohol abstinence before standard liver transplantation (SLT) for alcohol-associated liver disease (ALD) is commonly accepted. However, the 3-month mortality rate for alcohol-associated hepatitis (AH) patients with extremely high Model for End-Stage Liver Disease (MELD) scores (≥30) exceeds 50%, suggesting insufficient time for these patients to achieve sobriety. Current data on outcomes for non-abstinent individuals in this high-risk group undergoing early liver transplantation (ELT) is limited. MATERIAL AND METHODS This single-center observational study (May 2002 to October 2023) involved 1410 liver transplantation (LT) patients. After excluding those with a MELD score <30 (n=1178), no alcohol use (n=166), hepatocellular carcinoma (n=7), viral hepatitis (n=24), and other liver failure (n=1), 34 recipients with ALD were identified. Patients were divided into Group A (abstinence prior to transplant) and Group NA (non-abstinence prior to transplant) based on pre-transplant drinking status, with clinical factors and long-term outcomes compared. RESULTS Among LT recipients who had AH, 94.1% (n=32) were male, with a median daily alcohol consumption of 174 grams and a drinking history of 20 years. Group A had 12 abstinent recipients, 6 of whom maintained sobriety for over 6 months before LT. Long-term survival rates were similar between Group NA and Group A (1, 3, and 5 years after transplant: 75.3%, 69.5%, and 52.1% vs 83.3%, 58.3%, and 48.6%; P=0.908). CONCLUSIONS Pre-transplant alcohol abstinence did not correlate with improved survival in severe AH patients, suggesting that such patients should not be disqualified from LT based solely on alcohol history.

BACKGROUND Delayed graft function remains a common and clinically relevant complication following kidney transplantation, yet reliable early prediction tools are limited. This small-scale, retrospective, exploratory study investigated whether routine hematologic inflammatory indices, such as the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and prognostic inflammatory value (PIV), when considered alongside donor-recipient demographic characteristics, predict the need for early posttransplant dialysis. MATERIAL AND METHODS Retrospective analysis of 33 cadaveric kidney transplant recipients was performed. Catorigization into dialysis (n=14) and non-dialysis (n=19) groups was based on early posttransplant dialysis requirement. SII, SIRI, and PIV were calculated from pretransplant laboratory parameters. Given the exploratory study design, analyses were primarily descriptive, supported by univariate comparisons and logistic regression with bootstrap resampling. RESULTS Recipients requiring dialysis tended to receive kidneys from older donors, although this did not reach statistical significance. Monocyte count was significantly lower in the dialysis group (P=0.032). Inflammatory indices, including SII, SIRI, and PIV, showed no significant differences (P>0.05). Logistic regression analyses did not identify SII, SIRI, or PIV as independent dialysis predictors. However, bootstrap resampling showed consistent, although non-significant, directional trends, suggesting higher donor age and inflammatory burden among recipients requiring dialysis. CONCLUSIONS This study provides preliminary insights into the potential role of combined hematologic inflammatory indices in the context of delayed graft function, underscoring the need for larger, prospective studies to clarify whether inflammatory burden and donor-related factors can be integrated into clinically useful prediction models for early dialysis after kidney transplantation.

BACKGROUND Intrahepatic cholangiocarcinoma (ICC) can be an incidental finding in liver explants following liver transplantation (LT). This study aimed to evaluate the long-term post-transplant outcomes of patients with ICC. MATERIAL AND METHODS From 2003 to 2022, 25 patients with ICC were identified among 6,611 adult LT recipients through institutional database search. RESULTS The incidence of ICC among adult LT recipients was 0.4%. All cases were incidental findings in explanted livers. The mean ICC tumor size was 2.7±1.6 cm, and 22 patients had single ICC lesion. Concurrent second liver malignancies were found in 10 patients (40%): hepatocellular carcinoma (HCC) in 9 and combined HCC-cholangiocarcinoma in one. The 5-year all-type tumor recurrence (TR) and overall survival (OS) rates were 72.0% and 47.0%, respectively. The presence of second primary cancer had no significant impact on TR (P=0.832) or OS (P=0.533). Similarly, ICC tumor stage did not significantly affect TR (P=0.394) or OS (P=0.395). Among 15 patients with ICC alone, 11 (73.3%) experienced ICC recurrence. Of the 10 patients with concurrent malignancies, 7 (70.0%) experienced all-type TR: 5 with HCC and 2 with ICC. Notably, the 5-year ICC recurrence and OS rates in 5 patients with very early-stage ICC and no HCC recurrence were 20.0% and 80.0%, respectively. CONCLUSIONS ICC is a rare incidental finding in LT recipients, often coexisting with concurrent second liver malignancy. Overall prognosis following LT for ICC remains poor, except for those with very early-stage disease. Because all incidences of TR occurred within 5 years after transplant, rigorous surveillance is essential during this period.

BACKGROUND Acute lung injury (ALI) after liver transplantation (LT) is a critical complication negatively affecting transplant outcomes and patient survival. However, effective biomarkers for early diagnosis remain unidentified. This study aimed to identify hub biomarkers and signaling pathways involved in post-LT ALI through integrated bioinformatics and machine-learning analyses and to validate their diagnostic potential. MATERIAL AND METHODS Differential gene expression analysis identified 27 differentially expressed genes (DEGs). Functional enrichment analyses revealed significant involvement in cytokine-mediated signaling, particularly within the NF-kB and TNF pathways. Single-sample gene set enrichment analysis (ssGSEA) evaluated immune infiltration. Machine-learning algorithms identified crucial biomarkers for ALI prediction. Transcription factor-hub gene and competitive endogenous RNA (ceRNA) networks were constructed. Single-cell RNA sequencing (scRNA-seq) and enzyme-linked immunosorbent assay (ELISA) analyses validated biomarker expression patterns in relation to ALI. RESULTS Hub biomarkers identified included CXCL3, CD48, and IRAK3. ssGSEA revealed prominent macrophage and neutrophil infiltration associated with ALI. Machine-learning models confirmed CXCL3, CD48, and IRAK3 as reliable predictive biomarkers, which were incorporated into a robust diagnostic nomogram. scRNA-seq analysis showed cell-type-specific expression patterns for CXCL3, CD48, and IRAK3, with heterogeneous associations across datasets. ELISA validated significantly altered protein levels of CXCL3, CD48, and IRAK3 in post-transplant ALI cases compared with controls. CONCLUSIONS CXCL3, CD48, and IRAK3 are novel and promising diagnostic biomarkers for predicting post-LT ALI. These findings provide foundational insights that could support improved diagnosis, prevention strategies, and targeted therapeutic interventions, ultimately enhancing patient outcomes after liver transplantation.

BACKGROUND Liver transplantation remains the only curative treatment modality for patients with end-stage liver disease. The worldwide shortage of donor organs has contributed to the use of fatty livers. However, the long-term survival of recipients who underwent transplantation with fatty livers remains unclear. MATERIAL AND METHODS All orthotopic liver transplantations (OLT) conducted from January 1, 2002, to December 31, 2013, at Hannover Medical School were primarily included (N=337). The assessment of hepatic steatosis was based mainly on histopathology of biopsies, but also included ultrasound and computed tomography imaging and macroscopic organ evaluation. The data were retrospectively analyzed using univariable and multivariable regression analyses and Kaplan-Meier statistics. RESULTS Kaplan-Meier statistics demonstrated a significantly reduced long-term survival for orthotopic liver transplantation of fatty liver allografts, mainly due to increased initial cellular damage and early (in-house) mortality. In the multivariate Cox regression analysis, recipient age (P=0.007; hazard ratio [HR], 1.027); occurrence of postoperative complications (P=0.001; HR, 2.187), and allograft steatosis (P=0.041; HR, 1.427) were independently associated with inferior survival. CONCLUSIONS The results identify fatty liver allografts as an independent risk factor associated with reduced short- and long-term survival after orthotopic liver transplantation. These findings highlight the necessity for strategies to improve outcomes and triggers additional research in the field of organ preservation.

BACKGROUND Recent research has highlighted DNA methylation as a promising diagnostic biomarker for hepatocellular carcinoma (HCC). Fatty Acyl-CoA Reductase 1 (FAR1) exhibits a high propensity for methylation in HCC. This study aimed to evaluate diagnostic and prognostic potential of FAR1 methylation in liver transplantation (LT) recipients with HCC. MATERIAL AND METHODS This analysis used droplet digital polymerase chain reaction to quantify FAR1 methylation levels in stored pretransplant blood samples. The study cohort (n=48) comprised 25 liver cirrhosis patients with HCC, 13 with cirrhosis but no HCC, and 10 healthy donors. RESULTS Median and mean methylation levels of FAR1 in these groups were 4 copies, zero copies, and zero copies, and 31.6±74.5, 1.5±3.5, and 0.1±0.4 copies, respectively (p<0.001). Receiver operating characteristic curve analysis revealed area under the curve of 0.832 for FAR1, outperforming a-fetoprotein (AFP; 0.737) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 0.732). A cut-off value of 1 copy for FAR1, defined by Youden's Index (J=0.599), yielded sensitivity of 82.6% and specificity of 77.3%, surpassing diagnostic capacities of AFP and PIVKA-II. Combining FAR1 >1 copy with AFP >7.5 ng/mL or PIVKA-II >40 mAU/mL increased the sensitivity to 91.3%, with specificity of 72.7% and overall accuracy of 82.2%. There was no significant correlation between FAR1 methylation levels and tumor recurrence or overall survival when using a cut-off of 1 copy. CONCLUSIONS These findings suggest that FAR1 methylation is a valuable biomarker for diagnosing HCC in patients with advanced liver disease awaiting transplantation. Further large-scale investigations are necessary to validate clinical efficacy.

BACKGROUND The availability of homologous vein allografts is limited. Therefore, prosthetic vascular grafts can be used as alternatives for middle hepatic vein (MHV) reconstruction during living-donor liver transplantation (LDLT). This study evaluated the short- and long-term patency of MHV reconstructions using Hemashield vascular grafts and assessed their effect on post-transplant survival. MATERIAL AND METHODS This retrospective observational study included 149 adult LDLT recipients who underwent MHV reconstruction using Hemashield grafts at a single institution. Graft patency and survival outcomes were assessed over long-term follow-up. RESULTS The mean recipient age was 56.2±7.7 years, and the mean graft-to-recipient weight ratio was 1.06±0.25. V5 reconstruction was achieved through single, double, and triple anastomoses in 111, 32, and 2 patients, respectively. V8 reconstruction in 116, 20, and one patient was achieved through single, double, and triple anastomoses, respectively. In 100 and 49 cases, we used Hemashield grafts with diameters of 10 mm and 12 mm, respectively. Three patients (2.0%) developed early thrombosis that necessitated stent placement. The cumulative conduit occlusion-free survival rates were 81.0% at 3 months, 57.9% at 1 year, 48.7% at 3 years, and 43.8% at 5 years. Overall patient survival rates were 95.3% at 1 year, 89.1% at 3 years, and 85.7% at 5 years. No cases of graft migration or conduit-related infection were identified. CONCLUSIONS MHV reconstruction using Hemashield grafts demonstrated acceptable short- and long-term patency, with no migration or infection. These findings support the use of Hemashield grafts as a reliable and effective prosthetic option for MHV reconstruction during LDLT.

Delayed graft function (DGF) is a common and critical complication following kidney transplantation, marked by acute kidney injury necessitating dialysis within the first postoperative week. Early detection of patients at risk is crucial for optimizing perioperative management and enhancing graft outcomes. While novel biomarkers have been suggested, their clinical application remains limited. This review explores the potential of complete blood count (CBC) parameters and derived indices as cost-effective, accessible alternatives. This narrative review synthesizes findings from studies examining the relationship between CBC parameters - such as hemoglobin, white blood cell count, and platelet count, and hematological indices like neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) - and DGF risk in kidney transplantation. A comprehensive literature search was conducted across major biomedical databases using targeted keywords. Selected studies were analyzed to assess the predictive value, underlying mechanisms, and clinical utility of these parameters. This review highlights a significant association between specific CBC parameters and DGF risk. Notably, low pre- or perioperative hemoglobin levels, significant perioperative hemoglobin drops, elevated pre- or post-transplant NLR, and altered PLR are correlated with increased DGF risk. These associations are thought to reflect underlying pathophysiological mechanisms, including inflammatory responses, ischemia-reperfusion injury, and immune cell activation. However, variability in study design, sampling time points, donor types, and DGF definitions complicates interpretation, underscoring the need for prospective multicenter validation. CBC-derived parameters demonstrate promising associations with DGF risk, particularly low pre-transplant hemoglobin levels and perioperative declines >1.3 g/dL. Preoperative NLR >3.5 and postoperative leukocyte ratios may aid in early graft dysfunction detection. Despite inconsistent evidence for platelet-related indices, further prospective multicenter studies are essential to confirm clinical utility and establish standardized cutoff values.