• 17q12 deletion
• HNF1β
• congenital hypopituitarism
• liver disease
• neonatal cholestasis
• pituitary stalk interruption syndrome

• Biliary atresia
• Hyperbilirubinemia
• Jaundice
• Kasai

• Humans
• Biliary Atresia/diagnosis
• Biliary Atresia/surgery
• Preoperative Care/methods
• Infant, Newborn
• Infant

• Saudi Arabia
• idiopathic neonatal hepatitis
• liver disease
• next-generation sequence
• whole exome sequence

• Biliary atresia
• Diagnostic model
• Neonatal cholestasis

• Infant
• Infant, Newborn
• Humans
• Biliary Atresia/diagnostic imaging
• Biliary Atresia/complications
• Retrospective Studies
• Ultrasonography
• Cholestasis/etiology
• Gallbladder Diseases
• Early Diagnosis
• Diagnosis, Differential

• Guangzhou Institute of Pediatrics, Guangzhou Women and Childrens Medical Center
• Guangzhou Women and Children’s Medical Centre
• the Science and Technology Programme of Guangzhou

• delivery
• digital
• portable electronic applications
• pregnancy
• smartphone
• telehealth
• telemedicine
• virtual clinics

• Pregnancy
• Humans
• Female
• Hong Kong
• Pregnant Women
• Cross-Sectional Studies
• Prospective Studies
• Telemedicine

• cognition disorders/physiopathology
• congenital hypopituitarism
• growth hormone
• growth hormone deficiency
• hormone replacement therapy
• hypoglycaemia
• newborn

• Cholestasis
• Hyperbilirubinemia
• Panhypopituitarism

• Biliary Atresia
• Machine Learning
• Neonatal Cholestasis
• Prediction
• XGBoost

• MNSs blood group system
• anti-M
• hemolytic disease of the fetus and newborn

• 2021JH2/10300045 Liaoning Science and Technology Program

• NICCD
• SLC25A13
• citrin deficiency
• novel variant
• prognosis

• Jaundice
• Neonatology

Objectives

To present a nationwide retrospective analysis of the sequelae and aftereffects of different liver biopsy methods in the care of pediatric patients with biliary atresia.

Methods

The National Inpatient Sample 2001-2013 database was queried for a primary diagnosis of biliary atresia and stratified based on biopsy type including percutaneous, surgical, laparoscopic, and transjugular. Patient demographics, length of stay, hospital costs, type of treatment, and mortality were compared by biopsy type. One-way analysis of variance test and multivariable logistic regression were used for analysis with α < 0.05.

Results

A total of 4,306 patients with biliary atresia were identified, of whom 2,293 underwent no biopsy, and 723 and 1,080 underwent a percutaneous or surgical biopsy, respectively. Significant differences in socio-demographics were demonstrated between the biopsy types. The length of stay and hospital charges were statistically significantly different between the biopsy types where patients without biopsies had the smallest length compared to percutaneous, surgical, and combination of biopsies. Overall, the Kasai procedure was done more frequently compared to direct liver transplantation, and compared to other biopsy types, undergoing a combination of biopsies had the highest odds of undergoing either procedure.

Conclusions

When comparing different biopsy methods, surgical biopsies of the liver outperformed percutaneous biopsies in hospital utilization and progression to definitive treatments with the Kasai procedure. Our research indicated that vulnerable populations such as minorities or the indigent may undergo inferior treatments or infrequently undergo definitive treatment. The need for definitive diagnostic guidelines is understated in patients with biliary atresia.

Few studies have described the aetiologies of neonatal cholestasis, and the overall neonatal cholestasis-related mortality (NCM) rate is unclear. We investigated the aetiology and outcome of neonatal cholestasis in a tertiary hospital and developed an NCM prediction model for these patients.

Patients aged <100 days with serum direct bilirubin (DB) levels of >1.0 mg/dL were retrospectively screened. Diagnostic and laboratory data during the 8-week follow-up period after enrolment between 2005 and 2020 were extracted digitally, and medical charts were reviewed manually by clinicians. Logistic regression was used to derive a prediction model for the 1-year mortality outcome of neonatal cholestasis, and performance evaluation and external validation were conducted for the NCM prediction model.

We enrolled 4028 neonates with DB of >1.0 mg/dL at least once. Prematurity and birth injury (35.4%), complex heart anomalies (18.6%), liver diseases (11.4%), and gastrointestinal anomalies (9.2%) were the most common aetiologies; 398 (9.9%) patients died before one year of age. The peak value of DB was positively correlated to the 1-year mortality rate. In the multivariate analysis, simple laboratory indices, including platelet, prothrombin time, aspartate aminotransferase, albumin, direct bilirubin, creatinine, and C-reactive protein, were independent predictors of 1-year mortality outcome of complete-case subjects. Using these laboratory indices, a logistic regression-based NCM prediction model was constructed. It showed acceptable performances on discrimination (area under the curve, 0.916), calibration (slope, 1.04) and Brier scoring (0.072). The external validation of the sample (n = 920) from two other centres also revealed similar performance profiles of the NCM model.

Various aetiologies of neonatal cholestasis were identified in a tertiary hospital, resulting in unfavourable outcomes of a large proportion. The NCM prediction model may have the potential to help clinicians to be aware of high-risk neonatal cholestasis.

• Biliary atresia
• Cytomegalovirus
• Diagnosis
• Neonatal cholestasis

• admission indicator
• bilirubin encephalopathy
• complication
• exchange transfusion therapy
• neonatal hyperbilirubinemia
• phototherapy failure
• predictive model

• Arabs
• Kasai portoenterostomy
• biliary atresia
• liver transplantation
• neonatal cholestasis

• Edward syndrome
• Patau syndrome
• conjugated hyperbilirubinemia
• screening
• total parenteral nutrition

• cholestasis
• cholestatic jaundice
• fat-soluble vitamins
• micronutrients

Here we describe for the first time double paternal uniparental isodisomy (iUPD) 7 and 15 in a baby boy with features in the Beckwith–Wiedemann syndrome spectrum (BWSp) (placentomegaly, hyperinsulinism, enlarged viscera, hemangiomas, and earlobe creases) in addition to conjugated hyperbilirubinemia. His phenotype was also reminiscent of genome-wide paternal uniparental isodisomy. We discuss the most likely origin of the UPDs: a maternal double monosomy 7 and 15 rescued by duplication of the paternal chromosomes after fertilization. So far, paternal UPD7 is not associated with an abnormal phenotype, whereas paternal UPD15 causes Angelman syndrome. Methylation analysis for other clinically relevant imprinting disorders, including BWSp, was normal. Therefore, we hypothesized that the double UPD affected other imprinted genes. To look for such effects, patient fibroblast RNA was isolated and analyzed for differential expression compared to six controls. We did not find apparent transcription differences in imprinted genes outside Chromosomes 7 and 15 in patient fibroblast. PEG10 (7q21.3) was the only paternally imprinted gene on these chromosomes up-regulated beyond double-dose expectation (sixfold). We speculate that a high PEG10 level could have a growth-promoting effect as his phenotype was not related to aberrations in BWS locus on 11p15.5 after DNA, RNA, and methylation testing. However, many genes in gene sets associated with growth were up-regulated. This case broadens the phenotypic spectrum of UPDs but does not show evidence of involvement of an imprinted gene network.

• conjugated hyperbilirubinemia
• hyperinsulinemic hypoglycemia
• large placenta
• overgrowth

• hepatitis
• jaundice
• liver
• neonatal
• transient

• Kasai portoenterostomy
• biliary atresia
• idiopathic neonatal hepatitis
• progressive familial intrahepatic cholestasis

• General practitioner
• Icterus
• Jaundice

• Alpha-1-antitrypsin deficiency
• Biliary atresia
• Diagnostic decision algorithm
• Multivariate prediction models
• Neonatal cholestasis
• Transient neonatal cholestasis

Investigators from different parts of the world are calling for a re-evaluation of the role of liver biopsy (LB) in the evaluation of infantile cholestasis (IC), especially in the light of emerging non-invasive diagnostic technologies. Therefore, this retrospective single-center study was conducted to determine the impact of LB on the diagnosis and management of IC in a cohort from Arabs.

From 2007 until 2019, 533 cases of IC were referred for evaluation. All infants who underwent LB were included in the study. We categorized the yield of LB into: (1) defined specific diagnosis; (2) excluded an important diagnosis. A single pathologist reviewed and made the histology report.

122 LB specimens met the inclusion criteria. The main indication for LB was a high suspicion of biliary atresia (BA) [high gamma-glutamyl transferase (GGT) cholestasis and pale stool] in 46 cases (37.8%). Liver biopsy had sensitivity of 86.4%, specificity (66.7%), PPV (70.4%), NPV (84.2%) in diagnosing BA. LB had a direct impact on clinical management in 52 cases (42.6%): (1) The true diagnosis was suggested by LB in 36 cases; (2) LB excluded BA and avoided intraoperative cholangiogram in 16 cases with high suspicion of BA. Among the 76 cases with low suspicion of BA, LB suggested the true diagnosis or helped to initiate specific management in 8 cases only (10.5%). In contrast, molecular testing confirmed the diagnosis in 48 (63%).

LB continues to be an important tool in the workup of cases with a high suspicion of BA. The low yield of LB in cases with low suspicion of BA calls for a re-evaluation of its role in these cases in whom early incorporation of cholestasis sequencing gene  panels can have a better diagnostic yield.

• Cholestasis
• Indications
• Infant
• Liver biopsy
• Pathology
• Saudi Arabia

• Biliary atresia
• Neonatal cholestasis
• Neonatal hepatitis
• Paucity of intrahepatic bile ducts

• cholestasis
• cytomegalovirus
• liver diseases
• neonatal hyperbilirubinemia
• neonatal intensive care (unit)
• neonatal jaundice
• preterm infants

• biliary atresia
• hepatobiliary scintigraphy scan
• neonatal cholestasis
• preterm neonate

• Cholestasis/complications
• Cholestasis/diagnosis
• Cholestasis/etiology
• Decision Trees
• Diagnosis, Differential
• General Practice
• Humans
• Liver Diseases/diagnosis
• Liver Diseases/etiology
• Medicine

• children
• hyperurticemia
• inflammatory response
• kawasaki disease

• Case-Control Studies
• Child, Preschool
• Female
• Humans
• Hyperbilirubinemia/complications
• Male
• Mucocutaneous Lymph Node Syndrome/etiology

• Conjugated bilirubin
• cardiac surgery
• hyperbilirubinaemia
• post-operative outcomes

• Hepatitis A
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Pregnancy
• Vaccination

Infantile cholestatic hepatopathy (ICH) is a clinical syndrome characterized by the accumulation of cytotoxic bile acids in infancy, leading to serious liver cirrhosis or liver failure. The aetiology of ICH is complicated and some of them is unknown. Regardless of the aetiology, the finial pathology of ICH is hepatocyte apoptosis caused by severe and persistent cholestasis. It is already known that activation of calcium-sensing receptor (CaSR) could lead to the apoptosis of cardiomyocytes. However, the mechanism by CaSR-mediated cholestasis-related hepatocyte apoptosis is not fully understood. Li-Dan-He-Ji (LDHJ), a Traditional Chinese Medicine prescription, was developed to treat ICH. Another aim of this study was to investigate the possible mechanisms of LDHJ in cholestasis-related hepatocyte apoptosis. Using the primary hepatocytes, we first investigated the molecular mechanism of CaSR-mediated hepatocyte apoptosis in cholestasis. Then we prepared LDHJ granules and used ultra-high-performance liquid chromatography to identify the predominant drugs; confirmed the stability of the main substances; and for cell experiments screened forsythoside-A, emodin and chlorogenic acid as the three active substances of LDHJ granules. In the young rats with ANIT-induced intrahepatic cholestasis and the primary hepatocytes with TCDC-induced cholestasis-related hepatocyte apoptosis, the levels of liver injury and cholestasis-related biomarkers, calcium-sensing receptor (CaSR), hepatocyte apoptosis, Bax/Bcl-2 ratio, Cytochrome-C, caspase-3, phosphorylated-c-Jun NH₂-terminal kinase (p-JNK)/JNK, and p-P38/P38 were all increased, while the levels of p-extracellular signal-regulated kinase (p-ERK)/ERK were decreased. However, LDHJ granules and its three active substances effectively reversed these changes. Furthermore, the three active substances reduced the increases in the intracellular calcium concentration ([Ca²⁺]_i) and ROS levels and attenuated the dissipation of the mitochondria membrane potential in the TCDC-induced primary hepatocytes. The opposite results were obtained from the TCDC-induced primary hepatocytes treated with an agonist of CaSR (GdCl₃) plus forsythoside-A, emodin or chlorogenic acid. Based on the results from in vivo and in vitro studies, LDHJ functions as an antagonist of CaSR to regulate hepatocyte apoptosis in cholestasis through the mitochondrial pathway and mitogen-activated protein kinase pathway.

• Li-Dan-He-Ji (LDHJ)
• calcium-sensing receptor (CaSR)
• chlorogenic acid
• emodin
• forsythoside-A
• hepatocyte apoptosis
• infantile cholestasis

• Abnormalities, Multiple/diagnosis
• Humans
• Hyperbilirubinemia, Neonatal/diagnosis
• Infant, Newborn
• Infant, Premature
• Intensive Care Units, Neonatal

• cholestasis risk factors
• neonatal cholestasis
• neonatal cholestasis epidemiology
• neonatal cholestasis survival
• next generation sequencing panel
• transient cholestasis

• Cholestasis
• gastroenterology
• leukemia
• oncology

• Biliary atresia
• Neonatal cholestasis
• Neonatal hepatitis
• Paucity of intrahepatic bile ducts

• Cholestasis
• Hyperbilirubinemia
• Hypopituitarism

• Diagnosis, Differential
• Female
• Hormone Replacement Therapy
• Humans
• Hypopituitarism/complications
• Hypopituitarism/congenital
• Hypopituitarism/diagnosis
• Hypopituitarism/physiopathology
• Infant
• Liver/abnormalities
• Liver Diseases/diagnosis
• Liver Diseases/etiology
• Liver Diseases/physiopathology
• Male
• Transaminases/blood
• Turkey

Total parenteral nutrition (TPN) and biliary atresia (BA) are common causes of cholestasis in infancy. The diagnosis of BA is time sensitive due to an inverse correlation between age at intervention (hepatic portoenterostomy - HPE) and survival without liver transplantation. Clinical, laboratory, and histologic features of BA and parenteral nutrition associated cholestasis (PNAC) are similar, creating a diagnostic dilemma for cholestatic infants on parenteral nutrition. There is limited published information about the natural history of PNAC including time to resolution, or diagnostic tests that distinguish BA from other etiologies of cholestasis.

We present a case of a child diagnosed with BA whose cholestasis began while receiving TPN. His clinical course was notable for transient resolution of his cholestasis after stopping parenteral nutrition and ultimate intraoperative diagnosis.

Clinicians who care for patients who frequently receive TPN should be aware that clinical, laboratory, imaging, and biopsy findings can be similar between BA and PNAC.

• Biliary atresia
• Case report
• Cholestasis
• Liver biopsy
• Total parenteral nutrition

• Biliary atresia
• Hepatoportoenterostomy
• Kasai procedure
• Minimally invasive surgery

• Cholestasis
• Direct hyperbilirubinemia
• Gastroschisis
• Outcomes
• Resource utilization

• Female
• Gastroschisis/complications
• Gastroschisis/therapy
• Gestational Age
• Humans
• Hyperbilirubinemia/diagnosis
• Hyperbilirubinemia/etiology
• Infant, Newborn
• Male
• Parenteral Nutrition, Total/adverse effects
• Retrospective Studies
• Treatment Outcome

• HPD
• direct hyperbilirubinemia
• hawkinsinuria
• heterozygous mutation
• tyrosine

Neonatal cholestasis (NC) is a diagnostic dilemma frequently countered in a neonatal care unit. Early diagnosis is vital for achieving an optimal patient outcome as many causes of cholestasis such as biliary atresia are time-sensitive and amenable to treatment if analyzed and treated early. Nonetheless, it is not generally simple to analyze these cases right on time as some of them are regularly missed due to the presence of pigmented stools, lack of newborn metabolic screening, and named as instances of prolonged jaundice. In this manner, we prescribe to explore all reasons for prolonged jaundice stretching out past 14 days in neonates. Besides, we suggest that stool card ought to be a piece of release rundown for all newborn children being released from the nursery. This is of most extreme significance in the nation like India where guaranteeing customary follow-up is as yet a tough assignment. These stool cards will help in the early determination of patients with NC particularly biliary atresia and guarantee their auspicious cure. Another reason which needs exceptional say is parenteral nutrition–associated liver illness, as the proportion of preterm babies is getting greater and greater with better neonatal care. These extreme preterm infants are in the requirement for prolonged (>14 days) total parenteral nourishment because of which they are at high hazard for NC contrasted with their more developed peers. In this survey, we will give an understanding of clinical approach, differential diagnosis, and clinical review of NC.

• biliary atresia
• hepatoportoenterostomy
• liver biopsy
• neonatal cholestasis
• neonatal jaundice
• radionuclide scan