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 chronic
liver disease who needs a transplant but is not
eligible.
Dr.
Ira M. Jacobson
Weill
Medical College of Cornell University
Chief,
Division of Gastroenterology & Hepatology
New
York Presbyterian Hospital-Cornell Campus
Director,
Gastrointestinal & Liver Service
New
York, NY
April
2001
2.
When do you believe we should take the initiative to get on a transplant
list? Should we leave this in our Drs hands? Are symptoms a factor or just
the labs and disease stage?
Answer
One
should go on a transplant list when there are impending signs of liver failure,
or variceal bleeding, or ascites (fluid in the abdomen), or intractable itching,
or progressive jaundice. Every case is a little different.
Dr.
Andrew Mason
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
12/16/2002
Question
14
Are the
red blood counts affected by PBC? What are the most important labs for PBC?
Answer
14
The red
blood count can be affected by the consequences of portal hypertension if
the high venous pressures in the
veins coming
from the stomach to the liver make blood ooze from any lesions in the stomach.
Most lab
tests are important but rising bilirubin levels can be fairly predictive
for the need of liver transplantation.
Dr.
Andrew Mason
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
18
My
question: If a person with liver disease related to Hep C and complications
preventing a transplant, why can't some of the person's liver be removed,
as a liver can regrow in a matter of weeks. Wouldn't this give a person more
time?
Answer
18
Cirrhotic
livers grow back less easily and are still cirrhotic. Therefore, the operation
would be both unnecessary and dangerous.
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
1.)
I have a question for the doctors, I have no medical background. I was wondering,
with a live donor transplant the donor gives part of his/her liver to the
person in need and the donor's liver regenerates itself. The transplants
liver also takes the new section and regenerates or grows. What would happen
to a PBC liver if part of it were surgically removed? Would it regenerate
on it own, and would it still have the PBC or would it be disease free? Is
this a possibility?
Answer
Living-
donor transplantatation has significantly helped the liver-donor shortage
especially in the pediatric are group. It is just recently becoming a more
accepted option for adults. Using this technique, for an adult with PBC,
for example, the donor, donates part of his or her liver to the PBC patient.
The PBC patient has his or her liver totally removed, and the part of the
donor's liver put in its place. It will eventually grow to a normal sized
liver. Only "part" of the PBC liver is not removed, the whole liver is removed.
However,
in theory, if part of a PBC liver is surgically removed, if cirrhosis ( stage
4 PBC) were already present, the liver could not regenerate. If cirrhosis
were not present, the liver could regenerate, but the newly regenerated liver
would still have PBC.
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
January
2000
12.)
Has part of a transplanted liver ever been used as a donor in a live transplant?
Answer
Living-donor
transplantation is significantly helping the liver-donor shortage. To my
knowledge, a transplanted liver has not as yet been used as a donor liver.
Dr.
Hugo E. Vargas
Medical
Director, Transplantation
University of Pittsburgh Medical Center
Pittsburgh,
PA
June
2000
17.)
How long would you estimate a woman age 45 diagnosed with PBC stage 4 (by
biopsy) stay healthy enough before requiring a transplant? Which would more
likely increase the chances of being listed for transplant, symptoms or increased
labs?
Answer
I
unfortunately do not have enough information to answer that. Mathematical
scores for PBC usually require knowledge of PT, Bilirubin, age and use of
diuretics. The rule of thumb you should use is if you already have cirrhosis
(stage 4), jaundice and decreasing albumin you will need a transplant sooner
than if you don't have any of these, but please ask your doctor with all
the specifics on hand.
Dr.
Nathan Bass
Professor
of Medicine, Medical Director, Liver
Transplantation
Program,
University
of California
San
Francisco
5.)
What are the five most important indicators for liver transplant? Are they
the same indicators for prognosis? How long is the average wait on a transplant
list or does it depend on the facility?
Answer
The
indicators that are officially in use constitute the variables that are used
to calculate a child Pugh score. Three are laboratory variables, two are
clinical. They are: serum albumin, serium bilirubin, prothrombin time, ascites
and encephalopathy. The average wait for transplantation depends on many
factors including stage of listing, blood type and facility location.
Dr.
Nathan Bass
Professor
of Medicine, Medical Director, Liver
Transplantation
Program,
University
of California
San
Francisco
Question 5
I am blood type A negative with positive antibodies (my 2 children were rh positive) and I am wondering if I would have possible problems looking for a donor. Besides blood what else has to match when you consider a possible donor.
Answer
The blood type matching rules are simple. In terms of the recipient, O can only receive from O, A from A or O, B from B or O, and AB from A, B, Ab or O. The Rh blood group (the "postive/negative") does not matter at all, so either of your children are potential donors for you. The other detail important in a living donor match is body size - usually we will want someone within 20% of your weight. There are many other factors that go into living donor selection though, including motivation, liver anatomy, weight, and many health details.
Dr.
Nathan Bass
Professor
of Medicine, Medical Director, Liver
Transplantation
Program,
University
of California
San
Francisco
2000-2001
7.)
What are the qualifications for getting a live donor transplant? I know about
blood type, but what about the rest. Is it ethnic background, age, weight,
height etc.
Answer
Adult-to-adult
living liver donation is a very exciting, new, and so far remarkably successful
procedure. It is also a big procedure for the donor- more so than donating
a kidney. Any patient who is considered a candidate for a liver transplant
could be a recipient from a live donor. Some problems may hamper this option,
such as having a portal vein blockage, but this is potentially manageable
too. Age is not an issue. We have evaluated one patient who was 70 as a living
donor recipient. The donor, on the other hand is generally going to have
to be youngish (less than 55), in excellent health (including no liver disease),
a non-smoker, light to non-drinker, not very overweight, no previous major
abdominal surgery, and motivated by deep concern and care for the potential
recipient. The donor need not be related, but this may help the outcome in
terms of less rejection. The donor must have a matching ABO blood type (O
to O, A to A, etc.) or be a blood type O (universal donor - can donate to
any blood type). Finally, the donor should match the recipient in size or
be a bit larger. Potential donors need to undergo a very careful health
evaluation as well as evaluation of the size and blood vessel anatomy of
their livers.
Dr.
Nathan Bass
Professor
of Medicine, Medical Director, Liver
Transplantation
Program,
University
of California
San
Francisco
January
2002
15.)
Question
I
am stage 3 PBC, and sometimes have pain in the liver area, but this is my
only symptom. When should a person in stage 3 be evaluated for the transplant
list? What is the criteria?
Answer
Stage
3 disease is a histological definition, i.e., this is purely the appearance
of the liver on a liver biopsy. If occasional liver pain is your only symptom,
it may still be early for you to undergo a transplant evaluation. Liver pain
is a well-recognized symptom in PBC. The cause is not clear, but it may include
stress on the thin capsule that covers the liver which we know is rich in
nerve fibers and very sensitive to stretching. However, many patients may
have varying amounts of liver pain or discomfort without evidence of advanced
liver disease. The usual indications for a liver transplant evaluation include
abnormal levels of serum bilirubin, serum albumin or prothrombin time. also,
any symptoms of edema, ascites (fluid in the abdomen) or altered nervous
system function known as hepatic encephalopathy. Patients with severe symptoms
of disease including itching, pain or fatigue may also qualify for an evaluation,
even though they still have early disease by the other usual criteria.
Dr.
Nathan Bass
Professor
of Medicine, Medical Director, Liver
Transplantation
Program,
University
of California
San
Francisco
January
2002
13.)
Question
I
understand that there are at least two different variants of PBC: One that
is more rapidly progressing & that is likely to result in transplant
or death within about 5-8 years of the onset of symptoms. The other a more
slowly progressing form that may never require transplant. Is there any
difference in the antibodies, genetic information, or reactivity to particular
enzymes or proteins that can be identified between these 2 variants? Is there
any way to predict which form of PBC a patient has?
Answer
I
do not think that there is convincing evidence for two distinct extreme types
of PBC. Rather, there appears to be a continuum of disease severity. In other
words, PBC progresses in most cases, but the rate of progression varies greatly
among individual patients.
Asymptomatic
patients have substantially longer life expectancies than symptomatic ones,
but their survival is still less than that of healthy individuals. The likelihood
that a patient will progress rapidly or will need a liver transplant will
most clearly depend upon the severity of disease at the time of presentation
(e.g., a patient presenting with jaundice or ascites has advanced disease),
and the rate of disease progression as monitored over a period of time. There
are scoring systems such as the Mayo PBC Prognostic Index or the new MELD
Score which a physician can use to determine an individual patient's general
prognosis or likelihood of mortality from the disease over a given time period.
These scoring systems are not crystal balls, however, and only provide a
statistical probability of an individual's prognosis. The key factors in
these scoring systems are age and liver function including serum bilirubin
level, serum albumin level, prothrombin time and signs of fluid retention
such as edema fluid. The MELD score also looks at kidney function. Your question
about other clinical or biochemical markers of more rapidly progressive disease
is interesting as there is some evidence for this. Interestingly, patients
whose disease presents with the very frightening symptom of bleeding from
varices often have less in the way of signs of cholestasis, and may actually
preserve their liver function for longer. Some information that suggests
that if an asymptomatic patient has other diseases, such as thyroiditis,
sicca syndrome, and scleroderma, survival may be compromised, although not
clearly just from liver disease. Granulomas seen on a liver biopsy have been
associated with better survival. Neither the presence of antimitochondrial
antibodies nor their level affects survival.
There
have been many studies attempting to identify genes that determine susceptibility
to PBC, but few studies have attempted to identify genes that affect the
rate of progression or natural history of the disease. Recent studies suggest
that a variant in the gene that produces a protein that is important in the
process of inflammation (tumor necrosis factor alpha) but this needs to be
confirmed.
The Mount Sinai Medical Center
New
York, New York 10029
October
1999
3.)
If blood type is A negative, does that mean when, and if, a person needs
a transplant, the donor's blood type needs to be A negative, or is type A
sufficient for a match. Also, would Liver Transplant still be considered
when the patient has a congenital absence of the right kidney, provided the
serum creatinine is within normal limits?
Answer
Several
factors are important in matching a recipient and donor for transplant. One
is liver size. The other is the recipient’s blood group. Matching a
recipient with Blood type A to a donor with type A is usually sufficient.
It is possible to cross match certain blood types, although results have
not been as good as those with a perfect blood group match, and it is generally
not done.
Different
centers have different guidelines about accepting patients as potential liver
transplant candidates. It depends on the centers experiences and their expertise
in general. I cannot speak for other centers, but congenital absence of a
kidney would not necessarily be an exclusion for liver transplant at our
center (Mount Sinai Medical Center, New York).
The Mount Sinai Medical Center
New
York, New York 10029
February
2000
24.)
Question
I
would like to know what the statistics are on what percentage of people with
PBC ever get to the stage that they would require a transplant.
Answer
I
am not aware of any such statistic. One recent study found that survival
in PBC patients without cirrhosis was comparable to that of an age and sex
matched control population of patients. Mortality was slightly worse for
those patients that had developed cirrhosis. Since many patients are first
diagnosed in their 50s or 60s, and the disease can span several decades,
many will die from natural causes before they do from PBC. With that caveat,
it is my belief that fewer and fewer patients with PBC are requiring transplants.
The reasons for that are not clear.
Alfred
L. Baker, M.D.
Division
of Gastroenterology & Hepatology
Northwestern Memorial Hospital
Chicago,
IL
8/20/2002
Question
19
a. I am
concerned that the new MELD scoring will be detrimental to PBCers receiving
a transplant. I have heard this from many sources. What are your thoughts?
b. How much does age factor into receiving a transplant?
Answer 19
a. The United Network for Organ Sharing (UNOS) mandated a new policy - the
Model for End Stage Liver Disease. (MELD) - to govern the distribution of
donated organs to transplant centers beginning February 27, 2002. This
change was designed to give organs to the sickest patients. In my view the
fundamental problem in organ distribution is not the system used for allocation
but rather the limited number of donor organs available. Thus, whatever system
is instituted, some patients will wait for organs longer than other. I think
it is too early to assess the precise effect of MELD on organ availability
for PBC patients, but such data will be forthcoming in the next year.
b. A patient's age does not enter into calculation of the MELD score so UNOS
does not limit distribution of organ's to older patients. Many transplant
centers do not offer the procedure to patients older than 70 years of age.
Alfred
L. Baker, M.D.
Division
of Gastroenterology & Hepatology
Northwestern Memorial Hospital
Chicago,
IL
2000-2001
Question
17
Since
everything is processed through the liver, is there any reason a pre or post
transplant PBC patient should avoid hair color, or nail polish?
Answer
We
recommend that all patients who receive liver transplants avoid hair coloring
and permanents for the first few weeks after the procedure. Otherwise, patients
with PBC do not need to avoid these cosmetic enhancements.
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 3
At what point in the progression of PBC should an individual usually be referred
for transplant evaluation (i.e. Blood levels…)?
Answer 3
Patients who have evidence of rising bilirubin are usually referred for
transplant evaluation. Increased bilirubin is the single most prognostic
laboratory test although, a more refined prognostic index is the Mayo risk
score. This may be calculated and also give prognostic information. Availability
of a liver transplant is dependent on laboratory test results. The current
organ allocation system uses a MELD score and this score is dependent on
bilirubin, INR and creatinine lab values. Patients are generally referred
for transplant evaluation after their MELD rises to approximately 10 points.
Such a patient would not immediately be transplanted but would be followed
as the MELD score rose bringing transplantation close.
Thomas Shaw-Stiffel, MD,
MMM
Medical Director,
Living
Donor Liver Transplantation
Center
for Liver Diseases
Pittsburgh,
PA
9/22/03
Question
2 I know this disease varies from individual to individual, but from Stage
4 PBC, what is the "typical" range of life expectancy before transplant?
Do younger patients get any preferential treatment on listing?
Answer
2 This also varies considerably. With ursodiol, the progression can be slowed
and liver transplant even prevented according to the trials published in
1998. So without specific lab values to assess severity of disease, having
stage 4 is less helpful in and of itself. NO, younger patients do not get
preferential treatment.
The Mount Sinai Medical Center
New
York, New York 10029
February
2000
22.)
Question
I
know that PBC varies from individual to individual, but if a patient is diagnosed
in Stage 1 and progresses to stage 4 in 6 years using medication what is
the "typical" range of life expectancy before transplant or death? Do younger
patients have any preferential treatment on listing?
Answer
I
am assuming that the staging the question refers to is based on liver biopsy.
With that assumption, the question is whether progressing from the earliest
lesion of PBC to cirrhosis in 6 years is a negative finding. Liver biopsy
findings can be misleading when it comes to PBC. The staging can vary from
place to place in the liver. As a result, liver biopsies are subject to sampling
errors, and studies have not found any correlation between the histologic
stage of the disease (findings found on liver biopsy) and clinical findings
(how well the patients does). That said, studies suggest that the prognosis
is not quite as good for those that develop cirrhosis compared with those
that don't. Nonetheless, many patients with liver biopsy findings indicative
of cirrhosis live normal asymptomatic lives for prolonged periods of time.
Younger
patients do not get preferential treatment on listing. For one thing, what
one person considers a "younger patient" might not meet another person's
definition.
University
of Pittsburgh Physicians
Division
of
Transplant
Surgery
March
02, 2000
Question
When
does one who has PBC get listed on a transplant list?
Are
Biopsy's always on the mark as to what stage a person is in?
I
suffer from PBC Stage 2 and live in Upstate NY. Is it possible to be listed
at other hospitals or does one need to be within a certain distance of the
hospital?
Answer
As
you know, Primary Biliary Cirrhosis, PBC, is thought to be an autoimmune
liver disease, which is more frequent in women, whose course is variable,
but generally lasting many years. Some develop complications within a few
years, other live with the disease for 25-30 years. It is not understood
what factors affect the rate of developing life threatening complications.
As
with other liver diseases, the complications relate to portal hypertension
and inability of the liver to function normally. This is manifest by: esophagel
varices and ascites (fluid in the abdomen) due to portal hypertension, confusion
or encephalopathy due to inability of the liver to clear toxins, itching
or pruritis due to inability of the liver to excrete bilirubin and bile salts,
and weakened bones or osteoporosis due to the inability of the body to absorb
calcium.
Once
a patient develops enough of these problems, then one should be considered
for transplantation. A rough guide for being put on the waiting list can
be determined by a scale known as the Childs-Pugh score. It takes 3 biochemical
measurements, serum albumin, prothrombin time, total bilirubin and 2 clinical
measurements, presence of ascites (fluid in the abdomen) and encephalopathy
(confusion). It assigns a number of points to various levels of derangement.
The more points you have, the worse the liver disease.
The
minimum number of points you can have is 5, the most is 15. The greater number
of points, the more likely that you will develop complications, including
life threatening complications.
It
has been determined that a minimum of 7 points is needed to be even listed
on the transplant list. This is because lower scores than that are not associated
with a significant risk of dying. Nevertheless, if there are extenuating
circumstances, someone can be listed, however this must be approved by a
special committee. Even if one meets the minimum 7 points for listing, they
can only be listed in the lowest urgency category, i.e. Status 3.
As
one's liver disease progresses, then he/she will get more points and can
move to the next level, i.e. Status 2B, when the Childs score reaches 10.
To get to the highest level, Status 2A, one must be on life support and in
the ICU. Obviously it would be best to get a transplant well before this
happens.
The
best advice that I can give you is to have close follow up by your
hepatologist/gastroenterologist and keep your transplant program notified
of any changes in your condition
Howard J. Worman, M. D.
Associate Professor of Medicine and Anatomy and Cell Biology
College of Physicians and Surgeons
Columbia University
New York, NY
9-29-03
Question 1
At what point in the progression of PBC is an individual usually referred for transplant evaluation (i.e. blood levels....)?
Answer 1
Several mathematical models based on clinical, laboratory and histological criteria have been devised to attempt to predict the progression of PBC. One of the better-known models is the "Mayo" model, which is an equation that takes these parameters into consideration.
Putting these mathematical models aside, the blood bilirubin concentrations is probably the best prognostic indicator of all laboratory values in PBC. A blood bilirubin concentration of 6 mg/dl is associated with a mean survival of about 2 years (this number is from before the days of ursodiol). Therefore, given organ availability in most parts of the United States, once the serum bilirubin concentration reaches 4 mg/dl a patient with PBC should be referred for transplantation evaluation.
Any patient with PBC who develops signs of liver dysfunction or portal hypertension (e.g. ascites, bleeding esophageal varices) should also be referred for transplant evaluation regardless of the blood bilirubin concentration.