Does amyloid ß precursor protein gene expression have a role in diagnosis of biliary atresia?

Aim of the study: Biliary atresia (BA) is an important cause of surgical jaundice. Although the precise etiology is unknown, ß-amyloid (Aß) has been observed around the bile ducts in BA livers. It is unclear whether Aß plays a role in the pathogenesis of this disease. This study aims to assess the amyloid ß precursor protein (APP) gene expression in infants with BA in comparison with other causes of neonatal cholestasis. This could help explore the role of Aß in the pathogenesis and diagnosis of BA. Material and methods: A prospective study was conducted at the outpatient clinic of Paediatric Hepatology, Gastroenterology, and Nutrition Department, National Liver Institute, Menoufia University, Shebin El Kom, Menoufia, Egypt during the period March 2022 to December 2022. Clinical data were gathered and laboratory and radiological investigations were conducted including ß precursor protein gene expression measured in liver biopsies of the three groups using quantitative real-time PCR (qPCR). Results: Gene expression of APP was considerably higher in the BA group (p = 0.0001) compared to neonatal cholestasis (NC) patients. Gamma glutamyl transferase (GGT) and APP had a positive correlation (p = 0.001). No significant association was found between APP and fibrosis. APP was noticeably higher in BA than NC other than BA. Also, APP in BA was higher (statistically significant, p = 0.0001) than the control. There was no statistically significant difference among NC, BA, and control groups regarding APP (p = 0.07). Both males and females did not show significant differences as regards APP (p = 0.851). Age did not have a statistically significant correlation with APP (p = 0.532). Also, there were no correlations between APP and alkaline phosphatase (ALP), aspartate transaminase (AST), or total bilirubin (TB) (p > 0.05). Conclusions: We concluded that the development and identification of BA may depend on the liver expression of serum APP. Surgeons may be able to carry out early intraoperative cholangiography for BA confirmation if the combination of APP with GGT and other hepatic function parameters exhibits a high predictive potential as a diagnostic test for BA. To evaluate this hypothesis, more research with sizable sample numbers is necessary.

Pediatric living donor liver transplantation (LDLT): Short- and long-term outcomes during sixteen years period at a single centre- A retrospective cohort study.

Background and objectives: Pediatric living donor liver transplantation (LDLT) is an effective tool for managing pediatric patients with end-stage liver disease (ESLD) with good long-term graft and patient survival, especially after improvement in peri-operative care, surgical tools and techniques; however, the morbidity and mortality after such a procedure are still a challenging matter. The study aimed to analyze short-and long-term outcomes after pediatric LDLT in a single centre. Methods: We retrospectively analyzed 67 pediatric patients who underwent LDLT in the period from April 2003 to July 2018. The overall male/female ratio was 40/27. Results: Forty-one (61.2%) of patients had ≥1 early and/or late morbidities; the early (less than 3months) and late (≥3months) ones affected 36(53.7%) and 12(17.9%) of them respectively. The 16-year graft and patient survivals were 35(52.2%) while early and late mortalities were 23(34.3%) and 9(13.4%) respectively. Sepsis and chronic rejection were the most frequent causes of early and late mortalities respectively. Moreover, more packed RBCs transfusion units, bacterial infections, and pulmonary complications were independent predictors of poor patient survival. Conclusions: More packed RBCs transfusion units intra-operatively, and post-liver transplant (LT) bacterial infection, sepsis, chronic rejection, as well as pulmonary complications had a negative insult on our patients' outcomes, so proper management of them is mandatory for improving outcomes after pediatric LDLT.

Autoantibodies: are they a clue for liver diseases?

Introduction: Autoantibody testing has contributed to both biological and clinical insights in managing patients with liver disease. These autoantibodies often have clinical value for the diagnosis, disease activity and/or prognosis. Aim of the study: We aimed to investigate the potential application of auto-antibodies in different etiologies of non-autoimmune liver diseases. Material and methods: This study was conducted on 53 infants and children with chronic liver diseases. The patients were subjected to clinical history and examination, laboratory investigations and abdominal ultrasound. Serum of all infants and children was tested for measurement of antiprothrombin antibody and anti-b2-glycoprotein I (ab2GPI) and anticardiolipin (ACL) auto-antibodies using a fully-automated enzyme linked immunosorbent assay (ELISA) system. Results: The mean age of the infants with cholestatic liver diseases was significantly lower than those with metabolic liver diseases, hepatitis C virus (HCV) and vascular liver diseases (p < 0.05). The gender distribution was proportionate in all groups (p = 0.703). Autoantibodies showed significant variations among different etiologies of chronic liver diseases. he incidence of ab2GPI and ACL was significantly increased in both HCV (94.7% and 78.9%, respectively) and vascular liver diseases patients (90.9% and 72.7%, respectively) (p < 0.05). Antiprothrombin antibodies were found in 81.8% of vascular liver disease patients. Interestingly, all types of autoantibodies were deficient in cholestatic and metabolic liver diseases. Conclusions: Testing for liver-related autoantibodies should be included in the workup of patients with chronic liver diseases. Further studies are needed to explain the cause-effect association of ACL, ab2GPI and antiprothrombin with chronic HCV and vascular liver diseases.

Short- and long-term outcomes after Kasai operation for type III biliary atresia: Twenty years of experience in a single tertiary Egyptian center-A retrospective cohort study.

Kasai portoenterostomy(KPE) is the treatment of choice for the fatal devastating infantile type III biliary atresia (BA). The study aimed to analyze short-and long-term outcomes after this procedure and their predictors in a tertiary center. METHODS: We retrospectively analyzed 410 infants who underwent KPE for type III BA in the period from February 2000 to December 2019. The overall male/female ratio was 186/224. RESULTS: The early (>6months) complications involved 187(45.6%) of our infants with a higher incidence of early cholangitis that affected 108(26.3%) of them. The jaundice clearance at the 6th post-operative month that reached 138(33.7%) of them had an independent correlation with mild portal tracts ductal and/or ductular proliferation, using postoperative steroids therapy, and absence of early postoperative cholangitis. The early infant mortality that affected 70(17.1%) of our patients was mostly from sepsis. On the other hand, late (<6months) patients complications and mortalities affected 256(62.4%) and 240(58.5%) of patients respectively; moreover, liver failure and sepsis were the most frequent causes of late mortalities in non-transplanted and transplanted cases respectively. Lastly, the long-term (20-year) native liver survival (NLS) that reached 91(22.2%) of patients had an independent correlation with age at operation ≤ 90 days, higher preoperative mean serum alb, portal tract fibrosis grades F0 and F1, absence of intraoperative bleeding, absence of post-operative cholangitis, the occurrence of jaundice clearance at the 6th postoperative month and absence of post-operative portal hypertension (PHN). CONCLUSIONS: Sepsis had a direct effect on early and late patient mortalities after Kasai operation for type III BA; moreover, patient age at operation<90 days, higher fibrosis grades, the occurrence of postoperative cholangitis and PHN, and persistence of post-operative jaundice had negative insult on long-term postoperative outcome. So, it is crucial to modulate these factors for a better outcome.

Pediatric chronic liver failure-sequential organ failure assessment score and outcome of acute liver failure in children.

AIM OF THE STUDY: Liver transplantation remains the only definitive treatment for children with acute liver failure proven to have irreversible liver injury. Many prognostic models have been used for outcome prediction in pediatric acute liver failure to select patients in a real need of liver transplantation, but unfortunately all have shown inconsistent reproducibility and prognostic accuracy. The aim of this study was to evaluate the pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score as a predictor of pediatric acute liver failure outcome. MATERIAL AND METHODS: Clinical and laboratory data of 41 children with acute liver failure admitted to the National Liver Institute - Menoufia University were collected retrospectively and used for calculation of both pCLIF-SOFA and Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores on the day of admission, then statistical analysis was performed to identify the ability of these scores to predict the outcome. RESULTS: According to the outcome, children enrolled in this study were allocated to survived (n = 16) and died (n = 25) groups, which were age and sex matched. The non-survival group had significantly higher values of both pCLIF-SOFA score (11 [7-13]) and PELD/MELD score (36 [18-42]) than those of the survival group (8 [7-11], 27.5 [15-45]; p < 0.001, p = 0.004) respectively. Both pCLIF-SOFA and PELD/MELD scores at cut-off values > 8 and > 30 respectively on admission could predict death in children with acute liver failure (ALF) with high sensitivity, but with higher specificity, positive and negative predictive values for pCLIF-SOFA. CONCLUSIONS: pCLIF-SOFA is a good predictor of death in pediatric acute liver failure.