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Dr. Nathan Bass Answers Our Questions
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 identifygenes 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.
14.) Question
I am in a study at Einestein Medical Center in Philadelphia, PA. It is a blind study, which includes taking Actigal every night and taking Methotrexate once a week, (5 tiny pills). Have there been any new discoveries made lately, on how Methotrexate helps put the disease of PBC into remission.
Do you have any facts or statistics?
Answer
Methotrexate has been used in a number of diseases for its anti-inflammatory and immune modulating effects. These include psoriasis (a skin disease) and rheumatoid arthritis. Some earlier observations made by experienced physicians in patients with PBC who were treated with methotrexate for other disease suggested that methotrexate could improve blood tests and liver biopsy findings. In order to determine whether this is a real or significant effect, with a benefit in terms of quality of life as well as life expectancy, a large, randomized study is currently underway. You are probably participating in this study which is a national, multicenter study currently being conducted at a number of medical centers. Some small studies have reported that with short periods of treatment, a clear benefit of methotrexate is not evident. However, the current large multicenter study will have the advantage of including a large number of patients followed for up to 10 years. When the results of this study are published, I believe we will know whether there is any real benefit or not from methotrexate in PBC patients.
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.
16.) Question
Some believe PBC is caused by chemicals. If this is true why wouldn't the liver heal itself if they stayed away from bad chemicals such as bleach, ammonia, gas, smoke, and motors oils?
Answer
The evidence for a role for chemicals in causing PBC is very new, and certainly interesting. If this turns out to be important, then the reason the liver may not simply heal itself after removal from the responsible chemical is that chemicals may be only part of the mechanism. For example, a particular chemical may trigger a key disease process in a genetically susceptible individual. The disease process may then be self-sustaining as a result of the immune system behaving in a disordered fashion. This may also derive from the individual's genetic makeup. Under circumstances of chronic chemical exposure, the liver may never quite heal completely because it is injured on a chronic or repeated basis, similar to the way repeated exposure to excessive alcohol over years may lead to cirrhosis. However, it is certainly unlikely that PBC is related in any way to chronic chemical exposure.
17.) Question
We have been told that taking Actigall or Urso can lower our lab results but the PBC still progress. If this is true, how would we know our PBC is progressing? Can PBC progress without other symptoms appearing?
Answer
This is an important question that has been discussed and debated extensively. I think most experts now believe that Ursodiol (aka Urso, Actigall) significantly slows but does not stop the progression of PBC. Available studies support the view that improvement in laboratory tests is indeed associated with an improvement in life expectancy, but the process of PBC still continues. Disease progression occurs first at the level of liver cell and tissue structure and function and more often than not, is asymptomatic or not perceived through a change in symptoms until these changes are quite advanced. Liver biopsy is not a completely reliable (or necessary) way to monitor disease progression. Early warnings of disease progression are usually provided by laboratory tests of liver function such as serum bilirubin and albumin levels.
18.) Question
Drinking at least 8 ounces of water per day is recommended for those with liver disease. Must it be water or can it be other fluids such as juice and herbal tea? Do you recommend a special diet for PBC?
Answer
Usually it will not matter in which reasonable form one take in fluid. Fruit juices contain more calories and potassium. Overweight or diabetic patients or patients taking potassium-sparing diuretics (e.g., spironolactone) may need to be cautious with these. Herbal teas are usually fine, especially the common commercially available types. Specialized herbal teas obtained from herbal medicine practitioners or web sites should be checked with your physician, as there are some herbal products that may actually cause liver disease. Diet in PBC depends on stage of disease. There is no medically recognized "special" or healing diet for PBC per se, but there are certainly important dietary aspects to the management of patients with this disease. Patients at all stages of disease may benefit from a multivitamin and trace mineral supplement. Calcium supplements are also recommended to prevent and treat bone thinning. Patients with very early disease can eat almost anything that agrees with them, but it is wise to adhere to a generally balanced, healthy cardiovascular diet. Patients with more advanced disease, especially with evidence of fluid retention should limit their salt intake to 2 grams or less per day. Limiting protein intake is very rarely indicated and may be harmful. Only patients with very advanced disease who have severe hepatic encephalopathy which is difficult to control with medication are candidates for carefully controlled protein restriction under medical supervision. Some patients with PBC are intolerant of fatty foods as these may cause diarrhea. In these cases, patients should reduce their intake of fat but consume more in the way of carbohydrate calories to meet their daily requirement. Patients with established cirrhosis may want to avoid raw shellfish. This is general advice for patients with all types of cirrhosis who are particularly susceptible to a rare but extremely serious type of food poisoning that can result from eating raw shellfish.
