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Conjugated Hyperbilirubinemia Workup

  • Author: Richard A Weisiger, MD, PhD; Chief Editor: BS Anand, MD  more...
Updated: Jan 05, 2016

Approach Considerations

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. [11]
  • 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,[12] such as biliary atresia, the most common cause of neonatal cholestasis.[9] 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.[12]


Imaging Studies


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
Contributor Information and Disclosures

Richard A Weisiger, MD, PhD Emeritus Professor, Department of Internal Medicine, University of California, San Francisco, School of Medicine

Richard A Weisiger, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Society for Clinical Investigation

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.


Vivek V Gumaste, MD Associate Professor of Medicine, Mount Sinai School of Medicine of New York University; Adjunct Clinical Assistant, Mount Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center at Elmhurst; Program Director of GI Fellowship (Independent Program); Regional Director of Gastroenterology, Queens Health Network

Vivek V Gumaste, MD is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Gross liver specimen from a patient with Dubin-Johnson syndrome showing multiple areas of dark pigmentation. Image courtesy of Cirilo Sotelo-Avila, MD.
Microscopic histology of the liver in Dubin-Johnson syndrome showing multiple areas of granulated pigment. Fontana Mason stain. Image courtesy of Cirilo Sotelo-Avila, MD.
Liver biopsy specimen showing ground-glass appearance of hepatocytes in a patient with hepatitis B.
Plain abdominal radiograph in a patient with a clinical diagnosis of acute cholecystitis. The diagnosis was confirmed by means of abdominal ultrasonography. The radiograph shows faint opacities in the region of the gallbladder fossa and dilated loops of small bowel in the epigastrium and midabdomen secondary to localized ileus.
A 26-year-old man known to be human immunodeficiency virus (HIV) positive presented with pain in the right upper quadrant and mild jaundice. Axial sonogram through the gallbladder (GB) and pancreas (P) shows sludge within the gallbladder and the lower common bile duct (arrow). A diagnosis of acalculous cholecystitis was confirmed. A = aorta; IVC = inferior vena cava; S = splenic vein.
Table. Differential Diagnosis of Conjugated Hyperbilirubinemia
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

Veno-occlusive disease

Sclerosing cholangitis

B. Inflammation Without Infection B. Damage to or Obstruction of Larger Bile Ducts
Toxic liver injury

Drug toxicity (eg, acetaminophen)

Halothane hepatitis

Alcoholic hepatitis

Iron overload (hemochromatosis)

Copper overload (Wilson disease)

Autoimmune hepatitis


Sclerosing cholangitis

AIDS cholangiopathy

Hepatic arterial chemotherapy

Postsurgical strictures

Bile duct cancers

Developmental disorders of the bile ducts (eg, Caroli)

Extrinsic compression of the bile duct


Acute pancreatitis

C. Metabolic Dysfunction C. Diffuse Infiltrative Diseases
Ischemia ("shock liver")

Acute fatty liver of pregnancy

Alpha-1 antitrypsin deficiency


Reye syndrome

Total parenteral nutrition

Granulomatous diseases


Disseminated mycobacterial infections


Wegener granulomatosis


Diffuse malignancy

D. Inborn Errors of Metabolism D. Diseases That Interfere with Biliary Secretion of Bilirubin
Dubin-Johnson syndrome

Rotor syndrome

Benign recurrent cholestasis

Drug-induced cholestasis, as with the following:

- Chlorpromazine

- Erythromycin

- Estrogens

- Anabolic steroids

- Many others

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