Physical Examination 

The general assessment should include assessment of the patient's nutritional status. Temporal and proximal muscle wasting suggests long-standing diseases such as pancreatic cancer or cirrhosis. Stigmata of chronic liver

disease, including spider nevi, palmar erythema, gynecomastia,

caput medusae, Dupuytren's contractures, parotid gland

enlargement, and testicular atrophy are commonly seen in

advanced alcoholic (Laennec's) cirrhosis and occasionally

in other types of cirrhosis. An enlarged left supraclavicular

node (Virchow's node) or periumbilical nodule (Sister Mary

Joseph's nodule) suggests an abdominal malignancy. Jugular

venous distention, a sign of right-sided heart failure, suggests

hepatic congestion. Right pleural effusion, in the absence of

clinically apparent ascites, may be seen in advanced cirrhosis.

The abdominal examination should focus on the size and

consistency of the liver, whether the spleen is palpable and

hence enlarged, and whether there is ascites present. Patients

with cirrhosis may have an enlarged left lobe of the liver, which

is felt below the xiphoid, and an enlarged spleen. A grossly

enlarged nodular liver or an obvious abdominal mass suggests

malignancy. An enlarged tender liver could be viral or alcoholic

hepatitis; an infiltrative process such as amyloid; or, less

often, an acutely congested liver secondary to right-sided heart

failure. Severe right upper quadrant tenderness with respiratory

arrest on inspiration (Murphy's sign) suggests cholecystitis

or, occasionally, ascending cholangitis. Ascites in the

presence of jaundice suggests either cirrhosis or malignancy

with peritoneal spread.

Laboratory Tests When the physician encounters a patient

with unexplained jaundice, there is a battery of tests that are

helpful in the initial evaluation. These include total and direct

serum bilirubin with fractionation, aminotransferases, alkaline

phosphatase, albumin, and prothrombin time tests. Enzyme

tests [alanine aminotransferase (ALT), aspartate aminotransferase

(AST), and alkaline phosphatase (ALP)] are helpful in differentiating

between a hepatocellular process and a cholestatic

process (Table 302-1; Fig. 42-1 ), a critical step in determining

what additional workup is indicated. Patients with a hepatocellular

process generally have a disproportionate rise in the aminotransferases

compared to the ALP. Patients with a cholestatic

process have a disproportionate rise in the ALP compared to the

aminotransferases. The bilirubin can be prominently elevated in both hepatocellular and cholestatic conditions and, therefore, is

not necessarily helpful in differentiating between the two.

In addition to the enzyme tests, all jaundiced patients should

have additional blood tests, specifically an albumin level and a

prothrombin time, to assess liver function. A low albumin level

suggests a chronic process such as cirrhosis or cancer. A normal

albumin level is suggestive of a more acute process such as viral

hepatitis or choledocholithiasis. An elevated prothrombin time

indicates either vitamin K deficiency due to prolonged jaundice

and malabsorption of vitamin K or significant hepatocellular

dysfunction. The failure of the prothrombin time to correct

with parenteral administration of vitamin K indicates severe

hepatocellular injury.

The results of the bilirubin, enzyme tests, albumin, and prothrombin

time tests will usually indicate whether a jaundiced

patient has a hepatocellular or a cholestatic disease, as well as

some indication of the duration and severity of the disease. The

causes and evaluationof hepatocellular and cholestatic diseases

are quite different.

Hepatocellular Conditions Hepatocellular diseases that can cause

jaundice include viral hepatitis, drug or environmental toxicity,

alcohol, and end-stage cirrhosis from any cause ( Table 42-2 ).

Wilson's disease, once believed to occur primarily in young

adults, should be considered in all adults if no other cause of jaundice

is found. Autoimmune hepatitis is typically seen in young to

middle-aged women but may affect men and women of any age.

Alcoholic hepatitis can be differentiated from viral and toxinrelated

hepatitis by the pattern of the aminotransferases. Patients

with alcoholic hepatitis typically have an AST:ALT ratio of at least

2:1. The AST rarely exceeds 300 U/L. Patients with acute viral

hepatitis and toxin-related injury severe enough to produce jaundice

typically have aminotransferases > 500 U/L, with the ALT

greater than or equal to the AST.The degree of aminotransferase

elevation can occasionally help in differentiating between hepatocellular

and cholestatic processes. While ALT and AST values

less than 8 times normal may be seen in either hepatocellular

or cholestatic liver disease, values 25 times normal or higher are

seen primarily in acute hepatocellular diseases. Patients withjaundice from cirrhosis can have normal or only slight elevations

of the aminotransferases.

When the physician determines that the patient has a hepatocellular

disease, appropriate testing for acute viral hepatitis includes

a hepatitis A IgM antibody, a hepatitis B surface antigen and core

IgM antibody, and a hepatitis C viral RNA test. It can take many

weeks for the hepatitis C antibody to become detectable, making

it an unreliable test if acute hepatitis C is suspected. Depending

on circumstances, studies for hepatitis D and E, Epstein-Barr

virus (EBV), and cytomegalovirus (CMV) may be indicated.

Ceruloplasmin is the initial screening test for Wilson's disease.

Testing for autoimmune hepatitis usually includes an antinuclear

antibody and measurement of specific immunoglobulins.

Drug-induced hepatocellular injury can be classified either

as predictable or unpredictable. Predictable drug reactions are

dose-dependent and affect all patients who ingest a toxic dose

of the drug in question. The classic example is acetaminophen

hepatotoxicity. Unpredictable or idiosyncratic drug reactions

are not dose-dependent and occur in a minority of patients. A

great number of drugs can cause idiosyncratic hepatic injury.

Environmental toxins are also an important cause of hepatocellular

injury. Examples include industrial chemicals such as vinyl

chloride, herbal preparations containing pyrrolizidine alkaloids

(Jamaica bush tea) and Kava Kava, and the mushrooms Amanita

phalloides or A. verna that contain highly hepatotoxic amatoxins.