A 1-month-old girl is evaluated for persistent jaundice. The infant was born at 39 weeks’ gestation to a healthy 28-year-old woman with no family history of medical problems. The delivery was cesarean after premature rupture of membranes with a birth weight of 3200 g and Apgar scores of 9 and 9 at 1 and 5 minutes, respectively. She had passage of meconium on the first day of life, and she was mildly jaundiced at the time of discharge from the hospital on day 2 of life. During the past several days, the patient has been having acholic stools and darkly stained urine. On examination, she is deeply jaundiced; the cardiopulmonary examination is unremarkable. The liver is palpable and firm. No other abdominal masses are identified. The laboratory evaluations reveal a normal CBC, total bilirubin and direct bilirubin levels of 28 mg/dL and 24 mg/dL, respectively, and serum levels of aspartate aminotransferase/alanine aminotransferase (AST/ALT) and alkaline phosphatase of 300/250 U/L and 950 IU/L, respectively.
What are the differential diagnoses?
What is your next step(s)?
Should this be urgently evaluated or electively and definitively diagnosed?
ANSWERS TO CASE 53: Neonatal Jaundice (Persistent)
Summary: A newborn female infant with no identifiable prenatal problems has persistent jaundice and abnormalities in her liver function tests.
• Differential diagnoses: Neonatal hepatitis; TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex) infections; metabolic diseases (α 1-antitrypsin deficiency, cystic fibrosis, and others); biliary atresia; and choledochal cyst.
• Next step(s): After the initial laboratory studies are performed, the evaluation should simultaneously include TORCH/metabolic studies (as listed in Table 53–1), abdominal ultrasound, and hepatoiminodiacetic acid (HIDA) scan (99mTc-labeled iminodiacetic acid).
• Timing: Hyperbilirubinemia in the neonate that persists beyond 2 weeks of age is rarely physiologic, particularly when it is predominantly conjugated bilirubin. Because surgical correction of biliary atresia is optimally performed before 8 weeks of age (12 weeks maximum), urgent evaluation and potentially preoperative preparation are warranted over 5 to 6 days.
Jaundice is a common finding during the neonatal period, where it is observed in 60% of term infants and 80% of preterm infants. Newborn jaundice occurs most commonly as the result of “physiologic jaundice,” which develops primarily from the combined effects of high circulating levels of hemoglobin and immature mechanism for bilirubin conjugation in newborns. When it occurs, physiologic jaundice is usually evident by days 2 to 3 and resolves by days 5 to 7 of life. By definition, jaundice that persists beyond 2 weeks is considered pathologic, and the mechanisms responsible for pathologic jaundice include biliary obstruction, increased hemoglobin load, and liver dysfunction.
This patient history is fairly typical of those referred for surgical consultation in the evaluation of neonatal jaundice. Usually, the infant has no specific symptoms. Physical findings include acholic stools and, occasionally, a palpable, firm liver. The timing and pattern of jaundice onset can give some clues as to the diagnosis (eg, hemolytic diseases often present early and are more progressive/severe). The degree of conjugated hyperbilirubinemia offers a key distinguishing direction as to how to approach the workup. Table 53–1 lists the causes of neonatal hyperbilirubinemia and some of their distinguishing characteristics. Metabolic and infectious causes should be investigated. A prompt evaluation includes an abdominal ultrasound, HIDA scan, and percutaneous liver biopsy. If the imaging studies do not rule out biliary atresia, operative exploration with intraoperative cholangiogram is indicated.
Table 53–1 • CLINICAL MANAGEMENT OF PERSISTENT JAUNDICE IN CHILDREN
Surgical reconstruction for biliary atresia is a Kasai portoenterostomy and a hepaticojejunostomy for choledochal cyst.
1. Be familiar with the differential diagnosis for neonatal jaundice.
2. Be familiar with the diagnostic approach and initial supportive management of patients with neonatal jaundice.
3. Be familiar with the treatment for biliary atresia and choledochal cyst.
APPROACH TO: Neonatal Obstructive Jaundice
CHOLEDOCHAL CYST: Congenital anatomic malformation of a bile duct, including cystic dilatation of the extrahepatic bile duct or the large intrahepatic bile duct.
BILIARY ATRESIA: Congenital or developed stricture or absence of the major bile ducts that drain bile from the liver.
The precise etiology of biliary atresia is unknown. Various theories include viral infections and autoimmune processes. Histologically, the biliary tracts contain inflammatory cells surrounding obliterated ductules. The liver shows signs of cholestasis and, in later stages, fibrosis. Grossly, the most common finding is fibrosis of the entire extrahepatic biliary tree, followed by proximal duct fibrosis with distal duct patency.
Similar to biliary atresia, the exact etiology of choledochal cysts is unknown. A widely held theory is that the common bile duct and pancreatic duct share a common channel leading to retrograde reflux of pancreatic juice into the choledochus with subsequent cystic dilation. There are five types of choledochal cysts, but the fusiform, or type I, comprises 90% of all lesions.
Preoperative Management and Surgical Treatment of Biliary Atresia and Choledochal Cysts
Prior to surgical intervention, these patients must be evaluated for coagulation abnormalities, anemia, and hypoproteinemia. Correction of coagulopathy usually requires both vitamin K and fresh-frozen plasma. Anemia may be of moderate severity requiring the availability of cross-matched blood. Parents should be made aware of the prognosis of biliary atresia preoperatively. Conversely, the surgical management of choledochal cyst carries an excellent prognosis.
The surgical management of biliary atresia consists of operative exploration of the porta hepatis with intraoperative cholangiogram. If dye does not enter the duodenum, the limited right upper quadrant incision is extended and the extrahepatic biliary tree is dissected up to the level of the portal plate. The portal plate is transected flush with but not into the liver. This exposes the biliary ductules that drain bile. A Roux-en-Y limb of jejunum is attached to the porta in a retrocolic manner. Jejunal valves, stomas, and other approaches were used previously, but these have fallen out of favor because of complexity and lack of improved outcomes with the more complex procedures. Similarly, choledochal cysts are excised, but instead of fashioning the limb of jejunum to the porta, it is attached to the bifurcating hepatic ducts at their confluence.
The three main complications of the surgical management of biliary atresia are cholangitis, cessation of bile flow, and portal hypertension. Cholangitis is the most frequent complication occurring after portoenterostomyand is manifest by fever, leukocytosis, and elevations in the bilirubin. Treatment includes intravenous antibiotics against gram-negative organisms and steroids. Cessation of bile flow can be related to progression of the disease, cholangitis, or Roux-limb obstruction (rare). Treatment is based on steroids and other choleretic agents. Portal hypertension is a late complication of portoenterostomy, and it occurs even in those that are successful in terms of bile flow. The complications of variceal bleeding can usually be managed, and the symptoms may progress when cirrhosis worsens.
Biliary atresia—before the introduction of the Kasai procedure, the survival rates were less than 5% at 12 months. With hepatoenterostomy 30% to 50% of patients have good long-term results. Ultimately, only 20% of patients undergoing portoenterostomy survive into adulthood without liver transplant. Factors that affect early bile flow after operation are age, immediate bile flow (technically sound operation), and degree of parenchymal disease at diagnosis. The presence and size of ductules in the hilum are of controversial prognostic significance. The prognosis for choledochal cyst surgery—excision of the choledochal cyst and Roux-en-Y hepaticojejunostomy—is excellent.
53.1 A 2-year-old male child is noted by his pediatrician to have progressive jaundice. There is a suspicion of biliary atresia. Which of the following imaging studies is most definitive in its ability to diagnose biliary atresia?
A. Abdominal ultrasound
B. HIDA scan
C. Intraoperative cholangiogram
D. Magnetic resonance cholangiopancreatography
E. Percutaneous CT-guided cholangiography
53.2 A 140-day-old infant with a mixed hyperbilirubinemia undergoes a percutaneous liver biopsy, HIDA scan, and abdominal sonography that are consistent with biliary atresia. Metabolic and infectious evaluations are negative. Which of the following is the best management for this patient?
A. Kasai procedure (portoenterostomy)
B. Listing for liver transplant
C. Open liver biopsy and cholangiogram
D. Tube cholecystostomy
E. CT-guided percutaneous biliary drainage
53.3 An 18-month-old child who underwent a successful Kasai procedure as an infant returns with fever, leukocytosis, and a new onset hyperbilirubinemia. Which of the following is the best initial management?
A. Revision of portoenterostomy
B. Corticosteroids and antibiotics
C. Corticosteroids alone
D. Antibiotics alone
E. Percutaneous drainage of the biliary system
53.1 C. Although abdominal ultrasound and HIDA scan are used as suggestive evidence of biliary atresia, they do not definitively rule it in or out. For example, approximately 10% to 15% of biliary atresia cases have visible, normally distended gallbladders. It is not uncommon for patients with biliary hypoplasia (Alagille syndrome) to have no excretion of tracer into the duodenum on HIDA scan. The only definitive way to diagnose biliary atresia is by operative exploration and intraoperative cholangiogram. Magnetic resonance cholangiopancreatography is not routinely used to evaluate the neonatal biliary tract.
53.2 B. After 120 days of life, portoenterostomy is rarely indicated. Although there have been occasional successful procedures, these are the overwhelming exception. A cholangiogram and liver biopsy may be useful, but they will not alter the therapy—meaning that a finding of biliary atresia would not prompt a portoenterostomy. Therefore, a standard approach to these infants is referral for liver transplant after 120 days of life.
53.1 B. The child described has a classic clinical presentation of post-Kasai cholangitis. This is a frequent complication of portoenterostomy. Revision of the portoenterostomy is rarely indicated. Occasionally this is done for the functioning Kasai that acutely fails—usually in the immediate postoperative period. The findings of fever, leukocytosis, and rising bilirubin suggest cholangitis. Standard management includes supportive measures, blood cultures, antibiotics against gram-negative organisms, and steroids (function as choleretic and anti-inflammatory).
Jaundice in the neonate beyond 2 weeks of age is rarely physiologic, especially when involving mainly conjugated bilirubin.
The most common complication after portoenterostomy is cholangitis.
Neonates with biliary atresia or choledochal cysts should be assessed for coagulopathy prior to surgery.
Warner BW. Pediatric surgery. In: Townsend CM Jr, Beauchamp RD, Evers BM, eds. Sabiston Textbook of Surgery. 18th ed. Philadelphia, PA: Saunders Elsevier; 2008:2047-2089.
Yamataka A, Kato Y, Miyano T. Biliary tract disorders and portal hypertension. In: Holcomb III GW, Murphy JP, eds. Ashcraft’s Pediatric Surgery. 5th ed. Philadelphia, PA: Saunders Elsevier; 2010:557-577.