Journal Club: azathioprine metabolites predict remission in autoimmune hepatitis

Today’s journal club centered on the metabolites of azathioprine (aza) and how they affect the clinical course of autoimmune hepatitis.  Recall that aza is a prodrug, which is cleaved to 6-MP.  This is then metabolized by TPMP and XO to inactive forms.  Only 0.3% of people are homozygous for the defective TPMP enzyme (thereby incurring higher risk for marrow toxicity and leukopenia).

The active (TGN) and inactive (MeMPN) metabolites were followed with each clinical visit (in comparison to previous studies that recorded one-time values) over a two year period.   Those that remained in remission had higher average values of TGN, suggesting that there was more apoptosis of autoimmune lymphocytes.  Levels > 220 best predicted remission.  Surprisingly, higher TGN levels did not predict leukopenia.

Azathioprine can cause a cholestatic reaction (there was one in this study) or hepatitis, but let’s not forget that it can cause many vascular adverse events such as nodular regenerative hyperplasia (NRH), peliosis hepatis and sinusoidal obstruction syndrome.

In sum, the audience did not feel that the results of this study would change the management of their autoimmune hepatitis patients.  For a look at the article, from a recent issue of Hepatology, you can click on the link below:

azathioprine metabolites

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