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.