Definition
• Impaired bile sec by the liver w/ subseq ↑ serum total and direct bili; often w/ jaundice
• Biliary hepatic congestion → chronic hepatic inflammation → fibrosis and cirrhosis
Etiology (Pediatr Rev 2004;25:388; Pediatr Rev 2007;28:83)
• Neonatal obstructive cholestasis: Biliary atresia, choledochal cysts, bile duct paucity (Alagille syndrome as well as nonsyndromic), neonatal sclerosing cholangitis, inspissated bile syndrome, cholecystitis, bile sludging, CF
• Child and young adult: Choledochal cyst, cholecystitis, tumor, primary biliary cirrhosis, primary sclerosing cholangitis, missed neonatal diagnosis (Alagille, nonsyndromic bile duct paucity, Caroli disease)
Selected Clinical Manifestations, Evaluation, and Treatment
• Presentation varies based on age, etiology, severity, and duration of illness
• Biliary atresia: Most common cause of extra-hepatic cholestasis in 1st mo of life (33%)
• Complete blockage of bile outflow 2/2 complete or partial destruction or absence of extrahepatic bile ducts. (Clin Liver Dis 2006;10:73; Pediatr Rev 2006;27:243)
• Results in ∼50% of all pediatric liver transplants; most freq hepatic cause of death
• P/w jaundice at 3–6 wk of life, otherwise healthy; rare embryonic form at birth
• Subclinically, BA pts w/ T/D bili ↑ on DOL 1-2 (Pediatrics 2011;128:e1428)
• Rapidly progressive process w/ continuing inflammation and fibrosis/destruction
• Prenatal form (less common) assoc w/ polysplenia, malro, CDH in 10–15%
• Etiology unknown, proposed viral association; reovirus, CMV, HPV, rotavirus C
• Evaluation: Can screen generally w/ stool color cards (Pediatrics 2011;128:e1209)
• Most p/w elevated direct bilirubin and evaluated for other causes (above)
• Abd U/S: R/o other structural disease, looking for the absence of gall bladder though nonspecific finding, pathognomonic finding is triangular cord sign
• HIDA scan: If tracer to intestines, argues against dx, but may need to repeat as biliary atresia is a progressive disease; most people use phenobarb ×5 d prior
• MRI cholangiography and liver bx also good but sensitivities too low to exclude biliary atresia if strongly suspected
• Intraoperative cholangiogram (or ERCP where available) necessary to rule out if above equivocal; if present, surgical correction at time of study
• Rx w/ Kasai hepatic portojejunostomy (anastomosis of porta hepatis to Roux en Y), which allows for small patent bile ducts to drain restoring bile flow
• Success related to pt age at correction w/ 80% <2 mo but only 20% >3 mo
• Kasai is essentially palliative and these patients eventually go on to transplant
• Cholelithiasis: Rare in pediatrics (0.15–0.22%) except sickle cell, other hemolytic dzs, CF, obesity, OCP use, chronic TPN, ileal resection. Has 4:1 
:
predominance, inc to 11–22:1 in adolescence (Curr Opin Pediatr 1997;9:276; Pediatr Rev 2009;30:368)
• Pigment stones (hemolytic dz, TPN, ileal resection), cholesterol stones in others
• Acalculous cholecystitis almost always post-op or assoc w/ other severe illness
• Asymptomatic generally but can develop cholecystitis, choledocholithiasis, or pancreatitis, w/ jaundice, RUQ pain, vomiting +/− fever
• Do not always see elevated bilirubin with uncomplicated cholecystitis; if present, consider cholangitis (pus under pressure), choledocholithiasis (stone in CBD)
• Radiographs demonstrate radiopaque stones in 36–47% (vs. 15% adults)
• Abd U/S check for + Murphy sign (tender RUQ), and thickened wall (4–5 mm)
• Sens 84% and spec 95% in adults; likely higher in children given habitus
• HIDA scan: If dx suspected clinically but U/S equivocal; sens 97%, spec 90%
• Rx: IVFs, Abx (ceftriaxone or quinolone + flagyl), surgery or ERCP once patient is stable and infection/inflammation has quieted on antibiotics
• Primary sclerosing cholangitis: Progressive chronic inflam of intra & extra hepatic biliary ducts (small or large ducts). (Curr Gastroenterol Rep 2010;12:195)
• Mean age of dx is 13 yr (2:1 M:F), 80% assoc w/ IBD (UC in 85% cases)
• ⅔ pts w/ sx at dx; intermittent abd pain (40%) & fatigue (25%) w/ subseq anorexia & weight loss. 20% w/ fever; other signs – HSM, jaundice, and pruritus. Other AI dz 5%
• Labs w/ elevated GGT/AP +/− AST/ALT, but 90% w/ nml bilirubin, also w/ + ANCA staining peripheral nucleus (>70%), + ANA (50%), and SMA (25%)
• See high serum and urine copper (2/2 bile flow obs), ceruloplasm high/nml
• Diagnosis: Cholangiography or ERCP can visualize large duct narrowing/dilation but not w/ small ducts, need liver bx to dx small duct predominant PSC
• MRCP excellent option for noninvasive imaging of intra/extrahepatic ducts
• No specific rx; ursodiol for sx relief, no mortality benefit w/ anti-inflammatories, if cirrhosis and liver failure then liver transplant; w/o xplt mean lifespan 12 yr
• Increased incidence of colorectal CA and cholangiocarcinoma in later adult life