Annals of Transplantation最新文献

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.

BACKGROUND Liver transplantation (LT) involves substantial intraoperative blood loss and postoperative complications, yet the relationship between these factors remains incompletely defined. This study aimed to evaluate the impact of excessive intraoperative blood loss (EIBL) on postoperative complication rates. MATERIAL AND METHODS We enrolled adult patients who underwent liver transplantation at 5 centers from January 2015 to June 2024. Patients were categorized into EIBL (blood loss ≥1000 mL) and non-EIBL groups. Univariate and multivariate logistic regression analyses were performed to identify EIBL risk factors and to assess its effect on postoperative complications, with adjustment for confounders such as age, sex, and comorbidities. Risk factors for specific complications were also examined. RESULTS In total, 822 patients were included. Univariate and multivariate logistic regression analyses indicated that benign disease, previous major abdominal surgery, pre-LT intensive care unit stay, and preoperative albumin below 38 g/L were independent risk factors for EIBL. EIBL was significantly associated with postoperative biliary complications and severe complications (Clavien-Dindo grade ≥3). Further regression confirmed EIBL as an independent risk factor for biliary complications (P=0.034) and Clavien-Dindo grade 3 or higher complications (P=0.042). Kaplan-Meier analysis showed that the 5-year survival rate was significantly lower in the EIBL group than in the non-EIBL group (P=0.010). CONCLUSIONS Comprehensive preoperative assessment and meticulous surgical practice can reduce EIBL risk, thereby decreasing postoperative complications after LT and improving long-term survival.

BACKGROUND Knowledge of the concordance between portal vein (PV) and bile duct (BD) anatomy is essential for planning living donor liver transplantation (LDLT) and hepatobiliary surgery. Unrecognized variants can result in bile leakage, vascular injury, or graft-related complications; therefore, accurate preoperative mapping is mandatory. Because the PV and BD systems develop in parallel during embryogenesis, an anatomical relationship between them has been proposed, but available data remain limited and inconsistent. This retrospective study of 423 living liver donors aimed to evaluate the association between PV and BD types and to determine whether biliary anatomy can be anticipated from preoperative vascular imaging. MATERIAL AND METHODS Donor grafts were categorized as right or left lobe. Portal vein anatomy was assessed with triphasic CT angiography. Intraoperative cholangiography (IOC) was routinely performed for every donor to define BD anatomy. RESULTS A statistically significant association was found between PV and BD types (P=0.0028). BD variations were more frequent in donors with PV Type 2 and Type 3. Notably, 21% of donors with PV Type 1 had BD Type 3. In right-lobe donors, "classical concordance" (PV1-BD1) was observed in 57.7% (n=222), whereas in left-lobe donors it was 34.2% (n=13). Overall "anatomical concordance" (direct PV-BD type match) was 64.9% in right-lobe and 52.6% in left-lobe donors. CONCLUSIONS PV and BD anatomies are significantly related, supporting the concept of parallel embryological development. However, relevant biliary variants can occur even in donors with normal PV anatomy, particularly in left-lobe grafts. Thus, PV type alone is not sufficient to predict biliary complexity, and IOC together with meticulous preoperative evaluation remains essential in LDLT.

BACKGROUND The Coronavirus disease 2019 (COVID-19) pandemic disrupted transplant programs worldwide. Transplant recipients are especially vulnerable to the effects of SARS-CoV-2 infection due to immunosuppression. This study assessed the impact of the COVID-19 pandemic on kidney transplant outcomes. MATERIAL AND METHODS We performed a single-center, retrospective cohort study of the kidney transplant program in the Czech Republic. The analysis included 145 recipients transplanted from 138 donors between 2015 and 2022. Cohorts were defined by donor procurement before the pandemic (n=94) or during the pandemic (n=44). The analysis focused on short- and long-term graft and patient outcomes of both groups. RESULTS No significant differences were found in postoperative kidney graft function (P=0.160) or overall survival before and during the pandemic. The 1- and 3-year survival rates before the pandemic were 96.0% and 90.9%. During the pandemic, they were 97.8% at both time points (P=0.092). Deathcensored failure-free survival was 95.9% and 90.4% at 1 and 3 years before the pandemic versus 95.6% at 1 and 3 years during the pandemic, respectively (P=0.377). Estimated glomerular filtration rate at 7 days (P=0.233) and 1 month (P=0.893) did not differ between vaccinated and non-vaccinated recipients. CONCLUSIONS The COVID-19 pandemic had no significant impact on the short- or long-term outcomes of the kidney transplantation program. These data support sustaining standard kidney transplantation programs during health crises.

BACKGROUND Complete pathological response (CPR) after transcatheter arterial chemoembolization (TACE) is associated with improved posttransplant outcomes in patients with hepatocellular carcinoma (HCC). This study evaluated the prognostic significance of TACE-induced CPR in patients with HCC who underwent liver transplantation (LT). MATERIAL AND METHODS The records of 2238 patients who underwent primary LT for HCC between January 2006 and December 2020 were retrospectively reviewed; of these, 253 achieved explant pathology-confirmed TACE-induced CPR. Their clinical outcomes were analyzed. RESULTS These 253 patients underwent an average of 2.2±2.3 TACE sessions. The median number of non-viable tumors was 1, and the median maximal tumor size was 1.6 cm. At 1, 3, 5, 10, and 15 years, cumulative post-LT recurrence rates were 1.2%, 3.3%, 3.3%, 5.6%, and 5.6%, respectively; overall patient survival rates were 96.0%, 93.7%, 92.4%, 91.3%, and 82.1%, respectively. Larger tumors (>2 cm) and multiple non-viable tumors were independently associated with higher recurrence and reduced survival rates (P≤0.036). Cluster analysis identified patients with multiple non-viable tumors larger than 2 cm as a high-risk group; others comprised a low-risk group. Recurrence (P<0.001) and survival (P=0.018) rates were significantly lower in the high-risk group than in the low-risk group. CONCLUSIONS TACE-induced CPR is a strong prognostic indicator of favorable long-term outcomes after LT in patients with HCC. Stratification based on non-viable tumor size and number can identify high-risk patients with CPR who require closer surveillance. Less intensive follow-up may be sufficient for low-risk patients.

BACKGROUND Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver tumor with poor prognosis. This retrospective study aimed to evaluate the outcomes and prognostic factors of 40 patients who underwent liver transplantation (LT) for cHCC-CC using data from the Korean Organ Transplant Registry (KOTRY). MATERIAL AND METHODS A cohort of 40 LT recipients diagnosed with cHCC-CC was selected from the KOTRY database between 2014 and 2019. Survival analyses were performed according to key clinicopathological variables, and risk factor analyses were conducted for overall survival (OS) and recurrence-free survival (RFS). RESULTS During a median follow-up of 21.4 months, 10 patients (25.0%) died and 9 patients (22.5%) experienced tumor recurrence. The 1-, 2-, and 3-year OS rates were 91.8%, 76.2%, and 59.3%, respectively, and the corresponding RFS rates were 88.8%, 70.5%, and 50.2%. Patients with a MELD score <20 (P=0.017) and a single tumor <3 cm (P=0.046) showed significantly better OS. On multivariate analysis, MELD score ≥20 (P=0.04), perineural invasion (P=0.04), and portal vein tumor thrombosis (P=0.005) were independent risk factors for poor OS, whereas microvascular invasion (P=0.01) was an independent risk factor for poor RFS. CONCLUSIONS LT can be a feasible treatment option for patients with early-stage cHCC-CC, providing favorable long-term survival. As most prognostic factors identified were pathology-related, further studies are needed to refine the selection criteria for LT candidates in this population.

BACKGROUND Advancements in transplant immunology and pharmacotherapy have led to improved outcomes in pediatric ABO-incompatible liver transplantation. However, the long-term dynamics of donor-specific versus non-donor-specific blood group antibodies (BGAs) in this population remain unclear. This study aimed to determine whether incomplete immune tolerance to donor-specific BGAs persists after ABO-incompatible liver transplantation. MATERIAL AND METHODS This retrospective study included 29 pediatric patients who underwent ABO-incompatible living donor liver transplantation with extended follow-up. Five of these patients exhibited persistent donor-specific BGA titers greater than 1: 64 (IgG or IgM) and received standardized preoperative immunosuppression; all 29 patients received intraoperative and postoperative immunosuppression. Demographic data, pre- and post-transplant BGA titers, and histopathological findings from liver biopsies were collected and analyzed. RESULTS All recipients were blood type O; 10 received grafts from blood type A donors, whereas 19 received grafts from blood type B donors. Donor-specific BGA titers (both IgG and IgM) remained persistently low and were significantly lower than non-donor-specific BGAs (P<0.001). Liver biopsy findings revealed mild to moderate antibody-mediated rejection in 5 patients. All patients achieved long-term survival. CONCLUSIONS The persistently low titers of donor-specific BGAs in pediatric ABO-incompatible living donor liver transplantation recipients may indicate a state of incomplete immune tolerance, possibly influenced by the developmental characteristics of the pediatric immune system and preconditioning with monoclonal antibodies. Further studies are warranted to confirm these findings and clarify the mechanisms underlying immune tolerance in this setting.

BACKGROUND Portal hypertension (PH) in end-stage liver disease remains a critical challenge, with traditional liver transplantation (LT) requiring a strict graft size criterion: graft-to-recipient weight ratio (GRWR) ³0.8%. Using small-for-size graft (SFSG) in auxiliary liver transplantation (ALT) as a "functional shunt" may offer a novel approach by retaining part of the native liver to buffer PH. MATERIAL AND METHODS A retrospective analysis was performed on 6 PH patients who underwent functional shunt with SFSG in ALT at Beijing Friendship Hospital from 2014 to 2018. Intraoperative parameters and postoperative monitoring data were collected to analyze the hepatic hemodynamic alterations. We performed descriptive analyses on relevant indicators to summarize hepatic hemodynamic changes and clinical outcomes after functional shunt. RESULTS No patients developed SFSS after functional shunt. Following the functional shunt procedure, the portal vein (PV) blood flow of the remnant native liver gradually declined to no perfusion, while hepatic artery flow velocity increased as part of a compensatory arterial buffer response. The PV blood flow of the graft increased gradually during the early postoperative period, but declined between day 5 to 10 after surgery, due to rising portal perfusion resistance. A subsequent increase was observed around day 10, and reached its peak approximately 1month after surgery, followed by a gradual decline toward stabilization. Abdominal drainage volume peaked between day 5 to 10 after surgery, and then decreased slowly, resolving around 1 month after functional shunt. CONCLUSIONS Functional shunt with SFSG in ALT appears to be promising and safe, and may expand the donor pool for PH patients who would otherwise be excluded from transplantation due to graft size criteria.