Dr. Marshall Kaplan
Chief,
Division of Gastroenterology
September 1999
Dr.
Kaplan gives us his thoughts on the following article
Methotrexate
and transplantation
WESTPORT,
Aug 30 (Reuters Health) - In patients with primary biliary cirrhosis, the
risk of death or transplantation is increased nearly threefold with long-term
use of low-dose methotrexate, according to the results of a 6-year,
placebo-controlled study.
Dr.
Mark T. Hendrickse and colleagues at
Patients
treated with methotrexate had significantly lower "...serum alkaline phosphatase,
gamma-glutamyltransferase, [IgM], IgG, and (after 24 months) aspartate
aminotransferase and alanine aminotransferase levels..." than controls. On
the other hand, clinical factors, such as Knodell inflammatory scores and
pruritus scores, were not significantly different between the two groups.
Moreover,
patients randomized to low-dose methotrexate actually had an increased risk
of death or liver transplantation, with a relative risk of 2.9, though this
association did reach statistical significance.
The
findings, published in the August issue of Gastroenterology, indicate that
use of methotrexate in patients with primary biliary cirrhosis should be
limited to the clinical trials setting, Dr. Hendrickse and colleagues conclude.
They point out that higher doses of the drug may have enhanced efficacy in
this population, but this was not tested in the current study.
Elsewhere
in the journal, Drs. Paul Angulo and E. Rolland Dickson of the Mayo Clinic
and Foundation in
The
editorialists note that several promising drugs are currently in development
for the treatment of primary biliary cirrhosis, but that ursodeoxycholic
acid should remain the initial treatment for this disease until further data
are available.
Date:
As
you can see, this is a controversial area. The British investigators used
approximately one half of the dose that I and others have found to be the
minimally effective dose. A colleague and I have published a paper in the
same issue of Gastroenterology that indicates that methotrexate improves
blood tests and liver biopsy findings in patients who respond incompletely
or not at all to ursodiol. I am in the tenth year of a double-blind trial
comparing methotrexate plus ursodiol to colchine plus ursodiol but, because
of the nature of the study, do not have any survival results yet. All that
I can say is that methotrexate appears to be effective in my patients, but
that I only use it in patients who have not responded fully to ursodioal
or colchicine.
David
Bernstein, M.D.
Director of
Question 4:
a. If sisters or mother/daughters have PBC, what are the chances of their
children or grandchildren getting PBC?
Answer
4a
While PBC may be found in families, it still remains uncommon that a mother
and child or two sisters will be affected. In published studies, the rate
of familial prevalence of the disease varies from 1-5% with American studies
at the lower end of this spectrum and British studies at the higher end of
this spectrum.
Dr. Howard Worman
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
Question 25
This
may be a radical thought, or maybe one already considered and dismissed for
good reason: Since many of us have autoimmune diseases other than just PBC,
I was wondering if the drugs used to suppress the immune system after transplant
(which probably decreases the chance of PBC recurring) could be used as therapy
years before transplant in order to control the symptoms of many of our
autoimmune diseases.
Answer
Many
medical investigators are considering your thought and it is neither "radical"
nor has it been "dismissed for good reason." Some of the same drugs used
to prevent transplant rejection such as tacrolimus, cyclosporin A and
mycophenolate mofetil are being investigated in the treatment of various
autoimmune disorders. More studies are necessary at this
time.
Howard
J. Worman, M. D.
Associate Professor of Medicine and Anatomy and
July
2003
Question
2
Why is CellCept being used in non-transplant, non-renal patients? What are
the Benefits? Side Effects? Do you know of studies done?
Answer 2
Mycophenolate mofetil (CellCept) is an immunosuppressive agents used to prevent
allograft (transplanted organ) rejection. As PBC is likely an autoimmune
disease, some investigators have hypothesized that mycophenolate mofetil
may be useful as a treatment. Nobody knows yet if it will work in PBC.
Mycophenolate mofetil is not approved for the treatment of PBC and a patient
should not take this medication unless it is part of an IBR-approved clinical
trial. I am aware of at least one trial of mycophenolate
mofetil
in patients with PBC.
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 1
What is your opinion of PBCers taking cholesterol lowering drugs, particularly
statins? Which, if any, is the safest to take? What about Milk Thistle?
Answer 1
Statins are particularly effective agents to lower cholesterol. The need
for cholesterol lowering agents in PBC is complicated by the fact that the
cardiac risk related to cholesterol elevation as a consequence of PBC is
not the same as risk from cholesterol elevation in the absence of liver disease.
However, some patients with PBC may have independent risk factors for coronary
artery disease such as a strong family disease of arteriosclerotic heart
disease, diabetes or smoking. Obviously, improvement in diet, avoiding smoking
and engaging exercise are the first steps to take. After this weight reduction
is often beneficial and medication is used last. A safe although less effective
alternative is the use of Welchol, however, if all these steps are ineffective,
and risk factors are present I have used statins in patients with PBC. These
drugs can be used safely, and since they also have an immune suppressive
effect studies are ongoing to look at a potential beneficial effect of statins
on the liver disease of patients with PBC. The major concern of statins is
they have been associated with elevation of biochemical liver tests.
I recommend that my patients with liver disease who use statins have liver
function tests monitored particularly during the first year of treatment.
Minor elevations of aminotransferase values (ALT, AST) is not a reason for
drug discontinuation but progressive rise is. The development of serious
liver injury with statins is quite unusual. Thus, in those patients who are
at high risk for development of arteriosclerotic heart disease and who have
cholesterol unresponsive to lifestyle modification I would use statins monitoring
liver tests periodically.
I am not aware of a significant difference in liver injury among the statins
and would treat each of the medications similarly. There is some difference
in the immune modulatory activity and some difference in the effectiveness
of cholesterol lowering.
Milk Thistle appears to be a safe adjunctive medication although it is of
limited value.
The Mount Sinai Medical Center
New
York, New York 10029
October
1999
4.)
Is there a direct impact on one's fatigue level if the thyroid as well as
LFT's are in the high ranges? Does any one blood test indicate fatigue? Do
symptoms of fatigue and general malaise correlate with stages of the disease?
Answer
Thyroid
disease, independent of liver disease, may cause fatigue, and thyroid disease
is more common in PBC than the general population. So, the answer to the
first part of the question is a definite yes.
However,
no blood test can predict fatigue in patients with liver disease. In fact,
the level of elevation of the liver blood tests has no bearing on fatigue.
As
well, fatigue can occur during any stage of the disease.
Fatigue
is reported in 60 to 90 percent of patients with PBC and the cause is unknown.
The fatigue may be intermittent, or it may occur for prolonged periods of
time.
The
subjective nature of the complaint has made it difficult to scientifically
study this symptom.
The Mount Sinai Medical Center
New
York, New York 10029
October
1999
5.)
Can you explain why some sufferers of pbc have chronic fatigue and others
are totally unaffected and can carry on as normal, and yet they have or have
had extreme itching?
Answer
The
subjective nature of the complaint (chronic fatigue) has made it difficult
to scientifically study this symptom. The same thing goes for itching. In
late stages, the itch may persist, although like fatigue, itching can also
be one of the earliest manifestations of the disease and it may or may not
persist with or without treatment.
Dr.
Howard Worman
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
April
2000
20.
Do you know of any studies being done on benign tumors in the liver. Can
these type of tumors become malignant? What effect, if any could these tumors
have on a person with PBC or other autoimmune liver disease?
Answer
There
are several different benign tumors of the liver. The most common is probably
cavernous hemangioma. Others include ademonas and hamartomas. Benign tumors
do not become malignant. The occurrence of a benign liver tumor in an individual
with PBC or another autoimmune liver disease is probably coincidental. I
am not aware of any studies showing that benign liver tumors are associated
with PBC or other autoimmune liver diseases. I also do not know of any data
showing that these tumors have any influence on disease progression or outcome
in PBC.
Dr.
Howard Worman
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
April
2000
21.
What is the estimated life span of a Transjugular Intrahepatic Portosystemic
Shunt (TIPS)? When an ultrasound is performed post-TIPS, there are several
values listed. What are the most important ones to determine if TIPS is working
properly?
Answer
Not
being an interventional radiologist, I am not an expert of TIPS. I'll try
my best to answer these questions as best I can. The initial success rate
of TIPS is high and the shunt is successfully placed in about 90% of cases.
Depending upon the published study, the rate of clogging of the shunt is
between 33% and 71% at one year. I don't know of any studies that look beyond
one year, but they may be out there.
I
do not know exactly what "values" are measured when an ultrasound is performed
to evaluate a TIPS. The most important parameter would be related to blood
flow through the shunt. This could be obtained by a Doppler scan estimates
the volume of blood flowing through the shunt in a given time period. You
should direct this question to a radiologist if you want to know the precise
values measured.
Dr.
Howard Worman
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
December
1999
Question 36
Do you see a lot of patients with kidney and bladder infections?
Are they common with people who have PBC?
Answer
Several studies suggest that urinary tract infections are more common in
women with PBC. Our own study (Parikh-Patel A., Gold, E. B., Worman, H.,
Krivy, K. E. and Gershwin, M. E.. Risk factors for primary biliary cirrhosis
in a cohort of patients from the United States. Hepatology. 2001;33:16-21)
showed an increase of vaginal or urinary tract infections in women with PBC
of approximately 4-fold compared to controls. Some investigators have even
hypothesized that having a urinary tract infection may be a "trigger" for
PBC in certain susceptible individuals. This hypothesis has not been
proven.
Dr.
Nathan Bass
Professor
of Medicine, Medical Director, Liver
Transplantation
Program,
University
of California
San
Francisco
2000-2001
11.)
PBCers & articles I've read state there's a higher incidence of breast
cancer in PBCers. Is there data showing this? If so, what could be a cause?
Or could it be the autoimmune process causing the higher
rate?
Answer
It
is unclear whether the risk for breast cancer is really increased in PBC.
Some early studies found this to be the case (Wolke, Am J Med 1984;76:1075;
Goudie, BMJ 1985; 291:1597) but this was not confirmed in later studies
(Witt-Sullivan, Hepatology 1990;12:98; Loot, Hepatology 1994; 20:101). The
theory was that a carcinogen that is normally excreted in the bile accumulated
in the body in PBC because of cholestasis. Of course, that was a theory based
on unconfirmed results. Cancer of the liver may occur in PBC, but compared
with many other causes of liver disease, is quite
rare.
Dr.
Howard Worman
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
5. Why
is it so many of us get those horrid cramps {charley horses} in feet, legs,
hands, neck, everywhere and they are so very intense and do not go away for
a while. We have discussed this in the digest numerous times and can't figure
it out. What is the normal cause of the cramps to someone who does not have
PBC?
Answer
I don't
think that cramps in the feet, legs, hands, neck, everywhere are associated
with PBC. Depending upon the study, between 4% and 50% of individuals with
PBC may have arthritis. Rare patients with PBC will have bone tenderness.
But muscle cramps just have not been reported to be associated with PBC.
The "normal" cause of cramps in someone who does not have PBC is probably
the same as in the members of your group. There are many different causes;
in the vast majority of cases, they are not
serious.
The Mount Sinai Medical Center
New
York, New York 10029
February
2000
19.)
Question
How
would doctors suggest we explain PBC fatigue to others? People always say,
"I'm tired too", and it's hard for them to understand the fatigue I have.
Do you have any suggestions to help with fatigue? Thanks!
Answer
That
is a difficult question. Yes, everyone experiences fatigue from time to time
but fatigue associated with liver disease has been studied extensively and
has been shown to be unrelated to other causes of fatigue (lack of sleep,
stress, depression etc.). Many describe the feeling as "hitting a wall".
Some
individuals have no choice but to succumb to the fatigue and plan on napping
each day. For most people, however, incorporating some sort of aerobic exercise
into the routine is the best treatment. Many people scoff at this suggestion
because when you feel tired, the last thing you want to do is exercise. Yet,
when exercise becomes part of your routine, the time invested generally pays
off by increasing your energy level. The principle is similar to a car battery
recharging itself.
Dr.
Hugo E. Vargas
Medical
Director, Transplantation
University of Pittsburgh Medical Center
Pittsburgh,
PA
June
2000
16.)
I have heard some people taking Carnitor to help with the fatigue. Can you
give me some information about what this drug does and what the indications
are for its use? Who should take it? Do you have suggestions for the PBC
fatigue?
Answer
Carnitine
metabolism has been found to be abnormal in patients with PBC. However, I
know of no study that links supplementation of Carnitine to improvement in
fatigue. The leading theories about the fatigue of PBC include endocrine
impairment, serotonin neurotransmitter abnormalities and possible autoimmune
effects.
Dr.
Howard Worman
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
February
2000
13.
I suffer fatigue on an ongoing daily basis. I have been told that since I
am on Urso and my blood work is good that my PBC is not the cause of the
fatigue. Yet here I am and so are many other PBCers I have listened too.
Please explain fatigue and PBC.
Answer
Some
patients with chronic liver diseases, including PBC, suffer from fatigue.
I am not aware of any study that correlates fatigue with "blood work" (presumably
you are referring to laboratory tests such as alkaline phosphatase activity,
etc.). To my knowledge, there is no direct association between fatigue in
liver disease and any laboratory test results. The cause of fatigue in chronic
liver disease is not clear. And it is often difficult or impossible to determine
if "fatigue" is a result of the underlying liver disease or something else
(e.g. depression). But fatigue can result from chronic liver disease.
There
is no single activity that can relieve fatigue. Medications are probably
not helpful. In part, maintaining a positive attitude may help ("I know I'm
tired but I'm not going to let it get to me."). This is not always possible
for individuals with severe fatigue. Arranging your daily schedule so that
you have time to rest may also help. Similarly, doing most of your activities
when you feel the best (e.g. early morning) may also be beneficial.
Finally,
a regular exercise program may help overcome fatigue. In the near future,
my colleague at Columbia Dr. Nora Bergasa plans to start a study of regular
exercise for fatigue associated with liver disease. Before starting an exercise
program, individuals with PBC should consult their
doctors.
The Mount Sinai Medical Center
New
York, New York 10029
February
2000
14)
Actigall does help my itching; does it do a better job of this if my pills
are spaced throughout the day instead of taking them all at once or just
twice a day?
Answer
Most
recommend dividing the dose of Actigall (ursodeoxycholic acid) based on the
dosing schedules that were used in the large studies proving benefit from
the drug. In the only study I know that specifically looked at dosing schedules,
it appeared that taking the drug once daily was as effective as dividing
the drug up (of course assuming the total daily dosage was the same). The
benefit of once a day dosing is perhaps increasing compliance with the medical
regime.
Alfred
L. Baker, M.D.
Division of Gastroenterology & Hepatology
Northwestern Memorial Hospital
Chicago,
IL
2000-2001
4.)
In reading many of the digest notes from other PBCers, I see that often their
LFTs go down into the normal range after starting Actigal or Urso. My LFTs,
after 10 1/2 years of Actigal have never been in the normal range although
my bilirubin continues to be in the normal range and my only symptoms are
Sjorgen's and mild itching and arthritis. Is this what is considered normal
for those with PBC?
Answer
Ursodeoxycholic
acid has been shown to delay the need for transplantation and perhaps to
improve survival in several controlled trials. The beneficial effect is probably
the greatest in individuals whose liver chemistry tests show the most
improvement. However, several studies suggest that a patient with a normal
serum bilirubin has a rather good prognosis, although perhaps not so good
as an individual whose liver chemistry tests are entirely normal after treatment.
For patients who do not have an optimal response to ursodeoxycholic acid,
additional treatments may be available, particularly by way of ongoing clinical
trials. Patients who have continuing symptoms and abnormal liver chemistry
tests related to PBC should consult their physician about the need for additional
evaluation and the possibility of further
treatment.
Alfred
L. Baker, M.D.
Division of Gastroenterology & Hepatology
Northwestern Memorial Hospital
Chicago, IL
8/8/2003
Question 1
Does PBC liver disease (damage) continue to progress while taking the regimen
of Ursodiol. There have been testimonials asserting that enzyme levels can
return to normal after taking the medication. Does liver damage and progression
stop while taking the Ursodiol?
Answer 1
A number of studies have shown that ursodioxicolic acid improves liver chemistry
tests in patients with PBC. Other trials demonstrate that this drug can slow
the progression of PBC, delaying the time until transplantation or death.
Thus, the drug is widely prescribed for PBC, but the effect is to slow disease
progression rather than to stop it.
David
Bernstein, M.D.
Chief,
Division of Gastroenterology
North
Shore University Hospital
Manhasset,
NY
July
2000
17.)
I have always been told that PBC will not actually improve, but the progress
can only be slowed by Actigall or URSO. Besides medications, can anything
else slow the progress of PBC? Have you observed improvement in the liver
condition in subsequent biopsies that would indicate a turnaround rather
than simply a lack of progress?
Answer
The
goal of treatment with URSO or Actigall is to suppress or reverse the underlying
process. URSO has been shown in studies to improve the inflammation seen
on liver biopsy but it does not seem to have an effect in reversing fibrosis.
It has, however, been shown to slow the progression of disease and delay
the need for liver transplantation. I personally have not observed significant
improvements on serial liver biopsies in many patients but I have noted the
lack of progression on therapy.
Unfortunately,
no other medications, including health food store and natural herbal products,
have been shown to slow the progression of disease.
Kris V. Kowdley, MD
Associate
Professor of Medicine
University
of Washington School of Medicine
Division of Gastroenterology/Hepatology
Seattle
WA
2001
Question 1
Some
claim Actigall reduces the lab numbers in those with PBC, but there are no
long term studies as to the effect of talking this drug long term. Even if
the numbers go down, is the disease still progressing? What does Acitgall
do exactly? What are the long term effects of taking this drug?
Answer
There
are early concerns that ursodiol may "whitewash" the lab tests in PBC without
change in outcome. We no know that ursodiol therapy improves survival in
PBC (especially those with moderately advanced disease), delays progression
of liver damage on liver biopsy and may reduce the development of varices.
We don't know exactly how ursodil works in PBC, but we think that it replaces
the toxic bile acids which can worsen liver injury. There are no known long
term complications associated with taking this medication although a few
patients complain of loose stool.
Dr. Howard Worman
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
April
2000
Question 35
I am confused about the benefits/purpose of taking Actigal/Urso - some doctors
say it doesn't do anything - others that it slows down the progression of
PBC - others that it "improves the numbers" but that doesn't really mean
anything. What are your comments on taking Actigall/Urso? If it slows down
progression of PBC-by how much? Do you have an idea of percentage of people
it slows progression? If your numbers (ALT-AST) improve -- what does that
mean?
Answer
I can't answer this question briefly. Doctors and experts on PBC will debate
these issues for days. In short, several studies do show that ursodiol (the
active ingredient in Urso and Actigall) slows the progression to cirrhosis
and decreases the number of patients who undergo liver transplantation during
several years of follow-up. So yes, there are some data showing that ursodiol
may "slow down the progression of PBC." It is unclear "by how much" or "in
what percentage of people" as the studies no studies have been designed to
answer these questions. It is not clear what it means if "your numbers improve."
There are no data available to answer this question. My personal feeling
is that the numbers you are referring to (ALT, AST, alkaline phosphatase)
do not mean anything in the long term outcome.
Dr.
Melissa Palmer Answers Our Questions
Specialty:
Gastroenterology and Hepatology
Medical
advisory board of the ALF New York Chapter
ALF
National Chapter Nutrition Education Subcommittee
November
1999
2.)
How often should liver biopsies be done on a patient already diagnosed with
PBC?
Answer
There
is no agreed upon, standardized "correct" time for patients with PBC to undergo
repeat liver biopsies, (if ever). Patients on a study protocol often are
required to have a biopsy performed at the beginning and at the end of the
study. However, patients not on a study, need never have a biopsy repeated
(so long as at least one biopsy was done in order to correctly diagnose and
stage the disease).
Dr.
Melissa Palmer Answers Our Questions
Specialty:
Gastroenterology and Hepatology
Medical
advisory board of the ALF New York Chapter
ALF
National Chapter Nutrition Education Subcommittee
April
2000
18.)
Combucha tea derived drinks are supposed to boost immune system. Do you think
they are beneficial? Do you recommend any special teas or other drinks?
Answer
I
am not aware of combucha tea, but green tea, camellia sinensis, contains
a high dose of catechin. Catechin is a plant chemical with proclaimed antioxidant
liver-protective properties. Experimentally induced liver damage in rats
has demonstrated the protective effects on the liver afforded by catechin.
However, human studies have failed to show similar results.
Judging
from the above questions, there appears to be a thirst for knowledge concerning
the effects of nutrition on liver disease, and the use of supplements on
liver disease. I therefore recommend all individuals with PBC to refer to
my book Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease", or to
my - website
www.liverdisease.com. In my book I have extensive
information on these topics relating specifically to individuals with
PBC.
Dr. Marshall Kaplan
Chief,
Division of Gastroenterology
New
England Medical Center
Boston,
MA
September
9, 1999
11.
What about the levels of liver enzymes reported after a liver panel (ALP
ALT etc), are they directly related to the amount of damage to the liver?
Answer
There
is no correlation between the serum levels of ALP, ALT or AST and the extent
of liver damage. This was recognized more than 40 years ago when these tests
were extensively studied. I fear that many younger doctors may not know this
older medical literature.
Howard
J. Worman, M. D.
Associate Professor of Medicine and Anatomy and Cell Biology
College of Physicians and Surgeons Columbia
University
July
2003
Question
5
Have there been any studies done on post-TX medications like Prograf and
Rapamune causing Joint and Muscle Pain? Or leading to osteoporosis?
Answer 5
I am not aware of any studies that have specifically looked at tacrolimus
(Prograf) or sirolimus (Rapamune) causing joint and muscle pain. However,
in clinical trials of these drugs, patients have reported these symptoms.
Osteoporosis is known to occur at an increased frequency after organ
transplantation and is probably aggravated by anti-rejection medications.
A few studies in laboratory animals suggest that bone loss may be faster
with cyclosporine A, somewhat less with tacrolimus and even less with sirolimus.
I am not aware of similar studies in human subjects but it is possible that
they have been done. If you are interested in published studies, you may
want to know about the National Library of Medicine resource Pub Med. You
can search the medical literature using Pub Med on the Internet. The URL
is:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
Andrew
Mason, MBBS MRCPI
Associate Professor of Medicine
Division of Gastroenterology, Department of Medicine,
University of Alberta, Edmonton, Canada
August
2000
Question
10
Have
you found a transmissible agent in PBC? Could we have contracted this or
could we possibly be contagious?
Are
all viruses human viruses? Just what is a retrovirus? Could this possibly
be another form of hepatitis or a
variation?
When do you expect the results of your research to be published? I personally
am glad to see someone
looking
for possible causal agents.
Answer
We have
found a transmissible agent in PBC and submitted a paper documenting infection
of biliary epithelial cells
with
PBC patients' tissues. In this paper we show that the transmissible factor
is produced by the infected biliary
epithelium
and can be passaged to other normal biliary epithelium cells, it is particulate,
and we can kill it with gamma irradiation. In further studies, we have found
that the agent has the structural and chemical properties of a retrovirus.
We have
not yet studied how the virus is transmitted to patients. I suspect that
the virus does not cause PBC in all patients that are infected as very few
people get PBC. It is thought that you need to have specific genes to get
PBC in the first place.
Not
all viruses are human viruses. In fact, most of our viruses appear to have
evolved from animal viruses in the first place. The name retrovirus is derived
from the reverse transcriptase gene that the virus uses to replicate. Other
viruses, such as hepatitis B virus, also use a reverse transcriptase gene
and although this is not considered to be part of the retrovirus family,
it appears to be descended from this group of viruses. The hepatitis virus
group is just a collection of different viruses that are associated with
hepatitis and they are not a distinct family. I think the PBC virus may turn
out to cause hepatitis as well but we will have to perform further studies
to prove this. We hope to publish all the viral discovery data
soon.
Alfred
L. Baker, M.D.
Division of Gastroenterology & Hepatology
Northwestern Memorial Hospital
Chicago,
IL
8/20/2002
Question
22
a. What opinion do you hold regarding hormone replacement therapy (premarin)
and its role in PBC?
b. If a person has taken hormone replacement for 20 + years do researchers
have any idea the affect it has on the PBC?
Answer 22
Several recent studies consider the benefits of hormonal replacement therapy
on cardiovascular disease and the risk of complications such as breast cancer.
I encourage my patients to consult their gynecologists to make a decision
about whether they should take hormonal replacement therapy to suppress
menopausal symptoms or for other reasons. However, hormonal replacement therapy
ordinarily does not injure the liver, even over many years of treatment.
It is reasonable to consider hormonal replacement by patch rather than by
mouth to minimize the liver's exposure to
medication.
Dr.
Marshall Kaplan
Chief, Division of Gastroenterology
New
England Medical Center
Boston,
MA
December
1999
13.)
Can PBC reoccur after a transplant and if so, how common is it?
Answer
It
is very rare for PBC to recur after OLT if adequate immunosuppression is
used. I have not seen it in any of the PBC patients who have had transplants
at NEMC since 1983. There is some controversy because researchers at UC Davis
and Mayo have considered recurrence to have occurred in some of their patients
who are well, have normal blood tests and normal liver biopsies but who have
a finding on liver biopsy that is only demonstrable using a research technique,
immunohistochemistry. In my opinion, no one knows what this finding really
means. I would not consider these patients to have recurrent
PBC.
Dr. Howard Worman
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
April
2000
Question 42
Other
than URSO what is the treatment to lower indirect bilirubin in a post transplant
PBC person?
Answer
There
are many causes of elevated bilirubin concentrations. Elevated bilirubin
in the blood per se is NOT something that is treated, except in infants in
whom very high concentrations of bilirubin can cause problems with the
undeveloped nervous system.
If
a patient has an elevated serum bilirubin in blood post-transplant or otherwise,
a diagnostic work-up must be performed to determine the causes. The underlying
cause is treated. URSO (ursodiol) is NOT indicated to "lower the bilirubin"
in any condition. It is used in PBC because in several studies it has been
shown to slow the progression of the disease, not because it lowers the blood
bilirubin concentration.
Dr.
Howard Worman
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
April
2000
Question 34
Could you please explain in layman's terms, the difference between Autoimmune
Cholangitis and Primary Biliary Cirrhosis? Is there a conclusive test for
AIC, and would it show up in a biopsy?
Answer
"Autoimmune cholangitis" is not a well-defined disease or condition. It is
a very confusing term and not all experts agree as to what it really means
or if it really exists. Some people use "autoimmune cholangitis" to refer
to what has also been called "AMA-negative PBC." This is the group of patients
who have most of the features of PBC but do not have detectable antimitochondrial
antibodies in their blood. I personally disapprove of these classifications
("autoimmune cholangitis" and "AMA-negative PBC") as recent data using more
sensitive tests show that many of these patients also have antimitochondrial
antibodies. Some reports suggest that patients with so-called "autoimmune
cholangitis" have features more commonly seen in autoimmune hepatitis. Some
doctors refer to this as "overlap syndrome." I'm also not really sure that
this is a specific disease or condition. In conclusion, it's not really clear
what "autoimmune cholangitis" is. Perhaps it is PBC with some different features.
Perhaps it's a separate disease. Until we know what causes bile duct damage
in PBC and similar conditions, nobody will know. More basic research is
necessary! There certainly is no "conclusive test for AIC." And there are
no definitive findings on biopsy either. Even in most cases PBC, the biopsy
finding are usually only "consistent with" the disease and not absolutely
diagnostic.
Dr.
Howard Worman
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
6.
Are there different kinds of PBC? Some of us seem to deteriorate much faster
than others in the group.
Answer
PBC
is a diagnosis based on clinical, laboratory, immunological, and histological
(liver biopsy) criteria. (For more information on the diagnosis of PBC, you
may want to see my recently published The Liver Disorders Sources, Lowell
House, 1999;
http://www.amazon.com/exec/obidos/ASIN/0737300906/diseaseofthelive). The cause(s) of PBC
is not known. Most likely, the cause(s) is the same in the large majority
of patients because most have the same histological (bile duct lesion) and
immunological (antimitochondrial antibodies) abnormalities. Having said all
this, it not clear why some individuals with PBC deteriorate faster than
others. Differences in environmental factors may be one reason, for example,
those who drink significant amounts of alcohol may have faster liver
deterioration. Genetic factors are also likely to be important. The occurrence
and course of many diseases are modified by various "susceptibility genes."
Hypothetically, genes encoding proteins involved in the immune response may
make a patient more susceptible to develop PBC or have a more rapidly progressive
course. At the present time, none of these susceptibility genes have been
identified. In brief, much more research is needed to answer this
question.
Dr.
Marshall Kaplan
Chief,
Division of Gastroenterology
New
England Medical Center
Boston,
MA
September
9, 1999
8.
There is a newly available supplement called SAM-e (S-adenosylmethionine).
The insert says that it's been studied extensively and clinically found to
promote and support liver health among other things. Physicians are encouraged
to contact the company for scientific information. The company is Nature
Made. Ph # is 1-800-276-2878. The company is Nature Made. Do you know anything
about this?
Answer
Yes.
I know a lot about it and used to use it in biochemical research 35 years
ago. It is one of many products that has no established role in the treatment
of liver disease, certainly no role in the treatment of PBC. I can only assume
that some entrepreneur or company hopes to make money by promoting its sale.
In contrast to "ethical drugs" e.g., URSO and Actigall, our government does
not regulate this industry, one which many of us feel should be more carefully
monitored.
Dr. Hugo E. Vargas
Medical
Director, Transplantation
University of Pittsburgh Medical Center
Pittsburgh, PA
November
1999
2.)
Fatigue plagues most everyone with PBC. It is debilitating -- really interfering
with life and daily plans. Please explain what causes the fatigue. Is any
research being done to solve this issue? Should one push to continue exercising
during a fatigue episode?
Answer
Fatigue
is not unique to PBC and is one of the more common problems in the setting
of chronic liver disease. Despite efforts to figure out why it develops,
it has been hard. It is particularly difficult to study because it is a complaint
that although real is difficult to measure. I recommend to my patients to
exercise as tolerated.
Dr. Howard Worman
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
1.
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.
Thomas
Shaw-Stiffel, MD,
Medical
Director,
Living
Donor Liver Transplantation
Univ
of Pittsburgh
Medical
Center - Presbyterian Hospital Center for Liver
Diseases
March
2003
Question
1
Have
there been any studies done for post-TX depression? Why does depression seem
to be common in PBC?
Answer
1
Not
aware of any such studies but they need to be done. PBC causes fatigue and
other nasty symptoms such as itchy skin, keeping many patients up all night
(or at least altering their sleep). The need for sleep to prevent depression
is currently under study (which is the main problem, depression and poor
sleep, or as some suspect, the reverse may be the
cause).
Howard
J. Worman, M. D.
Associate Professor of Medicine and Anatomy and Cell Biology
College of Physicians and Surgeons Columbia
University
July
2003
Question 6
What progress has been made with the development of an extracorporeal liver
aid device? Is such a device currently available and would it be of benefit
to anyone who is not eligible for a liver transplant?
Answer 6
Extracorporeal liver assist devices are currently being studied in humans
in clinical trials. They are being studied at several medical centers as
a "bridge" to liver transplantation; that is, to support someone with liver
failure in need of a transplant for a few days until a donor liver becomes
available. A lot of work still needs to be done. There are no such devices
yet for "long-term" use, such as for an individual with an end-stage c