Background/Purpose:

Auto-immune hepatitis (AIH), also known as lupoid hepatitis, is a chronic progressive disease of unknown aetiology. First-line therapy consists of corticosteroids alone or in combination with azathioprine. Cyclophosphamide, mycophenolate mofetil (MMF), and tacrolimus have also been used but some patients do not respond or experience toxicity. Rituximab is effective in other connective tissue diseases. The aim of this study was to evaluate the efficacy and safety of rituximab in patients with refractory AIH.

Methods:

We conducted a prospective open-label single centre trial in patients with seropositive biopsy-proven AIH resistant to conventional therapy including high dose corticosteroids and multiple immunosuppressants. Two infusions of rituximab 1000 mg two weeks apart were given, each preceded by 100mg methylprednisolone. Response was assessed at month 3 using biochemical parameters including alanine transaminase (ALT), bilirubin, and immunoglobulin G (IgG). B cell subsets were enumerated using highly sensitive flow cytometry with a lower limit of detection. Repeat cycles were given if the disease flared up with rising liver enzymes.

Results:

Between November 2007 and January 2013, 5 patients (3 females) with refractory AIH were treated with rituximab. Mean age was 25 years. Median follow-up duration was 26 months. All patients were positive for antinuclear antibody (ANA), 3 for anti-smooth muscle antibody (SMA), and 3 for anti-double stranded DNA. All of the patients achieved good response with marked improvements in clinical symptoms and laboratory abnormalities. Significant reductions were observed in the mean values of ALT and daily prednisolone dose after cycle 1 with trends to improvement in other parameters. Three patients to date required another cycle of rituximab after 18, 20, and 60 months and maintained good response. All patients exhibited B cell depletion by conventional flow cytometry (0.01×10⁹ cells/L), although complete B-cell depletion (<0.0001 x 10⁹cells/L) was seen in just 3 of the 8 cycles given; this did not appear to impact on the therapeutic outcome. One serious adverse event possibly related to treatment was observed; a patient, who had previously suffered from inflammatory bowel disease, developed a large bowel perforation six weeks after starting rituximab and stopping tacrolimus.

Conclusion:

Rituximab demonstrated efficacy in this group of patients with refractory seropositive AIH. This supports further evaluation of rituximab in AIH in larger studies.