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Guidelines on the diagnosis and management of autoimmune hepatitis (2021)
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摘要: 自身免疫性肝炎(autoimmune hepatitis, AIH)患者的临床特点包括血清氨基转移酶水平升高、高免疫球蛋白G血症、血清自身抗体阳性, 肝组织学上存在中重度界面性肝炎等。早期诊断和恰当治疗可显著改善AIH患者的生存期和生活质量, 减轻社会医疗负担。《自身免疫性肝炎诊断和治疗共识(2015)》在规范我国AIH的诊断和治疗方面发挥了积极作用。在此基础上, 2021年底中华医学会肝病分会组织有关专家结合最新进展制定本部指南, 旨在进一步提高我国AIH诊治水平。Abstract: Autoimmune hepatitis (AIH) is characterized by elevated serum aminotransferase and immunoglobulin G levels, seropositive results for autoantibodies and moderate to severe interface hepatitis in histologic findings. It will be most helpful in improving survival and life quality, if patients are diagnosed in the early stage and treated appropriately, which also helps relieve social medical burdens. Chinese consensus on the diagnosis and management of autoimmune hepatitis (2015) has contributed to standardizing the diagnosis and treatment of AIH. On the basis of the first consensus, at the end of 2021, under the organization of Chinese Society of Hepatology, experts devise this guide with latest advances aiming to further improve the level of diagnosis and management of autoimmune hepatitis.
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Key words:
- Hepatitis, Autoimmune /
- Diagnosis /
- Therapeutics /
- Practice Guideline
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图 1 AIH的药物治疗
注：*建议有条件时在使用前检测TPMT和NUDT15基因型和/或活性, 启动糖皮质激素2周后添加硫唑嘌呤(50~100 mg/d), 并注意监测血常规。失代偿期肝硬化患者不建议使用硫唑嘌呤。* *对于经泼尼松(龙)治疗后副作用严重者, 布地奈德可作为替代药物。但布地奈德在肝硬化患者中失去首过效应的优势, 有增加门静脉血栓形成的风险, 此外在急性重症AIH或急性肝功能衰竭中治疗作用未知, 因此上述情况下不建议使用。
表 1 推荐意见的证据等级和推荐强度等级
级别 详细说明 证据质量 高(A) 进一步研究不可能改变对该疗效评估结果的可信度 中(B) 进一步研究有可能影响该疗效评估结果的可信度, 且可能改变该评估结果 低或非常低(C) 进一步研究很有可能影响该疗效评估结果的可信度, 且很可能改变该评估结果 推荐强度 强(1) 明确显示干预措施利大于弊或弊大于利 弱(2) 利弊不确定或无论质量高低的证据均显示利弊相当 
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表 2 AIH综合诊断积分系统(1999年)
参数/临床特征 计分 参数/临床特征 计分 女性 +2 药物史 ALP(正常上限倍数)与AST(或ALT)(正常上限倍数)的比值 阳性 -4 阴性 +1 ＜1.5 +2 平均乙醇摄入量(g/d) 1.5~3.0 0 ＜25 +2 ＞3.0 -2 ＞60 -2 血清γ-球蛋白或IgG与正常值的比值 肝组织学检查 ＞2.0 +3 界面性肝炎 +3 1.5~2.0 +2 主要为淋巴-浆细胞浸润 +1 1.0~1.5 +1 肝细胞呈玫瑰花环样改变 +1 ＜1.0 0 无上述表现 -5 ANA, ASMA或LKM-1滴度 胆管改变 -3 ＞1∶80 +3 其他改变 -3 1∶80 +2 其他免疫性疾病 +2 1∶40 +1 其他可用的参数 ＜1∶40 0 其他特异性自身抗体(SLA/LP、LC-1、ASGPR、pANCA)阳性 +2 AMA阳性 -4 HLA-DR3或DR4 +1 肝炎病毒标志物 对治疗的反应 阳性 -3 完全 +2 阴性 +3 复发 +3 总积分的解释 治疗前 治疗后 明确的AIH ≥16 明确的AIH ≥18 可能的AIH 10~15 可能的AIH 12~17
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表 3 IAIHG的AIH简化诊断标准
变量 标准 分值 备注 ANA或SMA 1∶40 1 相当于我国常用的ANA 1∶100的最低滴度 ANA或SMA 1∶80 2 多项同时出现时最多2分 LKM-1 1∶40 2 SLA 阳性 2 IgG ＞正常值上限 1 ＞1.1倍正常值上限 2 肝组织学 符合AIH 1 界面性肝炎、汇管区和小叶内淋巴-浆细胞浸润、肝细胞玫瑰样花环以及穿入现象被认为是特征性肝组织学改变, 4项中具备3项为典型表现 典型AIH表现 2 排除病毒性肝炎 是 2 注：分值= 6分：AIH可能；分值≥7分：确诊AIH。
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表 4 AIH的鉴别诊断
疾病 临床表现和实验室检查 病理学表现 HCV感染 血清ANA可低滴度阳性或LKM-1阳性, IgG水平轻度升高；抗-HCV抗体和HCV RNA阳性 肝细胞脂肪变性、淋巴滤泡形成、肉芽肿形成 药物性肝损伤 药物史明确, 停用药物后好转；血清氨基转移酶水平升高和/或胆汁淤积表现 汇管区中性粒细胞和嗜酸粒细胞浸润、肝细胞大泡脂肪变性、肝细胞胆汁淤积, 纤维化程度一般较轻(低于S2) 代谢相关性脂肪性肝病 1/3患者血清ANA可低滴度阳性, 血清氨基转移酶轻度升高, 胰岛素抵抗表现 肝细胞呈大泡脂肪变性、肝窦纤维化、汇管区炎症较轻 Wilson病 血清ANA可阳性, 血清铜蓝蛋白低, 24 h尿铜升高, 可有角膜色素环(K-F环)阳性 存在肝细胞脂肪变性、空泡状核形成、汇管区炎症, 可伴界面炎, 可有大量铜沉着
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