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alpha-1-antitrypsin deficiency inducible?

Discussion in 'Internal Medicine and IM Subspecialties' started by Blondbondgirl, Jun 18, 2008.

  1. Blondbondgirl

    Blondbondgirl 5+ Year Member

    Aug 17, 2007
    Hi! I was having a conversation with someone about the possibility of liver disease (Hep C, cirrhosis, etc.) inducing anti-trypsin deficiency (obviously leading to emphysema). I had come across an article about it in the internet, but now I can't find it again. Does anyone know anything about this? Any literature? Thanks! :confused:
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  3. Uegis

    Uegis 1 Down 3 To Go 10+ Year Member

    Aug 15, 2004
    I have read about different mutations that have been induced in mice, but are you speaking of an inducible form of alpha-1 anti-trypsin in humans? That'd be news to me.

    BTW, Amy Winehouse has horrible emphysema from smoking too much crack at a very young age. Just a side note only remotely related to your question.
  4. DrWBD

    DrWBD Formerly 'wanna_be_do' Lifetime Donor Classifieds Approved 10+ Year Member

    May 2, 1999
    Long Island, NY USA
    I think the original poster is referring to cirrhosis causing A1AT deficiency due to impaired hepatic synthesis.

    Since no one else is answering, I'll volunteer. In most cirrhotics, there is still a small amount of liver reserve, just not enough. Cirrhosis may cause decreased levels of A1AT due to lack of functional hepatocytes, but once someone gets to that stage their life expectancy is so poor that any pulmonary manifestations of the low A1AT levels might not have time to develop. Unless they get transplanted, which would , I would think, correct the problem.
    Last edited: Jun 29, 2008
  5. BlackNDecker

    BlackNDecker Paid da cost 2 be da bo$$ 7+ Year Member

    Jun 8, 2005
    Pole Position
    From a viral genetics point of view, the Hepatitis virus may insert itself virtually anywhere within the chromosome. Since the liver is actively expressing hepatic enzymes, those sequences would be unwound, exposed, and vulnerable to viral insertion. If the virus inserted itself within the sequence coding a-1-antitrypsin you would anticipate abnormal expression and/or protein structure.

    In this instance, it would be the virus (and not the liver damage itself) resulting in decreased A1AT levels.

    Sounds theoretically possible...obviously you've exhausted PubMed and Ovid?
    Last edited: Jun 26, 2008
  6. Lasclalo

    Lasclalo 2+ Year Member

    Jun 3, 2007
    I dunno about inducible AAT, but I think the idea that Hep C would knock out the AAT gene through direct insertion is somewhat suspect. The virus would have to independently insert itself into or near the A1AT locus many, many times at exactly the same point in the chromosome in huge percentage of hepatocytes. I mean, hepatocytes are expressing lots of other things besides AAT (housekeeping genes, etc). Since my understanding is that insertion is a more-or-less random process in unwound genomic DNA, I think the odds of that are pretty small. Just my two cents and I guess it is theoretically possible.

    I don't know if anyone has done the research, but it could be that with active infection and inflammation, you alter the transcriptional profile of hepatocytes such that they no longer produce AAT. Good luck with your patient.
  7. jdh71

    jdh71 epiphany at nine thousand six hundred feet Physician 10+ Year Member

    Dec 14, 2006
    FEMA Camp, USA
    Saw my first clinic patient today and he was supposedly dx'd with the AAT def 6 years ago . . . in a 66 y/o male? Unfortunately, he wasn't there to see me about his AAT - pulm follows him closely for that - but a shoulder I got to inject (more fun, but obviously less intellectually stimulating) . . . it's just weird to see it show up that late in life . . . inducible? I don't know . . .
  8. BlackNDecker

    BlackNDecker Paid da cost 2 be da bo$$ 7+ Year Member

    Jun 8, 2005
    Pole Position
    Alternative-alternative idea...:rolleyes:

    I prefer your explanation: Altered expression profile in the context of liver inflammation...the simplest explanation is the most likey.
    Last edited: Jul 5, 2008

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