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Dr. Andrew Mason Answers Our Questions
Questions & Answers
May 2000
1.) Any ideas what causes Primary Biliary Cirrhosis? Since 95% are women diagnosed would it be safe to say the cause is hormonal? Do you know of any current PBC studies being down other than Dr. Gershwin's at UC Davis?
Answers
We have been working on the idea that an infection causes PBC. Researchers in my laboratory have been cloning and characterizing a novel human virus that may be associated with PBC. In collaboration with Dr. James Neuberger in Birmingham, UK, we have found that normal biliary epithelial cells can be transformed to appear like PBC diseased cells in the laboratory by mixing them with the presumed infectious agent from PBC patients. We hope to publish more details about the relationship between the virus and PBC soon.
There are obviously many other differences between the sexes apart from hormones, but we believe that they may play a pivotal role in PBC. For instance, we think that our virus may be stimulated by female hormones but we have not formally proven this yet.
2.) In your oppinion is it safe to take adult vitamins when diagnoed with PBC or any other autoimmune liver disease? Instead of taking adult vitamins would it better for PBCers to take children's vitamins?
Answer
I usually recommend that patients with autoimmune liver disease and biliary disorders take regular multivitamins with the recommended dosage of any brand. Patients with biliary disease and those taking oral corticosteroid treatments are prone to bone disease. Therefore, patients should ensure that the multivitamin tablet has vitamin D in it and take additional calcium supplements such as Tums or Oscal 1 to 1.5g per day.
3.) Can you recommned or suggest other treatments for PBC besides Actigall & Urso medications?
Answer
This is the only recommended treatment for PBC at present but several groups are trying alternative immune based and other therapies. We have conducted a pilot study using anti-viral treatment for PBC patients and found that the treatment was well tolerated. Although no one had a complete biochemical response, several patients with early disease had marked improvements in their liver biopsies after a year’s treatment. We will soon be commencing a second pilot study to assess efficacy and safety of a more potent anti-viral regimen for PBC patients.
4.) All my life I always recovered quickly from a flu or virus. Since I was diagnosed with PBC 3 years ago, it now takes weeks to recover from any type of illness (virus, flu, sinus infection), and I catch anything I come in contact with. Is this due to the PBC or in general the liver not functioning correctly?
Answer
The difficulty overcoming infectious disease is probably related to fatigue associated with chronic liver disease. However, PBC can be related to other disorders as well, such as thyroid and other autoimmune diseases. So, if you have any other specific problems, it is worth discussing these with your doctor.
5.) Do you know of any alternative methods used to help improve the liver and PBC such as Milk Thistle?
Answer
I usually tell patients that there are no good studies to indicate prescription of alternative medicines. Milk Thistle appears to be well tolerated but of unknown benefit. I am not aware of any other good alternative treatments but I always recommend a daily multivitamin with vitamin D as well as calcium supplements.
6.) What causes the decrease of vitamin D in a person with PBC? Shouldn't this be easily corrected by taking vitamin D orally?
Answer
Vitamin D is a fat soluble vitamin that can be inadequately absorbed in patients with biliary disease. This can be easily corrected by taking 400 IU vitamin D, which is the usual dose in a standard multivitamin tablet.
August 2000
Question 7
What is the correlation of labs, biopsy and symptoms? Isn't it true a person can have normal labs and the disease still progress?
Answer
The correlation of labs, biopsy and clinical symptoms is not absolute. The liver function tests and clinical symptoms can vary with episodes of deterioration as well as improvement. Even though the stage of the biopsy progresses from 1 through 4, the level of inflammation can also vary with progression of the disease.
For all patients we use a combination of liver function tests, liver biopsy and clinical symptoms to get a general idea of how severe the liver disease is. Unfortunately you are correct in thinking that a patient can have cirrhosis when the liver function tests appear to be relatively benign. However, it is also true to say that the bilirubin becomes raised with progressive liver disease when patients develop cirrhosis.
Question 8
A metaanlysis published in the Lancet, Volume 354, Page 1053, 25th September 1999, "Randomised controlled trials of ursodeoxycholic acid therapy for primary biliary cirrhoses, concludes that using UDCA as a standard therapy has to be checked again as the trials did prove a lack of effectiveness. What is your opinion?
Answer
Most Hepatologists believe that UDCA has some benefit for PBC patients but it is no panacea and will not cure the disease. The Lancet Meta-analysis merely confirmed what most physicians already know. It is clear that UDCA can contribute to an improvement in liver biopsy and liver function tests. However, it may not impact that much on delaying the onset of liver failure. I do not think that we will have to perform any further studies on UDCA as a single agent as we have a good idea about its utility. However, there are ongoing studies to assess UDCA as a combination therapy with other drugs such as methotrexate, I personally think that UDCA will be a good adjunct therapy with anti-viral treatment.
Question 9
Is it "normal" for Actigall/URSO to reduce the anti-mitochondrial antibodies?
Answer
We still do not know the precise role of anti-mitochondrial antibodies in PBC. At this time, they are considered a specific marker for PBC but there is no evidence to suggest that the titers vary with disease stage. In fact, AMA positive and negative patients with PBC have a similar disease process. Also, AMA are found in the serum of 70% of patients with PBC following liver transplantation, but only a proportion of these patients develop recurrent PBC in the new liver.
With regard to treatment, AMA levels may fall with global improvement in the disease process but it is not known why. So, patients taking Actigall/URSO can have decreased AMA but this is not necessarily a universal finding.
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.
Question 11
Are there any suggestions on lifestyle, diet, etc. that can delay the passing of one stage of PBC to the next one?
Answer
There are only a few general suggestions for lifestyle and diet for PBC patients. I advise all patients to exercise, watch their weight and take multivitamins with Vit. D as well as additional calcium (2 extra strength Tums for example) to avoid bone disease. However, there are no specific recommendations to delay disease progression.
Some patients with stage I PBC without symptoms can have a very benign course of disease. Once symptoms have developed, untreated patients are thought to have a variable course with a need for transplantation within 5 to 12 years. In untreated patients with worsening symptoms, the histologic progression can be as short as one stage every 1.5 years. However with treatment, the need for transplantation in symptomatic PBC patients varies from 7 to 15 years depending the progression of disease.
Question 12
Is there any possible connection between PBC and miticondria disease? I noticed that the doctor initially narrowed in on my diagnosis because of the miticondrial antibodies in my blood test and when I was searching for info on the drug Carnitine that PBC patients are talking about, I kept connecting with sites related to miticondrial disease. The vague descriptions that I have read of some miticondrial diseases do seem to have similarities with PBC. I am considering this as a possible genetic clue to diagnosing a mystery illness with my son since I do have PBC. Am I way off base?
Answer
A recent electron microscopy study reported that mitochondria are more numerous and swollen in PBC patients than controls but I have yet to see the evidence from these studies. It is also possible that the anti-mitochondrial antibodies damage the bile duct cell's mitochondria but there is no formal proof of this. The anti-mitochondrial antibodies are a very specific finding in patients with liver disease and this is why your doctor focused in on PBC.
With regard to carnitine, this is an essential factor that your mitochondria use for energy metabolism. Some patients take carnitine as a dietary supplement with liver disease.
