Challenges in Pediatric Liver Retransplantation: A Technical Perspective.

BACKGROUND/OBJECTIVES: Liver retransplantation (reLT) is the only option for pediatric patients experiencing graft loss. Despite recent advancements in surgical techniques and perioperative management, it remains a high-risk procedure. Our aim is to describe our experience in pediatric reLT, focusing on the technical aspects and surgical challenges. METHODS: We systematically analyzed surgical reports from pediatric reLT performed at our center between 2006 and 2023 to identify recurrent intraoperative findings and specific surgical techniques. We focused on challenges encountered during different phases of reLT, including hepatectomy, vascular, and biliary reconstruction. Additionally, we compared patient and graft survival rates among different groups. RESULTS: During the study period, 23 children underwent 25 reLT procedures at our center. Major surgical challenges included complex hepatectomy and vascular reconstructions, necessitating tailored approaches. Our analysis shows that patient and graft survival were significantly lower for reLT compared to primary transplantation (p = 0.002). Early reLT had a significantly lower graft survival compared to late reLT (p = 0.002), although patient survival was comparable (p = 0.278). Patient and graft survival rates were comparable between the first and second reLT (p = 0.300, p = 0.597). Patient survival tended to be higher after living-donor liver transplantation (LDLT) compared to deceased-donor liver transplantation (DDLT), although the difference was not statistically significant (p = 0.511). CONCLUSIONS: Pediatric reLT involves significant technical challenges and lower survival rates. Advances in perioperative management are crucial for improving outcomes. Further research is needed to optimize surgical strategies and evaluate the long-term benefits of LDLT in pediatric reLT.

Failure to Rescue Pediatric Recipients of Living Donor Liver Transplantation: A Single-Center Study of Technical Complications in 500 Primary Grafts.

BACKGROUND: The concept of failure to rescue (FTR) has been used to evaluate the quality of care in several surgical specialties but has not been well-studied after living donor liver transplantation (LDLT) in children. METHODS: This study retrospectively reviewed 500 pediatric LDLT performed at a single center between 1993 and 2022. The recipient outcomes were assessed by means of patient and graft survival rates, retransplantation rates, and arterial/portal/biliary complication rates. Graft and patient losses secondary to these complications were calculated regarding FTR for patients (FTRp) and grafts (FTRg). RESULTS: Overall 1- and 5-year patient survival rates were 94.5% and 92.1%, respectively, the corresponding figures for graft survival being 92.7% and 89.8%. One-year hepatic artery complication rate was 3.6% (n = 18 cases), the respective rates for portal vein complications and biliary complications being 5.7% (n = 57) and 15.6% (n = 101). One-year FTRp rates for hepatic artery thrombosis, portal vein thrombosis, anastomotic biliary stricture, and intrahepatic biliary stricture were 28.6%, 9.4%, 3.6%, and 0%, respectively. The corresponding FTRg rates being 21.4%, 6.3%, 0%, and 36.4%. CONCLUSION: Such novel analytical method may offer valuable insights for optimizing quality of care in pediatric LDLT.

Paediatric hepatocellular adenomas: Lessons from a systematic review of relevant literature.

Hepatocellular adenomas (HCAs) are rare benign liver tumours. Predisposing factors and complication rates appear to differ among children and adults. In the present study, we aimed to systematically characterise paediatric HCAs and determine their course, complications, and management. Medical history, clinical symptoms, imaging, histopathology, and genetics of children with HCAs were collected through a systematic and comprehensive review of the published literature. A total of 316 children with HCAs were included in the present study. HCAs were diagnosed primarily in girls (59.3%) and at a mean age of 11.5 (range 0-17.7) years. The majority (83.6%) of HCAs occurred in children with predisposing diseases, of which glycogen storage disease was the most common, followed by portosystemic shunts and MODY3 (maturity-onset diabetes of the young type 3). Each of these diseases leads to a well-defined HCA molecular pattern. A significant number of HCAs either bled (24.7%) or transformed (14.8%) over time. HCA transformation was significantly more frequent in children with portosystemic shunts and in ß-catenin-mutated HCAs, while haemorrhages were more frequent in children exposed to hormones and those with larger lesions. Management was primarily guided by any predisposing conditions and the number of lesions. Therefore, vascular shunts were closed when possible, while complicated lesions were resected. Liver transplantation has made it possible to treat adenomatosis, as well as any underlying diseases. Progress in understanding genetic and/or malformative contributions, which appear to be significant in paediatric HCAs, have provided insights into tumour pathogenesis and will further guide patient surveillance and management.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD. METHODS: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions. FINDINGS: We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions. INTERPRETATION: The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD. FUNDING: The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.

Duodenal obstruction: A rare complication of severe acute pancreatitis in children.

Duodenal obstruction (DO) is an uncommon complication of pancreatitis. It has been described in groove and severe acute and chronic pancreatitis in adults but, to the best of our knowledge, it has not yet been reported in pediatric acute pancreatitis. Current guidelines comment on management of several early and late-onset complications, but DO is not mentioned. We describe two patients with acute necrotizing pancreatitis who presented with several complications including walled-off necrosis and DO. In adults, DO is generally managed with adapted nutrition but may require surgical bypass, such as gastroenterostomy. Our patients were managed conservatively and fully recovered 2 months after DO diagnosis. DO may require lengthy hospitalizations and markedly restrict patients' quality of life; however, prolonged conservative treatment was effective in our patients and should be considered even in severe pediatric cases.

Towards a Standardized Classification of the Hepatobiliary Manifestations in Cystic Fibrosis (CFHBI): A Joint ESPGHAN/NASPGHAN Position Paper.

The broad spectrum of hepatobiliary involvement in cystic fibrosis (CF) has been commonly referred to as cystic fibrosis liver disease (CFLD). However, differences in the definitions of CFLD have led to variations in reported prevalence, incidence rates, and standardized recommendations for diagnosis and therapies. Harmonizing the description of the spectrum of hepatobiliary involvement in all people with CF (pwCF) is deemed essential for providing a reliable account of the natural history, which in turn supports the development of meaningful clinical outcomes in patient care and research. Recognizing this necessity, The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) commissioned and tasked a committee to develop and propose a systematic classification of the CF hepatobiliary manifestations to increase uniformity, accuracy, and comparability for clinical, registry, and research purposes. This report describes the committee's combined expert position statement on hepatobiliary involvement in CF, which has been endorsed by NASPGHAN and ESPGHAN. We recommend using CFHBI (Cystic Fibrosis Hepato-Biliary Involvement) as the updated term to describe and classify all hepatobiliary manifestations in all pwCF. CFHBI encompasses the current extensive spectrum of phenotypical, clinical, or diagnostic expressions of liver involvement observed in pwCF. We present a schematic categorization of CFHBI, which may also be used to track and classify the changes and development of CFHBI in pwCF over time. The proposed classification for CFHBI is based on expert consensus and has not been validated for clinical practice and research purposes. Achieving validation should be an important aim for future research.

Long-term follow-up after retrosternal ileocolic esophagoplasty in two cases of long-gap esophageal atresia: why it is still a valid option as a rescue strategy.

Introduction: Esophageal replacement surgery in children is sometimes necessary for long-gap esophageal atresia. Ileocolic esophagoplasty in the retrosternal space can serve as a good alternative technique in case of hostile posterior mediastinum. We present two cases of successful ileocolic transposition performed at 6 months of age. Methods: Esophageal replacement was performed through a midline laparotomy incision associated with a left cervical approach. The ileocolic transplant was pediculized on the right superior colic artery after ligating the right colic and ileocolic vessels. A retrosternal tunnel was created, and the ileocolic transplant pulled through it to reach the cervical region. Proximally, esophageal-ileal anastomosis and, distally, colonic-gastric anastomosis were performed. Ileocolic continuity was repaired. Results: There were no early postoperative complications. In both cases, the patients presented oral feeding difficulties during the first 6 postoperative months. Thereafter, full oral feeding was achieved, and both patients were clinically asymptomatic during the following 18 and 20 years, respectively, with satisfactory oral radiological assessments, showing no redundancy or inappropriate growth of the graft and no anastomotic stricture. Currently, these patients do not complain of dysphagia, pathological reflux, or respiratory symptoms. Conclusion: When native esophagus preservation in long-gap esophageal atresia is estimated unfeasible, ileocolic transposition in the retrosternal space might be considered a good and safe option, particularly in those difficult cases after multiple previous surgical attempts and mediastinitis. This technique is putatively associated with a beneficial anti-reflux effect, thanks to the presence of the ileocecal valve, in preventing cervical peptic esophagitis. Long-term follow-up confirms that the transposed colon in the retrosternal space did not suffer any abnormal modification in size and growth.

Deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax: a case report.

BACKGROUND: Deoxyguanosine kinase deficiency is mainly manifested by hepatic and neurological damage, hence it belongs to the hepatocerebral form of mitochondrial deoxyribonucleic acid depletion syndrome. The association between deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax has not currently been reported. CASE PRESENTATION: A 12-year-old Russian boy with deoxyguanosine kinase deficiency, a recipient of a liver transplant with amyotrophy secondary to his mitochondriopathy, presented with recurrent spontaneous bilateral pneumothorax refractory to drainage and surgery. CONCLUSION: To our knowledge, this is the first documented case of deoxyguanosine kinase deficiency associated with recurrent spontaneous pneumothorax, which could be considered a late complication of deoxyguanosine kinase deficiency. At this point, this is only an association and further studies and research need to be performed to help confirm the pathogenesis of this association.

Identification of Iatrogenic Perforation in Pediatric Gastrointestinal Endoscopy.

OBJECTIVES: Iatrogenic viscus perforation in pediatric gastrointestinal endoscopy (GIE) is a very rare, yet potentially life-threatening event. There are no evidence-based recommendations relating to immediate post-procedure follow-up to identify perforations and allow for timely management. This study aims to characterize the presentation of children with post-GIE perforation to better rationalize post-procedure recommendations. METHODS: Retrospective study based on unrestricted pooled data from centers throughout Europe, North America, and the Middle East affiliated with the Endoscopy Special Interest Groups of European Society for Paediatric Gastroenterology Hepatology and Nutrition and North American Society for Pediatric Gastroenterology Hepatology and Nutrition. Procedural and patient data relating to clinical presentation of the perforation were recorded on standardized REDCap case-report forms. RESULTS: Fifty-nine cases of viscus perforation were recorded [median age 6 years (interquartile range 3-13)]; 29 of 59 (49%) occurred following esophagogastroduodenoscopy, 26 of 59 (44%) following ileocolonoscopy, with 2 of 59 (3%) cases each following balloon enteroscopy and endoscopic retrograde cholangiopancreatography; 28 of 59 (48%) of perforations were identified during the procedure [26/28 (93%) endoscopically, 2/28 (7%) by fluoroscopy], and a further 5 of 59 (9%) identified within 4 hours. Overall 80% of perforations were identified within 12 hours. Among perforations identified subsequent to the procedure 19 of 31 (61%) presented with pain, 16 of 31 (52%) presented with fever, and 10 of 31 (32%) presented with abdominal rigidity or dyspnea; 30 of 59 (51%) were managed surgically, 17 of 59 (29%) managed conservatively, and 9 of 59 (15%) endoscopically; 4 of 59 (7%) patients died, all following esophageal perforation. CONCLUSIONS: Iatrogenic perforation was identified immediately in over half of cases and in 80% of cases within 12 hours. This novel data can be utilized to generate guiding principles of post-procedural follow-up and monitoring. PLAIN LANGUAGE SUMMARY: Bowel perforation following pediatric gastrointestinal endoscopy is very rare with no evidence to base post-procedure follow-up for high-risk procedures. We found that half were identified immediately with the large majority identified within 12 hours, mostly due to pain and fever.

Characterization, evolution and risk factors of diabetes and prediabetes in a pediatric cohort of renal and liver transplant recipients.

Background: Hyperglycemia (HG) and prediabetes are rarely sought in pediatric liver (LT) and renal (RT) transplantation, yet their presence indicates a high risk of diabetes and cardiovascular disease. The objectives of our DIABGRAFT study were to retrospectively (rDIABGRAFT) and longitudinally (pDIABGRAFT) characterize HG and (pre)diabetes in a cohort of children with LT or/and RT. Methods: We retrospectively analyzed risk factors of HG from 195 children with LT from 2012 to 2019 and twenty children with RT from 2005 to 2019 at Cliniques universitaires Saint-Luc. In addition, we prospectively followed four LT and four RT children to evaluate the evolution of their glucose metabolism. Results: Our rDIABGRAFT study showed that 25% and 35% of LT and RT children respectively presented transient HG and 20% of RT developed diabetes. The occurrence of HG was associated with the use of glucocorticoids and with acute events as graft rejection and infection. In our pDIABGRAFT cohort, biological markers of diabetes were in the normal range for HbA1C, fasting glucose and insulin levels. However, oral glucose tolerance test and glucose sensors showed insulin resistance, impaired glucose tolerance and HG in the post-prandial afternoon period. Conclusion: Our study shows that children with LT and RT were more at risk of developing HG when glucocorticoids were required and that HbA1C and fasting glucose lack sensitivity for early detection of glucose intolerance. Also, measurement of glycemia immediately after the transplantation and in postprandial period is key to detect dysglycemia since insulin resistance prevailed in our cohort. ClinicalTrialsgov ID: NCT05464043.

Genomic Microsatellite Signatures Identify Germline Mismatch Repair Deficiency and Risk of Cancer Onset.

PURPOSE: Diagnosis of Mismatch Repair Deficiency (MMRD) is crucial for tumor management and early detection in patients with the cancer predisposition syndrome constitutional mismatch repair deficiency (CMMRD). Current diagnostic tools are cumbersome and inconsistent both in childhood cancers and in determining germline MMRD. PATIENTS AND METHODS: We developed and analyzed a functional Low-pass Genomic Instability Characterization (LOGIC) assay to detect MMRD. The diagnostic performance of LOGIC was compared with that of current established assays including tumor mutational burden, immunohistochemistry, and the microsatellite instability panel. LOGIC was then applied to various normal tissues of patients with CMMRD with comprehensive clinical data including age of cancer presentation. RESULTS: Overall, LOGIC was 100% sensitive and specific in detecting MMRD in childhood cancers (N = 376). It was more sensitive than the microsatellite instability panel (14%, P = 4.3 × 10-12), immunohistochemistry (86%, P = 4.6 × 10-3), or tumor mutational burden (80%, P = 9.1 × 10-4). LOGIC was able to distinguish CMMRD from other cancer predisposition syndromes using blood and saliva DNA (P < .0001, n = 277). In normal cells, MMRDness scores differed between tissues (GI > blood > brain), increased over time in the same individual, and revealed genotype-phenotype associations within the mismatch repair genes. Importantly, increased MMRDness score was associated with younger age of first cancer presentation in individuals with CMMRD (P = 2.2 × 10-5). CONCLUSION: LOGIC was a robust tool for the diagnosis of MMRD in multiple cancer types and in normal tissues. LOGIC may inform therapeutic cancer decisions, provide rapid diagnosis of germline MMRD, and support tailored surveillance for individuals with CMMRD.

Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler.

Post-operative bacterial infections are a leading cause of mortality and morbidity after ongoing liver transplantation. Bacteria causing these infections in the hospital setting can exhibit high degrees of resistance to multiple types of antibiotics, which leads to major therapeutic hurdles. Alternate ways of treating these antibiotic-resistant infections are thus urgently needed. Phage therapy is one of them and consists in using selected bacteriophage viruses - viruses who specifically prey on bacteria, naturally found in various environmental samples - as bactericidal agents in replacement or in combination with antibiotics. The use of phage therapy raises various research questions to further characterize what determines therapeutic success or failure. In this work, we report the story of a toddler who suffered from extensively drug-resistant Pseudomonas aeruginosa sepsis after liver transplantation. He was treated by a bacteriophage-antibiotic intravenous combination therapy for 86 days. This salvage therapy was well tolerated, without antibody-mediated phage neutralization. It was associated with objective clinical and microbiological improvement, eventually allowing for liver retransplantation and complete resolution of all infections. Clear in vitro phage-antibiotic synergies were observed. The occurrence of bacterial phage resistance did not result in therapeutic failure, possibly due to phage-induced virulence tradeoffs, which we investigated in different experimental models.

Congenital etiologies of exocrine pancreatic insufficiency.

Congenital exocrine pancreatic insufficiency is a rare condition. In a vast majority of patients, exocrine dysfunction occurs as part of a multisystemic disease, the most prevalent being cystic fibrosis and Shwachman-Bodian-Diamond syndrome. Recent fundamental studies have increased our understanding of the pathophysiology of these diseases. Exocrine pancreatic dysfunction should be considered in children with failure to thrive and fatty stools. Treatment is mainly supportive and consists of pancreatic enzyme replacement and liposoluble vitamins supplementation.

Conservative management of congenital hepatic hemangioma complicated by ascites.

Involution of a rapidly involuting congenital hemangioma is an unknown cause of neonatal ascites. As involution phase is completed by 14 months after birth, conservative management with diuretics and drainage is possible and may avoid surgical resection.

Inherited pancreatic exocrine insufficiency and pancreatitis: When children transition to adult care.

Hereditary pancreatitis (HP) encompasses two distinct disease groups: the first manifests as congenital exocrine pancreatic insufficiency (EPI), and the second includes hereditary forms of pancreatitis. EPI represents the ultimate expression of gland function loss. Cystic fibrosis is by far the most frequent aetiology of early-onset EPI; genetics and a growing understanding of the disease mechanisms have paved the way for innovative and personalized treatment approaches. Efforts are ongoing to further decipher the pathophysiology and explore new therapies for other causes of EPI. HP occurs in patients carrying mutations in genes encoding digestive proteases or proteins playing an important role in proper pancreatic function and homeostasis. Improved sequencing techniques have led to the discovery of several causal and disease promoting genes. Most forms of HP have a paediatric onset but complications usually manifest during adulthood. Surveillance in experienced centres is mandatory to diagnose and address these complications in a timely manner.

Everolimus is Safe as a Second-/Third-Line Therapy in Pediatric Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) can lead to progressive fibrosis in patients refractory to conventional therapy with prednisolone and azathioprine. The use of mammalian target of rapamycin (mTOR) inhibitors has recently emerged in refractory AIH, but no data have been published about everolimus in pediatric AIH to date. Our aim was to share our experience about everolimus as a second-/third-line therapy in pediatric AIH. Methods: Pretransplant AIH patients aged 0-18 years who received everolimus therapy from 2014 to 2021 were retrospectively identified. All patients underwent regular plasma monitoring of everolimus trough levels to avoid toxicity and assess adherence. Special attention was paid to the clinical and biochemical occurrence of everolimus-related adverse events. Results: We report six difficult-to-treat AIH patients who received everolimus therapy for 8-46 months (median 28 months). No side effects were reported when everolimus plasma trough levels were in the therapeutic range. Liver transaminases improved in 5 of 6 patients at everolimus introduction and significantly decreased at the last follow-up (FU) in our cohort (P < 0.05). None of our patients achieved complete biochemical remission at the last FU and 3 of 6 admitted to have suboptimal adherence to therapy. Conclusions: Our data bring preliminary safety for the use of everolimus as a second-/third-line therapy in pediatric AIH. Although liver transaminases improved in our cohort, prospective studies are needed to determine if everolimus can induce long-term remission.

Is ABO-Incompatible Living Donor Liver Transplantation Really a Good Alternative for Pediatric Recipients?

BACKGROUND: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in solid organ transplantation. METHODS: A retrospective case-control study was conducted, comparing clinical outcomes of each of 34 consecutive pediatric ABOi LDLT recipients with those of 2 non-ABOi pairs (n = 68), matched according to pre-transplant diagnostic criteria, age, and date of transplantation. In addition, we studied the C4d immunostaining pattern in 22 ABOi and in 36 non-ABOi recipients whose liver biopsy was performed within the first 4 post-transplant weeks for suspected acute rejection. RESULTS: The incidence of biliary complications was higher in ABOi recipients (p < 0.05), as were the incidence of acute humoral rejection (p < 0.01) and the incidence of retransplantation (p < 0.05). All children who required retransplantation were older than 1 year at the time of ABOi LDLT. Positive C4d immunostaining was observed in 13/22 (59%) ABOi recipients versus 3/36 (8.3%) non-ABOi recipients (p < 0.0001). CONCLUSIONS: ABOi LDLT is a feasible option for pediatric end-stage liver disease but carries increased risks for the recipient, especially for children older than 1 year, even with a specific preparation protocol. C4d immunostaining may be a hallmark of acute humoral rejection in ABOi liver transplantation.

Sequential Treatment of Biliary Atresia With Kasai Hepatoportoenterostomy and Liver Transplantation: Benefits, Risks, and Outcome in 393 Children.

Introduction: Surgical treatment of biliary atresia (BA) is still based on sequential strategy with Kasai hepatoportoenterostomy (KP) followed by liver transplantation (LT), in case of complicated secondary biliary cirrhosis. Concerns have been expressed regarding the risks of LT related to previous KP, suggesting primary LT as an exclusive treatment of BA. Methods: Single-center retrospective analysis including 393 pediatric patients who underwent LT for BA from 1993 to 2018, categorized into two groups: with (KP) or without (NoKP) previous KP. Pre-LT clinical condition was estimated considering age at LT, time on waiting list, pediatric end-stage liver disease score (PELD), and presence of portal vein hypoplasia. Post-LT outcome was evaluated considering patient and graft survival rates, and need for early reoperation due to abdominal or graft-related complications (<45 days after LT). Results: Two-hundred ninety-six patients (75.3%) were categorized in the KP group, and 97 (24.7%) in the NoKP group. Median age at LT was 1.14 years in the KP group and 0.85 years in the NoKP group (p < 0.0001). PELD score was significantly less severe in KP patients (p < 0.05). One-year patient survival rates were 96.9 and 96.8% in the KP and NoKP groups, respectively (p = 0.43), and the corresponding graft survival was 92.5 and 94.8% (p = 0.97). The need for early reoperation was more frequent in the KP group (29.8%) vs. NoKP group (12.4%, p = 0.01). The rate of bowel perforation was non-significantly higher in the KP group (8.1%) vs. NoKP group (3.1%, p = 0.11). Conclusions: The sequential strategy including KP and LT allowed performing LT in patients with significant older age and better clinical conditions, when compared to those transplanted without previous KP. Patient and graft survivals were not impacted by previous KP. Although previous KP was associated with an increased rate of post-LT surgical complications, bowel perforation and bleeding did not occur significantly more frequently. Such results support the current strategy based on sequential treatment.