Factors associated with improved patient and graft survival beyond 1 year in pediatric liver transplantation.

With advances in surgical techniques, medical management, and more equitable allocation systems, children who receive a liver transplantation (LT) today can expect remarkable outcomes early after LT. However, beyond 1 year after transplant, attrition rates have not improved. We reviewed two separate eras (Era 1: January 1995-June 2004 vs. Era 2: July 2004-March 2018) of the Society of Pediatric Liver Transplantation registry to explore the evolution and associated factors contributing to late graft loss (LGL) and late mortality (LM). The fraction of long-term pediatric LT recipients surviving after 1 year with their first graft significantly improved (81.5% in Era 1 vs. 85.7% in Era 2; p < 0.0001). This improvement occurred despite significant changes in patient selection toward higher risk populations (p < 0.001) and without notable improvement in perioperative complications such as hepatic artery thrombosis (p = 0.24) and early posttransplant reoperation (p = 0.94) that have historically contributed to poor late-allograft outcomes. Improved outcomes were associated with changes in patient characteristics and perioperative practices, which subsequently impacted both early post-LT complications as well as other sequalae known to contribute to adverse events in long-term pediatric LT recipients. In conclusion, despite significant changes in patient selection toward higher risk populations, and without notable improvement in several perioperative complications known to contribute to poor late-allograft outcomes, significant improvements in LGL and a trend toward improvement in LM was seen in a more contemporary cohort of children receiving an LT.

Pediatric Liver Transplant Survival in Alagille Syndrome Is Comparable to Biliary Atresia-A Linked Database Analysis.

OBJECTIVES: This study aims to report liver transplantation (LT) outcomes and cardiac disease manifestations in children with Alagille Syndrome (ALGS) in a contemporary cohort. METHODS: This project used a novel linkage between the Scientific Registry of Transplant Recipients and Pediatric Health Information System databases. All children ≤21 years undergoing a first LT were identified (2002-2018). The presence of ALGS was identified using Scientific Registry of Transplant Recipients diagnosis coding. Subjects with ALGS were age-matched 1:2 to LT recipients with biliary atresia (BA). The Kaplan-Meier method and log-rank test were used to compare patient and graft survival between groups. RESULTS: A total of 156 LT recipients with ALGS were identified and matched to a control group of 312 LT recipients with BA. Children with ALGS were more likely to have an associated diagnosis of congenital heart disease (80.7% vs 16.4%; P = 0.001) compared with children with BA with 40 (25.6%) children with AGS requiring cardiac intervention (catheter or surgical) either before or after LT. Those patients with ALGS had a higher creatinine, laboratory MELD, and PELD scores before LT. No difference was observed regarding patient or graft survival between children with ALGS and children with BA ( P = 0.08 and P = 0.27, respectively). CONCLUSIONS: Despite increased rate of congenital heart defects and cardiac interventions, higher creatinine, and higher laboratory MELD/PELD scores at time of transplant, this study demonstrates that there is no difference in either patient or graft survival between patients with ALGS and BA.

Liver Transplantation in Children with Urea Cycle Disorders: The Importance of Minimizing Waiting Time.

Liver transplantation (LT) for children with urea cycle disorders (UCDs) is capable of correcting the enzymatic defect and preventing progressive neurologic injury. We describe the characteristics and outcomes of pediatric LT recipients with UCDs. We identified all pediatric (<18 years) LT candidates with UCDs in the United Network for Organ Sharing (UNOS) database (February 2002 to September 2020). Multivariable Cox and logistic regression were used to determine risk factors for graft loss and cognitive delay, respectively. Of 424 patients, 1.9% (8/424) experienced waitlist mortality and 95.0% underwent LT (403/424). The most frequently encountered UCDs in our cohort were ornithine transcarbamylase deficiency (46.2%), citrullinemia (20.3%), and argininosuccinic aciduria (ASA; 12.9%). The 1-, 3-, and 5-year graft survival rates were 90.4%, 86.3%, and 85.2%, respectively. Multivariable analysis showed a decreased risk of graft loss with increasing weight at LT (adjusted hazard ratio [aHR], 0.96; 95% confidence interval [CI], 0.94-0.99; P = 0.02), male sex (aHR, 0.49; 95% CI, 0.28-0.85; P = 0.01), and ASA diagnosis (aHR, 0.29; 95% CI, 0.09-0.98; P = 0.047), when adjusting for location (intensive care/hospital/home) and graft type (both P ≥ 0.65). In multivariable logistic regression, waitlist time (adjusted odds ratio [aOR], 1.10; 95% CI, 1.02-1.17; P = 0.009) and male sex (aOR, 1.71; 95% CI, 1.02-2.88; P = 0.04) were associated with increased odds of long-term cognitive delay. Waitlist duration is associated with a long-term risk of cognitive delay. Given excellent long-term outcomes, early LT evaluation should be considered in all children with UCDs to prevent progressive neurologic injury and optimize cognitive outcomes.

Liver transplantation for congenital hepatic fibrosis.

Congenital hepatic fibrosis (CHF) is a hereditary fibrocystic disease that can progress to portal hypertension and recurrent cholangitis requiring liver transplantation (LT). It can be associated with renal pathology and need for kidney transplantation (KT). We describe the clinical characteristics and outcomes of patients undergoing liver transplantation alone (LTA) and simultaneous liver-kidney transplantation (SLKT) for CHF using the Unites States Scientific Registry of Transplant Recipients. A total of 197 patients who received LT for CHF between 2002 and 2018 were identified - 87 (44.2%) received SLKT, 110 (55.8%) received LTA. The 1-, 3- and 5-year patient survival were 99.0%, 96.2% and 94.6%. The 1-, 3- and 5-year liver graft survival were 94.9%, 91.1% and 89.6%. No significant differences in patient or liver graft survival were observed between the SLKT and LTA groups, or between paediatric and adult recipients. 53.3% of patients with CHF necessitating LT also have significant renal disease requiring KT. Kidney graft survival for isolated KT prior to LT were poorer compared with KT performed simultaneously or after LT. Both LTA and SLKT for CHF are associated with excellent long-term outcomes in paediatric and adult patients.

Subacute Liver Failure Following Gene Replacement Therapy for Spinal Muscular Atrophy Type 1.

Spinal muscular atrophy is a neurodegenerative disease resulting from irreversible loss of anterior horn cells owing to biallelic deletions/mutations in the survival motor neuron (SMN) 1 gene. Gene replacement therapy using an adeno-associated virus vector containing the SMN gene was approved by the US Food and Drug Administration in May 2019. We report 2 cases of transient, drug-induced liver failure after this therapy.

Liver Transplantation for Propionic Acidemia: A Multicenter-linked Database Analysis.

OBJECTIVES: Propionic acidemia (PA) is a rare inborn error of metabolism resulting from deficiency in the enzyme necessary for catabolism of branched-chain amino acids, some odd chain fatty acids and cholesterol. Despite optimal medical management, PA often leads to acute and progressive neurological injury. Reports on liver transplantation (LT) as a cellular therapy are limited and varied. The objective of this study was to examine the largest collection of patients who underwent LT for PA. METHODS: Examining the Scientific Registry of Transplant Recipients and the Pediatric Health Information System administrative billing databases, we performed a multicenter, retrospective analysis of LT over a 16-year period. During this period, 4849 pediatric LT were performed out of which 23 were done for PA at 10 different centers. RESULTS: The majority of recipients were 5 years of age or younger and had status 1b exception points at the time of transplant. The 1-, 3-, and 5-year graft survival for PA LT recipients was 84.6% and the 1-, 3, and 5-year patient survival was 89.5%. There was no significant difference in graft or patient survival between PA and non-PA LT recipients. Despite historical data to the contrary, we did not find an increased incidence of hepatic arterial thrombosis in patients undergoing LT for PA. Patients in the PA LT group, however, had a significantly higher postoperative rate of readmission compared with the non-PA LT group (90.5% vs 72.8%, P = 0.021). CONCLUSION: LT for children with PA is a viable treatment option with acceptable outcomes.

Expanding analytic possibilities in pediatric solid organ transplantation through linkage of administrative and clinical registry databases.

Database linkage is a common strategy to expand analytic possibilities. Our group recently completed a linkage between the SRTR and PHIS databases for pediatric heart transplant recipients. The aim of this project was to expand the linkage between SRTR and PHIS to include liver, kidney, lung, heart-lung, and small bowel transplants. All patients (<21 years) who underwent liver, kidney, lung, heart-lung, or small bowel transplant were identified from the PHIS database using APR-DRG codes (2002-2018). Linkage was performed in a stepwise approach using indirect identifiers. Hospital costs were estimated based on hospital charges and cost-to-charge ratios, inflated to 2018 dollars and described by transplant type. A total of 14 061 patients overlapped between databases. Of these, 13 388 (95.2%) were uniquely linked. Linkage success ranged from 92.6% to 97.8% by organ system. A total of 12 940 (92%) patients had complete cost data. Hospitalization costs were greatest for patients undergoing small bowel transplantation with a median cost of $734 454 (IQR $336 174 - $1 504 167), followed by heart $565 386 (IQR $352 813 - $999 216), heart-lung $471 573 (IQR $328 523 - 992 438), lung $303 536 (IQR $215 383 - $612 749), liver $200 448 (IQR $130 880 - $357 897), and kidney transplant $94 796 (IQR $73 157 -$131 040). We report a robust linkage between the SRTR and PHIS databases, providing an invaluable tool to assess resource utilization in solid organ transplant recipients. Our analysis provides contemporary cost data for pediatric solid organ transplantation from the largest US sample reported to date. It also provides a platform for expanded analyses in the pediatric transplant population.

Contemporary management of hepatoblastoma.

PURPOSE OF REVIEW: Hepatoblastoma is the most common primary pediatric liver malignancy. The goal of treatment in hepatoblastoma is complete surgical resection. Recently published multinational collaborative studies are better defining risk factors for disease recurrence and guide optimal treatment strategy. RECENT FINDINGS: Successful margin-negative resection of hepatoblastoma is dependent on the location and extent of disease as defined by the PRETEXT classification. Liver transplantation is an appropriate treatment modality when complete oncological resection requires total hepatectomy. In general, advanced PRETEXT class as well as histologic features, age at presentation, tumoral production of α-feto protein and the presence of metastatic disease adversely affect outcome. Hepatoblastoma is chemosensitive and significant downstaging can occur with the use of neoadjuvant chemotherapy allowing for less extensive hepatectomy. In addition, patients at moderate-to-high risk of postresection recurrence should receive neoadjuvant chemotherapy. Cisplatin-based chemotherapy can allow for resection of transplantation of patients with metastatic disease when complete metasatectomy can be achieved albeit with inferior results. SUMMARY: Treatment of hepatoblastoma with surgical resection or liver transplantation is associated with excellent long-term results in the setting of modern chemotherapy.

A Case of Salicylate Intoxication Complicated by Coagulopathy, Pulmonary Edema, and Pancreatitis.

The large availability of salicylic acid products makes them an often encountered source of poisoning in the emergency department. Even though in most cases the prognosis is good, with a low incidence of long-term morbidity and mortality, complications do occur, and some of those can be life threatening. We present an unusual case of salicylate intoxication in an adolescent in which several uncommon complications (severe coagulopathy, pulmonary edema, and pancreatitis) conjoined together. We review the literature and discuss the complications pathogenesis and differential diagnosis. We suggest that these potentially life-threatening complications be acknowledged, investigated, and rapidly treated.

Clinical and Histopathologic Characteristics of Acute Severe Hepatitis Associated With Human Herpesvirus 6 Infection.

Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 (P=0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 (P<0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8+ T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process.

Pediatric Metastatic Crohn's Disease of the Liver.

Metastatic Crohn's disease (MCD) is the manifestation of Crohn's disease outside of the gastrointestinal tract and most frequently involves mucocutaneous and pulmonary tissues. This is an uncommon phenomenon but is well characterized in the pediatric literature. In contrast, MCD affecting the liver has not previously been described in pediatrics. The pediatric gastroenterologist must be aware of the myriad of Crohn's disease-associated hepatopathies. We herein present the first reported case of pediatric MCD involving the liver and describe our targeted diagnostic evaluation and the patient's response to infliximab-dyyb.

Two Case Reports of FGF23-Induced Hypophosphatemia in Childhood Biliary Atresia.

Cholestatic liver disease has long been associated with childhood rickets, secondary to impaired absorption of fat-soluble vitamin D. Elevated serum levels of fibroblast growth factor 23 (FGF23), secondary to genetic defects or tumor-induced osteomalacia, causes hypophosphatemic rickets in childhood. We present 2 infants with end-stage liver disease due to biliary atresia (BA) who developed hypophosphatemia with renal phosphate wasting. Serum FGF23 levels were elevated more than 8 times the upper limit of normal, and the older infant showed radiographic evidence of rickets. Both infants required large supplements of phosphate in addition to calcitriol. Following liver transplantation, FGF23 normalized in both patients and phosphate and calcitriol supplementation were discontinued. Immunohistochemistry revealed ectopic overexpression of FGF23 by hepatocytes in the BA liver. These observations highlight a unique cause of hypophosphatemic rickets in childhood and suggest the need for further investigation into the relationship between BA and other cholestatic disorders, and bone metabolism.

[Spontanous pneumomediastinum after yoga practice - a case report]. / Sjálfsprottid loftmidmaeti eftir idkun jóga - sjúkratilfelli.

Pneumomediastinum is defined as interstitial air in the mediastinum, without any apparent precipating factor such as trauma, oesophageal perforation or infections. It is very uncommon and usually affects young otherwise healthy individuals. The most common symtoms are chest pain and dyspnea with subcutaneous emphysema found on examination. Treatment is usually conservative with pain relief. Here, we present an unusual case of a 23-year-old previously healthy male who was diagnosed with pneumomediastinum after practising yoga. This case demonstrates the need to study patients with chest pain of unknown cause in details to find causes.