Living Donor Liver Transplantation Recipients Research Articles

An updated analysis of retransplantation following living donor liver transplantation in the US: insights from the latest UNOS database.

There is no recent update on the clinical course of retransplantation(re-LT) after living-donor liver transplantation (LDLT) in the US using recent national data. The UNOS database (2002-2023) was used to explore patient characteristics in initial LT, comparing deceased-donor liver transplantation (DDLT) and LDLT for graft survival (GS), reasons for graft failure, and GS after re-LT. It assesses waitlist dropout and re-LT likelihood, categorizing re-LT cohort based on time to re-listing as acute or chronic (≤ or >1mo). Of 132,323 DDLT and 5,955 LDLT initial transplants, 3,848 DDLT and 302 LDLT recipients underwent re-LT. Of the 302 re-LT following LDLT, 156 were acute and 146 chronic. Primary non-function (PNF) was more common in DDLT, although the difference was not statistically significant (17.4%vs14.8% for LDLT; p=0.52). Vascular complications were significantly higher in LDLT (12.5%vs8.3% for DDLT; p<0.01). Acute re-LT showed a larger difference in PNF between DDLT and LDLT (49.7%vs32.0%; p<0.01). Status 1 patients were more common in DDLT (51.3%vs34.0% in LDLT; p<0.01). In the acute cohort, Kaplan-Meier curves indicated superior GS post-re-LT for initial LDLT recipients in both short-term and long-term (p=0.02 and <0.01, respectively), with no significant difference in the chronic cohort. No significant differences in waitlist dropout were observed, but the initial LDLT group had a higher re-LT likelihood in the acute cohort (sHR 1.40, p<0.01). A sensitivity analysis focusing on the most recent 10-year cohort revealed trends consistent with the overall study findings. LDLT recipients had better GS in re-LT than DDLT. Despite a higher severity of illness, the DDLT cohort was less likely to undergo re-LT.

Small graft size and hepatocellular carcinoma outcomes in living donor liver transplantation: a retrospective multicentric cohort study.

This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and HCC outcomes. Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014-2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR<0.7% vs. GRWR≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. The eligible cohort consisted of 2005 LDLT recipients (GRWR<0.7 [n=59] vs. GRWR≥0.7 [n=1946]). In the entire cohort, 5-year RFS was significantly lower in the GRWR<0.7 than in the GRWR≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR<0.7 was an independent risk factor for RFS (adjusted HR [aHR] 1.89, P =0.012), but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR<0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). A GRWR<0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.

Long-Term Outcomes of Recipients of Liver Transplants from Living Donors Treated with a Very Low-Calorie Diet.

The increasing prevalence of steatotic liver disease (SLD) in potential living donors is concerning, as it limits donor's availability amid rising demand. OPTIFAST very low-calorie diet (VLCD), a meal replacement product, effectively reduces weight and hepatic steatosis before transplantation. However, data on the outcomes of recipients of VLCD-treated donors are lacking. We conducted a single-center, retrospective study on 199 living donor liver transplant recipients at Toronto General Hospital, Canada, between January 2015 and January 2020. We compared the 1-year posttransplant outcomes between recipients who received organs from donors treated with VLCD (N = 34) for either weight loss or steatosis reduction, with those who did not require treatment (N = 165). Our analysis revealed no statistically significant differences in the rates of postoperative complications (23% vs 32.4%, p=0.3) or intensive care unit stays (70.9% vs 70.6%, p=1) between recipients of non-VLCD and VLCD grafts. Following adjusted multivariate logistic regression, receipt of VLCD grafts was not associated with increased hospital length of stay. In addition, one-year mortality did not differ between the two groups (4.2% non-VLCD recipients vs 2.9% VLCD recipients, p=0.6). OPTIFAST VLCD treatment for liver donors demonstrates positive and safe outcomes in recipients, expanding the pool of potential living donors for increased organ availability.

Changes in Pancreas Volume in Living Donor Liver Transplant Recipients.

Metabolic factors have a significant role in the morbidity and mortality associated with chronic liver disease. The pancreas has a central role in metabolism and metabolic risk factors but has been largely ignored in liver transplantation. Small pancreas volume has been demonstrated in pathologic conditions such as type 1 and 2 diabetes. This study assessed abdominal imaging before and after liver transplantation to determine if liver transplantation induces changes in pancreas volume in living donor liver transplant recipients. Our secondary outcome is to correlate pancreas volume with demographic, clinical, and outcome data. We conducted a retrospective study of pancreas volume in patients enrolled in the adult-to-adult living donor liver transplantation cohort study. Pancreas volume was manually calculated from 413 MRI or computed tomography images and correlated with imaging and clinical data. Pancreas volume declined by an average of 24% (87.8 ± 25.2 mL to 66.8 ± 20.4 mL, P < 0.0001), regardless of liver disease etiology. Pancreas volume correlated with portal blood flow, spleen volume, and liver enzyme levels. We found a correlation between smaller pancreas volume pretransplant and longer intensive care unit (ICU) stay across all patients (P < 0.05). Individuals with an ICU stay of <2 d had a larger average pancreas volume pretransplant than those with an ICU stay of 2 d or longer (91.2 mL versus 82.2 mL, P < 0.05). Pancreas volume is dynamic in liver transplant recipients and may reflect altered metabolism and risk of posttransplantation complications.

Is preoperative weight reduction of living-donor liver transplant recipients and donors harmful to postoperative outcomes?

AimAlthough the incidence of overweight and obese recipients and donors is increasing worldwide, few reports have focused on outcomes of preoperative weight reduction (WR) in living-donor liver transplantation (LDLT). We therefore examined the outcomes and the impact of WR on the postoperative course. MethodsWe analyzed 217 consecutive LDLT procedures performed from 2017 to 2022. We divided the recipients and donors into a WR group and non-WR group. ResultsTwenty-two recipients (10.1%) achieved WR (preoperative recipient WR [RWR] group), reducing their weight by 6.8% ± 6.0% within 2.2 ± 1.4 months with a significant decrease in body mass index (BMI) (p < 0.0001). The RWR group showed no significant differences in short-term postoperative outcomes (operative factors, postoperative liver function tests, amount of ascites, and morbidity) or in the graft survival rate as a long-term outcome (p = 0.24) compared with the non-RWR group. Forty-one (18.9%) donors achieved WR (preoperative donor WR [DWR] group), reducing their weight by 9.7% ± 6.3% within 3.2 ± 5.8 months with a significant decrease in BMI (p < 0.0001). Compared with the non-DWR group, the DWR group showed no significant differences in short-term postoperative outcomes between themselves and recipients or in the graft survival rate (p = 0.49). Furthermore, WR resulted in an increase to 32 donor-eligible and 6 recipient-eligible patients. ConclusionWR in LDLT recipients and donors had no harmful effect on postoperative outcomes and should lead to increase recipients’ chance of undergoing LDLT and to expand the donor pool.

Impact of Preformed Donor-specific Antibodies in Comparison to ABO Incompatibility in Living Donor Liver Transplantation: A Propensity Score-Matched Analysis.

Immunological factors play a pivotal role in the outcomes of solid organ transplantation. We aimed to elucidate the effects of donor-specific antibodies (DSAs) and ABO compatibility on living donor liver transplantation (LDLT) outcomes. A retrospective analysis was conducted on 584 LDLT recipients from 2015 to 2020. The recipients were stratified into 3 groups: ABO-compatible recipients without DSAs (group 1), ABO-compatible recipients with DSAs (group 2), and ABO-incompatible recipients without DSAs (group 3). Propensity score matching was used for balanced comparisons. In the matched comparisons, group 2 exhibited a higher incidence of T cell-mediated rejection compared with group 1 (22.7% versus 4.5%, P = 0.030). Despite this, the 5-y survival rates were similar between groups 1 and 2 (81.6% versus 95.5%, P = 0.085). Group 3, in comparison with group 1, showed elevated rates of cytomegalovirus infection (23.2% versus 7.3%, P = 0.008), T cell-mediated rejection (28.0% versus 7.3%, P = 0.001), and antibody-mediated rejection (13.4% versus 0%, P = 0.001). However, the survival rates were comparable between group 3 and group 1 (82.0% versus 86.5%, P = 0.220, respectively). Comparisons between group 2 and group 3 did not reveal significant differences in postoperative outcomes or survival rates (P > 0.05). DSA positivity and ABO incompatibility contribute to distinct posttransplant complications in LDLT. The integrated consideration of both factors in pretransplant assessment may enhance risk stratification and inform tailored interventions. Further research is required to corroborate these findings and provide mechanistic insights.

Effect of dexmedetomidine on the incidence of postoperative acute kidney injury in living donor liver transplantation recipients: A randomized controlled trial.

Acute kidney injury (AKI) is one of the most common complications after living-donor liver transplantation (LDLT) that has great impact on recipient and graft outcomes. Dexmedetomidine is reported to decrease the incidence of AKI. In the current study, we investigated whether intraoperative dexmedetomidine infusion would reduce the AKI following LDLT. In total, 205 adult patients undergoing elective LDLT were randomly assigned to the dexmedetomidine group (n=103) or the control group (n=102). Dexmedetomidine group received continuous dexmedetomidine infusion at a rate of 0.4mcgּ/kg/hr after the anesthesia induction until 2 hours after graft reperfusion. The primary outcome was to compare the incidence of AKI. Secondary outcomes included serial lactate levels during surgery, chronic kidney disease, major adverse cardiovascular events, early allograft dysfunction, graft failure, overall mortality, duration of mechanical ventilation, ICU and hospital length of stay. Intraoperative hemodynamic parameters were also collected. Of 205 recipients, 42.4% (n=87) developed AKI. The incidence of AKI was lower in the dexmedetomidine group (35.0%, n=36/103) compared with the control (50.0%, n=51/102) ( P =0.042). There were significantly lower lactate levels in the dexmedetomidine group after reperfusion (4.39 [3.99-4.8] vs 5.02 [4.62-5.42], P =0.031) until the end of surgery (4.23 [3.73-4.73] vs 5.35 [4.84-5.85], P =0.002). There were no significant differences in the other secondary outcomes besides lactate. Also, intraoperative mean blood pressure, cardiac output, and systemic vascular resistance did not show any difference. Our study suggests that intraoperative dexmedetomidine administration was associated with significantly decreased AKI incidence and lower intraoperative serum lactate levels in LDLT recipients, without untoward hemodynamic effects.

Malignancy After Living Donor Liver Transplantation

ObjectivesDe novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT). Patients and MethodsA total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study. ResultsDuring a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049). ConclusionThe survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT.

Ischemia and reperfusion-injured liver-derived exosomes elicit acute lung injury through miR-122-5p regulated alveolar macrophage polarization

Acute lung injury (ALI) is a common postoperative complication, particularly in pediatric patients after liver transplantation. Hepatic ischemia–reperfusion (HIR) increases the release of exosomes (IR-Exos) in peripheral circulation. However, the role of IR-Exos in the pathogenesis of ALI induced by HIR remains unclear. Here, we explored the role of exosomes derived from the HIR-injured liver in ALI development. Intravenous injection of IR-Exos caused lung inflammation in naive rats, whereas pretreatment with an inhibitor of exosomal secretion (GW4869) attenuated HIR-related lung injury. In vivo and in vitro results show that IR-Exos promoted proinflammatory responses and M1 macrophage polarization. Furthermore, miRNA profiling of serum identified miR-122-5p as the exosomal miRNA with the highest increase in young rats with HIR compared with controls. Additionally, IR-Exos transferred miR-122-5p to macrophages and promoted proinflammatory responses and M1 phenotype polarization by targeting suppressor of cytokine signaling protein 1(SOCS-1)/nuclear factor (NF)-κB. Importantly, the pathological role of exosomal miR-122-5p in initiating lung inflammation was reversed by inhibition of miR-122-5p. Clinically, high levels of miR-122-5p were found in serum and correlated to the severity of lung injury in pediatric living-donor liver transplant recipients with ALI. Taken together, our findings reveal that IR-Exos transfer liver-specific miR-122-5p to alveolar macrophages and elicit ALI by inducing M1 macrophage polarization via the SOCS-1/NF-κB signaling pathway.

Recipient Survival among Living Donor vs. Deceased Donor Liver Transplants for Acute Liver Failure in the United States.

Objectives: Acute liver failure (ALF) is associated with high morbidity and mortality. Timely liver transplantation (LT) is the only universally accepted therapy for ALF that is non-responsive to medical therapy. Data regarding the use of living donor LT (LDLT) for this indication in the US is scarce. Materials and Methods: United Network of Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) data from January 2002 to December 2020 were reviewed. Adult and pediatric recipients listed as status 1 were included. Demographics, clinical and laboratory data, and post-LT survival rates were compared for LDLT vs. DDLT recipients. Results: There were 180 LDLT (3.6%) and 4779 DDLT (96.4%) recipients with a diagnosis of ALF. The majority of recipients in the LDLT group were pediatric (n = 164, 91%) compared to the DDLT group (n = 1455, 30%), p < 0.001. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients (p = 0.15). Five-year post-LT survival was higher for pediatric recipients compared to adults in the LDLT group (84.2% vs. 62.5%, respectively, p < 0.001) and the DDLT group (82.8% vs. 78.7%, respectively, p < 0.001). Adults had a higher hazard of death compared to pediatric recipients in the LDLT group (HR = 3.560, 95% CI 1.612-7.844, p = 0.002) and the DDLT group (HR = 1.472, 95% CI 1.290-1.679, p < 0.001). In multivariate analysis results, the type of LT and age group were not associated with higher post-LT mortality. Conclusions: In the US, LDLT constitutes 3.6% of LTs for ALF. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients. Overall, there were superior post-LT outcomes for pediatric recipients compared to adults for LDLT and DDLT.

Immunotherapy Using Activated Natural Killer Cells Improves Postoperative Neutrophil-to-Lymphocyte Ratio and Long-Term Prognosis of Living Donor Liver Transplant Recipients With Hepatocellular Carcinoma

ObjectivePreoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic indicator in various malignancies; however, the impact of postoperative NLR on living donor liver transplant (LDLT) recipients is unknown. Immunotherapy with donor liver-derived activated natural killer (NK) cells may improve postoperative NLR by coactivating immune cells or suppressing activated neutrophils. This study aims to clarify the clinical significance of postoperative NLR in recipients after LDLT with HCC and assess whether immunotherapy improves postoperative NLR. MethodsWe conducted a retrospective study of LDLT recipients between 2001 and 2022 to evaluate the clinical significance of postoperative NLR. Furthermore, the correlation between postoperative NLR and the activation marker of infused NK cells was also evaluated. The postoperative NLR was examined 4 weeks after LDLT. ResultsThe postoperative high NLR group (N = 78) had preoperative lower NLR and higher model for end-stage liver disease and a higher rate of postoperative infection within 30 days after LDLT than the postoperative low NLR group (N = 41). Postoperative high NLR (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.01-6.79; P = .047) and nontreatment of immunotherapy (HR, 3.10; 95% CI, 1.33-7.22; P < .01) were independent risk factors for poor overall survival in multivariate analysis. Furthermore, the activation marker of infused NK cells is inversely correlated with decreased postoperative NLR. ConclusionsThe higher level of postoperative NLR was independently associated with poor prognosis in patients after LDLT with HCC. Immunotherapy using activated NK cells may improve postoperative NLR and long-term prognosis.

Early Graft Failure After Living-Donor Liver Transplant.

Living-donor liver transplantation (LDLT) has been increasing in the USA. While data exist on longer-term patient and graft outcomes, a contemporary analysis of short-term outcomes is needed. Evaluate short-term (30-day) graft failure rates and identify predictors associated with these outcomes. Adult (≥ 18) LDLT recipients from 01/2004 to 12/2021 were analyzed from the United States Scientific Registry of Transplant Recipients. Graft status at 30 days was assessed with graft failure defined as retransplantation or death. Comparison of continuous and categorical variables was performed and a multivariable logistic regression was used to identify risk factors of early graft failure. During the study period, 4544 LDLTs were performed with a graft failure rate of 3.4% (155) at 30 days. Grafts from male donors (aOR: 0.63, CI 0.44-0.89), right lobe grafts (aOR: 0.40, CI 0.27-0.61), recipients aged > 60years (aOR: 0.52, CI 0.32-0.86), and higher recipient albumin (aOR: 0.73, CI 0.57-0.93) were associated with superior early graft outcomes, whereas Asian recipient race (vs. White; aOR: 3.75, CI 1.98-7.10) and a history of recipient PVT (aOR: 2.7, CI 1.52-4.78) were associated with inferior outcomes. LDLTs performed during the most recent 2016-2021 period (compared to 2004-2009 and 2010-2015) resulted in significantly superior outcomes (aOR: 0.45, p < 0.001). Our study demonstrates that while short-term adult LDLT graft failure is uncommon, there are opportunities for optimizing outcomes by prioritizing right lobe donation, improving candidate nutritional status, and careful pre-transplant risk assessment of candidates with known PVT. Notably, a period effect exists whereby increased LDLT experience in the most recent era correlated with improved outcomes.

Reconstruction of all hepatic arteries in right lobe grafts with 2 hepatic arteries and zero percent hepatic artery thrombosis.

Hepatic artery thrombosis (HAT) is a common cause of graft loss in living-donor liver transplantation, occurring in ~2.5%-8% of patients. Some right lobe grafts have 2 hepatic arteries (HAs), and the optimal reconstruction technique remains controversial. This study aimed to identify risk factors for HAT and to evaluate the efficacy of reconstructing 2 HAs in right lobe grafts. This retrospective, single-center study analyzed 1601 living-donor liver transplantation recipients with a right liver graft and divided them into 1 HA (n = 1524) and 2 HA (n = 77) groups. The reconstruction of all HAs was performed using a microscope with an interrupted suture. The primary outcome was any HAT event. Of the 1601 patients, 37.8% had a history of transcatheter arterial chemoembolization, and 130 underwent pretransplant hepatectomy. Extra-anatomical arterial reconstruction was performed in 38 cases (2.4%). HAT occurred in 1.2% of patients (20/1601) who underwent surgical revascularization. In the multivariate analysis, undergoing pretransplant hepatectomy ( p = 0.008), having a female donor ( p = 0.02), having a smaller graft-to-recipient weight ratio ( p = 0.002), and undergoing extra-anatomical reconstruction ( p = 0.001) were identified as risk factors for HAT. However, having 2 HA openings in right liver grafts was not a risk factor for HAT in our series. Kaplan-Meier survival analysis showed no significant difference in graft survival and patient survival rates between the 1 HA and 2 HA groups ( p = 0.09, p = 0.97). In our series, although the smaller HA in the 2 HA group should increase the risk of HAT, HAT did not occur in this group. Therefore, reconstructing both HAs when possible may be a reasonable approach in living-donor liver transplantation using a right liver graft with 2 HA openings.

Dimethyloxalylglycine pretreatment of living donor alleviates both donor and graft liver ischemia-reperfusion injury in rats.

Background: Under the circumstance of the increasing waiting list for liver transplantation, living donor liver transplantation (LDLT) can alleviate the shortage of liver donors to some extent. However, how to reduce both donor and graft ischemia-reperfusion injury (IRI) is still an unsolved problem in LDLT. Hypoxia-induced transcription factor 1 (HIF1) activation is considered an important mechanism of cellular adaptation to hypoxia, and early activation of HIF1 may be a new way to alleviate liver IRI. Therefore, we aimed to investigate the impact of the HIF1 stabilizer dimethyloxalylglycine (DMOG) on IRI and the survival rate of donors and recipients of rat LDLT. Methods: Seventy percent partial liver resection and 30% partial liver transplantation were used to simulate donor and recipient of clinical LDLT. Rats were treated with DMOG (40mg/kg) or with an equivalent amount of saline. The expression of HIF1 and downstream targets was analyzed after 2h of reperfusion. Liver function and histopathology, apoptosis and oxidative stress levels were detected 6h after reperfusion. At the same time, the 7-day survival rate of rats was calculated. Results: DMOG pretreatment significantly reduced IR-induced injury in the donor and recipient, which was manifested by reducing liver function damage and promoting tissue recovery. Meanwhile, compared with the untreated group, the oxidative stress level and the cell apoptosis rate were decreased in the group pretreated with DMOG. In addition, the transcription and expression of HIF1 target genes in the DMOG group were significantly enhanced. Remarkably, DMOG also increased the survival rate of the recipient. Conclusion: This study provides the first evidence that DMOG pretreatment of donors significantly alleviates liver IRI in both donors and recipients and increases the survival rate of recipients in LDLT. Therefore, DMOG may be a promising strategy for improving LDLT in the future.

Prevalence of HCC among Living Donor Liver Transplant Recipients and Effect on Outcome Georgian Experience

: Liver transplantation (LT) may be the best curative treatment that offers a chance of cure for the tumor and the underlying cirrhosis by complete extirpation of both. Hepatocellular Carcinoma (HCC) is a formidable global health challenge, representing one of the most prevalent primary liver malignancies with increasing incidence rates worldwide. It sets the stage for a comprehensive exploration of how LDLT has redefined the paradigms of treatment for HCC and contributed to enhanced patient outcomes. To answer the question of this paper we used cross sectional study design among 84 Living Donor Liver Transplant Recipients. After collecting data analyzing patient’s medical cards we have found that out of 84 recipients 12 (11%) had a Hepatocellular Carcinoma, out of this 8 (6.7%) recipients dead and 4 (3.3%) is alive. We may have challenges such as: Diagnostic Challenges, Treatment Options, and Selection Criteria for LDLT in HCC. The relationship between HCC and LDLT is a dynamic and evolving field. LDLT has significantly expanded the therapeutic options for selected HCC patients, offering hope for improved outcomes. However, the intricate interplay between patient selection, surgical techniques, and post-transplant care underscores the importance of a multidisciplinary approach to HCC management. Ongoing research and advances in both HCC treatment and LDLT continue to shape the landscape of this complex disease and transplantation strategy.&#x0D;

Neighborhood-level social determinants of health measures independently predict receipt of living donor liver transplantation in the United States.

Disparities exist in the access to living donor liver transplantation (LDLT) in the United States. However, the association of neighborhood-level social determinants of health (SDoH) on the receipt of LDLT is not well-established. This was a retrospective cohort study of adult liver transplant recipients between January 1, 2005 and December 31, 2021 at centers performing LDLT using the United Network for Organ Sharing database, which was linked through patients' ZIP code to a set of 24 neighborhood-level SDoH measures from different data sources. Temporal trends and center differences in neighborhood Social Deprivation Index (SDI), a validated scale of socioeconomic deprivation ranging from 0 to 100 (0=least disadvantaged), were assessed by transplant type. Multivariable logistic regression evaluated the association of increasing SDI on receipt of LDLT [vs. deceased donor liver transplantation (DDLT)]. There were 51,721 DDLT and 4026 LDLT recipients at 59 LDLT-performing centers during the study period. Of the 24 neighborhood-level SDoH measures studied, the SDI was most different between the 2 transplant types, with LDLT recipients having lower SDI (ie, less socioeconomic disadvantage) than DDLT recipients (median SDI 37 vs. 47; p < 0.001). The median difference in SDI between the LDLT and DDLT groups significantly decreased from 13 in 2005 to 3 in 2021 ( p = 0.003). In the final model, the SDI quintile was independently associated with transplant type ( p < 0.001) with a threshold SDI of ~40, above which increasing SDI was significantly associated with reduced odds of LDLT (vs. reference SDI 1-20). As a neighborhood-level SDoH measure, SDI is useful for evaluating disparities in the context of LDLT. Center outreach efforts that aim to reduce disparities in LDLT could preferentially target US ZIP codes with SDI > 40.

High Number of Plasma Exchanges Increases the Risk of Bacterial Infection in ABO-incompatible Living Donor Liver Transplantation.

Bacterial infections are major complications that cause significant mortality and morbidity in living donor liver transplantation (LDLT). The risk of bacterial infection has not been studied in ABO-incompatible (ABOi) recipients with a desensitization protocol in relation to the number of plasma exchanges (PEs). Therefore, we aimed to analyze the risk of bacterial infection in ABOi LDLT recipients with a high number of PEs compared with recipients with a low number of PEs. A retrospective study was performed with 681 adult LDLT recipients, of whom 171 ABOi LDLT recipients were categorized into the high (n = 52) or low (n = 119) PE groups based on a cutoff value of 6 PE sessions. We compared bacterial infections and postoperative bacteremia within 6 mo after liver transplantation with the ABO-compatible (ABOc) LDLT group (n = 510) as a control group. The high PE group showed a bacterial infection rate of 49.9% and a postoperative bacteremia rate of 28.8%, which were significantly higher than those of the low PE group (31.1%, 17.8%) and the ABOc group (26.7%, 18.0%). In multivariate analysis, the high PE group was found to have a 2.4-fold higher risk of bacterial infection (P = 0.008). This group presented a lower 5-y survival rate of 58.6% compared with the other 2 groups (81.5% and 78.5%; P = 0.030 and 0.001). A high number of preoperative PEs increases bacterial infection rate and postoperative bacteremia in ABOi LDLT.

Comparison of Fibrinogen Concentrate and Cryoprecipitate on Major Thromboembolic Events after Living Donor Liver Transplantation

(1) Background: Liver transplantation (LT) is associated with significant hemorrhage and massive transfusions. Fibrinogen replacement has a key role in treating massive bleeding during LT and hypofibrinogenemia is treated by fibrinogen concentrate or cryoprecipitate. However, these two products are known to be associated with major thromboembolism events (MTEs). We aimed to compare the effect of fibrinogen concentrate and cryoprecipitate on MTEs in living donor LT (LDLT) recipients. (2) Methods: We analyzed 206 patients who underwent LDLT between January 2021 and March 2022. The patients were divided into two groups according to fibrinogen concentrate or cryoprecipitate use. We compared the incidence of MTEs between the two groups. In addition, we performed multiple logistic regression analyses to identify the risk factors for MTEs. (3) Results: There was no significant difference in the incidence of MTEs (16 [14.7%] vs. 14 [14.4%], p = 1.000) between the cryoprecipitate group and fibrinogen concentrate group. In the multivariate analysis, cryoprecipitate (OR 2.09, 95%CI 0.85–5.11, p = 0.107) and fibrinogen concentrate (OR 2.05, 95%CI 0.82–5.12, p = 0.126) were not significantly associated with MTEs. (4) Conclusions: there was no significant difference in the incidence of MTEs between cryoprecipitate and fibrinogen concentrate in LDLT recipients.

Outcomes of living donor liver transplantation recipients with high model for end-stage liver disease score over 35: a Korean national registry study

Outcomes of living donor liver transplantation recipients with high model for end-stage liver disease score over 35: a Korean national registry study

Donor-derived regulatory dendritic cell infusion modulates effector CD8+ T cell and NK cell responses after liver transplantation.

Immune cell-based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are innate immune cells that down-regulate alloimmune responses in preclinical models. Here, we performed clinical monitoring and comprehensive assessment of peripheral and allograft tissue immune cell populations in DCreg-infused live-donor liver transplant (LDLT) recipients up to 12 months (M) after transplant. Thirteen patients were given a single infusion of donor-derived DCreg 1 week before transplant (STUDY) and were compared with 40 propensity-matched standard-of-care (SOC) patients. Donor-derived DCreg infusion was well tolerated in all STUDY patients. There were no differences in postoperative complications or biopsy-confirmed acute rejection compared with SOC patients up to 12M. DCreg administration was associated with lower frequencies of effector T-bet+Eomes+CD8+ T cells and CD16bright natural killer (NK) cells and an increase in putative tolerogenic CD141+CD163+ DCs compared with SOC at 12M. Antidonor proliferative capacity of interferon-γ+ (IFN-γ+) CD4+ and CD8+ T cells was lower compared with antithird party responses in STUDY participants, but not in SOC patients, at 12M. In addition, lower circulating concentrations of interleukin-12p40 (IL-12p40), IFN-γ, and CXCL10 were detected in STUDY participants compared with SOC patients at 12M. Analysis of 12M allograft biopsies revealed lower frequencies of graft-infiltrating CD8+ T cells, as well as attenuation of cytolytic TH1 effector genes and pathways among intragraft CD8+ T cells and NK cells, in DCreg-infused patients. These reductions may be conducive to reduced dependence on immunosuppressive drug therapy or immunosuppression withdrawal.