Abstract

Recently, Riveiro-Barciela et al. [1] evaluated the efficacy and safety of rituximab in 35 patients with autoimmune hepatitis (AIH) and its variant forms. In their study population, 14 patients with AIH were refractory to standard therapy and non-standard therapies such as mycophenolate mofetil (MMF) or tacrolimus. Rituximab induced a complete biochemical response in 86% (12/14) of this group of patients. These results are promising for the treatment of refractory AIH, but no alternative therapies are available for AIH patients who do not respond to rituximab or other biological therapies [2]. Therefore, better effective treatment strategies are needed for refractory AIH [3]. Here, we would like to report on the case of difficult-to-treat AIH that did not respond to standard and non-standard therapies (MMF, tacrolimus and rituximab) but showed complete biochemical response with Janus kinase (JAK) inhibitor (tofacitinib) therapy. Our female patient was diagnosed with AIH in when she was 18 years old. She was initially treated with a combination of prednisolone (40 mg/day) and azathioprine (100 mg/day), with only achieving partial remission following 18 months of therapy (Figure 1). The therapy of patient was converted to MMF at 2000 mg/day. The patient used MMF during the period of 6 months, but her AST was 625 (range: 0–33 IU/L) and ALT was 472 (range: 7–34 IU/L). MMF was switched to tacrolimus (4–8 mg/day), but aminotransferase levels did not improve during 10 months of therapy. The additional trail of two rituximab (1000 mg) infusions was also failed to improve liver biochemical tests. We finally tried, a regimen of high-dose prednisolone (500 mg/day for 3 days, followed by tapering) combined with azathioprine (2 mg/kg/day). Following 17 months of this treatment, AST was 98 IU/L and ALT 85 IU/L and IgG levels (2460 mg/dL range: 610–1540 mg/dL) were still high. The patient subsequently developed pulmonary symptoms, leading to further investigations and was diagnosed with bronchiolitis obliterans organising pneumonia (BOOP). Tofacitinib was recommended as a treatment option. The patient was started on tofacitinib alongside a low-dose corticosteroid (5 mg/day). After 3 months of this therapy, she showed a complete biochemical response (AST was 19 IU/L, ALT was 17 IU/L, and IgG was 1240 mg/dL). Currently, Janus kinase (JAK) inhibitors such as tofacitinib is commonly used in the treatment of conventional therapy refractory systemic autoimmune conditions. Our observation suggests that this therapy also can be an alternative treatment option in difficult-to-treat cases of AIH. C.E., D.T.G., D.A. and M.A.K. interpreted data and prepared the manuscript for the final submission. The authors declare no conflicts of interest. All relevant data are presented in the manuscript.