Metastatic tumor to the liver may be completely occult or may produce a clinical or laboratory picture compatible with hepatomegaly of unknown origin; normal liver with elevated ALP levels simulating bone disease; active cirrhosis; or obstructive jaundice. The liver is a frequent target for metastases, some of the most common primary sites being lung, breast, prostate, and both the upper and lower GI tract. Earlier reports frequently stated that metastases to a cirrhotic liver were rare, but later studies have disproved this. By far the most frequently noted abnormality is hepatic enlargement. About 25% of patients with metastatic tumor to the liver become jaundiced, and another 25% have elevated bilirubin levels (usually with the conjugated fraction predominating) without clinically evident jaundice. Occasionally patients develop jaundice with relatively little hepatic tissue replacement. In about 10% of patients the bilirubin levels are high enough (>10 mg/100 ml; 170 µmol/L) to simulate obstruction of the common bile duct. A significant minority of patients with tumor in the liver may have physical findings compatible with portal hypertension or cirrhosis.

In 50%-60% of patients with metastatic carcinoma to the liver the serum bilirubin level is normal, whereas ALP levels are elevated in about 80% of patients (range, 42%-100%) and GGT in about 88% (45%-100%). Therefore, ALP or GGT levels are frequently elevated in nonjaundiced patients with liver metastases, and ALP elevation may occur in some instances when only a relatively few tumor nodules are present. The most typical pattern for metastatic carcinoma to the liver is a normal bilirubin level, normal AST level, and elevated GGT and/or ALP level of liver origin. If the serum bilirubin level is elevated, the typical metastatic tumor pattern becomes less typical or is obscured, because many of these patients develop mildly abnormal AST values suggestive of mild acute hepatocellular damage in addition to the elevated ALP level. Diagnosis is much more difficult when liver function test results other than ALP or GGT are abnormal since these other test results can be elevated (at least temporarily) from any of a considerable variety of etiologies. Unfortunately, only about one third (or less) of metastatic tumor cases have elevated ALP or GGT levels and normal AST levels. Finally, whether or not a patient has elevated bilirubin, ALP or GGT may be elevated due to nonhepatic etiology (i.e., phenytoin therapy, sepsis). Some investigators report that carcinoembryonic antigen (CEA) is more sensitive in detecting colon cancer metastasis to the liver than is ALP, but this is a minority opinion.

As mentioned previously, a liver scan (radionuclide, CT, or ultrasound) is very useful. Liver biopsy is usually necessary for definite diagnosis. Biopsy sometimes may demonstrate tumor when other tests are normal, equivocal, or conflicting, or when the biopsy is performed because of some other preliminary diagnosis.