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History and physical examination

History should include the following information:

  • Medications.

  • Use of drugs

  • Use of alcohol

  • Hepatitis risk factors

  • History of abdominal operations, including gallbladder surgery.

  • History of inherited disorders including liver diseases and hemolytic disorders

  • HIV status

  • Travel history

  • Exposure to toxic substances.


A history of fever, particularly when associated with chills or right upper quadrant pain and/or a history of prior biliary surgery, is suggestive of acute cholangitis.

Symptoms such as anorexia, malaise, and myalgias may suggest viral hepatitis.

The physical examination may reveal a Courvoisier sign or signs of chronic liver failure/portal

hypertension such as ascites, splenomegaly, spider angiomata, and gynecomastia. Certain findings suggest specific diseases such as hyperpigmentation in hemochromatosis, a Kayser-Fleischer ring in Wilson's disease, and xanthomas in primary biliary cirrhosis.

Screening laboratory studies

Initial laboratory tests include measurements of

a. serum total and unconjugated (indirect) bilirubin,

b. alkaline phosphotase,

c. aminotransferases (AST & ALT)

d. prothrombin time, and

e. albumin.

The presence or absence of abnormalities and the type of abnormalities should help to separate the various causes of jaundice.

  • Normal liver enzymes suggest that the jaundice is not due to hepatic injury or biliary tract disease. In such patients, hemolysis or inherited disorders of bilirubin metabolism may be responsible for the hyperbilirubinemia.

  • The inherited disorders associated with isolated unconjugated hyperbilirubinemia are Gilbert's and Crigler-Najjar syndrome; the disorders associated with isolated conjugated

  • hyperbilirubinemia are Rotor and Dubin-Johnson syndrome.

  • A predominant elevation in serum alkaline phosphotase Alk. phosphotase > ALT) in relation to aminotransferases (AST and ALT) usually reflects biliary obstruction or intrahepatic cholestasis.

Increased serum alkaline phosphotase is also found in granulomatous liver diseases, such as tuberculosis or sarcoidosis. These conditions may or may not be associated with jaundice.

An elevation in the serum alkaline phosphotase concentration can also be derived from extrahepatic tissues, particularly bone. Extrahepatic disorders do not cause jaundice except in rare cases, such as bone tumors metastasizing to the liver. If necessary, the serum activities of the canalicular enzymes gammaglutamyl (GGTP) transpeptidase and 5'-nucleotidase can be measured to confirm the hepatic origin of alkaline phosphotase.

  • Predominant elevation (ALT> Alk. phosphotase) of serum transaminase activity suggests that jaundice is caused by alcoholic hepatitis. Alcoholic hepatitis is associated with a disproportionate elevation of AST compared to ALT with both values being less than 300 IU/L. This ratio is usually greater than 2.0, a value rarely seen in other forms of liver disease.

  • Indicators of more severe hepatocellular disease with impaired synthetic function include otherwise unexplained hypoalbuminemia and a prolonged prothrombin time which does not correct with vitamin K.

This approach to the use of liver enzymes provides a broad guideline for the initial distinction between the different causes of jaundice. exceptions include, viral hepatitis which can present as a predominantly cholestatic syndrome with marked pruritus. Unless the patient has risk factors for viral hepatitis, it is difficult to distinguish this clinically from other causes of cholestasis.