There are a number of tests that can be used to evaluate liver function. These tests include biochemical tests, radiologic tests, and pathologic tests.
Serum biochemical tests, also commonly referred to as “liver function tests,” can be used to (1) detect the presence of liver disease, (2) distinguish among different types of liver disorders, (3) gauge the extent of known liver damage, and (4) follow the response to treatment. However, serum biochemical tests have shortcomings. They lack sensitivity and specificity; they can be normal in patients with serious liver disease and abnormal in patients with diseases that do not affect the liver. Liver tests rarely suggest a specific diagnosis; rather, they suggest a general category of liver disease, such as hepatocellular or cholestatic, which then further directs the evaluation. The liver carries out thousands of biochemical functions, most of which cannot be easily measured by blood tests. Laboratory tests measure only a limited number of these functions. In fact, many tests, such as the aminotransferases and alkaline phosphatase, do not measure liver function at all. Rather, they detect liver cell damage or interference with bile flow. Thus, no one biochemical test enables the clinician to accurately assess the liver’s total functional capacity.
To increase the sensitivity and the specificity of biochemical tests in the detection of liver disease, it is best to use them as a battery. Tests usually employed in clinical practice include the bilirubin, aminotransferases, alkaline phosphatase, albumin, and prothrombin time tests. When more than one of these tests provide abnormal findings or the findings are persistently abnormal on serial determinations, the probability of liver disease is high. When all test results are normal, the probability of missing occult liver disease is low.
Bilirubin, a breakdown product of the porphyrin ring of heme-containing proteins, is found in the blood in two fractions—conjugated and unconjugated (See also Chap. 45). The unconjugated fraction, also termed the indirect fraction, is insoluble in water and is bound to albumin in the blood. The conjugated (direct) bilirubin fraction is water-soluble and can therefore be excreted by the kidney. Normal values of total serum bilirubin are reported between 1 and 1.5 mg/dL with 95% of a normal population falling between 0.2 and 0.9 mg/dL. If the direct-acting fraction is <15% of the total, the bilirubin can be considered to all be indirect. The most frequently reported upper limit of normal for conjugated bilirubin is 0.3 mg/dL.
Elevation of the unconjugated fraction of bilirubin is rarely due to liver disease. An isolated elevation of unconjugated bilirubin is seen primarily in hemolytic disorders and in a number of genetic conditions such as Crigler-Najjar and Gilbert’s syndromes (Chap. 45). Isolated unconjugated hyperbilirubinemia (bilirubin elevated but <15% direct) should prompt a workup for hemolysis (Fig. 330-1). In the absence of hemolysis, an isolated, unconjugated hyperbilirubinemia in an otherwise healthy patient can be attributed to Gilbert’s syndrome, and no further evaluation is required.
Algorithm for the evaluation of chronically abnormal liver tests. AMA, antimitochondrial antibody; ANA, antinuclear antibody; Bx, ...