Visual Diagnosis

Sources:1. Slack Health Care Books, http://www.slackbooks.com2. Fischer & Vandemark. (1945). J Bone Joint Surg Am.;27:695-698.

Pediatrics Morning Report:A 6 week old with direct

hyperbilirubinemiaRobyn Rogers, MD

Sahar Rooholamini, MDDecember 9, 2009

Case Presentation

• You’re the Green Team (GI) resident and you’re called to admit a patient.

• You’re told: “This is a 6 week old male from an outside hospital who has direct hyperbilirubinemia and needs a work-up.”

• What is your initial differential diagnosis?• What do you want to know?

Learning Objectives

• Generate and understand the differential diagnosis for conjugated hyperbilirubinemia in an infant

• Understand the essential elements of the history and physical in conjugated hyperbilirubinemia

• Learn the general diagnostic and therapeutic approaches to conjugated hyperbilirubinemia

Physiologic vs. Non-physiologic Jaundice

Physiologic • Caused by structural and

functional immaturity of neonatal hepatobiliary system

• Almost always unconjugated hyperbilirubinemia

• Expected to resolve by 2 weeks of life

• Ex: breastfeeding and breast milk jaundice

Non-physiologic• Variety of causes• Present at birth or

persistent beyond 2 weeks of life

• Conjugated hyperbilirubinemia is a potential RED FLAG at any age and requires follow-up

• Associated with other signs or symptoms

Definitions and Epidemiology• Conjugated hyperbilirubinemia = Serum direct

bili > 1 mg/dL (if total bili <5 mg/dL), or > 20% of total bilirubin

• AKA “neonatal cholestasis” • Affects 1 in 2500 births• Most common causes:

– Neonatal Hepatitis 70-80% of cases, – Biliary Atresia usually term infants

– Alpha-1 Antitrypsin Deficiency• 10-15% of cases

Bilirubin conjugation and excretion

Bloomer J (2006). Gastroenterology and Hepatology: Liver. Edited by Mark Feldman (series editor). Published by Current Medicine Group. Obtained through Lane Medical Library.

Differential Diagnosis of Conjugated Hyperbilirubinemia

• Anatomic approach–Intrahepatic vs. extrahepatic causes

• Physiologic approach–Impaired bile formation (hepatocyte

problem) vs. obstruction to bile flow (either within or outside liver)

Impaired bile formation– Acute liver damage (hypoxia, ischemia, acidosis)– Infection/sepsis

• Bacterial: E. coli, GBS, Listeria, TB, syphilis• Viral: HIV, hepatitides, Rubella, CMV, HSV• Parasitic: Toxoplasma

– Genetic/Metabolic diseases (abbreviated list)• Alpha-1 antitrypsin deficiency• IEM: Galactosemia, tyrosinemia; lipid and bile salt metabolic defects• Cystic Fibrosis

– Endocrine disorders (hypothyroidism, hypopituitarism)

– Toxin or Drug-induced damage– TPN-related liver disease– Idiopathic Neonatal Hepatitis (dx of exclusion)

Obstruction to Bile Flow

• Congenital anomalies– Biliary atresia– Choledochal cyst– Alagille syndrome (paucity of intrahepatic bile ducts)– Bile duct stenosis

• Other anatomic anomalies– Bile duct perforation or compression– Cholelithiasis/sludging

Alagille Syndrome(Arteriohepatic dysplasia)

History & Physical

• Family history • Prenatal, neonatal hx• Dietary hx, weight gain• Stooling pattern, color• Urine color• History of bruising or

bleeding• Irritability, seizures

• VS and growth parameters• Neurologic exam (e.g.,

tone, symmetry, reflexes)• Eye exam• Dysmorphic features• Jaundice• Heart murmur• Hepatosplenomegaly• Bruising/petechiae• Urine and stool

Initial Work-Up• A thorough H&P should guide subsequent testing.• Total/direct bilirubin• Transaminases, Alkaline phosphatase, GGT• Synthetic liver function tests (coags, albumin)• UA, Ucx; blood and CSF cultures if indicated• CBC with reticulocyte count• Hepatitis panel, TORCH titers• TSH, Free T4• Serum Alpha 1-AT level +/- phenotype• Sweat chloride• Serum and urine organic/amino acids

Further Work-Up & Imaging• Ultrasound

– Keep patient NPO– Try to feed during exam to show gallbladder

contraction• Hepatobiliary scintigraphy (HIDA scan)

– Perform after 3-5 days of phenobarbital to promote bile flow, at 5 mg/kg/day

• Duodenal aspirate• MRCP/ERCP (not routinely recommended)

• Liver biopsy

Additional Case History

• Patient’s test results and hospital course• Post-discharge follow-up• This patient was initially admitted for a liver

biopsy for concern for biliary atresia…would you have biopsied him?

Management of Conjugated Hyperbilirubinemia

• Medical Management– Phenobarbital– Ursodiol– Rifampin– Cholestyramine

• Diet – Medium-chain triglycerides– Fat-soluble vitamin supplementation

• Surgical interventions– Kasai portoenterostomy– Liver transplantation

Summary and Take-Home Points

• Maintain a healthy skepticism about the working diagnosis on all of your patients.

• Approach conjugated hyperbilirubinemia with a broad differential diagnosis but focused work-up.

• A patient with jaundice persisting beyond 2-3 weeks of age needs further work-up, beginning with total and direct bilirubin measurements.

Thank you, Drs. Kerner and Fuentebella!

ReferencesFischer & Vandemark (1945). Sagittal Cleft (Butterfly) Vertebra.

Journal of Bone and Joint Surgery; 27:695-698.NASPGHAN (2004). Guideline for the Evaluation of Cholestatic

Jaundice in Infants. Journal of Pediatric Gastroenterology and Nutrition; 39:115–128.

Slack Health Care Books. Posterior Embryotoxon (image). http://www.slackbooks.com.

Venigalla & Gourley (2004). Neonatal cholestasis. Seminars in Perinatology; 28:348-355.

More clinical guidelines can be found here:http://www.naspghan.org/