Infantile cholestasis--advances in its understanding: new concepts. Tomar B S Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi Cholestasis is decrease or absence of bile flow into the duodenum. It can be either or in combination pathology of hepatocytes, intrahepatic bile ducts or extrahepatic bile ducts. Hepatocyte with their bile secretory apparatus and tight junction between hepatocytes are of specific importance in this. Bile is formed by several different energy-dependent transport processes. Secretion of bile is a complex metabolic process, which depends upon multiple structural and functional components in the hepatocytes and bile duct cells. The regulation of bile flow is regulated by many hormones. Bile is secreted in bile ducts having pressure of 15-25 cm of water. Rise in pressure in these bile ducts of more than 35 cm of water result suppression of bile flow and jaundice. A rise of conjugated serum bilirubin above the value of 400-500 mumol/L finds an alternate excretory pathway like urine. Various conditions are responsible for infantile cholestasis and can have different outcome of chronic cholestasis. These can be extrahepatic or intrahepatic and acute or chronic. Pathological consequences of infantile cholestasis are mainly because of malabsorption of fat and fat-soluble vitamins and hepatocellular dysfunctions. A battery of tests are required to diagnose the early infantile cholestasis. In the management of cholestasis diet rich in MCT is needed. Further, a high caloric intake up to 200 kcal/day to get adequate weight gain is desirable. Phototherapy, phenobarbitone and rifampicin is helpful in the pruritus of cholestasis by enhancing the excretion of bile. Ursodeoxycholic acid is specifically helpful in the cholestasis. A number of anti-inflammatory and immunosuppressive agents and a new compound, FK 506 has specific role in the management.

Diagnostic Efficacy of Advanced Ultrasonography Imaging Techniques in Infants with Biliary Atresia (BA): A Systematic Review and Meta-Analysis. Children (Basel, Switzerland) The early diagnosis of biliary atresia (BA) in cholestatic infants is critical to the success of the treatment. Intraoperative cholangiography (IOC), an invasive imaging technique, is the current strategy for the diagnosis of BA. Ultrasonography has advanced over recent years and emerging techniques such as shear wave elastography (SWE) have the potential to improve BA diagnosis. This review sought to evaluate the diagnostic efficacy of advanced ultrasonography techniques in the diagnosis of BA. Six databases (CINAHL, Medline, PubMed, Google Scholar, Web of Science (core collection), and Embase) were searched for studies assessing the diagnostic performance of advanced ultrasonography techniques in differentiating BA from non-BA causes of infantile cholestasis. The meta-analysis was performed using Meta-DiSc 1.4 and Comprehensive Meta-analysis v3 software. Quality Assessment of Diagnostic Accuracy Studies tool version 2 (QUADAS-2) assessed the risk of bias. Fifteen studies consisting of 2185 patients (BA = 1105; non-BA = 1080) met the inclusion criteria. SWE was the only advanced ultrasonography technique reported and had a good pooled diagnostic performance (sensitivity = 83%; specificity = 77%; AUC = 0.896). Liver stiffness indicators were significantly higher in BA compared to non-BA patients (p < 0.000). SWE could be a useful tool in differentiating BA from non-BA causes of infantile cholestasis. Future studies to assess the utility of other advanced ultrasonography techniques are recommended. 10.3390/children9111676

Emergencies in paediatric hepatology. Journal of hepatology The aetiology of several liver diseases in children is age specific and many of these conditions have significant and potentially long-term clinical repercussions if not diagnosed early and managed in a timely fashion. We address 5 clinical scenarios that cover most of the diagnostic and therapeutic emergencies in children: infants with liver disease; acute liver failure; management of bleeding varices; liver-based metabolic disorders; and liver tumours and trauma. A wide spectrum of conditions that cause liver disease in infants may present as conjugated jaundice, which could be the only symptom of time-sensitive disorders - such as biliary atresia, metabolic disorders, infections, and haematological/alloimmune disorders - wherein algorithmic multistage testing is required for accurate diagnosis. In infantile cholestasis, algorithmic multistage tests are necessary for an accurate early diagnosis, while vitamin K, specific milk formulae and disease-specific medications are essential to avoid mortality and long-term morbidity. Management of paediatric acute liver failure requires co-ordination with a liver transplant centre, safe transport and detailed age-specific aetiological work-up - clinical stabilisation with appropriate supportive care is central to survival if transplantation is indicated. Gastrointestinal bleeding may present as the initial manifestation or during follow-up in patients with portal vein thrombosis or chronic liver disease and can be managed pharmacologically, or with endoscopic/radiological interventions. Liver-based inborn errors of metabolism may present as encephalopathy that needs to be recognised and treated early to avoid further neurological sequelae and death. Liver tumours and liver trauma are both rare occurrences in children and are best managed by a multidisciplinary team in a specialist centre. 10.1016/j.jhep.2021.12.027

Treatment of Cholestasis in Infants and Young Children. Current gastroenterology reports PURPOSE OF REVIEW:Cholestasis is characterized by a conjugated hyperbilirubinemia secondary to impaired bile synthesis, transport, or excretion from the liver. It is always pathologic and can be indicative of an underlying hepatobiliary, genetic, or metabolic disorder, several of which require timely diagnosis to ensure proper management and optimal outcomes. This review provides an overview of the evaluation of cholestasis with a focus on current and emerging treatment strategies. RECENT FINDINGS:Increased accessibility of next generation sequencing (NGS) allows for utilization of genetic testing early in the diagnostic process. This may alter the clinical algorithm for diagnosis of cholestatic disorders. An enhanced understanding of the underlying pathophysiology may help guide future development of targeted therapies, such as ileal bile acid transporter (IBAT) inhibitors. These were recently approved for treatment of cholestatic pruritus in patients with Alagille syndrome and Progressive Familial Intrahepatic Cholestasis. Current management of cholestasis is aimed at the biochemical consequences of impaired bile flow, including malnutrition, pruritus, and progressive fibrosis. NGS has led to an enhanced understanding of biliary pathology and may guide development of future treatment modalities based on specific gene mutations. Rapid discernment of the underlying etiology is essential as new treatment modalities emerge. 10.1007/s11894-023-00891-8

Recent developments in diagnostics and treatment of neonatal cholestasis. Feldman Amy G,Sokol Ronald J Seminars in pediatric surgery Neonatal cholestasis is characterized by conjugated hyperbilirubinemia in the newborn and young infant and is a sign common to over 100 hepatobiliary and/or metabolic disorders. A timely evaluation for its etiology is critical in order to quickly identify treatable causes such as biliary atresia, many of which benefit from early therapy. An expanding group of molecularly defined disorders involving bile formation, canalicular transporters, tight junction proteins and inborn errors of metabolism are being continuously discovered because of advances in genetic testing and bioinformatics. The advent of next generation sequencing has transformed our ability to test for multiple genes and whole exome or whole genome sequencing within days to weeks, enabling rapid and affordable molecular diagnosis for disorders that cannot be directly diagnosed from standard blood tests or liver biopsy. Thus, our diagnostic algorithms for neonatal cholestasis are undergoing transformation, moving genetic sequencing to earlier in the evaluation pathway once biliary atresia, "red flag" disorders and treatable disorders are excluded. Current therapies focus on promoting bile flow, reducing pruritus, ensuring optimal nutrition, and monitoring for complications, without addressing the underlying cause of cholestasis in most instances. Our improved understanding of bile formation and the enterohepatic circulation of bile acids has led to emerging therapies for cholestasis which require appropriate pediatric clinical trials. Despite these advances, the cause and optimal therapy for biliary atresia remain elusive. The goals of this review are to outline the etiologies, diagnostic pathways and current and emerging management strategies for neonatal cholestasis. 10.1016/j.sempedsurg.2020.150945