Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA.
Dig Dis Sci. 2012 Aug;57(8):1996-2010. doi: 10.1007/s10620-012-2151-2. Epub 2012 Apr 3.
Current treatment strategies for autoimmune hepatitis are complicated by frequent relapse after drug withdrawal, medication intolerance, and refractory disease. The objective of this review is to describe advances that have improved treatment outcomes by defining the optimum objectives of initial therapy, managing relapse more effectively, identifying problematic patients early, and incorporating the new pharmacological interventions that have emerged as frontline and salvage therapies. Initial corticosteroid treatment should be continued until serum aminotransferase, γ-globulin, and immunoglobulin G levels are normal, and maintenance of this improvement for 3-8 months before liver tissue assessment. Improvement to normal liver tissue is the ideal histological result that justifies drug withdrawal, but it is achievable in only 22 % of patients. Minimum portal hepatitis, inactive cirrhosis, or minimally active cirrhosis is the most common treatment end point. Relapse after drug withdrawal warrants institution of a long-term maintenance regimen, preferably with azathioprine. Mathematical models can identify problematic adult patients early, as also can clinical phenotype (age ≤ 30 years and HLA DRB1 03), rapidity of treatment response (≤ 24 months), presence of antibodies to soluble liver antigen, and non-white ethnicity. The calcineurin inhibitors (cyclosporine and tacrolimus) can be effective in steroid-refractory disease; mycophenolate mofetil can be corticosteroid-sparing and effective for azathioprine intolerance; budesonide combined with azathioprine can be effective for treatment-naïve, non-cirrhotic patients. Standard treatment regimens for autoimmune hepatitis can be upgraded without adjustments that require major new expertise.
目前的自身免疫性肝炎治疗策略因停药后频繁复发、药物不耐受和难治性疾病而变得复杂。本综述的目的是描述通过定义初始治疗的最佳目标、更有效地管理复发、早期识别有问题的患者以及采用新出现的作为一线和挽救治疗的新药理学干预措施来改善治疗结果的进展。初始皮质类固醇治疗应持续到血清转氨酶、γ-球蛋白和免疫球蛋白 G 水平正常,并且在进行肝脏组织评估之前维持这种改善 3-8 个月。正常肝脏组织的改善是证明停药合理的理想组织学结果,但只有 22%的患者可以实现。最小的门脉肝炎、非活动性肝硬化或轻微活动肝硬化是最常见的治疗终点。停药后复发需要进行长期维持治疗方案,最好使用硫唑嘌呤。数学模型可以早期识别有问题的成年患者,临床表型(年龄≤30 岁和 HLA DRB1 03)、治疗反应的快速性(≤24 个月)、可溶性肝抗原抗体的存在以及非白种人也可以识别。钙调神经磷酸酶抑制剂(环孢素和他克莫司)可有效治疗皮质类固醇难治性疾病;霉酚酸酯可作为皮质类固醇的替代品,对硫唑嘌呤不耐受有效;布地奈德联合硫唑嘌呤可有效治疗未经治疗、非肝硬化患者。无需调整即可升级自身免疫性肝炎的标准治疗方案,无需新的专业知识。