Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear.

In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age into group I (donor age ≤17 years, n=647); group II (donor age 18-59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were compared among the three age groups and the four ACLF grades. Cox regression was also analyzed.

The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001). When we analyzed the different effects of donor age on OS with different ACLF grades, in groups II and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age.

Donor age is related to OS and graft survival of ACLF patients after transplantation, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Given the increasing demand of patients requiring liver transplants who are 70 years or older and may have health conditions, this study aimed to assess the outcomes of recipients of living donor liver transplants (LDLTs) in this age group. We conducted an analysis using a prospective registry that included all recipients of LDLT from January 2011 to May 2023. Patients were divided into 2 age groups, 18-69 years and 70 years or older, and their short-term and long-term outcomes were compared. We considered complications as major if they were grade ≥3a (Dindo-Clavien). Among 1018 recipients of LDLT, 71 (7%) were aged 70 years or older. The rates of posttransplant complications of any severity were comparable between the younger and older age groups (46.7% vs. 46%, p = 0.983), as were the rates of major complications (25% vs. 25%, p = 0.995) and in-hospital mortality (6% vs. 7%, p = 0.800). The 1-, 3-, and 5-year graft survival rates were 94%, 86%, and 81% in the younger group and 92%, 87%, and 65% in the older group ( p = 0.090). Similarly, the overall 1-, 3-, and 5-year recipient survival rates were 90%, 85%, and 86% in the younger group and 88%, 86%, and 65% in the older group ( p = 0.100). This study suggests that carefully selected elderly patients can undergo LDLT and achieve comparable short-term outcomes to their younger counterparts.

There is currently a supply and demand mismatch in liver transplantation, with more patients needing transplants than grafts available. The use of older donors is one potential way of expanding access to viable grafts. No national study has yet reported on outcomes of liver transplants with donors ≥70 y.

The US Scientific Registry of Transplant Recipients registry was queried for deceased donor LT (1988-2021). Balance-of-risk (BAR) score was calculated for each patient. The primary outcome was graft survival. Cubic spline curves were used to evaluate the full spectrum of donor ages.

A total of 148 960 livers met inclusion criteria: 5414 (3.6%) from donors ≥70 y and 4291 (2.9%) recipients ≥70 y. Within the overall cohort, graft survival decreased with increased donor and recipient age. Median graft survival within donors ≥70 y improved over time from 2.2 y (interquartile range [IQR] 0.2-9.8 y) in 1987-1999 to 9.6 y (IQR 3.2-11.6 y) in 2010-2019 (P < 0.0001). Elderly donors had equivalent outcomes to donors <70 y when transplanted in elderly recipients (≥70 y). Outcomes for young recipients that received grafts from elderly donor improved with time, with median survival of 10.1 y (IQR 3.9-11.5 y) in 2010-2019. BAR and survival outcomes following liver transplant (SOFT) scores predicted improved graft survival on time-to-event analysis in all donors aged >70 y. In low-risk recipients, evidenced by preallocation SOFT score <5, elderly donors had comparable outcomes to young (<40 y) and middle-aged donors (40-69 y). Increasing donor age was not associated with worse graft survival in transplants performed between 2010 and 2019.

Donors aged ≥70 y may be more comfortably considered for deceased donor liver transplantation, especially within low-risk recipients. The BAR and SOFT scores may be a useful guide for safely expanding the use of these theoretically riskier liver grafts.

The shortage of liver grafts compared to recipients necessitates precise organ assessment. This study aimed to develop a Machine learning (ML) model to predict postoperative delayed graft function (DGF) and visualize the decision-making process for clinical application.

Data from 5242 donor-recipient pairs who underwent liver transplantation (LT) at the top 10 liver transplant centers in China (January 2017 to December 2022) were collected. The dataset was divided into training and validation sets. Sixty-three variables, including demographics, donor characteristics, diagnosis, preoperative lab results, and surgical information were analyzed. The primary outcome was posttransplantation DGF and the second outcome was posttransplantation 1-month and 3-month survival. Recursive feature elimination selected critical variables, and models were built using ML algorithms and logistic regression. Model performance was evaluated by AUC, accuracy, sensitivity, and specificity. The best model was validated with an independent dataset of 394 LT cases (January to June 2023). The SHapley Additive exPlanations package interpreted the top model's decisions.

Among 5242 cases, 328 (6.26%) developed DGF, with 15 cases (3.81%) in the external validation set. Thirty critical features were selected. The eXtreme Gradient Boosting algorithm achieved the highest AUC (0.877) and accuracy (0.936) in the internal set, and a comparable AUC (0.776) and accuracy (0.957) in the external set. SHAP analysis identified short perfusion time, high donor serum sodium, excessive bleeding during transplantation, high donor γ-glutamyl transpeptidase, and blood glucose levels as top predictors of post-LT DGF. The proposed model AUC's 1-month survival prediction was 0.841 and the 3-month survival prediction was 0.834.

The developed model for predicting postoperative DGF demonstrated excellent predictive performance, aiding clinicians in evaluating donor grafts and making informed decisions.

The number of highly sensitized patients in need of a multiorgan transplant is increasing. Criteria informing their transplant candidacy, approaches to management on the waitlist, and protocols related to alloantibody monitoring vary widely. We convened a consensus conference to discuss these different practices in the United States and the United Kingdom and to review the contemporary outcomes of these challenging cases. A detailed analysis of the data regarding the liver allografts' immunoprotective effect on simultaneously transplanted other organs was also completed, and the prospect of the use of liver allografts primarily to facilitate transplantation of highly sensitized patients in need of other organs was discussed. The ethical and allocation-related issues about such prospect were debated with a goal to standardize the approach and provide an evidence-based pathway for pre-, peri-, and post-transplantation management for the highly sensitized multiorgan transplantation candidate.

Allograft rejection following solid-organ transplantation is a major cause of graft dysfunction and mortality. Current approaches to diagnosis rely on histology, which exhibits wide diagnostic variability and lacks access to molecular phenotypes that may stratify therapeutic response. Here, we leverage image-based spatial transcriptomics at sub-cellular resolution in longitudinal human cardiac biopsies to characterize transcriptional heterogeneity in 62 adult and pediatric heart transplant (HT) recipients during and following histologically-diagnosed rejection. Across 28 cell types, we identified significant differences in abundance in CD4 + and CD8 + T cells, fibroblasts, and endothelial cells across different biological classes of rejection (cellular, mixed, antibody-mediated). We observed a broad overlap in cellular transcriptional states across histologic rejection severity and biological class and significant heterogeneity within rejection severity grades that would qualify for immunomodulatory treatment. Individuals who had resolved rejection after therapy had a distinct transcriptomic profile relative to those with persistent rejection, including 216 genes across 6 cell types along pathways of inflammation, IL6-JAK-STAT3 signaling, IFNα/IFNγ response, and TNFα signaling. Spatial transcriptomics also identified genes linked to long-term prognostic outcomes post-HT. These results underscore importance of subtyping immunologic states during rejection to stratify immune-cardiac interactions following HT that are therapeutically relevant to short- and long-term rejection-related outcomes.

To assess factors affecting the cumulative lifespan of a transplanted liver.

Liver aging is different from other solid organs. It is unknown how old a liver can actually get after liver transplantation.

Deceased donor liver transplants from 1988 to 2021 were queried from the United States UNOS registry. Cumulative liver age was calculated as donor age + recipient graft survival.

In total, 184,515 livers were included. Most were donation after brain death donors (n = 175,343). The percentage of livers achieving >70, 80, 90, and 100 years cumulative age was 7.8% (n = 14,392), 1.9% (n = 3576), 0.3% (n = 528), and 0.01% (n = 21), respectively. The youngest donor age contributing to a cumulative liver age >90 years was 59 years, with posttransplant survival of 34 years. In pediatric recipients, 736 (4.4%) and 282 livers (1.7%) survived >50 and 60 years overall, respectively. Transplanted livers achieved cumulative age >90 years in 2.86 per 1000 and >100 years in 0.1 per 1000. The U.S. population at large has a cumulative "liver age" >90 years in 5.35 per 1000 persons, and >100 years in 0.2 per 1000. Livers aged >60 years at transplant experienced both improved cumulative survival ( P < 0.0001) and interestingly improved survival after transplantation ( P < 0.0001). Recipient warm ischemia time of >30 minutes was most predictive of reduced cumulative liver survival overall (n = 184,515, hazard ratio = 1.126, P < 0.001) and excluding patients with mortality in the first 6 months (n = 151,884, hazard ratio = 0.973, P < 0.001).

In summary, transplanted livers frequently get as old as those in the average population despite ischemic-reperfusion-injury and immunosuppression. The presented results justify using older donor livers regardless of donation type, even in sicker recipients with limited options.

Temocillin is a β-lactam antibiotic used for preventing or treating bacterial infections in liver-transplanted children. We characterized its pharmacokinetics in plasma and ascitic fluid and proposed dosing regimens that maximize the achievement of effective drug exposures in this patient group.

Patients aged 6-36 months received 25 mg/kg/12 h (n = 14) or 25 mg/kg/8 h (n = 23). Total and unbound temocillin concentrations were measured in plasma and ascitic fluid. Drug safety was monitored. Non-compartmental and population pharmacokinetic analyses were performed, together with Monte Carlo simulations.

No safety concerns were reported. For 25 mg/kg/12 h, the unbound mean (±standard deviation) Cmax and Cmin were 38 ± 16 and 2 ± 1 mg/L, respectively. For the 25 mg/kg/8 h dose, the unbound Cmax remained similar although the mean Cmin increased to 5 ± 3 mg/L. Protein binding was saturable. Median penetration in ascitic fluid from plasma was 82% (min-max: 63-95%). A three-compartment model with first-order elimination best described unbound pharmacokinetic profiles in plasma and ascitic fluid, with body weight and estimated glomerular filtration rate (GFR) as significant covariates. Monte Carlo simulations suggested that 90% probability of target attainment was achieved in both fluids with 25 mg/kg/12 h for MICs ≤4 mg/L, estimated GFR ≤180 mL/min/1.73 m2 or weight ≥6 kg, and with 25 mg/kg/8 h, for MICs ≤8 mg/L, GFR ≤120 mL/min/1.73 m2 or weight ≥11 kg.

Although adequate in many instances, the current dosing regimen is likely inadequate for patients with low body weight, high renal function, or bacteria with high MIC, emphasizing the need for patient-specific factors to be considered in dose selection. These data support the importance of paediatric pharmacokinetic studies to optimize drug dosing regimens.

Kidney dysfunction is a major determinant of prognosis in patients with decompensated cirrhosis awaiting transplantation. We hypothesized that for identical model for end-stage liver disease (MELD) scores at listing, outcomes before and after liver transplantation may vary if the predominant driver of the MELD score is serum creatinine (Cr) vs. serum bilirubin (Br) or international normalized ratio (INR).

We evaluated all adult patients registered for liver transplantation (LT) between 2016-2020 and excluded patients receiving MELD exceptions or undergoing dual organ transplantation. Using K-Means clustering analysis, we classified each patient as MELD-Br, MELD-INR or MELD-Cr depending on the dominant variable for their MELD score. The primary outcome was intent-to-treat (ITT) survival, defined as survival within 1 year from listing with or without LT.

MELD scores of LT waitlist registrants were clustered into three subtypes: MELD-Br (n = 13,658), MELD-INR (n = 13,809), and MELD-Cr (n = 12,412). One-year ITT survival rates were 78% (MELD-Br), 75% (MELD-INR), and 65% (MELD-Cr), p <0.01. ITT survival was lower for each MELD subtype for females compared to males (e.g. MELD-Cr: 63% females vs. 67% males, p <0.0001). The MELD-Cr subtype had the highest MELD at listing (MELD-Cr 23.4 vs. MELD-Br 19.2 vs. MELD-INR 21.0) and the largest decline in MELD over 3 months (23% vs. 12% vs. 21%). In adjusted analyses including MELD-Na, MELD-Cr was associated with higher waitlist mortality (hazard ratio 1.339, 95% CI 1.279-1.402) and lower LT rates (hazard ratio 0.688, 95% CI 0.664-0.713) compaed to the other subtypes.

For equivalent listing practices, registrants with the MELD-Cr subtype have lower ITT survival. MELD subtype may serve as a more sophisticated variable for dynamic assessment of mortality risk and to guide organ allocation.

The model for end-stage liver disease (MELD) score is an excellent predictor of waitlist mortality; however, our work highlights that the driver of a patient's MELD score matters and particularly those driven by elevated creatinine are associated with lower 1-year intent-to-treat survival. The 1-year intent-to-treat survival is also lower for women compared to men within the Cr-dominant subtype. These results are important for physicians and patients undergoing LT evaluation as creatinine may serve as a marker of prognosis and even if creatinine levels improve the prognosis remains poor, necessitating discussion about alternative pathways for transplant. Our work also highlights that the type of kidney injury matters, in that those with acute kidney injury were more likely to die or remain on the waitlist than those with chronic kidney disease within the creatinine-dominant subtype.

Pediatric liver transplantation provides substantial survival benefit. An emphasis on value-based practices has become a central theme in many surgical fields, but have not been well-studied in pediatric transplantation. Given an increasing focus on optimizing outcomes while containing costs, defining value in pediatric liver transplantation warrants investigation.

Pediatric end-stage liver disease -era deceased donor pediatric liver transplant recipients from 2/2002 to 2/2019 were identified using the United Network for Organ Sharing Standard Transplant Analysis file data (n = 5770). Liver centers were divided into volume tertiles (small, medium, and large), and recipients were stratified by age (0-4, 5-11, and 12-18 y). The value for the index transplant episode was defined as % graft survival ≥1 y divided by mean post-transplant length of stay. Nearest-neighbor Mahalanobis metric matching was used to account for confounding when assessing the impact of center volume on value.

Compared to small centers, large centers delivered better outcomes (1-y graft survival 93.7% versus 89.4%, P = 0.017) without increased resource utilization (length of stay 20.8 ± 15.6 d versus 19.6 ± 17.0, P = 0.281) during the 17-y study period. Mahalanobois-matched cohorts demonstrated a volume-value relationship (higher value care with better outcomes and decreased resource utilization) in the 0-4 age group, but not in older recipients. The 0-4 age group comprised the largest proportion of status 1B patients (21.8%, P < 0.001) and the highest utilization rate of partial liver allografts (40.9%, P < 0.001).

There is value in liver transplant volume in very young (0-4 y) deceased donor pediatric patients. Given improved survival of these patients in higher volume centers, regionalization of care may benefit this specific population of recipients.

Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension. The transition from compensated to decompensated cirrhosis involves hemodynamic changes leading to multiorgan dysfunction, managed predominantly in outpatient settings with regular monitoring. The mortality risk is elevated in decompensated patients. Therefore, diligent outpatient management should focus on regular medical follow-ups, medication adjustments, patient education, addressing emergent issues and evaluation for liver transplantation. The ultimate goal is to improve quality of life, prevent disease progression, reduce complications, and assess possible recompensation. This guide provides valuable recommendations for medical experts managing decompensated cirrhotic patients post-hospitalization.

Solid organ transplant recipients have an elevated risk of cancer following organ transplantation than the age-adjusted general population. We assessed incidence of head and neck squamous cell carcinoma (HNSCC) in heart, lung, and liver recipients.

This retrospective cohort study included 124,966 patients from the United States Scientific Registry of Transplant Recipients (SRTR) database who received heart, lung, or liver transplantation between 1991 and 2010. Follow-up data were available until 2018. Patients with prevalent HNSCC at transplantation were excluded. Incident cases of HNSCC post organ transplantation were identified, and incidence rates (per 100,000 person-years) were reported by gender, race, organ type, year and age at organ transplantation.

The majority of patients received liver transplantation (58.64 %), followed by heart (28.64 %), and lung (12.72 %) transplantation. During follow-up, 4.14 % patients developed HNSCC. Overall incidence rate of HNSCC was 426.76 per 100,000 person-years. Male recipients had a higher HNSCC incidence rate than female recipients (571.8 and 177.0 per 100,000 person-years, respectively). Lung recipients had the highest overall HNSCC incidence rate (1273.6 per 100,000 person-years), followed by heart (644.2 per 100,000 person-years), and liver recipients (207.1 per 100,000 person-years). Overall, an increase in HNSCC incidence rate was observed with increase in age at organ transplantation. An increase in incidence rates of HNSCC over time was observed in lung recipients; however, incidence rates decreased over time in heart recipients.

Solid organ transplant recipients have a high incidence of HNSCC following organ transplantation, and the incidence varies by type of organ received.

Tacrolimus and cyclosporine are common immunosuppressants utilized post-organ transplantation to manage allograft rejection. Both have narrow therapeutic indices and are frequently measured to support dose adjustments. Although nasogastric tubes are commonly used to provide nutritional support and serve as a route for immunosuppressant administration, they were never validated for such purposes.

To develop and validate a liquid chromatography - tandem mass spectrometry (LC-MS/MS) method for highly concentrated tacrolimus and cyclosporine samples prepared from pharmaceutical products to support the validation of feeding tube administration of these immunosuppressants.

The method involved stepwise dilutions with dimethyl sulfoxide before analysis using online sample preparation and LC-MS/MS. It was validated in a CLIA-certified clinical laboratory that measures immunosuppressants by LC-MS/MS and is designed to support clinical studies evaluating drug loss from feeding tubes.

The method was linear between 6.8 µg/mL and 75 µg/mL for tacrolimus, and between 0.9 mg/mL and 10 mg/mL for cyclosporine, with r2 > 0.99 and total precision <5 % at all QC levels. The method demonstrated good recovery using cyclosporine Certified Reference Material, tacrolimus European Pharmacopeia Reference Standard, and prepared pharmaceutical products. Minimal matrix effects were observed.

An analytical method was developed and validated for in vitro studies with simulated administration of tacrolimus or cyclosporine to assess loss during drug administration using feeding tubes.

Paediatric acute liver failure (PALF) is often characterised by its rapidity of onset and potential for significant morbidity and even mortality. Patients often develop multiorgan dysfunction/failure, including severe acute kidney injury (AKI). Whilst the management of PALF focuses on complications of hepatic dysfunction, the associated kidney impairment can significantly affect patient outcomes. Severe AKI requiring continuous kidney replacement therapy (CKRT) is a common complication of both PALF and liver transplantation. In both scenarios, the need for CKRT is a poor prognostic indicator. In adults, AKI has been shown to complicate ALF in 25-50% of cases. In PALF, the incidence of AKI is often higher compared to other critically ill paediatric ICU populations, with reports of up to 40% in some observational studies. Furthermore, those presenting with AKI regularly have a more severe grade of PALF at presentation. Observational studies in the paediatric population corroborate this, though data are not as robust-mainly reflecting single-centre cohorts. Perioperative benefits of CKRT include helping to clear water-soluble toxins such as ammonia, balancing electrolytes, preventing fluid overload, and managing raised intracranial pressure. As liver transplantation often takes 6-10 h, it is proposed that these benefits could be extended to the intraoperative period, avoiding any hiatus. Intraoperative CKRT (IoCKRT) has been shown to be practicable, safe and may help sicker recipients tolerate the operation with outcomes analogous with less ill patients not requiring IoCKRT. Here, we provide a comprehensive guide describing the rationale, practicalities, and current evidence base surrounding IoCKRT during transplantation in the paediatric population.

Although post liver transplant survival rates have significantly improved during the past 2-3 decades, the trend in intention-to-treat (ITT) survival (survival from waitlist addition) has not been well studied.

We conducted a retrospective analysis of Scientific Registry of Transplant Recipients data to determine the trend in ITT survival in liver transplant candidates. Adult (age ≧ 18 y) patients who were on the waitlist between the time period of March 1, 2002, to December 31, 2019 (n = 200 816) and deceased liver donors that were registered between the same time period (n = 152 593) were analyzed.

We found a constant increase in posttransplant survival rates; however, the ITT survival rates showed no statistically significant improvement through the study period. We observed significant linear increase in waitlist dropout rates over time. We also observed linear increase in liver nonutilization rate in both entire cases and brain-dead cases. Donor risk index increased significantly over the years; however, it was mostly driven by increase in donation after circulatory death cases; without donation after circulatory death cases, donor risk index was stable throughout the 17 y we observed.

The reason of the increased liver nonutilization rate is unclear; however, it is possible that reluctance to use high-risk organ to maintain better posttransplant outcomes contributed to this increase, which also could have led to increase in waitlist dropout rates and no improvements in ITT survival. Further investigation is warranted on the increased nonutilization rates to improve over all contribution of liver transplant to patient care.

Evidence for the long-term use of antiplatelet drugs to prevent hepatic vascular complications (HVC) is scarce in liver transplantation (LT).

From national claim data, LT recipients (about 80 % of living donor LT [LDLT]) without graft loss, HVC, or cardiovascular events within 1 year, were classified into those who took antiplatelets for ≥1 year (n = 1744) and for <1 year (n = 1975). Outcomes were compared after the 1-postoperative year index time point.

During a mean follow up of 4.5 years, the risk of graft loss was similar between the groups (aHR 1.16, P = 0.23). However, ≥1-year antiplatelet therapy was associated with a higher risk of graft loss after 3 years (aHR 2.19, P < 0.01). HVC (aHR 0.94, P = 0.87) and major adverse cardiac events (aHR 1.20, P = 0.46) did not correlate with antiplatelet therapy for both groups. In contrast, ≥1-year antiplatelet therapy showed a significantly higher risk of severe bleeding compared to <1-year antiplatelet therapy (aHR 2.24, P < 0.01). This trend was similar in the LDLT subgroup. In our cohort, antiplatelet therapy for ≥1 year did not improve graft survival or HVC; however, it increased the risk of severe bleeding.

We recommend against antiplatelet therapy for more than 1 year in clinically stable LT recipients.

To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P < 0.001), and longer ICU length of stay (P < 0.001). MELD and hemoglobin concentrations determined RBC requirements. For each unit of increase in the MELD score, 2% more RBC units were transfused, and non-transfusion was 0.83-fold less likely. For each 10-g/L higher hemoglobin concentration at baseline, 16% less RBC transfused, and non-transfusion was 1.95-fold more likely. Ascites was associated with 26% more RBC transfusions. With an increase of 2 mm from the baseline in the A10FIBTEM measurement of maximum clot firmness, non-transfusion was 1.14-fold more likely. A 10-min longer cold ischemia time was associated with 1% more RBC units transfused, and the presence of post-reperfusion syndrome with 45% more RBC units. We conclude that preoperative correction of anemia should be included in LT. An intervention to prevent severe hypotension and fibrinolysis during graft reperfusion should be explored.Trial register: European Clinical Trials Database (EudraCT 2018-002,510-13) and ClinicalTrials.gov (NCT01539057).

Liver transplantation is an increasingly frequent surgical procedure, with elevated rates of postoperative incisional hernias ranging from 5% to 46%. There are numerous known risk factors for incisional hernia, including the type of incision, patient sex, and presence of comorbidities such as diabetes, ascites, older age, and the use of steroids. Most studies on the treatment of incisional hernias in patients who have undergone liver transplantation have shown consistently high rates of complications. Consequently, we propose the use of nonvascular fascia for the symptomatic treatment of incisional hernias in patients with concomitant liver transplantation.

We performed our new technique on 8 patients, who had previously undergone liver transplantation, between January 2019 and January 2023. The patients were examined using imaging techniques during the follow-up period.

Of the 8 patients, 7 were liver transplant recipients and 1 was a combined liver-kidney transplant patient. The median donor age was 57 y (5-66 y), whereas the mean recipient age was 58 y (31-66 y). The median patient height and weight were 163 cm (117-185 cm) and 76 kg (17-104 kg), respectively. Immunosuppression did not change in fascia recipients. The median time between transplantation and hernia repair surgery was 41 mo (5-116 mo). The sizes of the aponeurotic defects varied from 6 × 6 to 25 × 20 cm. Two patients experienced complications: one experienced bulging that required reintervention and the other experienced surgical site seroma. There was no mortality related to the use of the technique, and none were reported during follow-up.

With its promising results, nonvascularized fascial transplantation can be a successful treatment for incisional hernias in patients who had previously received a liver transplant.

Orthotopic liver transplantation stands as the sole curative solution for end-stage liver disease. Nevertheless, the discrepancy between the demand and supply of grafts in transplant medicine greatly limits the success of this treatment. The increasing global shortage of organs necessitates the utilization of extended criteria donors (ECD) for liver transplantation, thereby increasing the risk of primary graft dysfunction (PGD). Primary graft dysfunction (PGD) encompasses early allograft dysfunction (EAD) and the more severe primary nonfunction (PNF), both of which stem from ischemia-reperfusion injury (IRI) and mitochondrial damage. Currently, the only effective treatment for PNF is secondary transplantation within the initial post-transplant week, and the occurrence of EAD suggests an elevated, albeit still uncertain, likelihood of retransplantation urgency. Nonetheless, the ongoing exploration of novel IRI mitigation strategies offers hope for future improvements in PGD outcomes. Establishing an intuitive and reliable tool to predict upcoming graft dysfunction is vital for early identification of high-risk patients and for making informed retransplantation decisions. Accurate diagnostics for PNF and EAD constitute essential initial steps in implementing future mitigation strategies. Recently, novel methods for PNF prediction have been developed, and several models for EAD assessments have been introduced. Here, we provide an overview of the currently scrutinized predictive tools for PNF and EAD evaluation strategies, accompanied by recommendations for future studies.

Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs.

To develop a model for predicting prognosis after LT in patients with HCC.

Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms.

The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability.

The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.

The aim of the study was to identify predictors of early tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT).

Retrospective cohort study in 237 consecutive liver recipients with HCC between 2016 and 2021. Multivariate logistic analysis was performed to identify predictors of early HCC recurrences. The impact of hypothermic-oxygenated perfusion (HOPE) on outcome was analyzed after propensity score weighting.

Early recurrences were observed in 15 cases. Microvascular invasion (OR 3.737, 95% CI 1.246-11.206, p = 0.019) and cold ischemia time (OR 1.155, 95% CI 1.001-1.333, p = 0.049) were independently associated with a lower risk of HCC recurrences. After balancing for relevant variables, patients in the HOPE group had lower rates of tumor recurrence (weighted OR 0.126, 95% CI 0.016-0.989, p = 0.049) and higher recurrence free survival (weighted HR 0.132, 95% CI 0.017-0.999, p = 0.050).

Reducing cold ischemia time and graft perfusion with HOPE can lead to lower rates of early HCC recurrences and higher recurrence-free survival.

Hepatic retransplantation is associated with higher morbidity and mortality when compared to primary transplantation. Given the scarcity of organs and the need for efficient allocation, evaluating parameters that can predict post-retransplant survival is crucial.

This study aimed to analyze prognostic scores and outcomes of hepatic retransplantation.

Data on primary transplants and retransplants carried out in the state of Paraná in 2019 and 2020 were analyzed. The two groups were compared based on 30-day survival and the main prognostic scores of the donor and recipient, namely Model for End-Stage Liver Disease (MELD), MELD-albumin (MELD-a), Donor MELD (D-MELD), Survival Outcomes Following Liver Transplantation (SOFT), Preallocation Score to Predict Survival Outcomes Following Liver Transplantation (P-SOFT), and Balance of Risk (BAR).

A total of 425 primary transplants and 30 retransplants were included in the study. The main etiology of hepatopathy in primary transplantation was ethylism (n=140; 31.0%), and the main reasons for retransplantation were primary graft dysfunction (n=10; 33.3%) and hepatic artery thrombosis (n=8; 26.2%). The 30-day survival rate was higher in primary transplants than in retransplants (80.5% vs. 36.7%, p=0.001). Prognostic scores were higher in retransplants than in primary transplants: MELD 30.6 vs. 20.7 (p=0.001); MELD-a 31.5 vs. 23.5 (p=0.001); D-MELD 1234.4 vs. 834.0 (p=0.034); SOFT 22.3 vs. 8.2 (p=0.001); P-SOFT 22.2 vs. 7.8 (p=0.001); and BAR 15.6 vs. 8.3 (p=0.001). No difference was found in terms of Donor Risk Index (DRI).

Retransplants exhibited lower survival rates at 30 days, as predicted by prognostic scores, but unrelated to the donor's condition.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Microvascular invasion (MVI) is a critical factor in predicting the recurrence and prognosis of hepatocellular carcinoma (HCC) after liver transplantation (LT). However, there is a lack of reliable preoperative predictors for MVI. The purpose of this study is to evaluate the potential of an 18F-FDG PET/CT-based nomogram in predicting MVI before LT for HCC.

83 HCC patients who obtained 18F-FDG PET/CT before LT were included in this retrospective research. To determine the parameters connected to MVI and to create a nomogram for MVI prediction, respectively, Logistic and Cox regression models were applied. Analyses of the calibration curve and receiver operating characteristic (ROC) curves were used to assess the model's capability to differentiate between clinical factors and metabolic data from PET/CT images.

Among the 83 patients analyzed, 41% were diagnosed with histologic MVI. Multivariate logistic regression analysis revealed that Child-Pugh stage, alpha-fetoprotein, number of tumors, CT Dmax, and Tumor-to-normal liver uptake ratio (TLR) were significant predictors of MVI. A nomogram was constructed using these predictors, which demonstrated strong calibration with a close agreement between predicted and actual MVI probabilities. The nomogram also showed excellent differentiation with an AUC of 0.965 (95% CI 0.925-1.000).

The nomogram based on 18F-FDG PET/CT metabolic characteristics is a reliable preoperative imaging biomarker for predicting MVI in HCC patients before undergoing LT. It has demonstrated excellent efficacy and high clinical applicability.

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 > 60 years (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.

Improved outcomes of liver disease in childhood and young adulthood have resulted in an increasing number of young adults (YA) entering adult liver services. The adult hepatologist therefore requires a working knowledge in diseases that arise almost exclusively in children and their complications in adulthood.

To provide adult hepatologists with succinct guidelines on aspects of transitional care in YA relevant to key disease aetiologies encountered in clinical practice.

A systematic literature search was undertaken using the Pubmed, Medline, Web of Knowledge and Cochrane database from 1980 to 2023. MeSH search terms relating to liver diseases ('cholestatic liver diseases', 'biliary atresia', 'metabolic', 'paediatric liver diseases', 'autoimmune liver diseases'), transition to adult care ('transition services', 'young adult services') and adolescent care were used. The quality of evidence and the grading of recommendations were appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

These guidelines deal with the transition of YA and address key aetiologies for the adult hepatologist under the following headings: (1) Models and provision of care; (2) screening and management of mental health disorders; (3) aetiologies; (4) timing and role of liver transplantation; and (5) sexual health and fertility.

These are the first nationally developed guidelines on the transition and management of childhood liver diseases in adulthood. They provide a framework upon which to base clinical care, which we envisage will lead to improved outcomes for YA with chronic liver disease.

Biliary atresia (BA) patients develop chronic liver disease after the Kasai operation and are eventually indicated for liver transplantation (LT). The purposes of this study were to analyze long-term outcomes after LT and risk factors that affect complications to reduce graft failure.

Overall, 145 pediatric patients who underwent LT between June 1996 and June 2020 after a diagnosis of BA were included. We performed a retrospective analysis of medical records and evaluated patient and graft survival, cumulative incidence of complications, risk factors, and the results of policy changes.

Patient and graft survival rates in over 20 years were 95.8% and 91.0%, respectively. Post-transplantation lymphoproliferative disease was frequently observed in the early period of immunosuppression within the first 1-2 years after LT. The incidence of cholangitis and rejection steadily increased over time. Weight-to-portal vein size was evaluated as a risk factor for cholangitis and bile duct strictures (OR = 12.82, p = 0.006 and OR = 16.54, p = 0.015, respectively). When evaluated using 2013 as a reference point, the split graft indication was expanded and the group that received LT after 2013 had a significantly lower survival over time compared with that of the group that received LT before 2013 (p = 0.006).

This study revealed time differences in prevalence of complications. The evaluation of weight-to-duct or vessel size is a more important factor in considering complications than the graft-to-recipient weight ratio. Survival outcomes may have been altered by a policy change that affects the donor type ratio in transplantation.

Long-term organ transplant survival remains suboptimal, and life-long immunosuppression predisposes transplant recipients to an increased risk of infection, malignancy, and kidney toxicity. Promoting the regulatory arm of the immune system by expanding Tregs may allow immunosuppression minimization and improve long-term graft outcomes. While low-dose IL-2 treatment can expand Tregs, it has a short half-life and off-target expansion of NK and effector T cells, limiting its clinical applicability. Here, we designed a humanized mutein IL-2 with high Treg selectivity and a prolonged half-life due to the fusion of an Fc domain, which we termed mIL-2. We showed selective and sustainable Treg expansion by mIL-2 in 2 murine models of skin transplantation. This expansion led to donor-specific tolerance through robust increases in polyclonal and antigen-specific Tregs, along with enhanced Treg-suppressive function. We also showed that Treg expansion by mIL-2 could overcome the failure of calcineurin inhibitors or costimulation blockade to prolong the survival of major-mismatched skin grafts. Validating its translational potential, mIL-2 induced a selective and sustainable in vivo Treg expansion in cynomolgus monkeys and showed selectivity for human Tregs in vitro and in a humanized mouse model. This work demonstrated that mIL-2 can enhance immune regulation and promote long-term allograft survival, potentially minimizing immunosuppression.

Intent-to-treat analysis follows patients from listing to death, regardless of their transplant status, and aims to provide a more holistic scope of the progress made in adult solid-organ transplantation.

Many studies have shown progress in waitlist and post-transplant survival for adult kidney, liver, heart, and lung transplants, but there is a need to provide a more comprehensive perspective of transplant outcomes for patients and their families.

Univariable and multivariable Cox regression analyses were used to analyze factors contributing to intent-to-treat survival in 813,862 adults listed for kidney, liver, heart, and lung transplants. The Kaplan-Meier method was used to examine changes in waitlist, post-transplant, and intent-to-treat survival. Transplantation rates were compared using χ2 tests.

Intent-to-treat survival has steadily increased for liver, heart, and lung transplants. The percentage of patients transplanted within 1 year significantly increased for heart (57.4% from 52.9%) and lung (73.5% from 33.2%). However, the percentage of patients transplanted within 1 year significantly decreased from 35.8% to 21.2% for kidney transplant. Notably, intent-to-treat survival has decreased for kidneys despite increases in waitlist and post-transplant survival, likely because of the decreased transplant rate.

Intent-to-treat survival steadily improved for liver, heart, and lung transplant over the 30-year study period. Continued advancements in allocation policy, immunosuppression, and improved care of patients on the waitlist may contribute to further progress in outcomes of all organs, but the increasing discrepancy in supply and demand of donor kidneys is alarming and has impeded the progress of kidney intent-to-treat survival.

Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P-L control efficiency, calculated as 1-L/P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L. Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (-0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P-L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P-L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation.

To develop and validate a prediction tool for pediatric acute liver failure (PALF) mortality risks that captures the rapid and heterogeneous clinical course for accurate and updated prediction.

Data included 1144 participants with PALF enrolled during three phases of the PALF registry study over 15 years. Using joint modeling, we built a dynamic prediction tool for mortality by combining longitudinal trajectories of multiple laboratory and clinical variables. The predictive performance for 7-day and 21-day mortality was assessed using the area under curve (AUC) through cross-validation and split-by-time validation.

We constructed a prognostic joint model that combines the temporal trajectories of international normalized ratio, total bilirubin, hepatic encephalopathy, platelet count, and serum creatinine. Dynamic prediction using updated information improved predictive performance over static prediction using the information at enrollment (Day 0) only. In cross-validation, AUC increased from 0.784 to 0.887 when measurements obtained between Days 1 and 2 were incorporated. AUC remained similar when we used the earlier subset of the sample for training and the later subset for testing.

Serial measurements of five variables in the first few days of PALF capture the dynamic clinical course of the disease and improve risk prediction for mortality. Continuous disease monitoring and updating risk prognosis are beneficial for timely and judicious medical decisions.

The process of transition to adult-based care encompasses a critical period in the life of an adolescent and young adult living with a chronic illness and one that comes with an increase in the risk of poor health outcomes. As yet, there is a dearth of empirical data to help optimize this process to ensure the best long-term outcome.

This study used a principal components analysis to determine specific constructs measured by a revised version of the transition readiness survey used in our clinic. We investigated changes in these constructs over time. We further investigated the relationship between the change in these constructs over time spent in a focused transition program with adherence.

The primary component underlying our transition readiness survey for patients and parents represented self-efficacy. Time spent in the transition program was an independent predictor of change in self-efficacy (rho 0.299, p = .015); however, the magnitude of that change had no relationship to adherence. Change in parent-proxy self-efficacy was found to have a statistically significant relationship with tacrolimus standard deviation (rho -0.301, p = .026). There was disagreement identified between patient and parent responses on the survey. Neither change in patient nor parent reports of self-efficacy was found to have a relationship with post-transfer adherence.

This study reaches the novel conclusion that self-efficacy and parent-proxy self-efficacy are dynamic concepts that change over time spent in a focused transition program. The patient-parent disagreement and the relationship between parent-proxy self-efficacy and adherence stress the importance of involving parents/guardians in the transition process as well.

The Starzl Network for Excellence in Pediatric Transplantation identified optimizing immunosuppression (IS) as a priority practice improvement area for patients, families, and providers. We aimed to evaluate associations between clinical characteristics, early IS, and outcomes.

We analyzed pediatric liver transplant (LT) data from 2013 to 2018 in the United Network for Organ Sharing (UNOS) and the Society of Pediatric Liver Transplantation (SPLIT) registries.

We included 2542 LT recipients in UNOS and 1590 in SPLIT. IS choice varied between centers with steroid induction and mycophenolate mofetil (MMF) use each ranging from 0% to 100% across centers. Clinical characteristics associated with early IS choice were inconsistent between the two data sets. T-cell depleting antibody use was associated with improved 1-year graft (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.34-0.76) and patient (HR 0.40, 95% CI 0.20-0.79) survival in UNOS but decreased 1-year patient survival (HR 4.12, 95% CI 1.31-12.93) and increased acute rejection (HR 1.58, 95% CI 1.07-2.34) in SPLIT. Non-T-cell depleting antibody use was not associated with differential risk of survival nor rejection. MMF use was associated with improved 1-year graft survival (HR 0.73, 95% CI 0.54-0.99) in UNOS only.

Variation exists in center choice of early IS regimen. UNOS and SPLIT data provide conflicting associations between IS and outcomes in multivariable analysis. These results highlight the need for future multicenter collaborative work to identify evidence-based IS best practices.