Liver transplant in a recently COVID-19 positive child with hepatoblastoma.

We describe the successful pediatric liver transplant for unresectable hepatoblastoma in a 4-year-old male with COVID-19 prior to transplant. The first negative NP swab was documented 1 month after initial diagnosis, when SARS-CoV-2 antibodies were also detected. The patient was actively listed for liver transplant after completing four blocks of a SIOPEL-4 based regimen due to his PRETEXT IV disease which remained unresectable. Following three additional negative NP swabs and resolution of symptoms for 4 weeks, he underwent a whole-organ pediatric liver transplant. COVID-19 positivity determined via NP swab SARS-CoV-2 real-time RT-PCR (Hologic Aptima SARS-CoV-2 RT-PCR assay). IgG and IgM total SARS- CoV-2 antibodies detected by Ortho Clinical Diagnostics VITROS® Immunodiagnostics Products Anti-SARS-CoV-2 Test. Patient received standard prednisone and tacrolimus-based immunosuppression without induction therapy following transplant. Post-transplant course was remarkable for neutropenia and thrombocytopenia, with discharge home on post-transplant day #11. Surveillance tests have remained negative with persistent SARS-CoV-2 IgG antibodies at 6 weeks after transplant. We describe one of the earliest, if not the first case of liver transplant following recent recovery from COVID-19 in a pediatric patient with a lethal malignant liver tumor. A better understanding of how to balance the risk profile of transplant in the setting of COVID-19 with disease progression if transplant is not performed is needed. We followed existing ASTS guidelines to document clearance of the viral infection and resolution of symptoms before transplant. This case highlights that pediatric liver transplantation can be safely performed upon clearance of COVID-19.

The pediatric solid organ transplant experience with COVID-19: An initial multi-center, multi-organ case series.

The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

A learning curve in using orphan liver allografts for transplantation.

Given the critical shortage of donor livers, marginal liver allografts have potential to increase donor supply. We investigate trends and long-term outcomes of liver transplant using national share allografts transplanted after rejection at the local and regional levels. We studied a cohort of 75 050 candidates listed in the Organ Procurement and Transplantation Network for liver transplantation between 2002 and 2016. We compared patients receiving national share and regional/local share allografts from 2002-2006, 2007-2011, and 2012-2016, performing multivariate Cox regression for graft survival. Recipient and center-level covariates that were not significant (P < .05) were removed. Graft survival of national share allografts improved over time. National share allografts had a 26% increased risk for graft failure in 2002-2006 but no impact on graft survival in 2007-2011 and 2012-2016. The cold ischemia time (CIT) of national share allografts decreased from 10.4 to 8.0 hours. We demonstrate that CIT had significant impact on graft survival using national share allografts (CIT <6 hours: hazard ratio 0.75 and CIT >12 hours: hazard ratio 1.25). Despite a trend toward sicker recipients and poorer quality allografts, graft survival outcomes using national share allografts have improved to benchmark levels. Reduction in cold ischemia time is a possible explanation.

The decreasing predictive power of MELD in an era of changing etiology of liver disease.

The field of liver transplantation has shifted considerably in the MELD era, including changing allocation, immunosuppression, and liver failure etiologies, as well as better supportive therapies. Our aim was to evaluate the predictive accuracy of the MELD score over time. The United Network for Organ Sharing provided de-identified data on 120 156 patients listed for liver transplant from 2002-2016. The ability of the MELD score to predict 90-day mortality was evaluated by a concordance (C-) statistic and corroborated with competing risk analysis. The MELD score's concordance with 90-day mortality has downtrended from 0.80 in 2003 to 0.70 in 2015. While lab MELD scores at listing and transplant climbed in that interval, score at waitlist death remained steady near 35. Listing age increased from 50 to 54 years. HCV-positive status at listing dropped from 33 to 17%. The concordance of MELD and mortality does not differ with age (>60 = 0.73, <60 = 0.74), but is lower in diseases that are increasing most rapidly-alcoholic liver disease and non-alcoholic fatty liver disease-and higher in those that are declining, particularly in HCV-positive patients (HCV positive = 0.77; negative = 0.73). While MELD still predicts mortality, its accuracy has decreased; changing etiology of disease may contribute.

No Gains in Long-term Survival After Liver Transplantation Over the Past Three Decades.

OBJECTIVE: The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year. SUMMARY OF BACKGROUND DATA: Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success. METHODS: We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression. RESULTS: There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P < 0.001). CONCLUSION: In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.

Impact of the Treating Hospital on Care Outcomes for Hepatocellular Carcinoma.

Multidisciplinary hepatocellular carcinoma (HCC) treatment is associated with optimal outcomes. There are few data analyzing the impact of treating hospitals' therapeutic offerings on survival. We performed a retrospective cohort study of patients aged 18-70 years with HCC in the National Cancer Database (2004-2012). Hospitals were categorized based on the level of treatment offered (Type I-nonsurgical; Type II-ablation; Type III-resection; Type IV-transplant). Associations between overall risk of death and hospital type were evaluated with multivariable Cox shared frailty modeling. Among 50,381 patients, 65% received care in Type IV hospitals, 26% in Type III, 3% in Type II, and 6% in Type I. Overall 5-year survival across modalities was highest at Type IV hospitals (untreated: Type IV-13.1% versus Type I-5.7%, Type II-7.0%, Type III-7.4% [log-rank, P < 0.001]; chemotherapy and/or radiation: Type IV-18.1% versus Type I-3.6%, Type II-4.6%, Type III-7.7% [log-rank, P < 0.001]; ablation: Type IV-33.3% versus Type II-13.6%, Type III-23.6% [log-rank, P < 0.001]; resection: Type IV-48.4% versus Type III-39.1% [log-rank, P < 0.001]). Risk of death demonstrated a dose-response relationship with the hospital type-Type I (ref); Type II (hazard ratio [HR] 0.81, 95% confidence interval [0.73-0.90]); Type III (HR 0.67 [0.62-0.72]); Type IV hospitals (HR 0.43 [0.39-0.47]). Conclusion: Although care at hospitals offering the full complement of HCC treatments is associated with decreased risk of death, one third of patients are not treated at these hospitals. These data can inform the value of health policy initiatives regarding regionalization of HCC care.

Intraoperative blood loss and transfusion during primary pediatric liver transplantation: A single-center experience.

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15-58) days compared to 11 (7-21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14-59) days compared to 11 (7-21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30-day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30-day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor.

Successful kidney transplantation in a small child with end-stage renal disease due to angiotensin receptor blocker fetopathy and atretic inferior vena cava.

Kidney transplantation is the treatment of choice in pediatric patients with end-stage renal disease. This population presents technical challenges particularly in those less than 20 kg due to anomalous anatomy, vascular access issues prior to transplantation, and a generally small size for age. Standard allograft outflow is usually achieved utilizing the iliac veins or IVC. When use of the iliocaval system is not feasible, alternative anastomosis must be considered. Herein, we report a case of a pediatric kidney transplantation where successful allograft outflow was achieved using the SMV when he was found to have an atretic IVC intraoperatively. In this setting, use of the portal system was required to achieve adequate allograft outflow. We created a donor iliac graft for added length to anastomose the renal vein with the SMV. In the setting of IVC occlusion with poor drainage, we utilized a patent vessel with larger caliber for outflow to reduce the risk of high venous pressures, allograft failure, venous rotation, and thrombosis. We conclude that the SMV may serve as an alternative outflow tract in the small pediatric patient and provides the vessel caliber needed to reduce the risks of complications.

Cold ischemia time is an important risk factor for post-liver transplant prolonged length of stay.

Risk analysis of cold ischemia time (CIT) in liver transplantation has largely focused on patient and graft survival. Posttransplant length of stay is a sensitive marker of morbidity and cost. We hypothesize that CIT is a risk factor for posttransplant prolonged length of stay (PLOS) and aim to conduct an hour-by-hour analysis of CIT and PLOS. We retrospectively reviewed all adult, first-time liver transplants between March 2002 and September 2016 in the United Network for Organ Sharing database. The 67,426 recipients were categorized by hourly CIT increments. Multivariate logistic regression of PLOS (defined as >30 days), CIT groups, and an extensive list of confounding variables was performed. Linear regression between length of stay and CIT as continuous variables was also performed. CIT 1-6 hours was protective against PLOS, whereas CIT >7 hours was associated with increased odds for PLOS. The lowest odds for PLOS were observed with 1-2 hours (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.45-0.92) and 2-3 hours (OR, 0.65; 95% CI, 0.55-0.78) of CIT. OR for PLOS steadily increased with increasing CIT, reaching the greatest odds for PLOS with 13-14 hours (OR, 2.05; 95% CI, 1.57-2.67) and 15-16 hours (OR, 2.06; 95% CI, 1.27-3.33) of CIT. Linear regression revealed a positive correlation between length of stay and CIT with a correlation coefficient of +0.35 (P < 0.001). In conclusion, post-liver transplant length of stay is sensitive to CIT, with a substantial increase in the odds of PLOS observed with nearly every additional hour of cold ischemia. We conclude that CIT should be minimized to protect against the morbidity and cost associated with posttransplant PLOS. Liver Transplantation 24 762-768 2018 AASLD.

Liver transplant length of stay (LOS) index: A novel predictive score for hospital length of stay following liver transplantation.

An index to predict hospital length of stay after liver transplantation could address unmet clinical needs. Length of stay is an important surrogate for hospital costs and efforts to limit stays can preserve our healthcare resources. Here, we devised a scoring system that predicts hospital length of stay following liver transplantation. We used univariate and multivariate analyses on 73 635 adult liver transplant recipient data and identified independent recipient and donor risk factors for prolonged hospital stay (>30 days). Multiple imputation was used to account for missing variables. We identified 22 factors as significant predictors of prolonged hospital stay, including the most significant risk factors: intensive care unit (ICU) admission (OR 1.75, CI 1.58-1.95) and previous transplant (OR 1.60, CI 1.47-1.75). The length of stay (LOS) index assigns weighted risk points to each significant factor in a scoring system to predict prolonged hospital stay after liver transplantation with a c-statistic of 0.75. The LOS index demonstrated good discrimination across the entire population, dividing the cohort into tertiles, which had odds ratios of 2.25 (CI 2.06-2.46) and 7.90 (7.29-8.56) for prolonged hospital stay (>30 days). The LOS index utilizes 22 significant donor and recipient factors to accurately predict hospital length of stay following liver transplantation. The index further demonstrates the basis for a clear clinical recommendation to mitigate risk of long hospitalization by minimizing cold ischemia time.

Portosystemic shunt as a bridge to liver transplantation in infants: A comparison of two techniques.

Portosystemic shunts can serve as a bridge to liver transplantation in patients with end-stage liver disease by providing portal decompression to treat life-threatening variceal bleeding and prevent recurrent episodes until an organ becomes available. The conventional TIPS procedure, however, is technically challenging to perform in infants due to the small size of their intrahepatic vasculature. We report two cases of emergent creation of portosystemic shunts as a bridge to liver transplantation in infants with life-threatening variceal bleeding using a conventional TIPS technique in the first case and a percutaneous DIPS technique in the other. Both procedures were successful at reducing the portosystemic pressure gradient and preventing further variceal bleeds until a liver transplant could be performed. The novel percutaneous DIPS procedure is a valuable alternative to the conventional TIPS in infants, as it is better suited for small or challenging intrahepatic vascular anatomy.

Poor outcomes for children on the wait list at low-volume kidney transplant centers in the United States.

BACKGROUND: Low case volume has been associated with worse survival outcomes in solid organ transplantation. Our aim was to analyze wait-list outcomes in conjunction with posttransplant outcomes. METHODS: We studied a cohort of 11,488 candidates waitlisted in the Organ Procurement and Transplantation Network (OPTN) for pediatric kidney transplant between 2002 and 2014, including both deceased- and living-donor transplants; 8757 (76 %) candidates received a transplant. Candidates were divided into four groups according to the average volume of yearly transplants performed in the listing center over a 12-year period: more than ten, six to nine, three to five, and fewer than three. We used multivariate Cox regression analysis to identify independent risk factors for wait list and posttransplant mortality. RESULTS: Twenty-seven percent of candidates were listed at low-volume centers in which fewer than three transplants were performed annually. These candidates had a limited transplant rate; only 49 % received a transplant versus 88 % in high-volume centers (more than ten transplants annually) (p < 0.001). Being listed at a low-volume center showed a fourfold increased risk for death while on the wait list [hazard ratio (HR) 4.0 in multivariate Cox regression and 6.1 in multivariate competing risk regression]. It was not a significant risk factor for posttransplant death in multivariate Cox regression. CONCLUSIONS: Pediatric transplant candidates are listed at low-volume transplant centers are transplanted less frequently and have a much greater risk of dying while on the wait list. Further studies are needed to elucidate the reasons behind the significant outcome differences.

Current techniques for pediatric liver transplantation.

PURPOSE OF REVIEW: Orthotopic liver transplantation in the pediatric population is a technically challenging undertaking, requiring highly specialized surgical techniques unique to this group. This review describes the most current method of transplantation for these patients. RECENT FINDINGS: Pediatric liver transplantation employs multiple modifications of standard transplant technique, including alternative methods of vascular and biliary anastomoses as well as technical variant grafts. We herein describe how these methods are employed in procurement, back-table preparation, hepatectomy, and allograft implantation. SUMMARY: This review provides concise direction of surgical technique for pediatric liver transplant recipients.

Selecting DCD Recipients Using Predictive Indices.

Donation after circulatory death (DCD) allografts might represent one of the largest untapped sources of liver allografts. Our aim was to identify independent recipient risk factors that predict mortality in DCD allograft recipients to preselect optimal candidates for successful transplantation. Furthermore, we compared the application of our newly constructed DCD Recipient Selector Index (RSI) score to previously developed models to determine superiority in predicting recipient survival. Methods: Using the Organ Procurement and Transplantation Network database, we performed univariate and multivariate retrospective analyses on 4228 DCD liver allograft recipients. Results: We identified 8 significant factors and incorporated them into the weighted RSI to predict 3-mo survival following DCD liver transplantation with a C-statistic of 0.6971. The most significant recipient risk factors were recipient serum sodium levels >150 mEq/L at transplant, recipient albumin <2.0 g/dL at transplant, and a history of portal vein thrombosis. Because Model for End-Stage Liver Disease (MELD) score components were included as individual predictors, the DCD RSI predicts survival independently of MELD. Upon comparison with 3 previous recipient risk scores-Balance of Risk, Renal Risk Index, Patient-Survival Outcomes Following Liver Transplantation-the DCD RSI was determined to be superior at selecting optimal candidates pre-DCD transplantation, yielding a C-statistic of 0.6971. Conclusions: After verifying the performance of predictive indices for selection of DCD recipients, the DCD RSI is best used to preselect patients for optimized outcomes after DCD transplantation. This can increase utilization of DCD donors by improving outcomes.

Ureteral stricture after pediatric kidney transplantation: Is there a role for percutaneous antegrade ureteroplasty?

INTRODUCTION: Ureteral obstruction following pediatric kidney transplantation occurs in 5-8% of cases. We describe our experience with percutaneous antegrade ureteroplasty for the treatment of ureteral stricture in pediatric kidney transplant patients. METHODS: We retrospectively reviewed all pediatric kidney transplantation patients who presented with ureteral stricture and underwent percutaneous antegrade ureteroplasty at our institution from July 2009 to July 2021. Variables included patient demographics, timing of presentation, location and extent of stricture, ureteroplasty technique and clinical outcomes. Our primary outcome was persistent obstruction of the kidney transplant. RESULTS: Twelve patients met inclusion criteria (4.2% of all transplants). Median age at time of ureteroplasty was 11.5 years (range: 3-17.5 years). Median time from kidney transplantation to ureteroplasty was 3 months. Patency was maintained in 50% of patients. Seven patients (58.3%) required additional surgery. Four patients developed vesicoureteral reflux. Patients with persistent obstruction had a longer time from transplant to ureteroplasty compared to those who achieved patency (19.3 vs 1.3 months, p = 0.0163). Of those treated within 6 months after transplantation, two patients (25%) required surgery for persistent obstruction (p = 0.06). All patients treated >1 year after transplantation had persistent obstruction following ureteroplasty (p = 0.06). CONCLUSION: Percutaneous antegrade ureteroplasty can be considered a viable minimally invasive treatment option for pediatric patients who develop early ureteral obstruction (<6 months) following kidney transplantation. In patients who are successfully treated with ureteroplasty, 67% can develop vesicoureteral reflux into the transplant kidney. Patients who fail early percutaneous ureteroplasty or develop obstruction >1 year after transplantation are best managed with surgical intervention.

Liver transplantation with donation after cardiac death donors: a comprehensive update.

BACKGROUND: Use of donation after cardiac death (DCD) donors has been proposed as an effective way to expand the availability of hepatic allografts used in orthotopic liver transplantation (OLT); yet, there remains no consensus in the medical literature as to how to choose optimal recipients and donors based on available information. METHODS: We queried the United Network of Organ Sharing/Organ Procurement and Transplantation Network database for hepatic DCD allografts used in OLT. As of March 31, 2011, 85,148 patients received hepatic allografts from donation-after-brain-death (DBD) donors, and 2351 patients received hepatic allografts from DCD donors. We performed survival analysis using log-rank and Kaplan-Meier tests. We performed univariate and multivariate analyses using the Cox proportional hazards model. All statistics were performed with SPSS 15.0. RESULTS: Patients receiving hepatic DCD allografts had significantly worse survival compared with patients receiving hepatic DBD allografts. Pediatric patients who received a hepatic DCD allograft had similar survival to those who received a hepatic DBD allograft. The optimal recipient-related characteristics were age <50 y, International Normalized Ratio <2.0, albumin >3.5 gm/dL, and cold ischemia time <8 h; optimal donor-related characteristics included age <50 y and donor warm ischemia time <20 min. CONCLUSIONS: By identifying certain characteristics, the transplant clinician's decision-making process can be assisted so that similar survival outcomes after OLT can be achieved with the use of hepatic DCD allografts.