Help me find newish research on Primary Biliary Cirrhosis
January 14, 2006 8:33 AM Subscribe
What are the newest treatments and studies involving Primary Biliary Cirrhosis? I don't have access to scholarly resources at home, but I am close to a major university.
I'm looking for the newest research possible; a lot of web resources are from quite a while ago and basically say "we don't know what causes it, but it can be treated with a hideously expensive drug that you take twice a day for the rest of your life, other than that, good luck." So: where should I start? Should I ask a reference librarian? Are there any articles I should dig out of the stacks? Books I should buy or borrow? Narrow, specialized articles for professionals are just as desirable as broad hepatology resources.
I'm looking for the newest research possible; a lot of web resources are from quite a while ago and basically say "we don't know what causes it, but it can be treated with a hideously expensive drug that you take twice a day for the rest of your life, other than that, good luck." So: where should I start? Should I ask a reference librarian? Are there any articles I should dig out of the stacks? Books I should buy or borrow? Narrow, specialized articles for professionals are just as desirable as broad hepatology resources.
Best answer: There were a couple of trials with methotrexate (in conjunction with standard ursodeoxycholic acid treatment - the "hideously expensive drug") that recently closed because it did harm and didn't work. Another trial with colchicine also closed because it didn't work. Glucocorticosteroids doesn't seem like it works.
Insulin-like growth factor I appears promising, but probably only for short-term therapy.
Overall it doesn't seem like therapeutic advances have really been made in the last decade or so since its very difficult to design good randomized trials because PBC is a very heterogeneous disease (and there are probably problems with developing highly satisfactory animal models).
Liver transplantation remains the only option for end-stage disease but recurrence of disease may be found in the graft. Also, liver transplantation brings with it a whole slew of problems. This paper also mentions immune modulation and retroviral therapy but while there are polymorphisms detected in TLR9 (an innate immune mechanism for the detection of bacterial/viral DNA), the polymorphisms doesn't correlate with function and disease outcome so those approached are probably really low percentage plays.
Sorry.
posted by PurplePorpoise at 11:14 AM on January 14, 2006
Insulin-like growth factor I appears promising, but probably only for short-term therapy.
Overall it doesn't seem like therapeutic advances have really been made in the last decade or so since its very difficult to design good randomized trials because PBC is a very heterogeneous disease (and there are probably problems with developing highly satisfactory animal models).
Liver transplantation remains the only option for end-stage disease but recurrence of disease may be found in the graft. Also, liver transplantation brings with it a whole slew of problems. This paper also mentions immune modulation and retroviral therapy but while there are polymorphisms detected in TLR9 (an innate immune mechanism for the detection of bacterial/viral DNA), the polymorphisms doesn't correlate with function and disease outcome so those approached are probably really low percentage plays.
Sorry.
posted by PurplePorpoise at 11:14 AM on January 14, 2006
Response by poster: No need to be sorry, PurplePorpoise. I'm much more interested in frank discussion and solid statistical evidence than in hiding the seriousness of the disease, and I thank you for your post. The Gut study concerns me the most, but I wasn't expecting much different. Anyone else with more data is welcome to comment.
posted by Optimus Chyme at 1:31 PM on January 14, 2006
posted by Optimus Chyme at 1:31 PM on January 14, 2006
If you do find an article on pubmed that you want to peruse in more detail than just the abstract and you don't want to trudge to the bio library to make a copy - send me the pubmed abstract and I can send you a pdf of the article.
posted by PurplePorpoise at 4:17 PM on January 14, 2006
posted by PurplePorpoise at 4:17 PM on January 14, 2006
Best answer: There's some good news out there; check your e-mail. The NEJM reviewed PBC in their 9/22/2005 issue; as it happens, when the New England Journal of Medicine reviews a topic, you can count on the review to be comprehensive, authoritative, and cutting-edge.
PBC is an auto-immune disease, where the body attacks itself using the immune systems designed to attack invaders; the target of the attack in PBC are antigens present in the mitochondria. Since mitochondria are present in every cell in the body, why this particular attack should destroy only the hepatic biliary system is yet unknown.
One of the more cheerful statements in the article:
PBC is an auto-immune disease, where the body attacks itself using the immune systems designed to attack invaders; the target of the attack in PBC are antigens present in the mitochondria. Since mitochondria are present in every cell in the body, why this particular attack should destroy only the hepatic biliary system is yet unknown.
One of the more cheerful statements in the article:
As a result of treatment in earlier stages of disease, the prognosis is much better now than it formerly was. The data on survival suggesting a poor prognosis were obtained from patients in whom the disease was diagnosed decades ago, when no effective medical treatment existed. Most patients with PBC are now treated with ursodiol; other drugs that may be effective are also used. In at least 25 to 30 percent of patients with PBC who are treated with ursodiol, a complete response occurs..posted by ikkyu2 at 2:28 AM on January 15, 2006
Response by poster: Thanks, ikkyu2. I got the article and will read it shortly. Since you mentioned AMA, what's weird about this particular case is that the labwork shows extremely high - just about off-the-chart - antinuclear antibodies but not antimitochondrial antibodies, the latter of which apparently occurs in less than five percent of cases. The initial diagnosis was autoimmune hepatitis because of the lab results, but a liver biopsy indicated factors highly associated with PBC. So the current course of treatment is Urso, and there's a followup in about six weeks and maybe there will be some more data available then but I doubt it.
It's pretty obvious from my layman's reading that I'm not a doctor and that my knowledge of the field is extremely limited. I appreciate all the input from the three of you and those who emailed best wishes; my deepest thanks.
posted by Optimus Chyme at 8:58 AM on January 15, 2006
It's pretty obvious from my layman's reading that I'm not a doctor and that my knowledge of the field is extremely limited. I appreciate all the input from the three of you and those who emailed best wishes; my deepest thanks.
posted by Optimus Chyme at 8:58 AM on January 15, 2006
This thread is closed to new comments.
One article from January 2006 references ursodeoxycholic acid, or Ursodiol (Actigall), so I imagine it is a very recent treatment.
NCBI, from which PubMed originates, has a number of resources. I found some hits in their Books resources as well. These are textbooks that are stored online and are accessible for free.
Have you searched your school's Ovid, LexisNexis or other online databases (if it has them)? This will usually search more than just PubMed (which happens to be public, but generally focuses on medical research).
Is your school affiliated with a medical school (if you're not in med school already)? The med school will have its own library — and its own librarians, who are paid to help you find exactly what you're looking for.
posted by Rothko at 9:03 AM on January 14, 2006