Jaundice, a yellow discoloration of the skin, sclerae, and mucous membranes, has been recognized for centuries as a sign of liver disease. Bilirubin, the pigmented product of heme metabolism, accumulates in the body primarily as a result of its affinity for elastin, imparting a yellow color to these tissues. Although hyperbilirubinemia is present when the total serum concentration of bilirubin exceeds 1.2 mg/dL, clinically jaundice is not recognizable in most patients until the total bilirubin concentration exceeds 3 mg/dL.

The etiology of hyperbilirubinemia may be prehepatic, hepatic, or posthepatic in origin. Prehepatic hyperbilirubinemia results from excess intravascular liberation (i.e., hemolysis); hepatic hyperbilirubinemia is caused by hepatocyte dysfunction (i.e., faulty uptake, metabolism, or excretion of bilirubin); posthepatic hyperbilirubinemia occurs when the removal of bilirubin from the biliary system is impaired (i.e., by common bile duct obstruction or intrahepatic cholestatic obstruction).

Splenomegaly may be noted in patients with intravascular hemolysis (e.g., sickle cell anemia) and in hepatic disorders producing portal hypertension (cirrhotic disorders). Estrogenization secondary to chronic acquired hepatic disease (e.g., Laennec cirrhosis) may produce gynecomastia, testicular atrophy, and sparse axillary and pubic hair. RUQ discomfort on palpation suggests hepatitis, cholecystitis, or extrahepatic biliary obstruction. A painless, palpable gallbladder (Courvoisier sign) with jaundice suggests carcinoma of the head of the pancreas. Needle tracks should suggest intravenous drug abuse and associated acquired infectious hepatitis.

A predominant unconjugated hyperbilirubinemia is noted in all prehepatic disorders, some drug-induced hepatic diseases, Gilbert disease, and the Crigler-Najjar syndrome. A predominant conjugated hyperbilirubinemia is observed in all posthepatic disorders, most drug-related hepatitic disorders, Dubin-Johnson and Rotor syndromes, and all other intrahepatic causes of hyperbilirubinemia.

An elevated serum AST and serum ALT suggest hepatocellular dysfunction, whereas a markedly elevated alkaline phosphatase suggests extrahepatic obstruction or intrahepatic cholestasis. An elevation of gamma-glutamyltranspeptidase or 5′-nucleotidase further confirms these two mechanisms of jaundice, respectively. The determination of hepatitis A antibody is specific for diagnosis of acute hepatitis A, and acute hepatitis B may be diagnosed by the presence of hepatitis B surface antigen (HB_sAg) or “e” antigen (HB_eAg). On occasion, levels of HB_sAg are too low to
be detected during acute infection, circumstances under which the diagnosis can be made by detecting the presence of IgM anti-HB_c (or antibody against core, “c,” antigen). Chronic active or chronic persistent hepatitis causes persistent viremia manifested as hepatitis B surface antigenemia; its presence may confound the diagnosis of an acute hepatitic process in these patients. Prolongation of the prothrombin time, an indication of depressed hepatic synthetic function, portends a poor prognosis in the patient with acute infectious hepatitis.