自身免疫性肝炎（AIH）是由不明原因免疫异常引起的急性或慢性肝脏炎症性疾病,不分年龄或性别,影响所有种族群体。AIH如果没有得到及时的治疗,可能会发展为肝硬化、肝衰竭,甚至导致死亡。目前一些诊断评分系统和肝活组织病理检查已成为诊断的标准,然而由于疾病表现的高度异质性,AIH诊断仍很有挑战性。大多数患者最初对一线治疗（糖皮质激素与硫唑嘌呤的联合治疗）有应答,然而,应答欠佳和因不良反应引起的不耐受也不少见,需要二线和（或）三线治疗。本文总结阐述诊断困难、一线药物治疗应答欠佳或不耐受的疑难AIH诊断和管理的最新进展,并归纳了目前国内外关于AIH治疗的新方法,为AIH的临床诊疗提供参考。

Autoimmune hepatitis（AIH）is an acute or chronic inflammatory disease of liver caused by unclear immune response that affects people from all ethnic groups irrespective of age or sex．If left untreated,AIH will lead to cirrhosis,liver failure,or death．A number of diagnostic scoring systems and histopathological examination of liver biopsies are now the standard for diagnosis．However,due to the high heterogeneity of the disease presentation,AIH diagnosing remains challenging．Most patients initially respond to first-line treatment,which is corticosteroids combined with azathioprine．However,insufficient response and intolerance due to side effects are also common,so some patients requires second-and/or third-line therapies．Here we summarized the latest progress in diagnosis and management of AIH with difficult diagnosis,poor response to first-line drug treatment or intolerance,as well as the new methods of AIH treatment worldwide,to provide reference for the clinical diagnosis and treatment of AIH．

目的 探讨华南地区自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征(AIH-PBC OS)临床特点,提高对该病的认识。方法 回顾性总结2010年1月—2020年1月期间收治的居住在华南地区AIH-PBC OS患者37 例,对患者的临床表现、血清学、影像学和病理学特点,伴发肝外自身免疫性疾病等情况进行分析。结果 37例AIH-PBC OS以女性(94.6%)为主,平均发病年龄(48.3±10.3)岁,确诊年龄(50.4±9.2)岁,病程(2.7±2.5)年。83.8%患者存在临床症状,以乏力纳差,身目黄染、尿黄及瘙痒最为常见。在所有患者中,诊断为慢性肝炎为45.9%,代偿性肝硬化为18.9%,失代偿性肝硬化为35.1%,合并肝外自身免疫性疾病占35.1%,以自身免疫性甲状腺疾病和干燥综合征最常见。血清谷丙转氨酶、谷草转氨酶、谷氨酰转肽酶、碱性磷酸酶、总胆红素、总胆固醇、低密度脂蛋白胆固醇水平均升高,失代偿肝硬化期患者血红蛋白和白蛋白下降(P<0.05)。近一半患者血清免疫球蛋白G、免疫球蛋白M和免疫球蛋白A水平升高,失代偿肝硬化期患者免疫球蛋白G升高最为明显(P<0.05)。自身抗体包括抗核抗体阳性率、抗线粒体抗体和(或)抗线粒体抗体M2型抗体阳性率、抗平滑肌抗体阳性率、抗核点蛋白抗体阳性率、抗核包膜蛋白抗体阳性率分别为92%、67.6%、10.8%、11.1%、13.8%。病理学提示AIH-PBC OS患者可见汇管区淋巴细胞和浆细胞浸润,肝小叶界面炎,并伴有不同程度小胆管病变,70.2%同时伴有AIH-PBC特征。肝脏影像学显示在所有患者中,29.7%存在肝硬化,18.9%存在门静脉高压,62.2%存在脾大,18.9%存在腹腔积液。结论 AIH-PBC OS同时具有AIH及PBC疾病的临床特点,病情较复杂、发病较隐蔽;同时伴有血脂代谢障碍,且容易并发肝外自身免疫性疾病。

目的 观察免疫球蛋白联合甲泼尼龙疗法对自身免疫性脑炎患者T淋巴细胞亚群、免疫球蛋白、白介素-6(IL-6)和CXC趋化因子13(CXC13)水平影响。方法 选取2017年1月—2020年3月本院收治的60例自身免疫性脑炎患者,采用随机数字表法分为观察组30例与对照组30例。对照组给予甲泼尼龙疗法,观察组在对照组结合免疫球蛋白治疗。两组均以4周后评价。比较两组疗效,治疗前后T淋巴细胞亚群、免疫球蛋白、IL-6、CXC13及简易智能精神状态检查量表(MMSE)变化。结果 观察组总有效率(83.33%)高于对照组(60.00%)(P<0.05)。观察组治疗后CD⁺₃、CD⁺₄和CD⁺₄/CD⁺₈高于对照组(P<0.05)。观察组治疗后血清IgA、IgG和IgM水平低于对照组(P<0.05)。观察组治疗后血清IL-6和CXC13水平低于对照组(P<0.05)。观察组治疗后MMSE评分高于对照组(P<0.05)。结论 免疫球蛋白联合甲泼尼龙疗法对自身免疫性脑炎患者疗效良好,且可增强机体细胞和体液免疫功能,降低IL-6和CXC13水平。

Objective To observe the effect of immunoglobulin combined with methylprednisolone on T lymphocyte subsets, immunoglobulin, interleukin-6 (IL-6) and CXC chemokine 13 (CXC13) in patients with autoimmune encephalitis. Methods 60 patients with autoimmune encephalitis admitted to our hospital from January 2017 to March 2020 were divided into 30 cases of observation group and 30 cases of control group. The control group was treated with methylprednisolone, and observation group was treated with immunoglobulin compared with the control group. The course of treatment in both groups was 4 weeks. The effects of the two groups were compared. The changes of T lymphocyte subsets, immunoglobulin, IL-6, CXC13 and MMSE before and after treatment were compared. Results Total effective rate (83.33%) of the observation group was higher than that of control group (60.00%) (P<0.05). After treatment, in the observation group, CD⁺₃, CD⁺₄ and CD⁺₄/CD⁺₈ were higher than that of control group (P<0.05); levels of serum IgA, IgG and IgM were lower than that of control group (P<0.05); serum levels of IL-6 and CXC13 were lower than that of control group (P<0.05); MMSE score was higher than that of control group (P<0.05). Conclusion Immunoglobulin combined with methylprednisolone is effective in the treatment of autoimmune encephalitis. It may enhance the cellular and humoral immune function, and reduce the levels of IL-6 and CXC13.