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Home > HEPATOLOGY Podcast > Significance of Azathioprine Metabolites for the Maintenance of Remission in Autoimmune Hepatitis
Podcast: HEPATOLOGY Podcast
Episode:

Significance of Azathioprine Metabolites for the Maintenance of Remission in Autoimmune Hepatitis
Category: Science & Medicine
Duration: 00:11:59
Publish Date: 2012-12-18 17:29:14
Description: Drs. Stephen Harrison and Harpreet Dhaliwal Azathioprine (AZA) is used to maintain remission in autoimmune hepatitis (AIH), but up to 18% of patients are unresponsive. AZA is a prodrug, and the formation of active thioguanine nucleotide (TGN) metabolites varies widely. We aimed to assess the relationship between AZA metabolite concentrations (i.e., TGNs and methylmercaptopurine nucleotides [MeMPNs]), thiopurine methyltransferase (TPMT) activity, therapeutic response, and toxicity in adult patients with AIH prescribed a stable dose of AZA for the maintenance of remission. Red blood cell (RBC) TGNs and MeMPNs were measured in serial blood samples over a 2-year period. The average TGNs (avTGNs) and MeMPNs (avMeMPNs) concentrations for each patient were used for analysis. Therapeutic response was defined as the ability to maintain remission, defined as a normal serum alanine aminotransferase (ALT) level (ALT 220 pmol/8 × 108 RBCs best predicted remission, with an odds ratio of 7.7 (P = 0.003). There was no association between TGN, MeMPN, or TPMT activity and the development of leucopenia. Two patients developed AZA-induced cholestasis and the avMeMPN concentration was higher in those patients, compared to those who did not (14,277 versus 1,416 pmol/8 × 108 RBCs). Conclusion: TGN concentrations of >220 pmol/8 × 108 RBCs are associated with remission. TGN measurement may help identify inadequate immunosupression. AZA-induced cholestasis was associated with increased MeMPN concentrations.
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