While obtaining azathioprine (AZA) metabolite levels in inflammatory bowel disease has proven clinical utility, there is less data with regard to autoimmune hepatitis (AIH).  Now a study of 70 adults with AIH reports that therapeutic levels of 6-thioguanine (TGN) (>220 pmol/8 x 10 to the 8th) are associated with remission (Hepatology 2012; 56: 1401-8).

Patients in this study had an average age of 61 years; the average participant had a diagnosis of AIH for 8 years at the start of the study. For induction of remission, patients had received a combination of prednisolone along with AZA.  AZA was started at 1 mg/kg/day and gradually increased to 2 mg/kg/day.  All patients had a complete response to steroids prior to AZA dose escalation.

Outcome from this study was characterized by ability to maintain remission with ALT <33 IU/L and/or relapse which was indicated by ALT >2 x ULN (upper limit of normal) or liver histology showing active disease.

Serial measurements of red blood cell TGN and methylmercaptopurine nucleotides (MeMPNs) were obtained over two years.

Results:

• 53 patients maintained remission and 17 did not.
• Those in remission tended to be receiving lower doses of AZA (1.7 vs 2 mg/kg/day) but had higher average TGN levels (237 vs 177 pmol/8 x 10 to the 8th)
• TGN levels >220 pmol/8 x 10 to the 8th best predicted remission
• There was no measurable difference in thiopurine methyltransferase (TPMT) activity between the two groups (remission vs relapse).
• Two patients developed cholestasis and this was associated with high MeMPN levels.

The authors note that several previous studies did not demonstrate a relationship between TGN levels and efficacy.  This is likely related to patient selection (all in remission at start in current study), repeated TGN levels, and the definition of remission.

Conclusion: Obtaining metabolites in adherent patients may be beneficial in patients with active disease to assist with dose modification and in individuals with potential AZA toxicity.

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