Lower 6-MMP/6-TG Ratio May Be a Therapeutic Target in Pediatric Autoimmune Hepatitis

Area of Science:

• Pediatric Gastroenterology
• Hepatology
• Clinical Pharmacology

Background:

• Azathioprine (AZA) is a primary treatment for pediatric autoimmune hepatitis (AIH).
• Individualizing AZA therapy using thiopurine metabolites to prevent toxicity requires further definition.

Purpose of the Study:

• To investigate the correlation between thiopurine metabolite levels and treatment outcomes in children with AIH.
• To determine if metabolite levels can predict or explain remission status in pediatric AIH.

Main Methods:

• Retrospective analysis of 56 children diagnosed with AIH (≤18 years) between 2001 and 2016.
• Correlation of thiopurine metabolite levels (6-thioguanine-nucleotide and 6-methyl-mercaptopurine) with liver function tests and remission status.
• Analysis of the 6-methyl-mercaptopurine/6-thioguanine-nucleotide ratio in relation to treatment response.

Main Results:

• No significant difference in 6-thioguanine-nucleotide levels was found between children in remission and those not in remission.
• No direct correlation was observed between 6-thioguanine-nucleotide or 6-methyl-mercaptopurine levels and alanine aminotransferase.
• A significantly lower 6-methyl-mercaptopurine/6-thioguanine-nucleotide ratio (<4) was associated with remission (OR 2.50, P=0.047).
• Allopurinol combined with low-dose AZA achieved remission in 5 out of 6 children with preferential 6-methyl-mercaptopurine production.

Conclusions:

• Thiopurine metabolite levels, especially the 6-methyl-mercaptopurine/6-thioguanine-nucleotide ratio, are valuable in managing AIH patients experiencing loss of remission.
• A 6-methyl-mercaptopurine/6-thioguanine-nucleotide ratio below 4, potentially managed with allopurinol, may be a strategy for achieving remission in AIH.