Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
Division of Pediatric Immunology and Allergy, Joe DiMaggio Children's Hospital, Hollywood, FL, USA.
Expert Opin Investig Drugs. 2020 Apr;29(4):385-398. doi: 10.1080/13543784.2020.1733527. Epub 2020 Feb 26.
: Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and juvenile autoimmune hepatitis (JAIH). The pathophysiologic features of each disease vary, but generally include presence of autoantibodies, cytokine abnormalities, and/or T and B cell autoreactivity.: This article compares conventional therapy with newer biologics available for treatment of autoimmune liver diseases. Conventional therapy involves the use of immunosuppressive agents, or other treatment modalities for specific autoimmune liver diseases such as ursodeoxycholic acid and fibrates for PBC. Biologics were developed to target the production of autoantibodies by B cells, the presence of proinflammatory cytokines, adhesion molecules or T and B cell activation.: Despite the promise of biologics being able to target specific cellular and humoral pathways, results have been generally poor, and safety has not been as expected. Cases of autoimmune hepatitis have also developed with the use of these biologicals. Reasons for the lack of success of biologics in treating autoimmune liver disease has led to a reevaluation of our understanding of underlying pathogenesis, demonstrating that while our knowledge of the immunity has improved over the past two decades, it is far from complete.
自身免疫性肝病包括自身免疫性肝炎（AIH）、原发性胆汁性胆管炎（PBC）、原发性硬化性胆管炎（PSC）和青少年自身免疫性肝炎（JAIH）。每种疾病的病理生理特征不同，但通常包括自身抗体、细胞因子异常和/或 T 细胞和 B 细胞自身反应性的存在。本文比较了用于治疗自身免疫性肝病的传统疗法和新型生物制剂。传统疗法包括使用免疫抑制剂或针对 PBC 等特定自身免疫性肝病的其他治疗方法，如熊去氧胆酸和贝特类药物。生物制剂的开发是为了针对 B 细胞产生的自身抗体、促炎细胞因子、黏附分子或 T 和 B 细胞的激活。尽管生物制剂有望针对特定的细胞和体液途径，但结果通常不佳，安全性也不如预期。在使用这些生物制剂的情况下，也出现了自身免疫性肝炎病例。生物制剂治疗自身免疫性肝病失败的原因导致了对潜在发病机制的重新评估，表明尽管我们在过去二十年中对免疫的了解有所提高，但还远远不够。
