Viral Hepatitis and Liver Disease Website Course

Evaluating Liver Test Abnormalities

Understanding the Pathophysiology of Liver Disease

for Health Care Providers

Acute Cholestasis

Abnormal liver test > Cholestatic pattern > Less than six months > Acute cholestasis


The differential diagnosis for acute cholestasis is wide and depends on the clinical setting and therefore careful history and physical examination are of great importance. The main causes of acute cholestasis are drug-induced liver injury (intrahepatic cholestasis) and bile duct obstruction (extrahepatic cholestasis), but there are additional diagnostic possibilities at each of these categories:

Intrahepatic cholestasis:

  • Drug-induced liver injury
  • Viral hepatitis
  • Alcoholic hepatitis
  • Sepsis
  • Total parenteral nutrition
  • Cholestasis of pregnancy
  • Primary biliary cirrhosis
  • PSC
  • Benign post-op cholestasis

Extrahepatic cholestasis:

  • Common bile duct obstruction
  • Stone (choledocolithiasis)
  • Tumor
  • Blood
  • Iatrogenic (ligation)

Medications (Not a complete list):

  • Antibiotics (Penicillins, Sulfonamides, Macrolides, Fluoroquinolones, Tetracyclines)
  • Antifungals (Terbinafine, Griseofulvin, Ketoconazole, Itraconazole)
  • Anabolic steroids
  • Anti-inflammatories(some)
  • Azathioprine
  • Barbiturates
  • Cyclosporine
  • Isoniazid
  • Oral contraceptives
  • Psychotropics (some)
  • Phenytoin
  • Rifampin
  • Tamoxifen


The clinical hallmark of cholestasis is the presence of PRURITUS. Patients should be specifically asked about the presence of pruritus. In general, pruritus presents earlier in cases of intrahepatic cholestasis. Initial questions aimed at determining the possible etiology of acute cholestatic injury are:

To investigate drug-induced liver injury:

Detailed medication history including over-the-counter medications, herbal remedies and health food supplements, particularly regarding recently prescribed medications.

To investigate choledocolithiasis:

Compatible clinical picture with epigastric or right upper quadrant pain, a history of biliary surgery and/or gallstones. It is crucial to investigate the presence of fever or shaking chills as this would indicate the presence of cholangitis. Patients who develop cholangitis should be hospitalized immediately.

To investigate acute viral hepatitis:

History of risk factors for viral hepatitis (intravenous drug use, unsafe sexual practices, or ingestion of raw shellfish in the past six months) or the presence of a prodrome (malaise, nausea, low grade fever).

To investigate alcoholic hepatitis:

Detailed alcohol ingestion history.

To investigate sepsis

Presence of sepsis from a source other than the biliary tree.

To investigate total parenteral nutrition (TPN):

History of TPN administration for more than 2-3 weeks.

Physical examination

The presence of jaundice, fever, abdominal tenderness, or Murphy's sign should be noted. Asymptomatic jaundice needs immediate attention.

Laboratory Investigation

Initial investigation should be directed at distinguishing between an intrahepatic or an extrahepatic acute cholestasis. The initial test is therefore abdominal ultrasonography to look for bile duct dilatation. The presence of bile duct dilatation on ultrasonography indicates that cholestasis is extrahepatic.

Liver biopsy is generally not indicated in acute cholestatic injury unless the etiology continues to be uncertain despite all pertinent investigations.