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Conjugated Hyperbilirubinemia Differential Diagnoses

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

Diagnostic Considerations

Consider the following conditions in the differential diagnosis of patients with suspected conjugated hyperbilirubinemia:

  • Cytomegalovirus (CMV) hepatitis
  • Drug toxicity, especially the following: acetaminophen, allopurinol, anabolic steroids, chlorpromazine, estrogens, halothane, isoniazid, methyldopa, phenytoin, protease inhibitors, quinidine, rifampicin, statins, and sulfa drugs
  • Exposure to environmental hepatotoxins (eg, beryllium, "nutraceuticals" [eg, herbal tea], organic solvents)
  • Acute fatty liver of pregnancy
  • Inherited disorders of bilirubin conjugation (eg, Rotor syndrome)
  • Liver congestion
  • Liver ischemia (shock liver)
  • Rejection of transplanted liver
  • Reye syndrome
  • Total parenteral nutrition (TPN) toxicity[6]
  • Veno-occlusive disease associated with chemotherapy

Differential Diagnoses

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. InfectionA. 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 InfectionB. 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 DysfunctionC. 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 MetabolismD. 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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