Neonatal cholestasis is a rare condition characterised by jaundice and conjugated hyperbilirubinemia. It may be related to a wide range of aetiologies, including obstruction of bile ducts, metabolic or genetic disorders, immaturity of the liver, parenteral nutrition, drug toxicity, and infections (1). Urgent medical therapy is required to correct potential clotting abnormalities because of vitamin K absorption deficiency, which may lead to severe bleeding (2). Among the various causes of neonatal cholestasis, biliary atresia (BA) needs urgent diagnosis and therapy because the success of the Kasai operation is closely related to the age of the patient; the prognosis declines progressively with increasing age at surgery, and the best long-term results are obtained when children are operated on in the first month of life (3,4).
BA can be highly suspected in the presence of the clinical triad of jaundice, acholic stools, and hepatomegaly (5). If, additionally, ultrasound scans, after strict fasting (the child ideally receiving intravenous fluids to prevent agitation and hypoglycaemia), show shrunk or absent gallbladder, then the probability of BA is high (6), and surgical exploration can be performed after rapid exclusion of the most common medical causes of neonatal cholestasis (7). However, in some cases, the clinical presentation may be less characteristic, and the gallbladder may appear normal on ultrasound scans, thus other investigations are required for diagnosis. Liver biopsy is useful because it may orient the diagnosis towards obstruction of large bile ducts (bile plugs, biliary proliferation, portal oedema, and fibrosis), but these signs are not specific and may be seen in the absence of biliary obstruction, for instance in progressive familial intrahepatic cholestasis type 3. Furthermore, these signs may be absent in the early stages of BA. Conventional hepatobiliary scintigraphy may show a lack of excretion of the isotope in severe cholestasis (8), although its specificity may be enhanced by premedications such as phenobarbitone, and/or association with single photon emission computed tomography (9). Therefore, hepatobiliary scintigraphy is often of little help in the routine diagnosis of cholestatic infants (10). Finally, in difficult cases, a cholangiogram is needed to assess the biliary tree and definitively confirm or exclude BA, and should not be delayed.
Magnetic resonance cholangiopancreatography still has insufficient resolution to rule out BA, and a reliable cholangiogram can be obtained by several methods: First, the classical “open” technique through a mini-laparotomy in the right upper quadrant allows visual inspection of the liver and gallbladder, aspirating the gallbladder content (colour assessment), performing the biliary opacification, eventually flushing the bile ducts, and performing a liver biopsy. The incision is extended if the diagnosis of BA is confirmed and the Kasai operation is required. The main advantage is the simplicity of this “all-in-one” technique, requiring 1 single operator and 1 single general anaesthesia, whereas its main disadvantage is the abdominal incision in case no further surgery is needed. Second, the laparoscopic technique provides the same information with 3 to 4 small incisions and may similarly be combined with a liver biopsy or a Kasai procedure during the same anaesthesia (11). It requires more sophisticated equipment and a surgeon accustomed to neonatal laparoscopy. Third, the percutaneous transhepatic cholangiogram (12) needs an experienced interventional radiologist and (if not performed in theatre) may be logistically difficult to combine with eventual surgery during the same anaesthesia. Bile can be aspirated from the gallbladder, and the bile ducts can be flushed (13). This technique does not visualise the liver and gallbladder, but may be combined with a percutaneous liver biopsy. Fourth, the endoscopic retrograde cholangiopancreatography (ERCP) requires an experienced endoscopist (14) and specific endoscopy equipment. Whatever the gallbladder status on ultrasonographic scans, ECRP may avoid a laparotomy and is, therefore, particularly attractive in children who underwent previous surgery (eg, for intestinal atresia, necrotising enterocolitis). Endoscopy allows visualisation of intraduodenal bile, but not of liver and gallbladder. The possibility to flush the bile ducts (especially the gallbladder) is limited as compared with surgical or percutaneous cholangiograms. According to each hospital setting, it may be difficult to combine ERCP with an immediate Kasai operation, if it is necessary. ERCP in adults has a 5% to 10% risk of significant complications, mainly pancreatitis, as well as peritonitis, haemorrhage, and cholangitis (15). About 90% of the pancreatitis after ERCP are mild, but moderate to severe episodes are possible (16).
Although the use of ERCP has been reported in children (17–19) and neonates (20–25), its results in the assessment of patients with neonatal cholestasis relied on limited series. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Shanmugam et al report the 10-year experience at King's College Hospital, London, UK, of ERCP in selected patients with neonatal cholestasis (26). Among 48 infants (selected from 3300 infants evaluated for neonatal cholestasis in the same period), cannulation failed in 3 (6%). In 25 patients the cholangiogram was suggestive of BA, which was confirmed at laparotomy in 22 (false-positive 12%). In 20 patients with a cholangiogram showing patent bile ducts, no BA was missed, 12 (60%) had an abnormal biliary tree, of whom 6 (30%) had neonatal sclerosing cholangitis. Although intraperitoneal extravasation of contrast was observed in 3 patients, none developed significant clinical peritonitis or pancreatitis. These data confirm that ERCP may be an interesting tool in the diagnostic panoply of neonatal cholestasis. However, its superiority as compared with the other types of cholangiograms remains to be demonstrated, and it may rather be considered as an additional tool that can be used in selected cases, rather than systematically. Because of the risk of severe complications, ERCP should be performed only by an experienced endoscopist (14). The overall logistics of the workup of neonatal cholestasis should also be considered according to the facilities available in each centre, to avoid unnecessary repetition of general anaesthesias.
1. McKiernan PJ. Neonatal cholestasis. Semin Neonatol 2002; 7:153–165.
2. Akiyama H, Okamura Y, Nagashima T, et al
. Intracranial hemorrhage and vitamin K deficiency associated with biliary atresia: summary of 15 cases and review of the literature. Pediatr Neurosurg 2006; 42:362–367.
3. Schreiber RA, Barker CC, Roberts EA, et al
. Biliary atresia: the Canadian experience. J Pediatr 2007; 151:659–665.
4. Serinet MO, Wildhaber B, Broue P, et al
. Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics 2009; 123:1280–1286.
5. Alagille D. Extrahepatic biliary atresia. Hepatology 1984; 4:7S–10S.
6. Chardot C. Biliary atresia. Orphanet J Rare Dis 2006; 1:28.
7. Gonzales E, Jacquemin E. Cholestases néonatales. Encyclopédie médico-chirurgicale. 2006;Pédiatrie(4.060-A-15):1–8.
8. Gilmour SM, Hershkop M, Reifen R, et al
. Outcome of hepatobiliary scanning in neonatal hepatitis syndrome. J Nucl Med 1997; 38:1279–1282.
9. Sevilla A, Howman-Giles R, Saleh H, et al
. Hepatobiliary scintigraphy with SPECT in infancy. Clin Nucl Med 2007; 32:16–23.
10. Moyer V, Freese DK, Whitington PF, et al
. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2004; 39:115–128.
11. Hay SA, Soliman HE, Sherif HM, et al
. Neonatal jaundice: the role of laparoscopy. J Pediatr Surg 2000; 35:1706–1709.
12. Nwomeh BC, Caniano DA, Hogan M. Definitive exclusion of biliary atresia in infants with cholestatic jaundice: the role of percutaneous cholecysto-cholangiography. Pediatr Surg Int 2007; 23:845–849.
13. Debray D, Pariente D, Gauthier F, et al
. Cholelithiasis in infancy: a study of 40 cases. J Pediatr 1993; 122:385–391.
14. NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy. NIH Consens State Sci Statements.
15. Mahnke D, Chen YK, Antillon MR, et al
. A prospective study of complications of endoscopic retrograde cholangiopancreatography and endoscopic ultrasound in an ambulatory endoscopy center. Clin Gastroenterol Hepatol 2006; 4:924–930.
16. Abdel Aziz AM, Lehman GA. Pancreatitis after endoscopic retrograde cholangio-pancreatography. World J Gastroenterol 2007; 13:2655–2668.
17. Allendorph M, Werlin SL, Geenen JE, et al
. Endoscopic retrograde cholangiopancreatography in children. J Pediatr 1987; 110:206–211.
18. Brown CW, Werlin SL, Geenen JE, et al
. The diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography in children. J Pediatr Gastroenterol Nutr 1993; 17:19–23.
19. el-Shabrawi M, Wilkinson ML, Portmann B, et al
. Primary sclerosing cholangitis in childhood. Gastroenterology 1987; 92(5 Pt 1):1226–1235.
20. Guelrud M, Jaen D, Mendoza S, et al
. ERCP in the diagnosis of extrahepatic biliary atresia. Gastrointest Endosc 1991; 37:522–526.
21. Iinuma Y, Narisawa R, Iwafuchi M, et al
. The role of endoscopic retrograde cholangiopancreatography in infants with cholestasis. J Pediatr Surg 2000; 35:545–549.
22. Ohnuma N, Takahashi T, Tanabe M, et al
. The role of ERCP in biliary atresia. Gastrointest Endosc 1997; 45:365–370.
23. Shirai Z, Toriya H, Maeshiro K, et al
. The usefulness of endoscopic retrograde cholangiopancreatography in infants and small children. Am J Gastroenterol 1993; 88:536–541.
24. Teng R, Yokohata K, Utsunomiya N, et al
. Endoscopic retrograde cholangiopancreatography in infants and children. J Gastroenterol 2000; 35:39–42.
25. Wilkinson ML, Mieli-Vergani G, Ball C, et al
. Endoscopic retrograde cholangiopancreatography in infantile cholestasis. Arch Dis Child 1991; 66:121–123.
26. Shanmugam NP, Harrison PM, Devlin J, et al. Selective use of endoscopic retrograde cholangiopancreatography in the diagnosis of biliary atresia in infants younger than 100 days. J Pediatr Gastroenterol Nutr
2009. In press.