Liver disease is the most important cause of increased aminotransaminase
activity in serum. In most types of liver disease, ALT activity is higher than that
of AST. Exceptions may be seen, however, in (1) alcoholic hepatitis, (2) hepatic
cirrhosis, and (3) liver neoplasia

The activity of ALT may be persistently normal in 15% to 50% of patients
with chronic hepatitis C, but the likelihood of continuously normal ALT activity
decreases with an increasing number of measurements

In acetaminopheninduced
hepatic injury, the peak of aminotransaminase activity is more than 85
times the URL in 90% of cases—a value rarely seen with acute viral hepatitis.
The activities of aminotransferases are also elevated in nonalcoholic fatty
liver disease (NAFLD). This disease includes a spectrum of liver pathology,
from simple steatosis to nonalcoholic steatohepatitis (NASH), in which
inflammatory changes and focal necrosis may progress to (1) liver fibrosis, (2)
cirrhosis, and (3) hepatic failure


Twofold to fivefold elevations of the activities of both enzymes occur in
patients with primary or metastatic carcinoma of the liver, with the activity of
AST usually higher than ALT activity, but their values are often within the
reference interval in the early stages of malignant infiltration of the liver.
Slight
or moderate elevations in AST and ALT activities have been observed after
administration of various medications, such as (1) nonsteroidal antiinflammatory
drugs, (2) antibiotics, (3) antiepileptic drugs, and (4) statins.
Over-the-counter medications and herbal preparations are also implicated. In
patients with (1) increased aminotransaminase activities, (2) negative viral
markers, and (3) a negative history for drugs or alcohol ingestion. The
diagnostic evaluation should include investigation of less common causes of
chronic hepatic injury such as (1) hemochromatosis, (2) Wilson disease, (3)
autoimmune hepatitis, (4) primary biliary cirrhosis, (5) sclerosing cholangitis,
(6) celiac disease, and (7) α1-antitrypsin deficiency.