自身免疫性肝炎的临床诊治

自身免疫性肝炎(AIH)是由异常自身免疫反应介导的肝实质炎症性病变,以高丙种球蛋白血症、血清自身抗体阳性和对免疫抑制治疗应答为特点[1].在环境因素、免疫耐受失衡和遗传易感状态的共同作用下,机体出现T淋巴细胞介导的针对肝抗原的异常免疫攻击,进而导致肝内进行性炎症坏死和纤维化过程.     

自身免疫性肝炎患者临床病理学特点的性别差异比较

目的 分析自身免疫性肝炎(AIH)患者临床病理学特点是否存在性别差异.方法 169例AIH患者分为男性患者组23例,女性患者组146例,对两组患者的临床资料及肝活组织病理学检查结果进行分析,比较两组患者的临床病理学特点.非正态连续变量的比较采用Mann-Whiteney U检验,分类构成比采用Chi-Squre检验,累积生物化学缓解率采用Kaplan-Meier法.结果 男、女患者组的一般情况、AST、碱性磷酸酶(ALP)、γ-谷氨酰转移酶(GGT)、总胆红素(Tbi)和肝组织学分级比较,差异均无统计学意义(P＞0.05).比较两组患者的血清γ-球蛋白、IgG、IgM、自身抗体阳性率及其伴发其他自身免疫性疾病,差异无统计学意义(P＞0.05).采用传统积分系统评估,男性患者组治疗前积分为14.4±2.3,低于女性患者组的16.6±2.6,两组比较,差异有统计学意义(Z=-3.728,P=0.000),采用简化积分系统评估,男性患者组积分为7.2±0.8,高于女性患者组的6.5±1.2,两组比较,差异有统计学意义(Z=-2.372,P=0.018).15例接受免疫抑制剂治疗的男性AIH患者中有12例达到生物化学缓解,其余3例目前为不完全缓解,累积生物化学缓解率为80％,中位缓解时间为3个月(95％CI为2.070～3.930).结论 AIH在临床及病理特点方面不存在性别间差异,肝功能异常的男性患者也应考虑AIH的可能,建议行肝活组织学检查以明确诊断.简化标准可很好地用于男性AIH患者的临床诊断.     

自身抗体阴性自身免疫性肝炎患者临床病理学特点

目的:分析自身抗体阴性自身免疫性肝炎(AIH)患者临床特点,并总结诊疗经验。方法:对167例AIH患者的临床和病理特点进行分析,将自身抗体阴性AIH患者定义为:符合国际自身免疫性肝炎小组(IAIHG)1999年描述性诊断标准且抗核抗体、抗平滑肌抗体、抗肝肾微粒体1型抗体和抗线粒体抗体均为阴性者。结果:167例中17例自身抗体阴性,占10.2%。自身抗体阳性和自身抗体阴性AIH患者在一般情况(诊断时年龄除外)、生化指标方面均无明显差异(P0.05)。自身抗体阴性组血清IgG水平低于自身抗体阳性组,差异有统计学意义(P=0.004)。两组肝组织学炎症分级无明显差异,而自身抗体阴性组中存在更多纤维化进展期患者(P0.001)。采用1999年诊断积分系统评估时,自身抗体阴性组中11例(64.7%)为可能性诊断,其余6例(35.3%)为确定性诊断;采用简化诊断积分系统重新评估后,仅3例(17.6%)达到可能性诊断,且无1例达到确定性诊断标准。与自身抗体阳性组相比,自身抗体阴性AIH患者接受24个月的免疫抑制治疗后累积完全生化缓解率为86%,两组患者无明显差异(P=0.658)。结论:自身抗体阴性AIH在国人中并非罕见,在应用免疫抑制治疗方面与自身抗体阳性AIH患者类似,能取得满意疗效。     

自身免疫性肝炎的诊断和治疗

自身免疫性肝炎(autoimmune hepatitis,AIH)是一种累及肝脏实质的特发性疾病.临床上,AIH以高血清转氨酶、高γ-球蛋白/Ig、高滴度自身抗体和肝组织学上以界面性肝炎(interface hepatitis)为特点,但需排除其他原因所致慢性肝病的可能.该病一般对糖皮质激素治疗应答良好.基于血清免疫学发现,AIH可分为二型:Ⅰ型AIH是最常见的疾病类型,与抗核抗体(ANA)和/或平滑肌抗体(SMA)、抗肌动蛋白抗体、非典型P-ANCA及抗可溶性肝抗原/肝胰抗体(抗SLA/LP)等有关;Ⅱ型AIH主要发生于儿童,以抗肝/肾微粒抗体1型(抗LKM -1)和抗肝细胞溶质-1抗体(抗LC-1)为主.大约有10％的患者血清自身抗体可呈阴性.按基因型可分为HLADR3( DRBI^0301)、HLA -B8和HLA - DR4CDRBI^0401,0405)等类.在存在相应的组织学改变的基础上,AIH的诊断还需结合临床和生化特点、血清自身抗体和免疫球蛋白水平.     

自身免疫性肝炎的诊治难点

近年我国自身免疫性肝炎（AIH）的检出率呈上升趋势,日益受到临床医师的关注。由于AIH的发病机制迄今不明且缺乏特异的诊断标准,临床工作中经常遇到不典型AIH,给诊断和治疗带来困惑。本文就AIH的诊治难点作一综述。     

自身免疫性肝炎的临床和病理

目的 研究自身免疫性肝炎（ａｕｔｏｉｍｍｕｎｅ ｈｅｐａｔｉｔｉｓ,ＡＩＨ）的临床表现,肝活检病理学特征。方法 回顾性总结１４例ＡＩＨ肝脏损害患者的临床表现及肝病理活检结果。结果 ＡＩＨ主要影响女性,女：男为１３：１,年龄２８－６６岁,伴有迁延性丙氨酸转氨酶（ａｌａｎｉｎｅ ｔｒａｓａｍｉｎａｓｅ,ＡＬＴ）和天冬氨酸转氨酶（ａｓｐａｒｔａｔｅ ｔｒａｎｓａｍｉｎａｓｅ,ＡＳＴ）异常,高球蛋白,高γ     

酒精性肝硬化与乙型肝炎肝硬化、丙型肝炎肝硬化及自身免疫性肝硬化临床特点对比分析

目的探讨酒精性肝硬化的临床特点及其与乙型肝炎（乙肝）肝硬化、丙型肝炎（丙肝）肝硬化和自身免疫性肝硬化临床特点的异同。方法总结和分析2002--2012年住我院的部分酒精性肝硬化患者（373例）的临床特点,并与同期住院的部分乙肝肝硬化患者（205例）、丙肝肝硬化患者（104例）和自身免疫性肝硬化患者（121例）的临床特点进行对比分析。结果酒精性肝硬化患者好发年龄段为40。59岁（68．36％）,尤其以40。49岁发病率最高,达到43．43％。与其他3种病因所致的肝硬化患者相比,酒精性肝硬化患者男性占绝大多数（98．66％）,差异有统计学意义（P〈O．01）。酒精性肝硬化患者的WBC、中性粒细胞绝对值、中性粒细胞绝对值／淋巴细胞绝对值比值和平均红细胞容积均明显高于其他3种病因所致的肝硬化患者,差异有统计学意义（P均〈O．01）。酒精性肝硬化患者的AST／ALT比值、TBIL和GGT／ALP比值均明显高于其他3种病因所致的肝硬化患者,差异有统计学意义（P均〈0．01）。结论酒精性肝硬化在我国的发病率不断升高,且与乙肝肝硬化、丙肝肝硬化和自身免疫性肝硬化相比有其独特的临床特点。应对酒精性肝硬化给予更多关注。     

慢性乙型肝炎合并自身免疫性肝炎的临床诊治分析

目的总结慢性乙型肝炎(CHB)合并自身免疫性肝炎(AIH)的临床诊断和治疗方法。方法回顾性分析2013年12月至2018年6月上海交通大学医学院附属仁济医院消化内科门诊随访的19例诊断为CHB合并AIH患者的临床表现、实验室检查、影像学、病理组织学特点、治疗及转归情况,正态分布计量资料治疗前后比较采用配对样本t检验;不符合正态分布的计量资料以中位数(四分位数间距)表示,治疗前后比较采用配对样本的Wilcoxon符号秩和检验。结果19例患者中男性5例、女性14例,发病年龄35~63(47.10±8.76)岁。CHB先于AIH诊断有12例,AIH先于CHB诊断有5例,AIH和CHB同时诊断有2例。明确诊断CHB合并AIH后,予以核苷(酸)类似物抗乙型肝炎病毒联合糖皮质激素治疗,并根据肝内炎症(炎症分级在G3及以上)及白细胞情况加用免疫抑制剂硫唑嘌呤或吗替麦考酚酯。治疗2周至16周不等(治疗中位时间6周),除1例刚诊断治疗随访中外,其余18例患者治疗前后生物化学指标、免疫球蛋白均明显下降,治疗前后指标差异均有统计学意义(P值均<0.05),HBV DNA均<20拷贝/ml。结论CHB合并AIH容易漏诊,需要结合临床特点、自身抗体、免疫球蛋白水平,尤其重视肝组织病理学特点进行综合诊断。对抗-HBc阳性使用免疫抑制剂治疗的患者,应加强对HBV DNA的监测,必要时需抗乙型肝炎病毒治疗。     

自身免疫性肝炎免疫学治疗进展

近年来自身免疫性肝炎(AIH)以其独特的临床和病理学特征,受到越来越多的关注。但目前其发病率和临床特征仍不十分清楚,尚需对其进行系统深入的研究。探讨了AIH的流行病学、病因和发病机制、临床特征及其诊断和治疗进展。指出TNFα中和性抗体、利妥昔单抗、全反式维甲酸和调节性T淋巴细胞移植在临床试验或AIH动物模型中均被证明对AIH有疗效。     

自身免疫性肝炎的诊断与治疗

自身免疫性肝炎(AIH)是一种病因和发病机制尚未明确的慢性进行性肝脏炎症性疾病,以高丙种球蛋白血症、血清自身抗体阳性和对免疫抑制治疗应答良好为特点。简要介绍了AIH的流行病学概况、临床特点以及近年来在AIH的诊断及治疗方面所取得的进展,强调早期诊断并给予正确治疗有助于改善其预后。     

单采血浆后自身抗体阳性慢性丙型肝炎患者肝组织的病理学特点

目的观察单采血浆后慢性丙型肝炎(CHC)患者自身抗体的检出率及其特点,了解自身抗体阳性CHC患者肝组织病理学特点。方法收集1992年1月-1995年12月甘肃省定西县医院和定西传染病专科医院的120例单采血浆后感染HCV的患者为试验组,另外选取同地区健康人群11例作为对照组。对CHC患者进行自身抗体检测;将自身抗体阳性组(n=44)与阴性组(n=76)肝组织病理学特点进行对比分析。计量资料组间比较采用t检验,计数资料组间比较采用χ~2检验。结果 120例单采血浆后CHC患者自身抗体检出率为36.7%(44/120),主要的自身抗体为抗核抗体,占21.7%。自身抗体阳性组较阴性组肝小叶内点灶状坏死炎症评分(2.11±0.88 vs 1.64±0.88,t=2.349,P=0.021)及汇管区内部细胆管反应评分(1.86±0.71 vs 1.13±0.66,t=4.217,P<0.001)明显升高;自身抗体阳性组肝小叶间胆管损伤比例较阴性组升高,差异有统计学意义(86.4%vs 55.3%,χ~2=12.129,P=0.001);而2组肝纤维化和肝脂肪变性程度差异无统计学意义(P值均>0.05)。结论单采血浆后CHC患者常见自身抗体阳性,自身抗体阳性者部分肝脏病理损伤较重。     

自身免疫性肝炎的病理特点

本文简要介绍了自身免疫性肝炎（AIH）发病机制的进展,阐述了AIH活动期和缓解期的病理形态特点及缓解的病理诊断标准。AIH的病理组织学特点为淋巴浆细胞性界面炎。急性加重或急性发病可呈现明显的小叶中心带坏死,这些病变中浆细胞成簇是诊断AIH的重要依据。肝穿病理形态有助于澄清其他自身抗体阳性的慢性肝病。并介绍了IgG4相关性自身免疫性肝炎和原位自身免疫性肝炎的病理特点     

自身免疫性肝炎86例临床、病理特点分析

为提高对自身免疫性肝炎(AIH)的诊治水平,采用国际自身免疫性肝炎小组(IAIHG)新修订的描述性诊 断标准和计分系统,对符合诊断的患者进行临床、生化、病理特点分析。86例AIH患者,女75例,男11例,高发年 龄为40～60岁,其中Ⅰ型80例(93．020k),Ⅱ型3例(3．49％);Ⅲ型3例(3．49％);肝功能生化检查表现为肝炎样改 变;实验室检查主要表现为高γ球蛋白血症,高IgG、ALP、γ-GT及甘油三酯增高,81．5％患者抗核抗体阳性:病理改 变以界板性肝炎,浆细胞浸润为主,78％的患者对免疫抑制剂治疗效佳。AIH患者多为中年女性,以血清自身抗体、 高γ球蛋白血症和肝组织活检呈界板性肝炎、浆细胞浸润,对免疫抑制治疗反应良好为特点。     

胆汁淤积型戊型肝炎106例临床特点分析

目的探讨戊型肝炎（戊肝）合并肝内胆汁淤积的临床特点。方法对106例胆汁淤积型戊肝的临床特点及治疗进行回顾性分析。结果106例胆汁淤积型戊肝中,59例为单纯戊肝（其中28例有长期大量饮酒史）,16例为乙、戊型肝炎病毒重叠感染,3例为丙、戊型肝炎病毒重叠感染。6例发展为重型肝炎,其中3例合并乙型肝炎,2例有长期饮酒史,1例为单纯性戊肝。经保肝、退黄等综合治疗,总治愈例数102例,3例发展为坏死后肝硬化（均为重型肝炎）,1例临床死亡。结论戊肝患者起病急,重症较多,易合并肝内胆汁淤积。经积极综合治疗（包括肾上腺皮质激素治疗及人工肝支持系统治疗）,预后良好,但病程长,部分患者因胆汁淤积时间长可能出现胆汁淤积性肝硬化。     

Comparison of clinical features and liver histology in acute and chronic autoimmune hepatitis.

Aim: We investigated the clinical and morphological features between acute and chronic autoimmune hepatitis (AIH) with or without acute exacerbation. Methods & Results: Serum total bilirubin on average was elevated to 12 mg/dL in acute AIH, alanine aminotransferase and aspartate aminotransferase peaked to more than 1000 U/L, and serum gamma-glutamyl transpeptidase was higher in the acute type compared with the chronic type without exacerbation. Serum immunoglobulin G was lowest in all other types of AIH. A liver biopsy showed interface or lobular hepatitis with lympho-plasmacytic infiltration, and rosette formations were frequently seen in acute AIH. There were morphological changes of central necrosis with plasmacytic infiltration and giant cell hepatitis. CK19-positive cholangiolar cells had proliferated in the periportal area with massive necrosis, and bile duct injuries were seen in acute AIH more frequently than in the chronic type. Conclusion: Laboratory data and liver histology in acute AIH differed from those of chronic AIH and were clarified for the diagnosis of acute AIH.     

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis

Aim:  Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20–30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients.
Methods:  A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique.
Results:  Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (≥ 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups.
Conclusions:  ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful.     

Clinical features of type 1 autoimmune hepatitis in adolescence and early adulthood

Aim:  The peak age of the presentation of autoimmune hepatitis (AIH) is between 40 years and 50 years. Elderly patients have been reported to have higher frequencies of concurrent thyroid or rheumatic diseases and histological cirrhosis and a lower occurrence of treatment failure. In this study, we assessed the clinical features of Japanese type 1 AIH in adolescence and early adulthood.
Methods:  Fifteen patients aged ≤ 30 years (group 1) were compared with 79 patients aged between 40 years and 50 years (group 2).
Results:  At presentation, patients aged ≤ 30 years accounted for 9% of the study population. Although frequencies of extrahepatic concurrent autoimmune diseases were similar between groups 1 and 2, a tendency toward a lower frequency of concurrent autoimmune thyroiditis was shown in group 1 (0 vs. 18%, P  = 0.08). Group 1 had a lower frequency of human leukocyte antigen DR4 (27 vs. 78%, P  = 0.002), and histological acute hepatitis was shown more frequently in group 1 (27 vs. 4%, P  = 0.002). However, there were no differences in frequencies of the normalization of serum transaminase levels after the introduction of corticosteroid treatment or relapse after the normalization of serum transaminase levels between the two groups.
Conclusions:  Japanese type 1 AIH patients in adolescence and early adulthood respond well to corticosteroid treatment. However, they may frequently show atypical features, and the diagnosis of type 1 AIH in adolescence and early adulthood may be difficult and should be made carefully.     

自身免疫性肝炎自身抗体检测情况的临床观察

探讨我国自身免疫性肝炎患者临床分型及各型非分型标志抗体出现情况.用免疫荧光法及酶免疫条带技术测定81例确诊自身免疫性肝炎患者血清自身抗体情况,并进行分类归纳统计.我国自身免疫性肝炎以1a亚型多见,本观察未见3型病例.1a亚型中除分型抗体ANA外,SMA及CS抗体的出现频率高于ACA、PNP/Sm、SSB抗体,SMA出现频率亦高于SSA、Jo-1、dsDNA,SMA及CS是1a亚型除分型抗体外较主要的自身抗体.     

The international autoimmune hepatitis score in chronic hepatitis C

SUMMARY. Clinical and laboratory findings of autoimmunity are common in chronic hepatitis C. Autoimmune hepatitis (AIH), a disease of unknown cause, has been defined by use of the International Autoimmune Hepatitis Group Score (AIH score), which quantifies clinical and laboratory parameters. To further validate the specificity of the International AIH score and investigate the similarities between hepatitis C and AIH, we measured the International Autoimmune Hepatitis Group Score in patients with well-defined chronic hepatitis C. Thirty consecutive non-cirrhotic patients with chronic hepatitis C were evaluated. Scoring was performed using both components of the AIH score: a set of minimum required parameters including laboratory and historical data and a second set of additional parameters dominated by histological criteria. Autoantibodies were positive in 21 of 30 hepatitis C patients and associated (patient or first-degree relative) autoimmune diseases were present in eight of 30 patients. Histologically, chronic active hepatitis with periportal piecemeal necrosis was seen in 24 of 30 patients and lymphoid follicles in 16 of 30 patients. No patient scored as probable or definite AIH using the minimum required parameters of the AIH score. When histological parameters were included, four of 30 patients scored as probable AIH but none as definite AIH. Therefore, AIH was excluded by the minimal and additional criteria of the AIH score in 86% of patients with hepatitis C despite a high prevalence of autoantibodies in these patients. We conclude that the criteria set forth by the International AIH scoring system defines a distinct disease although it shares some features with chronic hepatitis C. Modification of the AIH scoring system to include other commonly accepted risk factors for hepatitis C and additional histological parameters would further improve its specificity.