There are two general categories of “liver enzymes.” The first group includes
the alanine aminotransferase (ALT) and the aspartate aminotransferase
(AST), sometimes referred to as the SGPT and SGOT. These are enzymes that
are indicators of liver cell damage. The other frequently used liver
enzymes are the alkaline phosphatase and gamma-glutamyltranspeptidase
(GGT and GGTP) that indicate obstruction to the biliary system, either
within the liver or in the larger bile channels outside the liver.
The ALT and AST are enzymes that are located in liver cells and leak out and
make their way into the general circulation when liver cells are
injured. The ALT is thought to be a more specific indicator of liver
inflammation, since the AST may be elevated in diseases of other organs
such as heart disease or muscle disease.
ALT and AST are often used to monitor the course of chronic hepatitis and the
response to treatments, such as prednisone and interferon.
The alkaline phosphatase and the GGT are elevated in a large number of
disorders that affect the drainage of bile, such as a gallstone or tumor
blocking the common bile duct, or alcoholic liver disease or drug-induced
hepatitis, blocking the flow of bile in smaller bile channels within the
liver. The alkaline phosphatase is also found in other organs, such as
bone, placenta, and intestine.
For this reason, the GGT is utilized as a supplementary test to be sure that
the elevation of alkaline phosphatase is indeed coming from the liver or
the biliary tract. In contrast to the alkaline phosphatase, the GGT tends
not to be elevated in diseases of bone, placenta, or intestine. Mild or
moderate elevation of GGT in the presence of a normal alkaline
phosphatase is difficult to interpret and often caused by changes in the
liver cell enzymes induced by alcohol or medications, but without causing
injury to the liver.
For some reason many physicians continue to assume that if the enzyme levels
are low or near normal, that there is no cause for worry or need for
treatment. However, the studies which show that
THERE IS NO NECESSARY CORRELATION BETWEEN ENZYME LEVELS IN THE BLOOD AND THE
EXTENT OF LIVER DAMAGE
are too numerous to mention. I (C.D. Mazoff) know several individuals who had to insist on a liver biopsy,
only to find out that despite the low enzymes, they had grade 2 and grade 3 liver damage. One is dead, another is Joan King.
You may post her at jking@hepcbc.ca and she will tell you her story.
Hep C and ALT’s - What is Normal ?
Alan Franciscus
Twenty to thirty percent of people with HCV have persistently normal alanine
aminotransferase (ALT) levels. It is currently recommended that HCV+
individuals with normal ALT levels should not be treated with antiviral
medications and followed simply by measuring their ALT levels. However,
emerging data suggests that it may not be this simple. What does this
mean for the patient that has persistently normal ALT counts? Should
they be biopsied and treated? This is a ‘hot’ area of research and some
recent findings are changing the way the medical profession views this
group of HCV+ patients.
We know that most HCV+ individuals with persistently normal ALT levels have a
less serious disease progression and milder disease. The National
Institutes of Health (NIH) and European consensus conferences recommended
no liver biopsy or antiviral therapy in patients with persistently normal
ALT levels outside of clinical trials due to the assumed mild disease
progression and low response rates to current antiviral therapy. Some
medical professionals dismiss this group as healthy ‘carriers’ and offer
minimal medical follow-up. However, some of these patients with normal
ALT’s do not fit so neatly into this category and researchers are finding
that a small percentage of these patients may have moderate to severe
liver damage.
Alanine aminotransferease (ALT’s – formally called SGPT) is produced in the
liver in response to liver injury or cell death. This injury is not
specific to HCV inflammation, but can come from a variety of agents such
as alcohol, medications and other substances that can produce liver
injury. This is usually, but not always, the first indication that
someone may be infected with HCV. Normal values: 0-48 IU/L
It should be noted that many experts believe the normal ALT range value for
women should be lower than the range value for men. In fact, women
populate a large part of this ‘normal group’. The lower ALT levels in
women might be explained by the production of estrogen which is believed
to lower ALT levels.
Biopsy
In a recent study by Edmund J Bini and others (AASLD abstract #485) 43 patients
with persistently normal ALT levels and 96 with abnormal ALT levels were
followed. Normal levels were defined by 3 normal ALT readings taken at
least 1 month apart. The researchers found that the abnormal ALT levels
group had significantly more advanced liver disease than patients with
normal ALT’s. However, 28% of the patients with normal ALT’s had
advanced liver disease, which led the researchers to recommend that all
patients with normal ALT’s undergo a liver biopsy for disease staging.
In a different study by Luis Balart, MD and others, over 300 patients with
persistently normal ALT levels defined as 3 normal ALT levels readings
taken 6 weeks apart for a period of 6 months were studied. It was found
that most of these patients had mild liver disease, but a small
percentage had more advanced disease, and some patients were found to
have cirrhosis. Based on his study, Dr. Balart recommended that other
factors should be considered when evaluating these patients and a biopsy
should be considered.
Treatment
This is a much more complex issue. In a recent study conducted by
Dr. Mitchell L. Shiffman and colleagues, it was found that response to
interferon monotherapy was similar in both normal (58 patients) and
abnormal (37 patients) ALT level groups. The researchers concluded that
persons with persistently normal ALTs should undergo a liver biopsy and
considered for treatment if the liver is damaged. These findings have
been collaborated by previous studies.
However, some evidence suggests that antiviral treatment for a small segment of
this group could be counterproductive. Some patients do not respond to
treatment, but develop elevated ALT levels that continued to be elevated
after treatment is stopped. The big questions is – can antiviral
treatment for this subset of patients make the disease worse? This is a
very important issue that is now being studied.
This area of research is expanding and deserves more attention. It is hoped
that a patient with normal ALT values will at the very least be offered
additional liver function tests and a liver biopsy if necessary to
establish if severe disease is present and given the option for antiviral
treatment.
Common tests used to measure liver function:
Liver function tests include a variety of tests to help gauge the health of the
liver. Measuring ALT’s does not give a complete picture of liver health.
A list of the more common liver function tests follow with the normal
values listed. It is important to remember that ‘normal values’ vary
from lab-to-lab and can be influenced by the way the blood samples are
handled. Treatment decisions should never be made based on one test and
always consult with a medical professional to accurately interpret test
results.
Albumin is a blood protein produced by the liver. It is responsible
for keeping fluids and salts within blood vessels. If the liver does not
produce enough albumin, water retention in the form of swelling occurs
usually in the feet and ankles. Normal values: 3.2-5.0g
Alkaline Phosphatase (AP) is an enzyme mainly found in the liver and
is responsible for phosphorus metabolism, which delivers energy to the
cell. Elevated levels of AP along with elevated GGT indicate that
something is wrong in the liver. Normal values:
35-115 IU/L
Aspartate Aminotransferase (AST – formerly called SGOT) is a liver
enzyme used for amino acid metabolism. Elevated levels indicate liver
injury. Tests for this enzyme and ALT are the most frequently used blood
tests to watch changes in liver inflammation. Normal values: 0-42 IU/L
Bilirubin is a waste product produced by the liver. A healthy liver
will convert these bile salts into water-soluble substances that are
excreted by the body. When the liver is damaged it is unable to convert
these bile salts into a water-soluble substances leading into a buildup
of toxic yellowish liquid which produces jaundice (yellowing of the
skin). This is seen in some acute cases of hepatitis C and in end stage
liver disease. Normal values: 0-1.3mg
Gamma-Glutamyltranspepidase (GGT) is a liver enzyme used in
metabolizing glutamate (an amino acid). High levels of GGT may indicate
blockage and damage to bile ducts. Normal values:
30-60 IU/L
Platelets are blood cells that help the blood to clot. Low platelet
counts indicate liver damage. Platelets counts are also followed closely
during interferon therapy. Normal values: 130-400
thousand/MCL
HCV Advocate –
This information is provided by the Hepatitis C Support Project. Reprint permission is granted and encouraged with credit to the Hepatitis C Support Project.
