SERUM AMINOTERMINAL PEPTIDE OF TYPE III PROCOLLAGEN - HEPATIC FIBROSIS ============ From: Druid71@aol.com I have a patient who is a 66 yo WF that has been on longterm MTX for disabling psoriasis. Last year she completed another 1.5 g of MTX and was due for another liver biopsy, but the patient made it clear to both me and her gastrenterologist that she did want to have another biopsy. It was her feeling that the risks and discomfort of a liver biopsy outweighed the risk of possible hepatic fibrosis from the MTX. Since this pt is quite intelligent and well informed, both the gastroenterologist and I reluctantly agreed to forego another liver biopsy at this time. The pt takes MTX 5 mg q 12h X 3 doses each week and takes folic acid 1 mg qd on the days that she doesn't take MTX. (The folic acid has not adversely impacted the effectiveness of MTX in her case.) Her 3 previous liver biopsies were fine, she does not drink and she is mildly obese. I have been following her CBC and LFTs q 3mo and everything has been fine. Still, I feel a bit uncomfortable and am thinking about following the pt's serum aminoterminal peptide of Type III procollagen, which is supposed to be a bellweather of impending hepatic fibrosis. Has anyone had experience with this test and is anyone aware of a lab that performs this assay? William F. Pekruhn III, M.D. Chicopee, MA druid71@aol.com ================= From: "Rhett Drugge, M.D." This question has been studied in Manchester. Apparently the answer is no, but I have also run it by the medical laboratory group, MedLab-L run by Dr. Pat Letendre of the University of Alberta. At least we can find a lab which can run the test for you if there has been a successful modification of the test since the late 80's Manchester study. Rhett Drugge, M.D. ================== From: "Jerry D. Eisner" Make a note of her decision in your chart, after carefully discussing it with her. Then, save her the money for the lab test. Jerry Eisner ================== From: "Dr. Puritz" Unfortunately, the dilemma concerning what to do when a patient refuses liver biopsy is one that is common in all practices that use MTX. We are truly between the " devil and the deep blue sea ", and coming from a state in which the surfeit of attorneys approaches the absurd, I would probably vote to stop the MTX despite whatever you find out about blood tests. Believe me, the patient will not remember any of your warnings when her attorney serves you with papers. Another approach would be to refer her to the nearest medical center where they can take the responsibility. I know that some of you feel differently, and that the patient may suffer in this scenario. So be it. We didn't create the system. ================ From: bberman@mednet.med.miami.edu assay of aminoterminal peptide detected reversal of hepatitis-induced hepatic fibrosis following treatment with alpha-interferon (NEJM about 3 years ago). Our laboratory has tested carboxy terminal peptide levels in scleroderma, keloid and eosinophilic fasciitis patients and hve found that test unreliable. Brian Berman, M.D., Ph.D. ====================== From: Mark R Ling One could make a compelling case that a biopsy could be deferred, or even skipped altogether, given her long-term track record of safe use (I presume she has had consistently normal LFT's throughout in addition to her previously normal liver biopsies: also, I presume "normal" really means normal, not a Grade IIIA biopsy which is on the edge of "discontinue MTX). PIIINP levels remain investigational in this country to the best of my knowledge. There are commercially available ELISA assays, but I do not believe that they are run by any commercial lab, and it would therefore be incumbent on you (and difficult to do) to determine normal values. While Zachariae has published his successful use of this test, be aware that he still does not rely on it exclusively, generally performing a biopsy at the first 1.5 gm mark, and then repeats biosies if the PIIINP levels are elevated. Also be aware that there is a series of articles from the BJD from an English group which evaluated the test: in their hands it was neither sensitive or specific enough to lead them to recommend the test. (email me if you want the references). What you really need is a hepatology group like the one here who are comfortable with discontinuing biopsies in some settings: makes my life easier for sure. Mark Ling, M.D., Ph.D. ======================= From: Gfweb@aol.com What grounds does your hepatology group use to justify discontinuing liver Bxs? It seems to me that past performance does not reliably predict future outcome in either liver bx(or mutual funds). It seems dangerous to conclude that on the basis of a few good results an assumption of general safety can be made. Let's say that the incidence of 3 good biopsies followed by a bad one is 1 in 10, one could easily have a "run" of many normal biopsies before the statistically-predicted bad result would appear. Add to this the questionable practice of assuming that a 2 mm liver biopsy is a representative sample of a several Kg organ and the chance for mistakes is even greater. I've discussed this with several GI docs and can get no convincing explanations. Guy Webster ================ From: Mark R Ling complex question which can in no way be done justice in this limited discussion setting. In brief, one can question multiple assumptions behind our reliance on liver biopsies, ranging from the issue of whether MTX is indeed hepatotoxic in the first place, how reliable biopsies are (I agree with you fully that sampling error questions are unanswered), and what the mechanism of liver toxicity is. I'll take this up with you in detail when we next meet, Guy, hopefully in properly ostentatious setting. Mark Ling, M.D., Ph.D. Emory University Department of Dermatology Clinical Pharmacology Unit Atlanta, GA ===============