AMA and or ANA
PBCer
Questions to our Doctors
Panel
Marshall
Kaplan, M.D.
Chief, Division
of
Question
Does it happen
often that those with PBC will have positive AMA, and later negative AMA?
Many in the digest have had this happen and I thought once positive it wouldn't
change.
Answer
AMA TITERS tend
not to change very much with time. Changes are more often due to problems
with the assay. At least, this has been my experience in every such instance.
Some of the commercial labs have had problems with quality control.
Howard
Worman, M.D.
Division of Digestive
and Liver Diseases
Departments of Medicine and of Anatomy and
September l999
Question
Those with PBC
have positive or elevated AMA indicating the presence of antimitochondrial
antibodies. Are these antibodies what causes the
damage to our bile ducts and resulting cirrhosis. If not, do doctors know
what actually causes the damage to the bile ducts.
Answer
Nobody knows what
causes the bile duct damage in PBC. Some studies have suggested that a protein
similar or identical to the one recognized by the antimitochondrial antibodies
is present on the bile ducts of individuals with PBC. However, it is still
not clear if this is the target responsible for bile duct damage. Furthermore,
some individuals with PBC do not have detectable antimitochondrial antibodies.
In summary, much more research is needed to determine what actually causes
the damage to the bile ducts in PBC.
Andrew
Mason, M.D.
Medical Director
of Liver Transplantation Ochsner Clinic
Assistant Professor
of Medicine, Tulane University Medical Center
Assistant Professor
of Microbiology, Immunology, and Parasitology, Louisiana State University
Medical Center
New Orleans,
La
August 2000
Question
Is it "normal"
for Actigall/URSO to reduce the anti-mitochondrial antibodies?
Answer
We still do not
know the precise role of anti-mitochondrial antibodies in PBC. At this time,
they are considered a specific marker for PBC but there is no evidence to
suggest that the titers vary with disease stage. In fact, AMA positive and
negative patients with PBC have a similar disease process. Also, AMA are
found in the serum of 70% of patients with PBC following liver transplantation,
but only a proportion of these patients develop recurrent PBC in the new
liver.
With regard to
treatment, AMA levels may fall with global improvement in the disease process
but it is not known why. So, patients taking Actigall/URSO can have decreased
AMA but this is not necessarily a universal finding.
Andrew
Mason, M.D.
Medical Director
of Liver Transplantation Ochsner Clinic
Assistant Professor
of Medicine, Tulane University Medical Center
Assistant Professor
of Microbiology, Immunology, and Parasitology, Louisiana State University
Medical Center
New Orleans,
La
August 2000
Question
a. Some hepatologists
do not do or order biopsies now and say that the biopsy is no longer the
"gold standard" for PBC since blood tests, especially showing elevated AMA's
and certain relationships of LFT's, are an equally good indication for diagnosis.
What are your opinions?
Answer
a. Biopsies can
be done for 2 reasons. They help to make the diagnosis and also help to stage
the disease. As nearly all our PBC patients are in clinical trials, we usually
perform biopsies to help assess response to treatment
Young-Mee Lee, M.D. & Daniel
Pratt,
M.D.
Show
2001
Question
I needed to find
out the correct names of the ANA, AMA, & AMST and their purpose in diagnosis.
Are there any other tests that may be beneficial to indicate or rule out
PBC or any other liver disease?
Answer
AMA is
antimitochondrial antibody, positive in about 95% of PBC patients but found
in 2% of patients who do not have PBC. ANA is antinuclear antibody, a less
specific test. It is positive in patients with all sorts of different diseases
and also found in people with no obvious medical problem. I am not sure what
AMST is. ASMA is antismooth muscle antibody, present in some patients with
chronic hepatitis.
Nathan
Bass, M.D.,
PhD
Professor of Medicine, Medical Director, Liver
Transplantation
Program,
Show
2000-2001
Question
What causes the
AMA to increase in a PBC patient? Does it increase as the PBC progresses?
Is it possible for AMA to almost double over a period of a couple of years?
Answer
The AMA will often
increase, but I have known it to decrease as well (even to undetectable),
and to fluctuate. The condition known as "autoimmune
cholangitis is considered by some experts to be PBC without any appearance
of the AMA. Yes, it may certainly double or increase ten-fold over
a period of a few years. However, since we have no confident idea as to the
meaning of the AMA or its role in the disease process in PBC, why any of
these things happen is essentially unknown.
Nathan
M. Bass, MD,
PhD
Professor of Medicine
Medical Director, Liver Transplantation Program
University of California, San Francisco
11/4/2002
Question
a. What is the difference
in a PBCER with a negative AMA versus a positive AMA?
b. Does this change the symptoms or how the disease progresses?
Answer
Some experts believe that even AMA negative PBC
is often positive if a sufficiently sensitive and specific test is used,
but at least 5% of patients who appear to clinically have true PBC are AMA
negative. In general opinion is divided whether this represents true PBC
or another autoimmune hepatitis with some features closely similar to PBC.
The disease in these patients usually behaves like AMA positive PBC, and
responds similarly to ursodiol. This has raised some questions about the
actual role of the AMA in causing PBC.
Howard
J. Worman, M.
D.
Associate Professor of Medicine and Anatomy and
July
2003
Question
What causes the change to have a positive AMA at
one point and then a negative AMA at another? Would this happen more
in PBC or Autoimmune Cholengitis?
Answer
Recent studies using the most sensitive tests have shown that essentially
all patients with PBC (~99%) have a "positive AMA." The problem in
the clinical laboratory is that these very sensitive tests are not used.
The clinical laboratories use indirect immunofluorescence that is open to
subjective interpretation. For this reason, some individuals with low
titer AMA (a low concentration or weakly reactive antibodies) may have a
"positive" test at one time and a "negative" test at another time.
There may also be changes in the AMA titer over time in an individual patient
for reasons that are not clear. "Autoimmune cholangitis" is not a
well-defined disease entity and I cannot comment on it
Henry
C. Bodenheimer, Jr.,
MD
Chief, Division of Digestive Diseases
Beth Israel Medical Center
First Ave at 16th Street
New York, NY 10003
8/2/2003
Question
Why is it that some patients are negative to Antinuclear Antibodies (ANA),
Antismooth Muscle AB, and Antimitochondrial Ab (AMA) but have PBC as diagnosed
through liver biopsy?
Answer
Some patient have negative auto antibodies but have a clinical syndrome identical
seropositive PBC. This may be a recognition that
there are multiple insults being directed at the biliary tree and mitochondrial
antibody is only one marker of the immune response to this attack on the
biliary system. It is possible that patients may have biliary injury that
looks identical to PBC but not have the same immune process mediating this
injury an example may be a drug reaction or toxic injury to the bile ducts
which on biopsy may look similar to PBC. This apparent "immune mediated
cholangitis" is a term used for sero-negative PBC without mitochondrial antibody.
We have an imperfect understanding of the events initiating PBC and have
even less information regarding the progression and initiation of auto-immune
cholangitis. I think of these diseases similarly, and treat both the same
as long as the disease is focused on the bile ducts. At times some patient
will develop an immune mediated process against the liver cells (hepatocytes)
and act more like auto-immune hepatitis, such patients may be treated with
immune suppression such as prednisone and Imuran.
Howard
J. Worman, M. D.
Associate Professor
of Medicine and Anatomy and Cell Biology
College of Physicians
and Surgeons
Question
Why is it that
some patients are negative to Antinuclear
Antibodies(ANA),
Antismooth Muscle Ab, and Antimitochondrial Aba (AMA) but have PBC
as diagnosed through Liver Biopsy?
Answer
The diagnosis of
PBC is based on clinical (e.g. patients i a woman), laboratory (e.g. elevated
serum alkaline phosphatase), immunological (e.g. positive AMA) and histological
(consistent biopsy) criteria. All
of these must be considered in diagnosis.
About 90% of subjects
with PBC are women. Most are
middle aged when first diagnosed.
Therefore, being a woman is more consistent with PBC than being
a
man.
Blood testing for
alkaline phosphatase activity is of critical importance for the diagnosis
of PBC. It is elevated in virtually
every patient with the disease (assuming they are not yet taking
ursodiol). If the blood alkaline
phosphatase activity if not elevated, the diagnosis of PBC must be suspect.
If tests for AMA
are done using the most sensitive methods available in research laboratories,
virtually all patients with PBC have positive
tests. However, since the assays
used in routine clinical laboratories are less sensitive and less specific,
only about 90% to 95% of subjects with PBC will have
positive
AMA.
About 50% of subjects
with PBC will have ANA, which are found in many different conditions and
are not specific for the diagnosis of
PBC. Tests available only in
research laboratories can sometimes determine if the ANA is a type specific
for PBC. Antismooth muscle antibodies
are a very non-specific test of
limited utility
in the diagnosis of PBC. About
90% to 95% of subjects with PBC will have an elevated blood immunoglobulin
M (IgM) concentration.
In PBC, the biopsy
findings are usually "consistent with PBC" but not
"diagnostic." The diagnosis usually
can only be made when consistent biopsy results are obtained in the presence
of other compatible diagnostic criteria (AMA, elevated serum IgM, disease
in a middle aged woman, etc). In
rare instances, the liver biopsy may be diagnostic (stage I "florid bile
duct lesion").
So
an experienced doctor make the diagnosis of PBC
based on several criteria. In
the 5% to 10% of cases in which the AMA is negative in the routine clinical
laboratory, many of the other criteria must be met and a biopsy must certainly
at least be consistent.
END