Epigenetic considerations and the clinical reevaluation of the overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis
Epigenetic considerations and the clinical reevaluation of the overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis
复制标题
原发性胆汁性肝硬化和自身免疫性肝炎重叠综合征的表观遗传学考虑和临床重新评估
DOI：
10.1016/j.jaut.2012.10.004
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发表时间：
2013-03-01
影响因子：
12.8
通讯作者：
Ma, Xiong
中科院分区：
文献类型：
--
作者：
Wang, Qixia;Selmi, Carlo;Ma, Xiong
表观遗传变化在自身免疫性肝病的发病机制中至关重要。其中，对原发性胆汁性肝硬化 (PBC) 和自身免疫性肝炎 (AIR) 重叠综合征的定义和治疗达成的共识有限，我们评估了一系列连续的 PBC (n = 565) 和 AIR (n = 196) 患者，以确定一组皮质类固醇反应性 PBC-AIH 重叠综合征患者。在该系列中，根据分期或诊断需求，总共对 490 名患者进行了活检。结合国际 AIH 小组标准对活检进行审查，确定了 80 名疑似重叠综合征患者，其中 52 名患者同意参与该研究并接受皮质类固醇前瞻性治疗。其中，40/52 (77%) 在治疗 12 个月内实现了完整的生化反应（即正常 ALT、AST 和 IgG）。对 40 名应答者治疗前特征的调查显示，界面性肝炎更为严重。血清 IgG 水平 >= 1.3 倍正常上限时，类固醇反应的敏感性为 60%，特异性率为 97%，而使用更高的阈值（>= 2.0 倍）会将敏感性降低至 10%。当 PBC-AIH 巴黎标准应用于类固醇反应性患者时，29/40 (73%) 病例至少满足三项巴黎标准中的两项。应用最近设计的简化 IAIHG 评分系统，35/40 (88%) 的人“明确”诊断为 AIR。这项研究支持这样的假设：对皮质类固醇的完全缓解可能表示 PBC-AIH 重叠综合征的一种变异，可以在治疗前通过修改后的巴黎标准与简化的 IAIHG 评分系统相结合来识别这种变异。 (C) 2012 Elsevier Ltd. 保留所有权利。
Epigenetic changes are of crucial importance in the etiopathogenesis of autoimmune liver diseases. Among these, there is limited agreement on the definitions and treatment of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIR) overlap syndromes, we evaluated a large series of consecutive patients with PBC (n = 565) and AIR (n = 196) to identify a group of patients with corticosteroid-responsive PBC-AIH overlap syndrome. Within this series, a total of 490 patients were biopsied based upon staging or diagnostic needs. Review of the biopsies in conjunction with the International AIH Group criteria identified 80 patients with suspected overlap syndrome and 52 patients agreed to participate in the study and were prospectively treated with corticosteroids. Of these, 40/52 (77%) achieved a complete biochemical response (i.e. normal ALT, AST, and IgG) within 12 months of treatment. A survey of pretreatment characteristics of the 40 responders revealed more severe interface hepatitis. Serum IgG levels >= 1.3x the upper limit of normal had 60% sensitivity and 97% specificity rates for steroid-responsiveness while the use of a higher threshold (>= 2.0x) reduced sensitivity to 10%. When the Paris criteria for PBC-AIH were applied to the steroid-responsive patients, 29/40 (73%) cases fulfilled at least two of the three Paris criteria. Applying the recently designed simplified IAIHG scoring system, 35/40 (88%) had a "definite" diagnosis of AIR. This study supports the hypothesis that a complete response to corticosteroids may denote a variant of a PBC-AIH overlap syndrome which could be identified prior to treatment by modified Paris criteria in concert with the simplified IAIHG scoring system. (C) 2012 Elsevier Ltd. All rights reserved.