肝肾微粒体抗体Ⅰ型阳性的慢性丙肝病人的干扰素治疗

现已证实Ⅰ型肝肾微粒体抗体(LKM_1)与成人丙肝病毒感染引起的慢性肝炎有关。但在患者同时存在 LKM_1和病毒血症(HCVRNA 阳性)情况下,选择使用类固醇药物还是α-干扰素治疗颇为困难。类固醇类药物对自身免疫性疾病有益而对病毒性疾病有害;α-干扰素则可加重自身免疫功能紊乱。使用α-干扰素治疗6例 LKM_1和血清 HCV RNA阳性的病人,3例治疗反应与 LKM 阴性的慢性丙型肝炎病人相似,另3例2～5月之间转氨酶骤然升高,而 HCV RNA 持续阳性,     

自身免疫性肝炎与丙型肝炎伴自身免疫现象者抗体水平的比较及临床分析

近年来随着对丙型肝炎病毒(HCV)研究的发展，人们认识到HCV感染不仅可引起在慢性病毒性肝炎中普遍可见的肝组织损害，还可诱导自身免疫现象，有时不易与自身免疫性肝炎(AIH)相鉴别。研究通过对AIH和丙型肝炎伴自身免疫现象者血清自身抗体水平的检测，结合临床特征、丙氨酸氨基转移酶(ALT)、胆红素、γ-球蛋白水平和影像学检查结果，评价自身     

干扰素治疗慢性丙型肝炎期间潜在的自身免疫性肝炎被激发

对患有慢性丙型肝炎的患者采用干扰素治疗,可以改善血清转氨酶水平,且同时可降低病毒的复制,然而干扰素的长期使用可诱导自身抗体和自身免疫失调,而自身免疫反应可再次导致肝损伤。丙肝炎感染与自身免疫有关,故可认为,两者均可激发潜在的自身免疫肝炎。因此对自身免性肝炎与活动性丙型肝炎的区分很重要,为此,作者回顾了干扰     

丙型肝炎病毒感染及干扰素治疗与自身免疫

许多病毒感染能诱生自身免疫。自丙型肝炎病毒(HCV)发现已来,有许多报道述及HCV与自身免疫性疾病和血清自身免疫反应标志密切相关,并发现干扰素治疗可诱生自身免疫现象或加剧原已存在的这些自身免疫异常。本文就近年HCV相关的自身免疫的研究进展作一阐述。 1 HCV感染与自身抗体 已有许多研究表明,慢性丙型病毒性肝炎患者的自身抗体阳性率显著高于对照组。Clifford等对244例各种病因的慢性肝病患者所做的一份回顾性研究显示,诊断为HCV感染     

自身抗体阳性丙型肝炎患者的抗病毒治疗

丙型肝炎患者血清中自身抗体阳性有两种情况,一种是丙型肝炎伴发自身免疫反应,另一种是自身免疫性肝炎与丙型肝炎并存。前者可以使用干扰素抗病毒治疗,而后者使用干扰素治疗可能激活免疫系统而导致自身免疫性疾病加重。由于两者在临床上不易区分,因此阻碍了这部分患者的抗病毒治疗。     

丙型肝炎患者抗肝肾微粒体—1抗体的检测

抗肝肾微粒体-1抗体(anti-LKM-1)是自身免疫性肝炎Ⅱ型(AIH-Ⅱ)的特征,AIH-Ⅱ分为Ⅱa和Ⅱb。Ⅱa是指HCV阴性的患者(大多为女性),Ⅱb是指HCV阳性的患者(大多为年长男性)。单纯丙型肝炎,用干扰素治疗,可取得较好的疗效,若伴有自身免疫性肝炎,则疗效受一定影响。因为,后者用免疫抑制剂治疗,作用与干扰素不同。因此,检测丙型肝炎     

干扰素-α诱导甲状腺炎的临床分类和诊治原则

干扰素-α是多种恶性和良性疾病主要的治疗手段,尤其是慢性丙型肝炎。一些前瞻性研究表明接受干扰素治疗的慢性丙型肝炎患者中约15%可发展为临床甲状腺疾病,40%产生甲状腺自身抗体。这些不良反应可能导致干扰素治疗中断,或需减量用药。干扰素诱导甲状腺炎（IIT）已成为接受干扰素治疗患者的主要临床问题。IIT分为自身免疫性和非自身免疫性甲状腺炎。自身免疫性甲状腺炎表现为无临床症状的甲状腺自身抗体阳性、自身免疫性甲状腺功能减退（桥本氏甲状腺炎,     

合并自身免疫现象的丙型肝炎与自身免疫性肝炎及干扰素抗病毒治疗诱导的自身免疫现象

我国是病毒性肝炎的高发国家,由病毒性肝炎而并发的肝硬化、肝癌严重危害我国人民健康。与乙型肝炎病毒感染相比,丙型肝炎病毒(HCV)感染后更易慢性化,约占成人HCV感染者的80%,因此对慢性丙型肝炎患者进行积极的抗病毒治疗显得尤为重要。到目前为止,干扰素联合利巴韦林被国内外公认为抗HCV的最有效治疗方案,但干扰素在治疗丙型肝炎的过程中有时还可诱发甲状腺疾病、糖尿病、血小板减少症、溶血性贫血等多种肝外自身免疫损伤,重者不得不停用干扰素。事实上约1/3的慢性丙型肝炎在未接受干扰素治疗前就可能合并自身免疫现象或自身免疫病,临…     

慢性丙型肝炎与自身免疫性肝炎关联性研究

0 引言慢性丙型肝炎是由丙型肝炎病毒(HCV)感染所致的一种慢性肝脏炎症性疾病,易发展成肝硬化,并与原发性肝细胞癌的关系密切.据估计,全球约有1.7亿慢性HCV 感染者.在日本和欧美等国家,慢性HCV感染是慢性肝炎、肝硬化和原发性肝癌的主要病因.自身免疫性肝炎(autoimmune hepatitis,AIH)是一种原因不明的肝脏持续性炎症性疾病,是由于机体免疫系统对自身抗原的免疫耐受性丧失致使其攻击自身的肝组织抗原而导致肝组织炎症坏死.自身免疫性肝炎多见于成年女性,     

丙型肝炎与自身免疫性疾病

血清中存在自身抗体是丙型肝炎患者肝外自身免疫现象主要表现之一。此外还可伴有混合性冷球蛋白血症、肾小球肾炎、迟发性皮肤卟啉症、干燥综合征(sjogren’s综合征)、自身免疫性甲状腺炎、扁平苔癣、特发性血小板减少症等自身免疫性疾病。丙型肝炎病毒(HCV)相关的自身免疫性疾病易发生于老年、女性、HCV持续感染及伴有肝硬化的患者,但其发病机制至今尚未阐明,治疗策略也是我们将要面对的问题。 1．混合性冷球蛋白血症：其发生与HCV感染有关,主要是由于一种B淋巴细胞的良性增殖以及循环免疫复合物沉积于中小血管引起,导致多种器官和组织的病理损害。临床表现呈多样性,常见有紫癜、关节痛、全身性脉管炎、肾小球肾炎及周围神经性病变等。HCV感染可能在混合性冷球蛋白血症的发生中起重要作用。近90％的混合性冷球蛋白血症患者HCV     

Alopecia universalis after discontinuation of pegylated interferon and ribavirin combination therapy for hepatitis C: a case report

For the last decade, the combination therapy of pegylated interferon (Peg-IFN) plus ribavirin (RBV) has been considered as the standard of care treatment for chronic hepatitis C virus (HCV) infection. However, it has been associated with an increased incidence of many adverse cutaneous reactions and emergence of autoantibodies or even autoimmune diseases. We report a case of irreversible alopecia universalis (AU) with complete hair loss extended to the whole body, which started after discontinuation of Peg-IFN/RBV combination therapy for chronic HCV infection. In conclusion, this case represents an uncommon presentation of a common disease. Physicians must be aware of the potential adverse reactions of an antiviral therapy containing IFN, which might occur even after the discontinuation, and fully inform the patient at the beginning of his treatment course. We hope that interferon-free regimens will utterly supplant interferon-based therapy for most or all HCV patients avoiding the emergence of autoimmune manifestations.     

Autoantibodies in chronic hepatitis C: A clinical perspective

Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus(HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of glutenrelated seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon(IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmunedisease may be present or may be precipitated by IFNbased HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.     

Managing patients on interferon therapy

Interferon (IFN) has become the standard therapy for chronic hepatitis C. The use of IFN should be accompanied by adequate diagnosis and management using standard practices as well as new and sophisticated techniques now available. A liver biopsy performed prior to IFN therapy initiation remains the standard for adequate histological diagnosis of HCV disease as well as determination of disease severity and the presence of liver cirrhosis. ALT normalization is not adequate to determine complete short-term response to IFN treatment. Adverse effects resulting from IFN therapy include a flulike syndrome, hematologic effects, neuropsychiatric effects, and thyroid abnormalities. The majority of these can be adequately managed without discontinuation of IFN treatment. However, preexisting psychiatric conditions are a contraindication to IFN therapy. IFN treatment also is contraindicated in patients with autoimmune hepatitis (AIH). Therefore, it is important to distinguish AIH from chronic HCV infection using HCV-RNA analysis and determination of autoimmune titers (including anti-LKM antibodies, anti-SMA, and ANA). Recently reported adverse effects of IFN include respiratory and ocular effects. Serological diagnosis of HCV infection has evolved to the use of second- and third-generation ELISA tests. Although sophisticated, these tests cannot distinguish between active and quiescent infection, and therefore are of limited value in monitoring treatment response. Several other techniques have been suggested: the ratio between IgG and IgM class anti-HCV core antibodies, detection of antibodies against a glycosylated recombinant product of the E2 envelope glycoprotein, and several different polymerase chain reaction (PCR) techniques. The latter appears to be the most promising. Use of these techniques should be incorporated into the monitoring of IFN therapy to assist in the evaluation of adequate treatment response, the need for treatment alteration, and estimation of relapse risk upon treatment cessation.     

自身免疫性肝炎的诊断和治疗进展

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,多发于女性。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。早期诊断和治疗可显著缓解肝内炎症和纤维化,并能改善患者的预后和生活质量。     

Type C-chronic hepatitis patients who had autoimmune phenomenon and developed jaundice during interferon therapy

Of a total of 2342 patients with type-C chronic hepatitis treated with interferon (IFN) at this hospital, 3 patients developed jaundice during the course of IFN therapy, but all 3 of them exhibited negative conversion of hepatitis C virus (HCV)-RNA following readministration of IFN. All 3 patients were assessed as having "probable autoimmune hepatitis (AIH)" in accordance with the AIH scoring system, indicating association with an "autoimmune phenomenon". Readministration of IFN at a low-dose induced activation of the autoimmune phenomenon, leading to fulminant hepatocellular impairment. As a result, HCV-RNA content dropped dramatically, possibly contributing to the negative conversion of HCV-RNA noted following the readministration of IFN. At present, no adequate therapy has been established for type-C chronic hepatitis with autoimmune manifestations. However, in conclusion, our findings suggested that: IFN should be a frontline regiment: (1). if autoantibody titers are low or patients are rated as having "probable AIH" or lower in accordance with the AIH scoring system, indicating a strong link to chronic hepatitis or (2). if IFN is expected to be efficacious on the basis of genotype of HCV-RNA level; even if there is acute exacerbation of type-C chronic hepatitis, IFN should be re-administered in the HCV-RNA level has dropped subsequently.     

Fulminant hepatic failure in a case of autoimmune hepatitis in hepatitis C during peg-interferon-alpha 2b plus ribavirin treatment

A 27-year-old Caucasian female with hepatitis C virus (HCV) infection treated with interferon (IFN) who developed severe autoimmune hepatitis (AIH) is described. The infecting viral strain was of genotype Ib and the pre-treatment HCV viral load was at a high level. The patient was treated with pegylated IFN-alpha 2b and ribavirin,and her HCV-RNA became negative at wk 12,but after that she developed fulminant hepatic failure. The patient recovered after steroid pulse therapy consisting of methylprednisolone 1000 mg/d for three days which was administered twice. A needle liver biopsy revealed the typical pathological findings of AIH.     

Autoimmune hepatitis in a HIV-HCV co-infected patient: diagnostic ant therapeutic difficulties

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic inflammatory hepatic disorder, characterized by hypergammaglobulinemia and autoantibodies. In some cases, AIH can be associated with another liver disease; such as the hepatitis C-AIH overlap syndrome, which diagnosis and treatment may be delicate. EXEGESE: We report a type 1 AIH case in a HIV-HCV co-infected woman. AIH remission and HCV eradication were obtained with prednisone and interferon plus ribavirine. AIH relapse appeared with corticosteroid withdrawal and a new remission was obtained with immunosuppressive treatment associating prednisone and azathioprine, without opportunistic infection. CONCLUSION: This case illustrates diagnostic and therapeutic difficulties of hepatitis C-AIH overlap syndromes in an HIV-infected patient. To our knowledge, it is the first AIH case report in a HIV-HCV co-infected patient.     

自身免疫性肝炎与系统性红斑狼疮性肝损伤临床特征对比

目的比较自身免疫性肝炎（AIH）与系统性红斑狼疮（SLE）性肝损伤在临床表现、血清学检查及病理学上的异同点。方法回顾性分析44例自身免疫性肝炎与26例狼疮性肝损伤的临床资料、血清学检查及病理学特点。结果AIH以女性多发,发病高峰为（47.32±13.61）岁,临床表现以消化系统为主,以ALT、AST升高,高球蛋白血症及IgG升高为主要特征,存在多种自身抗体,伴发其他自身免疫性疾病比率高,病理有特征性改变,对激素及免疫抑制剂有效,病情呈波动性变化。SLE以女性多发,发病高峰（33.46±14.32）岁,临床表现多样化,肝损伤为初发患者一过性ALT、AST升高,有明显低补体血症,存在多种自身抗体,并发其他自身免疫性疾病比率低,病理无特征性改变,激素治疗有效。结论AIH、SLE均以女性多发,有过敏史的比率高于正常人群,激素治疗有效;AIH肝损伤重,呈波动性变化,易伴发其他自身免疫性疾病,SLE肝损伤轻,多为一过性,可累及全身多个系统,二者为相互独立的疾病。     

Autoantibodies and defined target autoantigens in autoimmune hepatitis: an overview

Autoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by hypergammaglobulinaemia, non-organ and liver-related autoantibodies, association with HLA-DR3 or DR4 and a favourable response to immunosuppression. The current classification of AIH and the several autoantibodies/target autoantigens found in this disease are reported. The importance of these markers in the differential diagnosis and the study of pathogenesis of AIH is also given. AIH is subdivided into two major types: AIH type 1 (AIH-1) and AIH type 2 (AIH-2). AIH-1 is characterised by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Antineutrophil cytoplasmic autoantibodies (ANCA), in most cases of perinuclear pattern (p-ANCA), by the indirect immunofluorescence assay, antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of individuals who are seronegative for ANA/SMA. AIH-2 is characterised by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). For these reasons, the distinction between AIH and chronic viral hepatitis is of particular importance. Cytochrome P450 2D6 (CYP2D6) is the major target autoantigen of anti-LKM-1 autoantibodies in both conditions (AIH-2 and HCV infection). Recent data have demonstrated the expression of CYP2D6 on the surface of hepatocytes, suggesting a pathogenetic role of anti-LKM-1 autoantibodies in liver injury. Family 1 of UDP-glycuronosyltransferases has been identified as the target autoantigen of anti-LKM-3. The molecular target of anti-SLA/LP autoantibodies has been identified recently as a 50 kDa protein with unknown structure and function. A liver-specific enzyme, the formiminotransferase cyclodeaminase, was identified as the target autoantigen of anti-LC1 autoantibodies. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate better with the severity of AIH and the response to treatment. The latter may suggest a pathogenic role of these autoantibodies in the hepatocellular damage in AIH. In general, however, autoantibodies should not be used to monitor treatment or to predict AIH activity or outcome. Finally, current knowledge concerning a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyglandular syndrome type-1 (APS-1), is also discussed. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies found in AIH as a disease component of APS-1. However, anti-LM autoantibodies have also been described in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target autoantigen of anti-LM autoantibodies in both disease entities.