CHALF Score: A Novel Tool to Rapidly Risk Stratify Children in Need of Liver Transplant Evaluation During Acute Liver Failure.

BACKGROUND: Pediatric acute liver failure (PALF) can require emergent liver transplantation (LT, >25%) or lead to death (~15%). Existing models cannot predict clinical trajectory or survival with native liver (SNL). We aimed to create a predictive model for PALF clinical outcomes based on admission variables. METHODS: A retrospective, single-center PALF cohort (April 2003 to January 2022) was identified using International Classification of Disease codes, selected using National Institutes of Health PALF Study Group (PALFSG) criteria, and grouped by clinical outcome (SNL, LT, or death). Significant admission variables were advanced for feature selection using least absolute shrinkage and selection operator regression with bootstrapping (5000×). A predictive model of SNL versus LT or death was created using logistic regression and validated using PALFSG data. RESULTS: Our single-center cohort included 147 patients (58% SNL, 32% LT, 10% expired), while the PALFSG validation cohort included 492 patients (50% SNL, 35% LT, 15% expired). Admission variables associated with SNL included albumin (odds ratio [OR], 16; P < 0.01), ammonia (OR, 2.37; P < 0.01), and total bilirubin (OR, 2.25; P < 0.001). A model using these variables predicted SNL versus LT or death with high accuracy (accuracy [0.75 training, 0.70 validation], area under the curve [0.83 training, 0.78 validation]). A scaled score (CHLA-acute liver failure score) was created that predicted SNL versus LT or death with greater accuracy (C statistic 0.83) than Pediatric End-Stage Liver Disease (C statistic 0.76) and admission liver injury unit (C statistic 0.76) scores. CONCLUSIONS: The CHLA-acute liver failure score predicts SNL versus LT or mortality in PALF using admission laboratories with high accuracy. This novel, externally validated model offers an objective guide for urgent referral to a pediatric LT center.

Evaluation of technical urinary tract complications in kidney transplantation recipients with a prolonged dialysis history.

BACKGROUND: The kidney transplant waiting list continues to expand, resulting in prolonged dialysis times exceeding 8 years before transplantation in some regions. The relationship between long-term dialysis and urinary tract complications after kidney transplant remains largely unexplored. This study aims to evaluate post-kidney transplant complications in patients with a history of prolonged dialysis. METHODS: A single-center, retrospective cohort study of patients maintained on dialysis ≥8 years before kidney transplant between January 2000 and July 2020 was conducted. Clinical variables, including demographics and comorbidities, were reviewed. The primary objective was the development of a technical urinary tract complication. Secondary outcomes included any postoperative complication by type, stratified by medical and surgical complications. RESULTS: Overall, 376 patients met the inclusion criteria. The mean pre-kidney transplant dialysis time was 10.2 ± 2.6 years. The majority (65.7%) of the study participants were anuric. Four patients (1.1%) experienced a urine leak, and 8 patients (2.1%) had a ureteral stricture. Any complication was observed in 111 (29.5%) patients, with urinary tract infections being the most common. Urinary catheters remained in place for a median of 4 (3, 5) days. Drains were commonly used (62.8%) for a median of 5 (4, 6) days. CONCLUSION: In our large, single-center experience with kidney transplants in high-risk patients with prolonged dialysis and anuria, the technical urinary tract complications rate remained low. With the current literature consisting of small cohorts and having relatively short pre-kidney transplant dialysis periods, our analysis addresses the shortcomings of the literature while suggesting that this patient population may not truly be "high risk."

Living donor liver paired exchange between pediatric and adult recipients due to donor graft size mismatch.

Living donor liver transplantation is an effective means to decrease organ shortage. However, many potential living donors are currently being denied due to ABO incompatibility or inadequate donor liver volume. Liver paired exchange (LPE) provides a practical solution to overcome these obstacles, and yet the first case of LPE in the United States was only recently reported in 2020. Here, we report world's first case of LPE involving pediatric and adult recipients to avoid surgical complexity of the pediatric recipient and to increase the graft-to-recipient weight ratio of the adult recipient between 2 ABO compatible pairs. As living donor liver transplantation becomes more widely adopted, the need for pair exchange to improve surgical safety and postoperative outcomes between 2 ABO compatible pairs is likely to increase.

Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation.

Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO 2 ) to assess risk factors for waitlist mortality and post-LT survival. Among 3082 pediatric LT recipients included in the study, 124 patients (4%) received MELD/PELD exception points for HPS. Patients with HPS were a median age of 9 years (interquartile range: 6, 12 years), 54.8% were girls, and 54% were White. Most patients (87.9%) were listed with laboratory MELD/PELD scores <15. Waitlist mortality for patients with HPS exception points was rare and not different from patients without HPS. When stratified by pre-LT PaO 2 , hypoxemia severity was not associated with differences in 1-, 3-, or 5-year survival rates after LT ( p = 0.13). However, patients with HPS showed a slightly lower survival rate at 5 years compared with patients without HPS (88.7% vs. 93.4%; p = 0.04). MELD/PELD exceptions for children with HPS mitigated waitlist mortality, and recipients with HPS experienced excellent 5-year survival after LT, although slightly lower than in patients without HPS. Unlike adults with HPS, the severity of pre-LT hypoxemia in children does not impact post-LT survival. These data suggest that adult criteria for granting MELD/PELD exception points may not appropriately capture HPS severity in pediatric patients. Further prospective multicenter studies to examine the risk factors predicting negative survival outcomes in children with HPS are warranted.

Immunologic benefits of maternal living donor allografts in pediatric liver transplantation: fewer rejection episodes and no evidence of de novo allosensitization.

BACKGROUND: Pediatric liver transplant (LT) recipients of maternal living liver donor (LLD) grafts have been reported to experience fewer rejection episodes. However, it is unclear whether this benefit translates to reduction in developing donor-specific antibody (DSA) among maternal-LLD recipients. The aim of this study was to compare immunologic outcomes among maternal-LLD, non-maternal-LLD, and deceased donor liver transplant (DDLT) recipients. METHODS: Children (≤18 years) who underwent LT between 1/1998 and 12/2019 at two high-volume LT centers in North America were evaluated. Patients were divided into three groups by type of graft received (maternal-LLD, non-maternal LLD, and DDLT). Clinical variables and outcomes were compared according to each graft type. RESULTS: A total of 450 pediatric primary LT were analyzed: 275 (61.1%) DDLT, 73 (16.2%) maternal-LLD, and 102 (22.6%) non-maternal-LLD. Children receiving LLD grafts were less likely to develop rejection when compared to the DDLT group (DDLT 46.9% vs. maternal-LLD 31.5% vs. non-maternal-LLD 28.4%, p = 0.001). There was no difference in rejection rates between maternal and non-maternal-LLD recipients. A higher percentage of maternal-LLD recipients were on immunosuppression monotherapy compared to non-maternal-LLD and DDLT recipients (6.7% vs. 1.2 vs. 2.4%, respectively). A subgroup of 68 patients were tested for DSA post-LT. Maternal-LLD recipients were less likely to develop de novo DSA (maternal-LLD 11.8% vs. non-maternal-LLD 19.3% vs. DDLT 43%, p = 0.018). None of the maternal-LLD recipients developed antibody-mediated rejection. CONCLUSIONS: These data support the concept of immunologic benefit of maternal-LLD in pediatric LT, with lower rates of rejection and allosensitization post-LT when compared to DDLT recipients.

Clinical Value of Surveillance Biopsies in Pediatric Liver Transplantation.

Although pediatric liver transplantation (LT) results in excellent long-term outcomes, a high incidence of early acute cellular rejection and late graft fibrosis persists. Routine measurement of allograft enzymes may not reliably detect rejection episodes, identify candidates for immunosuppression minimization, or indicate allograft fibrosis. Surveillance biopsies (SBs) can provide valuable information in this regard, but their role in pediatric LT is not fully established. A retrospective cohort of 236 pediatric LT recipients from a high-volume center was studied to characterize the risks and benefits of SB versus for-cause biopsies (FCBs). The study population was 47.1% male and 54.7% Hispanic, and 31% received living donor grafts. Our data suggest that patients in the SB group had better transplant outcomes (rejection-free, graft, and patient survival) compared with patients who had FCBs or who never underwent biopsy. Among 817 biopsies obtained from 236 patients, 150 (18.4%) were SBs. Only 6 patients had a biopsy-related complication, and none were observed in the SB subset. Graft biochemical blood tests did not accurately predict rejection severity on biopsy, with aspartate aminotransferase area under the receiver operating characteristic curve (AUROC) 0.66, alanine aminotransferase AUROC 0.65 (very poor predictions), and gamma-glutamyltransferase AUROC 0.58 (no prediction). SBs identified subclinical rejection in 18.6% of biopsies, whereas 63.3% of SBs had evidence of fibrosis. SBs prompted changes in immunosuppression including dose reduction. Our experience suggests that SB in pediatric LT is safe, offers valuable information about subclinical rejection episodes, and can guide management of immunosuppression, including minimization. Improved outcomes with SB were likely multifactorial, potentially relating to a more favorable early posttransplant course and possible effect of management optimization through SB. Further multicenter studies are needed to examine the role of SBs on long-term outcomes in pediatric LT.

Pediatric kidney transplantation, a technical update.

PURPOSE OF REVIEW: Pediatric kidney transplantation is the definitive therapy for infants and children suffering from renal failure. It is a distinct endeavor demanding specialized care for optimal results. This includes a dedicated preoperative workup accounting for unique predisposing urologic conditions, specialized surgical techniques, and careful hemodynamic monitoring and maintenance. RECENT FINDINGS: Historically, size-matched renal allografts from pediatric donors to pediatric recipients suffered from poor outcomes. Advances in surgical technique performed at high volume centers have shown that these operations can be performed safely, helping expand the donor pool for these patients. Concurrently, transplantation of increasingly small for size infants with complex medical and surgical backgrounds has become a reality. SUMMARY: On a policy front, efforts to expand access to size-matched organs, combined with advances in medical management and immunosuppression have seen pediatric renal transplantation reach new heights. Now, these breakthroughs are heightened by the ability to transplant such organs into the smallest infants. The net result will be diminished transplant waiting times and, accordingly, improved quality of life and longevity for children suffering from renal failure.

Surgical shunts for extrahepatic portal vein obstruction in pediatric patients: a systematic review.

BACKGROUND: Extrahepatic portal vein obstruction (EHPVO) causes portal hypertension in noncirrhotic children. Among surgical treatments, it is unclear whether the meso-Rex shunt (MRS) or portosystemic shunt (PSS) offers lower post-operative morbidity and superior patency over time. Our objective was to evaluate long-term outcomes comparing MRS and PSS for pediatric patients with EHPVO. METHODS: A systematic review was conducted of articles reporting children undergoing surgical shunts for EHPVO from 1/2000-2/2020. Of 87 articles screened, 22 were eligible for inclusion. The primary outcome was shunt thrombosis and secondary outcomes included non-operative complications, stenosis, and re-operation. RESULTS: Eighteen of 22 studies were of good quality and four had fair quality. Of 461 patients included, 340 underwent MRS and 121 underwent PSS. MRS were associated with a higher rate of post-operative thrombosis when compared to PSS (14.1% vs 5.8%, p = 0.021). There were 40/340 MRS patients (11.8%) that required at least one re-operation for either shunt thrombosis or stenosis, versus 5/121 PSS patients (4.1%), p = 0.019. CONCLUSION: Both MRS and PSS result in acceptable long-term patency rates, but the more technically demanding MRS is associated with higher post-shunt thrombosis, often requiring further operative intervention. This study suggests that PSS may offer advantages for pediatric patients with EHPVO.

Biliary Internal Stents and Biliary Complications in Adult Liver Transplantation.

BACKGROUND: Biliary complications in liver transplantation (LT) can cause significant morbidity or even lead to a potential graft loss and patient mortality. Oftentimes biliary internal stents (ISs) are used at the time of LT to lower the risk for or prevent these biliary complications; however, their efficacy and outcomes remain controversial. METHODS: A retrospective cohort study was conducted on all of the adult patients who underwent a deceased-donor LT (DDLT) with an end-to-end choledococholedocostomy. An IS was placed across the biliary anastomosis, passing through the ampulla. We compared the demographic profiles and various outcomes between the 2 groups (no-IS group vs IS group) and examined risk factors associated with anastomotic biliary complications. RESULTS: The study comprised 350 patients in the no-IS group and 132 patients in the IS group. Anastomotic biliary fistula (ABF) occurred in 5 (1.4%) and 1 (0.8%) patients in the no-IS group and the IS group, respectively (P = .55). Anastomotic biliary stricture (ABS) occurred in 53 (15.1%) and 18 (13.6%) patients, respectively (P = .68). No significant difference was found in the overall biliary complications between the 2 groups (P = .33). In multivariate logistic regression analysis, acute rejection was the only risk factor for ABS (P = .02). One biliary complication-induced mortality occurred in the no-IS group in which the patient died of an ABF-induced hepatic artery pseudoaneurysm rupture. CONCLUSION: The use of biliary ISs in DDLT did not reduce the overall risk for biliary complications, but more research is needed to draw definite conclusions.

Pediatric kidney transplantation in the United States.

PURPOSE OF REVIEW: Pediatric kidney transplantation has made great strides over the preceding years. It has become an accepted and successful remedy for thousands of patients worldwide. For best outcomes, it must be viewed and treated as a distinct entity from adult transplantation with focus on the unique challenges particular to its cohort. RECENT FINDINGS: Although efforts have been made to decrease geographic disparity and increase allograft access throughout, an unintended consequence has been prolonged wait times for pediatric patients. Concurrently, ideally size-matched organs from older pediatric donors are also being bypassed. Nevertheless, advances in surgical technique and a better understanding of the limits of donor-recipient pairing have facilitated continued usage of adult kidneys for both infants and small for age children. Immunosuppression optimization has meant mean allograft survival measured in decades. SUMMARY: Enhanced access is needed to better size-matched organs for pediatric recipients, helping diminish wait times for the youngest patients, and improving their long-term prognosis. Longitudinal multicenter studies are needed to help standardize protocols, especially as it relates to optimal surgical and perioperative management. Advances in immunosuppression will continue to enhance patient and graft survival while minimizing adverse effects.

Should living donor liver transplant selection be subject to the same restrictions as deceased donor transplant?

PURPOSE OF REVIEW: In the United States, most of the liver allografts come from deceased donors, and our current liver recipient selection process is heavily centered on the ethical principle of utility to maximize the net benefit to the liver recipient community as a group rather than individuals due to the organ scarcity. Although living donor liver transplantation contributes less than 5% of total liver transplant in the United States, these living donor recipients are being subjected to the same selection process designed to benefit the group as a whole rather than the individuals. We would like to examine if these recipients who have living donors should be subjected to the same selection process. RECENT FINDINGS: There are several disease processes where liver transplantation is the only curative option, and recent studies have shown clear survival benefits with liver transplantation. SUMMARY: For those who have living donors, different selection criteria based on their specific disease, not based on the principle of utilization should be used to evaluate their candidacy.

Reno-portal shunt for liver transplant, an alternative inflow for recipients with grade III-IV portal vein thrombosis: Tips for a better outcome.

INTRODUCTION: Portal vein thrombosis (PVT) poses an extremely difficult problem in cirrhotic patients who are in need of a liver transplant. The prevalence of PVT in patients with cirrhosis ranges from 0.6% to 26% Nery et al. (2015) [1]. The presence of PVT is associated with more technically difficult liver transplant and in certain cases can be a contraindication to liver transplant. The only option for these patients with extensive PVT would be a multi-visceral transplant, the later unfortunately has a much higher morbidity and mortality compared to liver only transplant Smith et al. (2016) [2]. An alternative approach is needed to provide a safe and reliable outcome. PRESENTATION OF CASE: In this case series, we present our experience with reno-portal shunt as an alternative inflow for the liver allograft. DISCUSSION: This approach appears to be safe with good long-term outcome.Although this technique has been described before, we provide additional considerations that produced good outcomes in our patients. CONCLUSION: We believe that meticulous preoperative planning with high-resolution triple phase CT imaging with a measurement of the diameter of the spleno-renal shunt along with a duplex scan measuring flow through the shunt is key to a successful transplantation. Moreover, appropriate donor liver size is also of extreme importance to avoid portal hypoperfusion.

Pseudolymphoma (reactive lymphoid hyperplasia) of the liver: A clinical challenge.

Reactive lymphoid hyperplasia (RLH), also known as pseudolymphoma or nodular lymphoid lesion of the liver is an extremely rare condition, and only 51 hepatic RLH cases have been described in the literature since the first case was described in 1981. The majority of these cases were asymptomatic and incidentally found through radiological imaging. The precise etiology of hepatic RLH is still unknown, but relative high prevalence of autoimmune disorder in these cases suggests an immune-based liver disorder. Imaging features of hepatic RLH often suggest malignant lesions such as hepatocellular carcinoma and cholangiocarcinoma. In this report, we discuss two cases of hepatic RLH in patients with autoimmune hepatitis. We also present pathologic and magnetic resonance imaging findings, including one case utilizing a hepatocellular contrast agent, Eovist. Definitive diagnosis of hepatic RLH often requires surgical excision.