Henry C. Bodenheimer, Jr., MD
Chief, Division of Digestive Diseases
Beth Israel Medical Center
First Ave at 16th Street
New York, NY 10003

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. 

Question 2
Am I correct in assuming that those with PBC should not take smallpox vaccine? What are your thoughts about a PBCer living with others who have had the vaccine?

Answer 2
The smallpox vaccine is not recommended for the general population.  Those with significant illnesses including PBC should not be the first volunteers for this vaccine.  However, if the unfortunate event occurs where smallpox becomes a significant risk for those living in the United States, reassessment of the wisdom of taking the smallpox vaccine would be made on a case by case basis, depending upon the immune function and general health of the patient.  As regards spread of smallpox from a close contact, the smallpox vaccine is a live vaccine and individuals who are immune compromised may be at increased risk particularly when blistering lesions are present.  The current methodology calls for a cover for the vaccine area which makes the risk small.

Question 3
At what point in the progression of  PBC should an individual usually be referred for transplant evaluation (ie. 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.

Question 4
Why is it that some patients are negative to Antinuclear Antibodies (ANA), Antismooth Muscle AB, and Antimitochondrial Ab (AMA) but have PBC as diagnosed through liver biopsy?

Answer 4
Some patient have negative auto antibodies but have a clinical syndrome identical seropositive PBC.  This may be a recognition that there are multiple insults being directed at the biliary tree and mitochondrial antibody is only one marker of the immune response to this attack on the biliary system.  It is possible that patients may have biliary injury that looks identical to PBC but not have the same immune process mediating this injury an example may be a drug reaction or toxic injury to the bile ducts which on biopsy may look similar to PBC.  This apparent "immune mediated cholangitis" is a term used for sero-negative PBC without mitochondrial antibody.  We have an imperfect understanding of  the events initiating PBC and have even less information regarding the progression and initiation of auto-immune cholangitis.  I think of these diseases similarly, and treat both the same as long as the disease is focused on the bile ducts.  At times some patient will develop an immune mediated process against the liver cells (hepatocytes) and act more like auto-immune hepatitis, such patients may be treated with immune suppression such as prednisone and Imuran. 

Question 5
What could be the cause of thrombocytopenia in the early stages of PBC?

Answer 5
PBC may be associated with an autoimmune reaction against platelets called ITP.  When liver disease and splenomegaly is not sufficient to explain low platelets, such an immune reaction should be considered.  Other causes of thrombocytopenia are also possible, such a reaction to medication. 

Question 6
What is the difference between fibrosis and cirrhosis?  I thought they were both the same if they're not, can a person have both?

Answer 6
Fibrosis is the technical term for scaring.  As scaring progresses in the liver, the liver  develops regeneration and forms nodules of hepatocytes.  As the scaring increases blood flow to the liver decreases and portal hypertension develops.  As the scaring process increases the stage of scar tissue is seen to increase, and severe scaring is termed cirrhosis.  Patients with cirrhosis have the consequence of decreased blood flow of the liver which places patients at risk for development of esophageal varices and altered drug metabolism.

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