Jaundice and cholestasis

Last updated: July 25, 2023

Summarytoggle arrow icon

Jaundice, or icterus, is a yellowish discoloration of tissue caused by the accumulation of bilirubin deposits. Bilirubin deposition most commonly occurs in the skin and the sclerae and becomes apparent when bilirubin levels reach > 2 mg/dL. Jaundice can be divided into prehepatic, intrahepatic, and posthepatic etiologies. Prehepatic jaundice is caused by the accumulation of unconjugated bilirubin, which is due to either increased hemoglobin breakdown or impaired hepatic uptake. Intrahepatic jaundice may be caused by intrahepatic cholestasis, impaired bilirubin conjugation, or impaired excretion of bilirubin by the liver. Posthepatic jaundice is caused by the accumulation of conjugated hyperbilirubinemia usually due to extrahepatic cholestasis from biliary obstruction. In jaundice that arises from cholestasis, patients may present with pruritus, dark urine, and pale stools. Diagnosis is based on laboratory studies (e.g., liver function tests) and, in most cases, a transabdominal right upper quadrant (RUQ) ultrasound. The treatment of jaundice is determined by the underlying disease process and can often be complemented with symptomatic treatment (e.g., for pruritus) or ursodeoxycholic acid.

See also “Neonatal jaundice.”

Definitiontoggle arrow icon

Etiologytoggle arrow icon

Adult jaundice can be divided into prehepatic, intrahepatic, and posthepatic etiologies. See “Overview of mechanisms of neonatal jaundice” for etiologies of jaundice and kernicterus in neonates, e.g., hemolytic disease of the newborn, congenital hypothyroidism, biliary atresia.

The most common causes of adult hyperbilirubinemia can be remembered with the mnemonic “HOT Liver”: Hemolysis, Obstruction, Tumor, and Liver disease.

Prehepatic jaundice

Prehepatic jaundice is characterized by unconjugated hyperbilirubinemia most commonly caused by increased hemoglobin breakdown.

Causes of prehepatic jaundice [1][2]
Mechanism Etiologies
Ineffective erythropoiesis
Increased bilirubin production
Medication side effect (e.g., impaired hepatic uptake of bilirubin)

Consider choledocholithiasis as an alternative explanation for jaundice in patients with chronic hemolysis, since they have a high incidence of pigmented gallstones (see “Posthepatic jaundice”). [1]

Intrahepatic jaundice

Intrahepatic jaundice can vary from unconjugated hyperbilirubinemia to conjugated hyperbilirubinemia to a combination based on the etiology. See also “Acute liver failure.”

Hepatitis and cirrhosis can cause both conjugated and unconjugated hyperbilirubinemia.

Posthepatic jaundice

Posthepatic jaundice is characterized by conjugated hyperbilirubinemia caused by extrahepatic cholestasis from biliary obstruction.

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Cholestasis may be seen in the absence of jaundice, particularly during the early stages of cholestasis. Depending on the clinical scenario, jaundice and cholestasis may occur separately or concurrently.

Diagnosticstoggle arrow icon

Approach [1]

Overview of laboratory studies for jaundice [6]
Prehepatic jaundice Intrahepatic jaundice Extrahepatic jaundice
Indirect bilirubin
  • ↑↑
  • Normal
Direct bilirubin
  • Normal
  • ↑↑
Transaminases (AST, ALT)
  • Normal
  • Normal
Cholestatic enzymes (ALP, GGT)
  • Normal
  • ↑↑
Urinalysis Urine color
  • Dark urine
  • Very dark urine
Urinary bilirubin
  • Normal
  • ↑↑
Urinary urobilinogen
  • ↑↑
  • Normal or ↑
  • [9]
Stool color
  • Dark
  • Variable: dark, pale, clay-colored
  • Pale, clay-colored

Ultrasound abdomen [10][11]

  • Commonly obtained for initial evaluation of all patients with jaundice
  • Preferred initial image for suspected cholestasis

Examples of findings in abdominal ultrasound [11][12]

Prehepatic jaundice

Intrahepatic jaundice
Extrahepatic jaundice

Additional imaging [10][11][13]

  • Modalities: CT abdomen with IV contrast, MRCP
  • Common indications
    • Second-line imaging if ultrasound is inconclusive
    • Often requested for better assessment of cholestasis
    • To guide diagnostic or therapeutic interventions and procedures
  • Findings: depend on the etiology
    • Hepatocellular injury: fibrotic changes, cirrhosis (e.g., nodular surface), general hepatic inflammation
    • Cholestasis
      • Dilated bile ducts
      • Cause of obstruction, e.g., stones , masses

Diagnostic procedures [10][11]

Depending on clinical suspicion, and in consultation with a specialist, additional diagnostic procedures may be necessary, including:

Differential diagnosestoggle arrow icon

In contrast to jaundice, pseudojaundice does not result in scleral icterus.

The differential diagnoses listed here are not exhaustive.

Unconjugated hyperbilirubinemiatoggle arrow icon


Gilbert syndrome is a cause of intrahepatic jaundice that causes unconjugated hyperbilirubinemia


Common laboratory findings for hemolysis: indirect bilirubin, LDH, and haptoglobin


Identify and treat the underlying cause of unconjugated hyperbilirubinemia.

Conditions associated with unconjugated hyperbilirubinemia can manifest with varying degrees of jaundice and abnormally elevated indirect bilirubin. Those that cause prehepatic jaundice can have low elevations (< 15%) of direct bilirubin. Most conditions that cause intrahepatic jaundice (with the exception of Gilbert syndrome) can also have some degree of unconjugated hyperbilirubinemia, but typically exhibit significantly elevated direct bilirubin (see “Conjugated hyperbilirubinemia”).

Common causes of unconjugated hyperbilirubinemia
Distinguishing clinical features Distinguishing diagnostic findings Management
Autoimmune hemolytic anemia [16]
Microangiopathic hemolytic anemia [17]
Hemolytic transfusion reaction [18]
Gilbert syndrome [19]
  • Treatment typically not required

Conjugated hyperbilirubinemiatoggle arrow icon



Determine whether the liver chemistries suggest a hepatocellular or cholestatic etiology. Consult gastroenterology for further guidance if the cause is unclear.

Common laboratory findings for cholestasis: alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and direct bilirubin

Hepatocellular injury

Provide supportive care and identify and treat the underlying condition in all patients. See also “Acute liver failure.”

Elevated hepatocellular enzymes (e.g., AST, ALT) and varying degrees of jaundice are commonly seen in conditions that cause hyperbilirubinemia due to hepatocellular injury. Although elevations of both direct and indirect bilirubin are possible, a predominantly high direct bilirubin is most common, leading to mostly conjugated hyperbilirubinemia.

Common causes of hyperbilirubinemia due to hepatocellular injury
Distinguishing clinical features Distinguishing diagnostic findings Management
Hepatitis A [1]
  • Provide supportive care.
  • See “Treatment” in “Hepatitis A” for details.
Cirrhosis [1]
  • Identify and treat the underlying etiology.
  • Provide supportive care.
  • Optimize fluid status.
  • Prevent complications.
  • See “Treatment of cirrhosis” for details.
Alcoholic hepatitis [22][23][24]
Late-stage severe acetaminophen toxicity [25]
Wilson disease [1][26]

An AST:ALT ratio > 1.5:1 suggests alcoholic hepatitis.




Varying degrees of jaundice and elevations of cholestatic enzymes (including ALP, GGT, and direct bilirubin) are seen in conditions that cause conjugated hyperbilirubinemia due to cholestasis.

Common cholestatic causes of conjugated hyperbilirubinemia
Diagnosis Distinguishing clinical features Distinguishing diagnostic findings Management
Primary biliary cholangitis [29]
Primary sclerosing cholangitis [1]

Obstructive biliary tract malignancy

  • Other diagnostic features depend on the type, location, and stage of the malignancy (e.g., tumor-specific markers).
Choledocholithiasis [30]
Acute cholangitis [31]
Biliary cyst [32]

Referencestoggle arrow icon

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