Second-line tacrolimus and mycophenolate mofetil in difficult-to-treat autoimmune hepatitis

INTRODUCTION: Azathioprine with corticosteroids is the first-line treatment for patients with autoimmune hepatitis (AIH). However, around 20% of patients require treatment alternatives, and second-line therapy for AIH is less well defined due to a lack of randomized controlled trials. We evaluated the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy. METHODS: We performed a retrospective analysis of second-line therapies with MMF or tacrolimus for patients with AIH. Biochemical parameters were collected at the change of therapy, after 6 and 12 months, and at the last follow-up. RESULTS: In total, 84/455 (18%) patients with AIH required second-line therapies, and 59 patients received MMF (47 patients) or tacrolimus (12 patients). Complete biochemical remission was achieved at a similar proportion in the tacrolimus group compared with MMF after 12 months (70.0% vs. 51.7%). In the subgroup of patients with insufficient response to first-line therapy, the rate of complete biochemical remission after 12 months was 70% in the tacrolimus group and 31% in the MMF group. Patients in the tacrolimus group had a higher mean ALT values compared with the MMF group and a higher prevalence of cirrhosis at the start of second-line therapy (50% vs. 19.1%). CONCLUSIONS: MMF and tacrolimus are effective and well-tolerated second-line therapies for AIH and should be part of the individualized second-line treatment algorithm of AIH. A trial of MMF is warranted after failure of first-line therapy. However, tacrolimus seems to be a safe and effective second-line option in patients with more advanced and aggressive disease.