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Liver disease is the most important cause of increased aminotransaminase activity in serum.The demonstration of macro-AST in serum is obtained by differential precipitation with polyethylene glycol (PEG) 6000 (see "Amylase" section later in this chapter)In viral hepatitis and other forms of liver disease associated with acute hepatic necrosis, serum AST and ALT activities are elevated even before the clinical signs and symptoms of disease (such as jaundice) appear. Activities for both enzymes may reach values as high as 100 times the URL, although 10-fold to 40-fold elevations are most frequently encountered. The most efficient aminotransferase threshold for diagnosing acute liver injury lies at seven times the URL (clinical sensitivity and specificity

95%).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 (see Chapter 37).Peak values of aminotransaminase activity occur between the 7th and 12th days; activities then gradually decrease, reaching physiological concentrations by the 3rd to 5th week if recovery is uneventful.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.Persistence of increased ALT activity for longer than 6 months after an episode of acute hepatitis is used to diagnose chronic hepatitis.Exceptions may be seen, however, in (1) alcoholic hepatitis, (2) hepatic cirrhosis, and (3) liver neoplasia.Most patients with chronic hepatitis have maximum ALT activities less than seven times theURL.In patients with acute hepatitis C, the activity of ALT should be measured periodically over the next 1 to 2 years to determine if it becomes and stays normal.The activities of aminotransferases are also elevated in nonalcoholic fatty liver disease (NAFLD).Peak activities bear no relationship to prognosis and may fall with worsening of the patient's condition.The clinical situation in toxic hepatitis is different from that in infectious hepatitis.In most types of liver disease, ALT activity is higher than that of AST.

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. In viral hepatitis and other forms of
liver
disease associated with acute hepatic necrosis, serum AST and ALT
activities
are elevated even before the clinical signs and symptoms of disease
(such as
jaundice) appear. Activities for both enzymes may reach values as
high as 100
times the URL, although 10-fold to 40-fold elevations are most
frequently
encountered. The most efficient aminotransferase threshold for
diagnosing
acute liver injury lies at seven times the URL (clinical sensitivity and
specificity

95%). Peak values of aminotransaminase activity occur between the
7th and
12th days; activities then gradually decrease, reaching physiological
concentrations by the 3rd to 5th week if recovery is uneventful. Peak
activities
bear no relationship to prognosis and may fall with worsening of the
patient’s
condition.
Persistence of increased ALT activity for longer than 6 months after an
episode of acute hepatitis is used to diagnose chronic hepatitis. Most
patients
with chronic hepatitis have maximum ALT activities less than seven
times theURL. 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 patients
with acute
hepatitis C, the activity of ALT should be measured periodically over
the next 1
to 2 years to determine if it becomes and stays normal. The clinical
situation in
toxic hepatitis is different from that in infectious hepatitis. 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 (see Chapter 37). NAFLD is now
considered to
be an additional feature of the “metabolic syndrome” with elevation of
serum
aminotransferase activities associated with (1) higher body mass
index, (2)
increased waist circumference, (3) elevated serum triglycerides, (4)
elevated
fasting insulin and (5) lower HDL cholesterol—all characteristic
features of this
syndrome.
Aminotransferase activities observed in cirrhosis vary with the status
of the
cirrhotic process and vary from the URL to four to five times higher,
with an
AST/ALT ratio (AAR) greater than 1. This appears to be attributable
to a
reduction in ALT production in a damaged liver, associated with
reducedclearance of AST in advancing liver fibrosis. An AAR ≥1 has ≈90%
positive
predictive value for diagnosing the presence of advanced fibrosis in
patients
with chronic liver disease. Furthermore, the extent of elevation in the
AAR has
been known to reflect the grade of fibrosis in these patients.
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.
Although serum activities of both AST and ALT become elevated
whenever
disease processes affect liver cell integrity, ALT is the more liver￾specific
enzyme. Serum elevations of ALT activity are rarely observed in
conditions
other than parenchymal liver disease. Thus the incremental benefit of
determination of AST, in addition to ALT, may be limited.
After acute myocardial infarction, increased AST activity appears in
serum(see Table 19-3). AST activity also is increased in progressive
muscular
dystrophy and dermatomyositis, although it is usually normal in other
types of
muscle disease, especially in those of neurogenic origin. Slight to
moderate AST
elevations are noted in hemolytic disease.
Several studies have described AST activities linked to
immunoglobulins, or
macro-AST. Typical findings include a persistent increase in serum
AST activity
in an asymptomatic patient, with absence of any demonstrable
pathology in
organs rich in AST. Increased AST activity reflects decreased
clearance of the
abnormal complex from plasma. Macro-AST has no known clinical
relevance.
However, identification is important to avoid unnecessary diagnostic
procedures in these patients. The demonstration of macro-AST in
serum is
obtained by differential precipitation with polyethylene glycol (PEG)
6000 (see
“Amylase” section later in this chapter)