AMA and or ANA
Doctors Panel
Answers the PBCers Questions
Marshall Kaplan, M.D.
Chief, Division of
Gastroenterology
September 9, 1999
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 Cell Biology
College of Physicians & Surgeons
Columbia University
New York, NY 10032
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,
Assistant Professor of
Microbiology, Immunology, and Parasitology,
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,
Assistant Professor of
Microbiology, Immunology, and Parasitology,
August 2000
Question
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
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
9-29-03
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