Conjugated Hyperbilirubinemia Workup

  • Author: Richard A Weisiger, MD, PhD; Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 5, 2012
 

Laboratory Studies

  • Appropriate initial laboratory testing in cases of conjugated hyperbilirubinemia depends on the clinical history and physical examination findings.[2, 3, 6, 7]
  • All patients should be tested for the following:
    • Complete blood cell (CBC) count to screen for hemolysis
    • Serum aminotransferases (aspartate aminotransferase [AST], alanine aminotransferase [ALT])
    • Serologic screen for 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 from bone or other causes.
    • Fractionated bilirubin
    • 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
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Imaging Studies

  • Abdominal ultrasonography should be performed to exclude biliary obstruction and to evaluate the liver parenchyma for possible cirrhosis, tumor, steatosis, or congestion.
    • Advantages
      • Safe
      • Noninvasive
      • Portable
      • Provides good visualization of the gallbladder, bile ducts, and cystic lesions
      • Can detect parenchymal liver disease, such as cirrhosis or infiltration, and signs of portal hypertension
    • Disadvantages
      • Limited resolution
      • May not detect common bile duct stones because of bowel gas
  • Abdominal computed tomography (CT) scans provide additional information about patients with abnormal ultrasonography scans, and CT scanning may be the initial imaging modality in some cases.
    • 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
      • More expensive and less portable than ultrasonography
      • Requires radiation exposure
      • Requires IV contrast medium for best results
      • Less sensitive than ultrasonography for gallbladder stones
  • 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.
    • 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
      • 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) 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.
    • 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 bile ducts
    • Disadvantages
      • 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) 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.
    • 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
      • 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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Contributor Information and Disclosures
Author

Richard A Weisiger, MD, PhD  Director, GI and Liver Faculty Practice, Professor, Department of Internal Medicine, University of California San Francisco

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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

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

Oscar S Brann, MD, FACP  Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group

Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

References

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  2. Muraca M, Fevery J, Blanckaert N. Analytic aspects and clinical interpretation of serum bilirubins. Semin Liver Dis. May 1988;8(2):137-47. [Medline].

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  12. [Best Evidence] Jangaard KA, Fell DB, Dodds L, Allen AC. Outcomes in a population of healthy term and near-term infants with serum bilirubin levels of >or=325 micromol/L (>or=19 mg/dL) who were born in Nova Scotia, Canada, between 1994 and 2000. Pediatrics. Jul 2008;122(1):119-24. [Medline].

  13. Jansen PL, Muller M. Early events in sepsis-associated cholestasis. Gastroenterology. Feb 1999;116(2):486-8. [Medline].

  14. Jedlitschky G, Leier I, Buchholz U, et al. ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem J. Oct 1 1997;327 (pt 1):305-10. [Medline]. [Full Text].

  15. Kamisako T, Leier I, Cui Y, et al. Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Hepatology. Aug 1999;30(2):485-90. [Medline]. [Full Text].

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Table 1
I. Acute or Chronic Hepatocellular DysfunctionII. Diseases That Prevent Flow of Bile into the Intestine
A. InfectionA. Damage to Intrahepatic Bile Ducts or Portal Tracts
Viral hepatitis A-ECytomegalovirus (CMV) hepatitisEpstein-Barr virus hepatitisSepsisPrimary biliary cirrhosis Graft versus host disease Veno-occlusive disease Sclerosing cholangitis
B. Inflammation Without InfectionB. Damage to or Obstruction of Larger Bile Ducts
Toxic liver injuryDrug toxicity (eg, acetaminophen)Halothane hepatitisAlcoholic hepatitisIron overload (hemochromatosis)Copper overload (Wilson disease)Autoimmune hepatitis Choledocholithiasis Sclerosing cholangitisAIDS cholangiopathyHepatic arterial chemotherapyPostsurgical stricturesBile duct cancersDevelopmental disorders of the bile ducts (eg, Caroli)Extrinsic compression of the bile ductTumorsAcute pancreatitis
C. Metabolic DysfunctionC. Diffuse Infiltrative Diseases
Ischemia ("shock liver")Acute fatty liver of pregnancyAlpha-1 antitrypsin deficiencyPreeclampsiaReye syndromeTotal parenteral nutrition Granulomatous diseasesSarcoidosisDisseminated mycobacterial infectionsLymphomaWegener granulomatosis Amyloidosis Diffuse malignancy
D. Inborn Errors of MetabolismD. Diseases That Interfere with Biliary Secretion of Bilirubin
Dubin-Johnson syndrome Rotor syndromeBenign recurrent cholestasisDrug-induced cholestasis, as with the following:- Chlorpromazine- Erythromycin- Estrogens- Anabolic steroids- Many others
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