Conjugated Hyperbilirubinemia Workup
- Author: Richard A Weisiger, MD, PhD; Chief Editor: BS Anand, MD more...
Appropriate initial laboratory testing in cases of conjugated hyperbilirubinemia depends on the clinical history and physical examination findings.[2, 3, 7, 8] Misdiagnosis of cholestatic jaundice potentially delays the identification of severe liver disease; investigate all cases of prolonged neonatal jaundice (>2 weeks after birth).[9, 10]
Obtain the following laboratory studies for all patients with suspected conjugated hyperbilirubinemia:
Complete blood cell (CBC) count to screen for hemolysis
Serum aminotransferases (aspartate aminotransferase [AST], alanine aminotransferase [ALT])
Serologic screen for viral hepatitis, including hepatitis C virus (HCV) antibody and hepatitis B surface antigen (HBsAg) or antihepatitis B core antibody (anti-HBcAb)
Alkaline phosphatase (ALP): If elevated or if an obstruction is suspected, images of the bile ducts should be obtained. Gamma-glutamyl transpeptidase (GGTP) results may help differentiate a hepatic source of the elevated ALP from bone or other causes.
Fractionated bilirubin: Devgun et al indicate a direct bilirubin concentration of 10 μmol/L or higher should be used to consider the presence of conjugated hyperbilirubinemia, provided that total bilirubin concentration is also above the reference interval. 
Blood alcohol or acetaminophen levels upon admission (may be useful in certain cases).
Antimitochondrial antibody when considering primary biliary cirrhosis
Antinuclear antibodies (ANAs), smooth-muscle antibodies, and other serologic studies when considering autoimmune hepatitis
Iron and genetic studies when considering hemochromatosis
Copper studies when considering Wilson disease
Alpha-1 antitrypsin fractionation and other studies when considering hereditary liver diseases
Biopsy is indicated in cases with causes in which irreversible liver damage may occur, such as biliary atresia, the most common cause of neonatal cholestasis. Talachian et al reported a significant delay between pediatric patients presenting with infantile cholestasis and subsequently undergoing liver biopsy in the setting of potential irreversible liver damage.
Abdominal ultrasonography should be performed to exclude biliary obstruction and to evaluate the liver parenchyma for possible cirrhosis, tumor, steatosis, or congestion.
Ultrasonography is safe, noninvasive, and portable. This image modality provides good visualization of the gallbladder, bile ducts, and cystic lesions and can detect parenchymal liver disease, such as cirrhosis or infiltration, and signs of portal hypertension.
However, ultrasonography also has a limited resolution, and it may not detect common bile duct stones because of the presence of bowel gas.
Computed tomography (CT) scans
Abdominal computed tomography (CT) scans provide additional information about patients with abnormal ultrasonography scans. CT scanning may be the initial imaging modality in some cases.
CT scanning offers the following advantages:
Better resolution than ultrasonography
Provides good evaluation of the entire bile duct
Can define the anatomy better than ultrasonography, especially if contrast agents are used
Better for evaluating suspected malignancies, especially with evaluation of the arterial phase
Permits guided needle biopsies
Disadvantages of CT scanning include the following:
More expensive and less portable than ultrasonography
Results in radiation exposure
Requires IV contrast medium for best results
Less sensitive than ultrasonography for gallbladder stones
Magnetic resonance imaging (MRI)
Abdominal magnetic resonance imaging (MRI) produces images comparable in quality to CT scans without patient exposure to ionizing radiation. Following administration of suitable contrast agents, detailed imaging of the biliary tract is possible. Magnetic resonance cholangiopancreatography (MRCP) may be particularly useful when evaluating cholestasis of pregnancy or patients who are too debilitated to tolerate traditional cholangiography.
MRI offers the following advantages:
Requires no exposure to ionizing radiation (ie, safe in pregnancy)
Permits multiple contrast agents and multiple scanning techniques, which enhance potential information content
Permits guided needle biopsies (open MRI systems only)
With special contrast agents, can evaluate bile and pancreatic ducts
Disadvantages of MRI include the following:
Not universally available
Cannot be used in most patients with metallic implants
Requires IV contrast medium for best results
Clinical experience is still somewhat limited
Endoscopic retrograde cholangiopancreatography (ERCP)
Endoscopic retrograde cholangiopancreatography (ERCP) is useful in cases where biliary obstruction is strongly suspected. It is the investigation of choice to detect and treat common bile duct stones and is also useful for making a diagnosis of pancreatic cancer. Other conditions in which ERCP may be useful include primary sclerosing cholangitis and the presence of choledochal cysts.
ERCP offers the following advantages:
Allows treatment of obstruction using sphincterotomy, stone extraction, stent placement, or balloon-dilation of strictures
Permits biopsies under direct visualization
Provides excellent visualization of the bile ducts
Disadvantages of ERCP include the following:
Requires conscious sedation and radiation exposure
May cause pancreatitis and other complications
Not always successful, especially after gastroduodenal surgery
Percutaneous transhepatic cholangiography (PTC or PTHC)
Percutaneous transhepatic cholangiography (PTC or PTHC) offers most of the diagnostic and therapeutic possibilities of ERCP and may be more readily available in some settings. It can be useful in cases in which ERCP has been unsuccessful or is not available.
PTC or PTHC offers the following advantages:
Successful in most cases of biliary obstruction
Allows treatment of obstruction by stone extraction, balloon-dilation of strictures, or stent placement
Permits biopsies or brush cytology
Provides excellent visualization of the bile ducts
Disadvantages of PTC or PTHC include the following advantages:
Typically more invasive than ERCP
May not be successful unless the bile ducts are dilated
Requires radiation exposure and use of contrast medium
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|I. Acute or Chronic Hepatocellular Dysfunction||II. Diseases That Prevent Flow of Bile into the Intestine|
|A. Infection||A. Damage to Intrahepatic Bile Ducts or Portal Tracts|
|Viral hepatitis A-E
Cytomegalovirus (CMV) hepatitis
Epstein-Barr virus hepatitis
|Primary biliary cirrhosis
Graft versus host disease
|B. Inflammation Without Infection||B. Damage to or Obstruction of Larger Bile Ducts|
|Toxic liver injury
Drug toxicity (eg, acetaminophen)
Iron overload (hemochromatosis)
Copper overload (Wilson disease)
Hepatic arterial chemotherapy
Bile duct cancers
Developmental disorders of the bile ducts (eg, Caroli)
Extrinsic compression of the bile duct
|C. Metabolic Dysfunction||C. Diffuse Infiltrative Diseases|
|Ischemia ("shock liver")
Acute fatty liver of pregnancy
Alpha-1 antitrypsin deficiency
Total parenteral nutrition
Disseminated mycobacterial infections
|D. Inborn Errors of Metabolism||D. Diseases That Interfere with Biliary Secretion of Bilirubin|
Benign recurrent cholestasis
|Drug-induced cholestasis, as with the following:
- Anabolic steroids
- Many others