You have been logged out of VisualDx or your session has expired.

Please reload this page and sign into VisualDx to continue.

  VisualDx Mobile   Select Language

Get VisualDx Mobile

There are VisualDx mobile apps available for iOS and Android devices.

You will need a VisualDx account to use the mobile apps.

Already have an account? Sign In or
sign up for a free trial.

Users with VisualDx accounts earn CME credits for using VisualDx.

Already have an account? Sign In or
sign up for a free trial.

Create a Personal Account

E-mail (username)
Verify Password
First Name
Last Name

Personal Account Created

Mobile Access

You can now download VisualDx for your iOS and Android devices. Launch the VisualDx app from your device and sign in using your VisualDx personal account username and password.

CME Certification

Sign in with your personal account to earn and claim CME credits through VisualDx. Credits can be earned by building a differential or looking up a diagnosis.

Version: 7.09.1401   (build 62b8f0e)
Select Language

Select Region

Send us your feedback

This field is required

Oops! There was an issue during submission. Please try again. If the problem persists, email with your feedback.

Thank You!

We appreciate your feedback and you will be hearing from us soon.


Share This Page

Thank You!

We have sent an e-mail with a link to the current page.


E-mail This Patient Information Sheet

Thank You!

We have sent an e-mail with this patient information.


Image Contributors


  • Christine Ahn MD
    Carl Allen DDS, MSD
    Brandon Ayres MD
    Howard P. Baden MD
    Robert Baran MD
    Keira Barr MD
    Gregory J. Basura MD, Ph.D
    Donald Belsito MD
    Jeffrey D. Bernhard MD
    Jesse Berry MD
    Victor Blanco MD
    Benjamin R. Bohaty MD
    William Bonnez MD
    Sarah Brenner MD
    Robert A. Briggaman MD
    Robert Brodell MD
    Roman Bronfenbrener MD
    Walter Brooks MD
    William Buckley MD
    Philip Bulterys MD, PhD (candidate)
    Susan Burgin MD
    Sonya Burton MD
    Sean P. Bush MD, FACEP
    Jeffrey Callen MD
    Scott Camazine MD
    Michael Cardwell
    Shelley D. Cathcart MD
    Robert Chalmers MD, MRCP, FRCP
    Chia-Yu Chu MD, PhD
    Flavio Ciferri MD
    Maria Rosa Cordisco MD
    Noah Craft MD, PhD
    John T. Crissey MD
    Harold E. Cross MD, PhD
    Charles Crutchfield III MD
    Adriana Cruz MD
    Donna Culton MD, PhD
    Bart J. Currie MBBS, FRACP, DTM&H
    Chicky Dadlani MD
    Alexander Dane DO
    C. Ralph Daniel III MD
    Thomas Darling MD, PhD
    William Delaney MD
    Damian P. DiCostanzo MD
    Ncoza Dlova MD
    James Earls MD
    Libby Edwards MD
    Melissa K. Egge MD
    Charles N. Ellis MD
    Rachel Ellis MD
    David Elpern MD
    Nancy Esterly MD
    Stephen Estes MD
    E. Dale Everett MD
    Janet Fairley MD
    David Feingold MD
    Benjamin Fisher MD
    Henry Foong MBBS, FRCP
    David Foster MD, MPH
    Brian D. Foy PhD
    Michael Franzblau MD
    Vincent Fulginiti MD
    Sunir J. Garg MD, FACS
    Kevin J. Geary MD
    Lowell Goldsmith MD, MPH
    Sethuraman Gomathy MD
    Bernardo Gontijo MD, PhD
    Kenneth Greer MD
    Kenneth G. Gross MD
    Alan Gruber MD
    Nathan D. Gundacker MD
    Akshya Gupta MD
    Vidal Haddad MSC, PhD, MD
    Edward Halperin MD, MA
    Ronald Hansen MD
    John Harvey
    Rizwan Hassan MD
    Michael Hawke MD
    Jason E. Hawkes MD
    Peter W. Heald MD
    David G. Hicks MD
    Sarah Hocker DO
    Ryan J. Hoefen MD, PhD
    Li-Yang Hsu MD
    William Huang MD
    Sanjana Iyengar MD
    Alvin H. Jacobs MD
    Shahbaz A. Janjua MD
    Joshua J. Jarvis MD
    Kit Johnson
    Robert Kalb MD
    A. Paul Kelly MD
    Henry Kempe MD
    Loren Ketai MD
    Sidney Klaus MD
    Ashwin Kosambia MD
    Jessica A. Kozel MD
    Carl Krucke
    Mario E. Lacouture MD
    Joseph Lam MD
    Alfred T. Lane MD
    Edith Lederman MD
    Nahyoung Grace Lee MD
    Pedro Legua MD, PhD
    Robert Levin MD
    Bethany Lewis MD
    Sue Lewis-Jones FRCP, FRCPCH
    Taisheng Li MD
    Christine Liang MD
    Shari Lipner MD, PhD
    Jason Maguire MD
    Mark Malek MD, MPH
    Jere Mammino DO
    Ricardo Mandojana MD
    Lynne Margesson MD
    Thomas J. Marrie MD
    Maydel Martinez MD
    Ralph Massey MD
    Patrick McCleskey MD
    Karen McKoy MD
    Thomas McMeekin MD
    Josette McMichael MD
    Somchai Meesiri MD
    Joseph F. Merola MD
    Mary Gail Mercurio MD
    Anis Miladi MD
    Larry E. Millikan MD
    Dan Milner Jr. MD
    Zaw Min MD
    Stephanie Montero
    Alastair Moore MD
    Keith Morley MD
    Dean Morrell MD
    Samuel Moschella MD
    Taimor Nawaz MD
    Vic Newcomer MD
    John Nguyen MD
    Matilda Nicholas MD
    Thomas P. Nigra MD
    Steven Oberlender MD, PhD
    Maria Teresa Ochoa MD
    Art Papier MD
    Lawrence Parish MD
    Tanner Parrent MD
    Mukesh Patel MD
    Lauren Patty-Daskivich MD
    David Peng MD, MPH
    Robert Penne MD
    Nitipong Permpalung MD
    Doug Powell MD
    Harold S. Rabinovitz MD
    Christopher J. Rapuano MD
    Sireesha Reddy MD
    Angela Restrepo MD, PhD
    Bertrand Richert MD, PhD
    J. Martin Rodriguez, MD, FACP
    Theodore Rosen MD
    Misha Rosenbach MD
    Scott Schiffman MD
    Robert H. Schosser MD
    Glynis A. Scott MD
    Carlos Seas MD, MSc
    Deniz Seçkin MD
    Daniel Sexton MD
    Paul K. Shitabata MD
    Tor Shwayder MD, FAAP, FAAD
    Elaine Siegfried MD
    Gene Sienkiewicz MD
    Christye Sisson
    Mary J. Spencer MD, FAAP
    Sarah Stein MD
    William Van Stoecker MD
    Frances J. Storrs MD
    Erik J. Stratman MD
    Lindsay C. Strowd MD
    Erika Summers MD
    Belinda Tan MD, PhD
    Robert Tomsick MD
    Jenny Valverde MD
    Vishalakshi Viswanath MD
    Susan Voci MD
    Lisa Wallin ANP, FCCWS
    Douglas Walsh MD
    Ryan R. Walsh MD
    George Watt MD
    Clayton E. Wheeler MD
    Sally-Ann Whelan MS, NP, CWOCN
    Jan Willems MD, PhD
    James Henry Willig MD, MPH
    Karen Wiss MD
    Vivian Wong MD, PhD
    Sook-Bin Woo MS, DMD, MMSc
    Jamie Woodcock MD
    Stephen J. Xenias MD
    Lisa Zaba MD
    Vijay Zawar MD
    Bonnnie Zhang MD
    Carolyn Ziemer MD


  • Am. Journal of Trop. Med & Hygiene
  • Armed Forces Pest Management Board
  • Blackwell Publishing
  • Bugwood Network
  • Centers For Disease Control and Prevention
  • Centro Internacional de Entrenamiento e Investigaciones Mèdicas (CIDEIM)
  • Dermatology Online Journal
  • East Carolina University (ECU), Division of Dermatology
  • International Atomic Energy Agency
  • Massachusetts Medical Society
  • Oxford University Press
  • Radiological Society of North America
  • Washington Hospital Center
  • Wikipedia
  • World Health Organization
ContentsSynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyAssociated MedicationsReferences
Other Resources UpToDate PubMed


Print Images (1)
Contributors: Michael W. Winter MD, Nishant H. Patel MD, Desiree Rivera-Nieves MD, Khaled Bittar MD
Other Resources UpToDate PubMed


Hyperbilirubinemia is defined as an excess of bilirubin in the blood. A patient can present with elevations in conjugated or unconjugated bilirubin.

Conjugated (direct):
An abnormal increase in conjugated bilirubin is typically due to biliary obstruction, intrahepatic cholestasis, or hepatocellular injury leading to jaundice. Patients present with a variety of symptoms based on the underlying etiology, such as chronic liver failure (eg, cirrhosis) or from an acute obstruction or infection (eg, acute alcoholic hepatitis, choledocholithiasis).

Regardless of the etiology, a direct hyperbilirubinemia coincides with scleral icterus and jaundice. Somnolence, asterixis, and hepatic encephalopathy can be observed in patients with decompensated liver failure, which often coincides with a direct hyperbilirubinemia.

Unconjugated (indirect):
An abnormal increase in indirect bilirubin due to overproduction of bilirubin, reduced bilirubin uptake, or impaired bilirubin conjugation. Patients may present with scleral icterus or jaundice, depending on the serum bilirubin level. An indirect hyperbilirubinemia can be caused by primary liver disease processes as well as extrahepatic processes. Intrahepatic cholestasis, biliary obstruction, and acute hepatocellular injury can all lead to an indirect hyperbilirubinemia. Other etiologies include hereditary liver diseases (eg, Gilbert syndrome, Dubin-Johnson syndrome, Crigler-Najjar syndrome), hemolysis, or impaired bilirubin uptake as seen in cirrhosis and congestive hepatopathy.

Symptoms associated with an indirect hyperbilirubinemia vary depending on the etiology. Mixed direct / indirect hyperbilirubinemia from choledocholithiasis will often present with right upper quadrant abdominal pain, while Gilbert syndrome is often painless and asymptomatic. Jaundice can be a hallmark seen in many, although not all, causes of indirect hyperbilirubinemia.

Common causes include, but are not limited to, the following.

  • Biliary obstruction – Leads to both conjugated and unconjugated hyperbilirubinemia as well as elevation of alkaline phosphatase. In adults, may be secondary to cholelithiasis, intrinsic or extrinsic tumors, primary sclerosing cholangitis, parasitic infections, lymphoma, acute and chronic pancreatitis, and strictures after procedures. In children, biliary obstruction is often secondary to choledochal cysts and cholelithiasis.
  • Intrahepatic cholestasis – Mimics biliary obstruction, but the bile ducts are patent. Patients also have elevated conjugated and unconjugated bilirubin as well as elevated serum alkaline phosphatase values. Conditions and factors leading to intrahepatic cholestasis are extensive and include viral hepatitis (A, B, C), alcoholic hepatitis, nonalcoholic steatohepatitis, primary biliary cirrhosis, sepsis, drugs and toxins (eg, ethinyl estradiol, chlorpromazine, and Jamaican bush tea), total parenteral nutrition, cholestasis of pregnancy, and postoperatively.
  • Hepatocellular injury – Leads to cellular injury and the release of intracellular proteins; thus patients present with unconjugated and conjugated hyperbilirubinemia, elevated alkaline phosphatase, elevated aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT). As this disease progresses, synthetic function of the liver is also impaired. Conditions causing direct hepatocellular injury are extensive and include various neoplastic processes, toxins and medications, infectious causes, inherited metabolic conditions, and sepsis.
  • Overproduction of bilirubin – Secondary to excessive heme breakdown in the setting of extravascular or intravascular hemolysis, extravasation of blood into tissues, or dyserythropoiesis.
  • Reduced bilirubin uptake – Due to impaired delivery of bilirubin to the liver from congestive heart failure or portosystemic shunts in patients with cirrhosis. Other causes include Gilbert syndrome, in which there is impaired hepatocyte uptake of bilirubin at the cell surface.
  • Impaired bilirubin conjugation – Result of decreased or absent UDP-glucuronosyltransferase activity found in conditions such as Crigler-Najjar syndromes type I and II and Gilbert syndrome.
For discussion of hyperbilirubinemia in neonates, see neonatal jaundice.


E80.6 – Other disorders of bilirubin metabolism

14783006 – Hyperbilirubinemia

Look For

Subscription Required

Diagnostic Pearls

Subscription Required

Differential Diagnosis & Pitfalls

Best Tests

Subscription Required

Management Pearls

Subscription Required


Subscription Required

Associated Medications

Subscription Required


Subscription Required

Last Reviewed: 04/20/2017
Last Updated: 06/06/2017
Copyright © 2018 VisualDx®. All rights reserved.
Print 1 Images
Hyperbilirubinemia : Jaundice, Hyperbilirubinemia, Scleral icterus
Clinical image of Hyperbilirubinemia
Copyright © 2018 VisualDx®. All rights reserved.