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Dr. Melissa Palmer Answers Our Questions
Question & Answers
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.
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).
3.) Have there been any studies on the relatioship between PBC symptomology and evolution and Sress Management Programme (Biofeedback , Relaxation , Cognitive Restructuring etc.?
Answer
To my knowledge, there have not be any studies done specifically on PBC symptomatology and stress management programs. However, it is important to utilize any form of stress management ( such as the one's you listed above), to assist with the treatment of any disease, including PBC.
4.) We know that PBC is an Auto Immune Disease. If our Immune systems are attacking our liver, why is it that we think a Liver Transplant would fix our problem dosn't it seem to reason that the immune system would then attack our new liver? Couldn't this then be the reason that we have some recurring PBC cases Post Transplant?
Answer
This ia a very good question that has sparked much debate among hepatologists for many years. It does appear that PBC can recur in the new liver. However, since this disease is so slowly progressive, it will take many years for any significant damage and/or symptoms to occur, if they occur at all. Therefore, a liver transplant would certainly fix the problem for most individuals.
5.) What is the difference between the two blood chemistry lab tests for bilirubin conjugated and bilirubin total? What does it mean if one is elevated and the other is not?
Answer
Bilirubin is the yellow-colored pigment that the liver produces when it recycles worn-out red blood cells. It exists in two forms: conjugated ( direct) and unconjugated (indirect ) bilirubin. Together they are known as total bilirubin.
Unconjugated bilirubin becomes elevated when blood is broken down faster than the processing abilities of the liver ( this is referred to as hemolysis).
Gilbert's Disease is the most common genetically acquired disease of abnormal bilirubin conjugation. It results in an elevated unconjugated bilirubin level on blood tests, but this is totally benign.
Conjugated bilirubin elevations, however, may signify the worsening of an underlying liver disorder.
6.) A large number of PBCers have been diagnosd with Costochronditis which affects the rib cartledge. I have read articles on this disease and all state the disease should disappear in a month or two. Some of us have had it for 1, 2 and 3 years and the pain can be severe..... What would be the reason it does not seem to improve in PBCers? Could it be the autoimmune system causing this? Do you have any suggestions?
Answer
Costocondritis is painful swelling of one or more costochondral articulations. This pain may mimic chest pains due to cardiac disease and digestive disorders. Therefore, a thorough evaluation for these diseases must be searched for by your physician. Rheumatoid arthritis must also be looked for, in addition to diseases of the ribs such as cancers ( although uncommon). Imaging studies and biopsy is sometimes necessary in order to make sure that the diagnosis is correct.
Unfortunatrely, often the pain of costochondritis may last many years in any individual, not just those with PBC. Treatment with pain medications and/or local steroid injections usually relieve symptoms. A discussion of pain medications for individuals with liver disease can be found on my website http://www.liverdisease.com.
January 2000
7.) Have there been any studies done on a connection between pbc and rheumatoid arthritis?
Answer
Have there been any studies done on a connection between pbcand rheumatoid arthritis? Since many rheumatologic disorders have an autoimmune origin, it is notsurprising that there is a high degree of association between rheumatologicdisorders and PBC. Rhematoid arthritis, which is characterized by joint aches and joint deformities, is often seen in people with PBC. Other rheumatologic disorders occuring in people with PBC include Sjogrenssyndrome, which is characterized by dry eyes and dry mouth, scleroderma,characterized by thickening and hardening of the skin and even some internalorgans, and raynauds phenomenon, that typically causes the fingertips toturn blue and become numb when exposed to cold weather or emotional stress.
8.) What is the effect on someone with PBC who has an extememly low "D" level?
Answer
Vitamin D is a fat soluble vitamin which is often poorly absorbed by individuals with PBC. Vitamin D supplementation with calcium is important as patients with PBC are prone to bone problems, including bone loss, bone pain, and bone fractures. These bone disorders are often a source of great suffering and can severely disable a person. In fact, sever bone disease coupled with recurrent bone fractures in people with PBC may be an indication that liver transplantation is warranted.
9.) Is there any current data or can you share information on the long term effects of immunosuppressive medications - such as Neoral, Prograf and Cyclosporin? There were indications that Prograf had more toxicity incidents, is this still the case? We all have concerns regarding the neuro and renal toxicities, malignancies, diabetes, etc.; and having some information on these medications would help in deciding which may be a better option.
Answer
Cyclosporine (Neoral) may cause kidney failure, but this is readiloy reversibleupon lowering the dosage. Due to changes in sugar and fat metabolismcaused by cyclosporine, the patient may be at increased risk of hypertensionand heart disease. Neoral may also affect the central nervous system -seizures, numbness, confusion, and halllucination have been experieincedby some people while on therapy. Increased hair growth, especiallyin brunettes, is common. A enlargement of the gums may occur often necessitating surgical correction. There also appears to be an increased risk of cancer.
Tacrolimus ( FK 506 oe Prograf) has similar side effects to those of Neoral. Tacrolimus has been associated with greater kidney and neurologicaldamage according to some, but not all studies. People may experieinseinsomnia, headache, and decreased alertness. Diabetes may occur,requiring an adjustment in dosage. Hypertension and high cholesterollevels can occur but less frequently than with Neoral. Less weight gainafter transplantation has been noted in patients. Some studies,although not all, have shown that a higher percentage of people may livelonger after transplantation if placed on tacrolimus.
10.) Can you tell me if PBC affects your menstrual cycle, and/or menopause? Can it induce menopause, or similar symptoms?
Answer
Most females with PBC have normal menstrual cycles. An exceptionto this may occur in females with stage 4 PBC ( cirrhosis) especially if decompensated (complicated by ascites, variceal bleeding, jaundice orencephalopathy).
11.) I was diagnosed with osteoporosis, and understand it is common in PBC. I was told to be careful of breaks because it will take longer for bones to heal. What are your suggestions for someone with osteoporosis. Would you discourage bouncing activities such horseback riding?
Answer
Osteoporosis ( a decrease in bone quantity) is the most common bone disorderin PBC. The hip and spine are the areas of the body most commonly affected. Thus, people with osteoporosis are susceptible to hip fractures and often suffer from bad backs. Bouncing activities should be avoided. Instead it is important to strengthen bones with weight bearing exercises using light weights. This should be incorporated with an aerobic exercise. Full discussion of these topics are beyond the scope of this chat, but entire chapters are devoted to these issues - osteoporosi sand exercise, in my book. I will incorporate these issues in my website- www.liverdisease.com on the next update.
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.
April 2000
13.) Do any of the doctors know if their are people who suffer from pernicious anemia and PBC. How many if any.
Answer
Pernicious anemia (PA) is the result of poor vitamin B12 absorption from a loss of a glycoprotein called intrinsic factor. Intrinsic factor is normally secreted by special cells in the stomach and is responsible for binding B12 and facilitating its uptake by cells in the small intestine - specifically the terminal ileum. The stomach cells of individuals with PA are also deficient in the secretion of hydrogen and thus these patients are known as suffering from achlorhydria - the absence of acid secretion by the stomach. PA , like PBC, is felt to be one of the autoimmune diseases. However, whether there is an increased incidence of PA in individuals with PBC is unknown. One should be aware however that a vitamin B12 deficiecy may develop in individuals with any chronic liver disease who maintain a strict vegetarian diet for long periods of time, such as those suffering from chronic encephalopathy. Finally, the older a person is, the more likely a vitamin B12 deficiency is to develop.
14.) I think it is strange that two of my sisters (one older and one younger), have Primary Bilary Cirrhosis and has had an adreneal gland tumor (as big as a grapefruit) removed. Two very rare diseases . I am wondering if the two diseases have any similaries. I have another sister and we are hoping these rare diseases will skip by us. Do you think these two diseases have anything in common. Any comments would be appreciated.
Answer
There has not been any noted association between PBC and adrenal gland tumors. However, PBC is felt to run in families and I recommend all family members, especially women to be tested for this disease.
15.) With the recent on-line discussions about taking "carnitor" to boost energy, can we get a doctor's opinion on it's potential effectiveness and safety for pbcers.
Answer
I am unfamiliar with "carnitor". However, any over-the-counter supplements the claim to boost energy is unlikely to do so. Furthermore, these supplements are not regulated by the FDA and thus have been found to sometimes contain substances such as ephedrine which may boost energy and may also be dangerous to your health. I recommend avoiding any supplements that make such claims until they are tested in regulated trial studies proving their claims.
16.) Why is it so difficult for some to digest meat, particularly red meat? It seems to stay in my system for hours.
Answer
Many gastrointestinal disorders have been associated with PBC, particulary gallstones and diarrhea. Many people with PBC especially those in advanced stages who are cholestatic are unable to digest fats efficiently. this is known as fat malabsorption.This is caused by a failure to secrete bile salts neccessary to absorb fats due to bile duct destruction. Since red meats tend to be particularly fatty, this may explain why it is difficult to digest. I recommend sticking with chicken and/or fish for animal protein. Again, you may find it helpful to refer to my book for more detailed nutritional advice.
17.) Can pbcers use plant derived products such as aloe vera to improve their condition ? ? Dermic gel containing aloe vera is good for skin problems and is a efiicient mean to drive moisture inside. It strengthens the immune system , which can be valueable for cancer for instance , but what could be the impact on autoimmune diseases? Do you know anything about this product?
Answer
There are no studies on aloe vera and PBC. However if used topically, aloe vera is unlikely to cause problems for individuals with PBC. However, it is also unlikely to have a significant impact on the long term course of autoimmune diseases.
18.) Combucha tea derived drinks, are supposed to boost immune system. Do you tink they are beneficial? Do you recomend 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 indiuced liver damage in raqts 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.
01/25/04
QUESTION 19
What type of diet do you suggest for those diagnosed with PBC? Should we lower our protein intake?
ANSWER 19
Unfortunately, a person with PBC cannot expect to walk into the doctor's office and request "a diet for PBC." Such an across-the-board diet simply does not exist. Many factors account for the unfeasibility of a standardized liver diet, including the stage of PBC (for example, stable liver disease - stage 1-2 without much damage versus unstable decompensated cirrhosis - stage 4 with complications such as ascites) in addition to one's other medical disorders even if unrelated to their liver disease, such as diabetes or heart disease. Each person has his or her own individual nutritional requirements, and these requirements may change over time.
Most people with PBC, especially those suffering from fatigue find that eating multiple small meals throughout the day is the best approach, as it maximizes energy levels and the ability to digest and absorb food. However, if one insists on eating three meals per day try to follow the saying - " eat breakfast like a king, lunch like prince and dinner like a pauper."
Notwithstanding the above information, an optimal diet for a person with stable PBC (modifications to be made as per individualized needs) might contain all of the factors listed below. (You'll note that this diet resembles a generalized healthy diet for all people-even those without liver disease. And, in fact, that's exactly what it is!)
o 60- to 70-percent carbohydrates-primarily complex carbohydrates, such as pasta and whole-grain breads.
o 20- to 30-percent protein-only lean animal protein and/or vegetable protein.
o 10- to 20-percent polyunsaturated fat.
o 8- to 12 eight-ounce glasses of water per day.
o 1,000 to 1,500 milligrams of sodium per day.
o Avoidance of excessive amounts of vitamins and minerals, especially vitamin A, vitamin B3, and iron.
o No alcohol.
o Avoidance of processed food.
o Liberal consumption of fresh organic fruits and vegetables.
o Avoidance of excessive caffeine consumption-no more than 1 to 3 cups of caffeine-containing beverages per day.
o Vitamin D and calcium supplement.
In reference specifically to protein, many people mistakenly believe that the more protein they consume, the better. Not only is this belief misguided, but for someone with severe liver damage such an approach to nutrition can actually be downright dangerous. The trouble is that a damaged liver cannot process as much protein as a healthy liver. And when a damaged liver gets unduly overloaded with protein, encephalopathy (a state of mental confusion that can lead to coma) may occur. Finally, diets high in protein have been demonstrated to enhance the activity of the cytochrome P450 enzyme system, which is responsible for drug metabolism. This enhanced activity increases the likelihood that a drug may be converted into a toxic byproduct capable of causing liver injury. People with unstable liver disease (decompensated cirrhosis) need to lower the percentage of animal protein they consume and they need to eat mostly vegetable sources of protein. A diet high in animal protein (which contains a lot of ammonia) may precipitate an episode of encephalopathy among these people. Researchers aren't exactly sure what causes encephalopathy, but they suspect that an excess of ammonia in the body may be one of the triggers. Some popular weight-loss diets involve the consumption of a very high amount of red meat animal protein. People with cirrhosis are advised to avoid any such diets.
QUESTION 20
I have experienced constant and debilitating diarrhea since before my PBC diagnosis, in 2/98. I have been tested for many possible causes, and everything turns out negative. Hence my hepatologist has stated that this is from PBC and that 25% of PBC patients will experience this. I would like the Doctors Panel opinion as to whether this is a PBC symptom, but even more so I would like to ask what the process is - most especially what causes the diarrhea - what medication might be recommended (I think I've tried everything there is but it never hurts to ask).
ANSWER 20
Diarrhea may have many causes in people with PBC. First, diarrhea may be a side effect of some medications used in the treatment of PBC, such as URSO and colchicine, or of cholestyramine, a medication used to control itching.
Second, people in advanced stages of PBC who are cholestatic are unable to absorb fats efficiently- a condition known as fat malabsorption. This is caused by a failure to secrete bile salts necessary to absorb fats due to bile duct destruction that occurs within the livers of people with PBC. The fats that these people are unable to absorb are eliminated from their bodies in their stools, which tend to be light in color, loose in consistency, and frothy in texture. These stools are characterized by their ability to float on top of water, and it commonly takes as many as five attempts to flush them down the toilet. This type of stool is known as steatorrhea. People with fat malabsorption are unable to absorb the fat-soluble vitamins - A,D,E, and K. Thus, it is usually necessary to correct these vitamin deficiencies promptly.
Third, an autoimmune disease known as celiac sprue can be the cause of diarrhea in people with PBC. Celiac sprue is a disease characterized by an inability to absorb gluten (a protein found in wheat, rye, oats, and barley). This is known as a gluten-intolerance. Celiac sprue is approximately ten times more likely to occur in people with PBC than among members of the general population. The association of PBC with celiac sprue is important to recognize since people suffering from these diseases jointly can obtain relief from diarrhea and its associated weight loss by adhering to a gluten-free diet.
Diarrhea can also be due to ulcerative colitis, which may require treatment with prednisone, a steroid medication, or diarrhea may be due to a pancreatic disorder, which requires treatment with pancreatic enzyme replacement. Therefore, it is important to accurately diagnose why a person with PBC has diarrhea, as the treatment differs greatly dependent upon the cause.
QUESTION 21
Does Ursodiol treatments help those diagnosed with PBC at early stage? Can it actually slow the disease progress? How is ursodiol treatments prescribed, according to weight or manufactures instructions?
ANSWER 21
Ursodeoxycholic acid (also known as UDCA or ursodiol) is the drug most commonly used to treat PBC. In fact, it is the only drug that is FDA approved for the treatment of PBC. Ursodeoxycholic acid was initially found to be beneficial for people with PBC in the early 1980s and became FDA approved in 1998. It is manufactured by Axcan Pharma (Mont Saint Hillaine, Quebec, Canada) under the brand name URSO 250. URSO 250 is taken with food in oral pill form at a dosage of 12 to 15 milligrams per kilograms of body weight each day administered in four divided doses. Each pill is 250 milligrams. Actigall is another brand name for ursodeoxycholic acid. Actigall is marketed by Watson (previously Novartis) in tablets of 300mg. This drug is not FDA approved for the treatment of PBC, therefore its use is considered "off label". Generic ursodeoxycholic acid is also available and known as ursodiol. Since ursodiol costs about 10 percent less than the brand name products (URSO 250 and Actigall), many insurance companies prefer its use for the treatment of PBC.
The exact mechanism by which ursodeoxycholic acid works in people with PBC is not known. However, it has been established that increasing the amount of UDCA in the body will generally decrease the amount of liver-toxic bile acids in the body. This, in turn, should diminish or prevent destruction of bile duct cells. In fact, in some studies, people treated with ursodeoxycholic acid have been shown to have decreased bile duct destruction. However, other studies have shown that UDCA does not prevent bile duct destruction. Instead, UDCA appears only to protect against the consequences of bile duct destruction. This finding explains that while UDCA can delay, it does not prevent, the progression of disease to cirrhosis in people with PBC.
UDCA provides significant benefits to people with PBC. Levels of liver function tests, IgM, AMA, and cholesterol typically show notable improvement. People find that UDCA, on occasion, relieves some of the symptoms associated with PBC, such as fatigue and itching. Most importantly, ursodeoxycholic acid has been found to slow the progression of PBC, and to delay the occurrence of cirrhosis. Thus, people with PBC who are treated with UDCA have been found to live longer, have less liver-related complications, and need liver transplants less often when compared with those who are not treated with UDCA. UDCA may also have the additional benefit of decreasing the recurrence of colon polyps, however, this finding needs to be confirmed by further studies. The beneficial effects of ursodeoxycholic acid are experienced by approximately 80 percent of people with PBC who use this medication. These effects are most likely to occur the sooner a person is treated-for example, when the person is treated during the first or second stage of the disease.
QUESTION 22
Is it dangerous for a person with PBC to get pregnant? Is there anything specific to watch for or do?
ANSWER 22
Women with primary biliary cirrhosis generally have uneventful pregnancies and deliveries.
However, some studies have noted a greater-than-average incidence of stillbirths, spontaneous abortions (miscarriage), and worsening liver function among these women. These events more commonly occurred in women with advanced liver disease - stage 4 disease. Cirrhosis (stage 4 PBC) is often associated with amenorrhoea (lack of menses) and infertility. Consequently, women with stage 4 disease-especially decompensated cirrhosis-may have difficulty conceiving. As a result of their advanced liver disease, women with decompensated cirrhosis who do conceive have an increased risk of serious complications during pregnancy.
Bleeding from esophageal varices is probably the biggest pregnancy-related health risk for women with decompensated cirrhosis. Variceal bleeding is most common during the second trimester, occurring in approximately 20 to 45 percent of women with portal hypertension. Ten percent of the time, women with decompensated cirrhosis experience variceal bleeding during labor and immediately after childbirth. Death of the mother from uncontrollable variceal hemorrhage occurs approximately 10 to 18 percent of the time during the course of pregnancy. Depending on the trimester, the baby may nevertheless have chance for survival. Women with decompensated cirrhosis who are thinking about becoming pregnant should undergo an upper endoscopy, which can assess the presence and degree of esophageal varices.
Pruritus can worsen during pregnancy and may be successfully and safely treated with cholestyramine. On the other hand, pruritus sometimes improves during pregnancy. Ursodiol is generally considered to be safe during pregnancy.
QUESTION 23
I would like to know what you measure and what the measurements are to identify that you have reached stage 4 of PBC.
QUESTION 24
How it is possible for a person to have Stage 3-4 via biopsy and yet have normal labs and no symptoms. Why is a biopsy "not the ideal test to begin with"? I know there are at least a few of us with this situation. I wonder if those of us in this situation are on the edge of a cliff and one morning we'll wake up itching, depressed and in the beginning stages of liver failure.
ANSWERS TO 23 & 24
I will answer question 23 and 24 together.
PBC may be diagnosed by a combination of the symptoms that a person is experiencing, the physical findings detected on an exam, the results of blood work, the findings of a liver biopsy, and the results from imaging studies.
As opposed to other liver disorders, PBC has been neatly classified into four distinct stages that can only be determined by a liver biopsy.
Stage 1 is characterized by the finding of damaged bile ducts. Granulomas-nodules filled with a variety of inflammatory cells-are often detected in this stage.
Stage 2 is characterized by the finding of a proliferation of small bile ducts known as bile ductules.
Stage 3 is characterized by fibrosis, and stage 4 is characterized by cirrhosis.
Occasionally, a single specimen from a liver biopsy may show evidence of more than one stage of the disease. In such cases, the most advanced stage present should be considered the correct stage. People may progress through the different stages at varied, and largely unpredictable, rates. For example, a person may stay in stage 1 for many years, and then rapidly progress from stage 2 to stage 3. Or a person may rapidly progress through stage 1 and then stay in stage 2 for many years.
There is a wide spectrum of symptoms associated with PBC. At one end of the spectrum, a person with PBC can be asymptomatic (have no symptoms). These people are typically found to have PBC during evaluation of elevated AP and GGTP levels found on blood tests. However, some asymptomatic people with PBC have normal levels of AP and GGTP. In these instances, a positive antimitochondrial antibody (AMA) is the sole indication that the disease is present. Up to 60 percent of people discovered to have PBC have no symptoms. Diagnosis in such people has become more common due to routine blood tests which are performed during the course of a regular check-up. Note, however, that most people who are initially asymptomatic eventually do develop symptoms. This occurs in about three to four years from the time of initial diagnosis. However, symptoms can take as long as ten years to manifest. Interestingly, even in advanced stages of PBC, some people will still have no symptoms.
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"Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease" book has been totally updated and the new version will be released May 2004 by
Penguin Putnam. It is now available for pre-orders on Amazon.com.
Dr. Palmer's book is a wealth of information and wonderful source for those diagnosed with PBC, especially newly diagnosed.
