BACKGROUND: Although most patients with autoimmune hepatitis (AIH) respond to treatment with prednisone and⁄or azathioprine, some patients are intolerant or refractory to standard therapy. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells and has demonstrated efficacy in other autoimmune conditions. AIMS: To evaluate the safety and efficacy of rituximab in patients with refractory AIH in an open-label, single-centre pilot study. METHODS: Six patients with definite, biopsy-proven AIH who failed prednisone and azathioprine treatment received two infusions of rituximab 1000 mg two weeks apart and were followed for 72 weeks. RESULTS: Rituximab was well tolerated with no serious adverse events. By week 24, mean (± SD) aspartate aminotransferase (AST) levels had significantly improved (90.0±23.3 U⁄L versus 31.3±4.2 U⁄L; P=0.03) and mean immunoglobulin G levels had fallen (16.4±2.0 g⁄L versus 11.5±1.1 g⁄L; P=0.056). The prednisone dose was weaned in three of four subjects, with one subject flaring after steroid withdrawal. Inflammation grade improved in all four subjects who underwent repeat liver biopsy at week 48. Regulatory T cell levels examined by FoxP3 immunohistochemistry paralleled inflammatory activity and did not increase on follow-up biopsies. There was no significant change in serum chemokine or cytokine levels from baseline to week 24 (n=5), although interferon-gamma-induced protein 10 levels improved in three of five subjects. CONCLUSIONS: Rituximab was safe, well tolerated and resulted in biochemical improvement in subjects with refractory AIH. These results support further investigation of rituximab as a treatment for AIH.
BACKGROUND: Although most patients with autoimmune hepatitis (AIH) respond to treatment with prednisone and⁄or azathioprine, some patients are intolerant or refractory to standard therapy. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells and has demonstrated efficacy in other autoimmune conditions. AIMS: To evaluate the safety and efficacy of rituximab in patients with refractory AIH in an open-label, single-centre pilot study. METHODS: Six patients with definite, biopsy-proven AIH who failed prednisone and azathioprine treatment received two infusions of rituximab 1000 mg two weeks apart and were followed for 72 weeks. RESULTS:Rituximab was well tolerated with no serious adverse events. By week 24, mean (± SD) aspartate aminotransferase (AST) levels had significantly improved (90.0±23.3 U⁄L versus 31.3±4.2 U⁄L; P=0.03) and mean immunoglobulin G levels had fallen (16.4±2.0 g⁄L versus 11.5±1.1 g⁄L; P=0.056). The prednisone dose was weaned in three of four subjects, with one subject flaring after steroid withdrawal. Inflammation grade improved in all four subjects who underwent repeat liver biopsy at week 48. Regulatory T cell levels examined by FoxP3 immunohistochemistry paralleled inflammatory activity and did not increase on follow-up biopsies. There was no significant change in serum chemokine or cytokine levels from baseline to week 24 (n=5), although interferon-gamma-induced protein 10 levels improved in three of five subjects. CONCLUSIONS:Rituximab was safe, well tolerated and resulted in biochemical improvement in subjects with refractory AIH. These results support further investigation of rituximab as a treatment for AIH.
Authors: Masanobu Tsuda; Yuki Moritoki; Zhe-Xiong Lian; Weici Zhang; Katsunori Yoshida; Kanji Wakabayashi; Guo-Xiang Yang; Toshio Nakatani; John Vierling; Keith Lindor; M Eric Gershwin; Christopher L Bowlus Journal: Hepatology Date: 2012-02 Impact factor: 17.425
Authors: F Alvarez; P A Berg; F B Bianchi; L Bianchi; A K Burroughs; E L Cancado; R W Chapman; W G Cooksley; A J Czaja; V J Desmet; P T Donaldson; A L Eddleston; L Fainboim; J Heathcote; J C Homberg; J H Hoofnagle; S Kakumu; E L Krawitt; I R Mackay; R N MacSween; W C Maddrey; M P Manns; I G McFarlane; K H Meyer zum Büschenfelde; M Zeniya Journal: J Hepatol Date: 1999-11 Impact factor: 25.083
Authors: F C Fervenza; F G Cosio; S B Erickson; U Specks; A M Herzenberg; J J Dillon; N Leung; I M Cohen; D N Wochos; E Bergstralh; M Hladunewich; D C Cattran Journal: Kidney Int Date: 2007-10-17 Impact factor: 10.612