The Use of Tacrolimus in Refractory Autoimmune Hepatitis in Children and Adults: A Single-Center Experience

Abstract

Introduction: Despite the progress in diagnosing and treating patients with autoimmune hepatitis (AIH), there is limited data on using alternative agents in patients who do not achieve remission to standard therapy. Corticosteroids, in conjunction with azathioprine, are the mainstay of treatment for AIH in children and adults. Tacrolimus, a calcineurin inhibitor, has been proposed as a promising salvage agent in both age groups. The aim of this study was to determine the efficacy and safety of tacrolimus in treating refractory AIH in both children and adults. Methods: The diagnosis of AIH was made based on the criteria that was established by the International Autoimmune Hepatitis Group. We identified all adult and pediatric patients with AIH who were treated with tacrolimus between 2008 and 2013. A total of 23 patients (17 adults and 6 children) were included in the study. Median age at time of AIH diagnosis was 20 years and median disease duration at time of prograf start was 18 months. Results: Biochemical response was noted in 68% of subjects; 41% had a partial response (ALT decreased by >50%, but not completely normalized) and 27% had complete response (normalization of ALT< 50 U/L), Figure. Paired comparison of pre and post tacrolimus treatment labs showed a substantial reduction in ALT levels 155.0 [61.0,318.0] vs 61.0 [22.0,163.0] p-value = 0.009. Concomitantly, serum creatinine significantly increased after treatment with tacrolimus 0.67 [0.50,0.70] vs 0.75 [0.70,1.1] p-value of 0.026. Treatment with tacrolimus was discontinued prematurely in two adults because of significant adverse events (n=1), and lack of efficacy (n=1) and one child because of adverse effects. Conclusion: Tacrolimus was relatively safe and effective in treating refractory AIH in both adults and children who did not respond to standard therapy.Figure 1