抗丙型肝炎药Valopicitabine

慢性丙型肝炎（简称丙肝）由丙肝病毒（HCV）感染引起，HCV属于黄病毒科，这种血源性包膜9．6kb（＋）HNA病毒变异迅速，故其感染难以医治。其症状为黄疸、疲劳、腹痛、食欲不振、恶心和呕吐，但是这些症状在HCV感染变为慢性前通常并不明显。大约75％。85％的急性HCV感染患者会发展为慢性肝炎。其原因尚不清楚。据世界卫生组织报道，全球约有2％的人群患有慢性丙肝。     

自身免疫性肝炎2例

<正>血清自身抗体阳性是自身免疫性肝炎(AIH)诊断的重要依据,但临床中大约20%患者虽然具有AIH的诸多指征,但血清自身抗体始终呈阴性,给临床诊断造成极大困扰。针对这一问题,笔者利用肝组织进行自身抗体免疫荧光染色诊断了2例自身免疫性肝炎,现报告如下。例1女,52岁。于1999-04无明显诱因出现乏力、食欲     

大鼠自身免疫性肝炎肝细胞特异性脂蛋白抗体水平与肝组织病变的关系

目的研究大鼠自身免疫性肝炎的肝细胞特异性脂蛋白（LSP）抗体水平与肝组织病变的关系。方法雄性3月龄Wistar大鼠20只，给予弗氏完全佐剂＋肝细胞特异性脂蛋白建立自身免疫性肝炎（AIH）模型。ELISA法检测动物模型血浆中LSP抗体水平并观察肝组织病理改变，研究两者之间的关系。结果（1）LSP抗体与肝组织病变程度的关系：LSP抗体〈1：642只，肝组织表现为CAHⅠ；1：64≤LSP抗体≤1：19214只，肝组织表现为CAHⅡ；LSP抗体〉1：1924只，其中1只肝组织表现为CAHⅡ，3只肝组织表现为CAHⅢ。（2）LSP抗体与肝纤维化指数（HFI）的关系：LSP抗体1：642只，HEI≤4分；1：64≤LSP抗体≤1：1924只．HFI〉4分；LSP抗体〉1：1924只，HFI〉4分。（3）LSP抗体与肝炎组织活动性指数（HAI）的关系：LSP抗体〈1：642只，HAI≤8分；1：64≤LSP抗体≤1：19214只，HAI〉8分；LSP抗体〉1：1924只，HAI〉8分。（4）LSP抗体与肝组织血管病变的关系：LSP抗体〈1：642只，血管病变为1级；1：64≤LSP抗体≤1：19214只，血管病变为2级；LSP抗体〉1：1924只，其中1只血管病变为2级，3只血管病变为3级。（5）LSP抗体与肝细胞表达血管内皮生长因子（VEGF）的关系：LSP抗体〈1：642只，1只动物VEGF表达呈弱阳性，另1只动物VEGF表达呈强阳性；1：64≤LSP抗体≤1：19214只，2只动物VEGF表达呈弱阳性，12只动物VEGF表达呈强阳性；LSP抗体〉1：1924只，VEGF表达均呈强阳性。结论自身免疫性肝炎大鼠模型外周血LSP抗体水平与肝组织病变程度呈正相关。     

慢性重型病毒性肝炎病理观察

目的 观察慢性重型病毒性肝炎病程中肝组织学的变化。方法 202例慢性重型病毒性肝炎患在不同病期进行肝穿刺作肝脏病理检查。结果 早、中期肝组织学主要表现为在慢性肝炎和小结节性肝硬变基础上出现大块或亚大块坏死;恢复期肝脏以大小结节混合型肝硬变为主,少数为重度慢性肝炎的病理表现;晚期和死亡肝组织结构严重破坏,肝细胞数量明显减少。结论 慢性重型病毒肝炎不同病期的组织学各有一定特点。病程中多次肝穿刺对该病病理诊断及预后判断有一定意义。     

检测肝组织自身抗体诊断自身免疫性肝炎

<正>血清自身抗体阳性是自身免疫性肝炎(AIH)诊断的重要依据,但临床中大约20%患者虽然具有AIH的诸多指征,但血清自身抗体始终阴性,给临床诊断造成极大困扰。针对     

肝灵宝治疗乙型病毒性肝炎初步观察

通过36例急性乙肝、慢性活动性肝炎及肝硬化患者的治疗观察,表明肝灵宝具有明显降酶、降浊作用,并能抑制γ-球蛋白升高,改善临床症状突出,对HBsAg阳性具有一定转阴作用,服药期间无任何副作用。     

恩替卡韦联合胸腺肽α1治疗慢性乙肝合并自身免疫性肝炎的临床研究

目的观察慢性乙肝合并自身免疫性肝炎患者抗病毒、调节免疫治疗的疗效。方法将56例慢性乙肝合并自身免疫性肝炎患者随机分为2组,A组29例,给予传统治疗;B组27例,给予传统治疗＋恩替卡韦＋胸腺肽α1;2组患者治疗观察48周。结果A组患者肝功能指标好转,血清肝纤维化指标下降,但与治疗前比较差异无统计学意义（P〉0．05）。B组患者肝功能指标、血清肝纤维化指标治疗24周、48周下降程度均优于A组（P〈0．01）。结论慢性乙肝合并自身免疫性肝炎患者抗病毒治疗联合胸腺肽α1调节免疫治疗可有效改善患者肝功能及肝纤维化。     

丙型肝炎治疗与靶向药物研究进展

丙型肝炎病毒（Hepatitis C virus，HCV）是1989年被确认的非甲非乙型肝炎主要病原体。HCV呈广泛流行态势，全球至少有1．7亿人被HCV感染，占总人口的3％。HCV一经感染，据估计约有55％-85％的感染者会发展为慢性感染，并有较高比例的感染者最终会发展为肝硬化、肝癌。HCV感染已经成为慢性肝炎、肝硬化及肝癌的主要病因。目前尚不能对HCV进行高效、稳定的体外培养，除人和黑猩猩外，还没有完全证实其它动物对HCV易感。高效体外培养体系和合适小动物模型的缺乏，严重阻碍了抗HCV药物的研究和评价。临床上正在使用的干扰素与利巴韦林联合疗法，虽可以在一定程度上控制病毒增殖，但仍有50％的丙型肝炎患者对治疗不敏感，研究和开发新型的抗HCV药物是当务之急。     

检测丙氨酸转氨酶及天门冬氨酸转氨酶在病毒性肝炎中的临床意义

目的探讨慢性乙型病毒性肝炎患者血清天门冬氨酸转氨酶与丙氨酸转氨酶比值和相关肝病的关系。方法187例慢性乙型病毒性肝炎患者,同时进行血清天门冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的检测,对比分析血清AST／ALT比值与肝脏病理诊断。结果慢性乙型病毒性肝炎患者中活动性肝硬化患者血清AST／ALT比值明显高于正常人及慢性肝炎轻度、中度和重度患者,肝纤维化程度S4期以上的患者血清AST／ALT比值高于S0～S3期的患者,差别均有显著性意义。结论血清AST／ALT比值对肝脏纤维化程度的判断及辅助诊断肝硬化有一定的指导意义。     

Autoimmune thyroiditis and myelosuppression following treatment with interferon-alpha for hepatitis C

CASE: We describe the case of a 48-year-old woman from Thailand diagnosed with chronic hepatitis C, who experienced a suppression of all blood cell counts accompanied by a newly developed clinically manifested autoimmune thyroid disorder after treatment with interferon alpha-2b (INF-alpha) 46 days after beginning of therapy a decrease of platelet, red and white blood cell counts became obvious. Concomitantly we observed an increase of FT4 and FT3 with a totally depressed TSH level 80 days after starting INF-alpha administration. Antibody assessment resulted in detection of high numbers of antithyroid-microsomal antibodies and antithyroglobulin antibodies. Thyroid hormone levels normalized under treatment with methimazole/propylthiouracil within 4.5 months. However, two months after cessation of antithyroid therapy increasing TSH levels and decreasing FT4 levels indicated a new tendency towards a hypothyroid state. CONCLUSION: We classify this case as an interferon-alpha-induced disorder of thyroid function accompanied by myelosuppression. A close monitoring for thyroid dysfunction, e.g. evaluation of TSH-levels before and after administration of INF-alpha is mandatory.     

Autoimmune phenomena in untreated and treated marginal zone lymphoma

INTRODUCTION: Current literature suggests an association between various autoimmune conditions and marginal zone lymphoma (MZL). However, these autoimmune conditions have not been comprehensively systematized to date. As a result, their clinical implications remain largely unknown. AREAS COVERED: The authors provide a comprehensive review of the existing literature on various autoimmune abnormalities documented in the course of MZL, as well as on autoimmune alterations induced by certain MZL therapies. EXPERT OPINION: The course of MZL is accompanied by a variety of hematologic and non-hematologic autoimmune disorders. Whereas some of them could be secondary and related to the course of the MZL, others may be primary and might even favor the development of MZL itself. In addition, authentic autoimmune conditions have been documented with the use of rituximab as a single agent and the nucleoside analogs. Therefore, we believe caution should be exerted with the use of these agents in MZL patients with evidence of autoimmune disorders, as exacerbation of autoimmune phenomena can be anticipated. While the heterogeneity of the MZL subtypes represents an inherent limitation, integration of emerging information from immunology research laboratories and clinical practice could translate into improved outcomes of this disease spectrum.     

Autoimmune phenomena in untreated and treated marginal zone lymphoma

Introduction: Current literature suggests an association between various autoimmune conditions and marginal zone lymphoma (MZL). However, these autoimmune conditions have not been comprehensively systematized to date. As a result, their clinical implications remain largely unknown.

Areas covered: The authors provide a comprehensive review of the existing literature on various autoimmune abnormalities documented in the course of MZL, as well as on autoimmune alterations induced by certain MZL therapies.

Expert opinion: The course of MZL is accompanied by a variety of hematologic and non-hematologic autoimmune disorders. Whereas some of them could be secondary and related to the course of the MZL, others may be primary and might even favor the development of MZL itself. In addition, authentic autoimmune conditions have been documented with the use of rituximab as a single agent and the nucleoside analogs. Therefore, we believe caution should be exerted with the use of these agents in MZL patients with evidence of autoimmune disorders, as exacerbation of autoimmune phenomena can be anticipated. While the heterogeneity of the MZL subtypes represents an inherent limitation, integration of emerging information from immunology research laboratories and clinical practice could translate into improved outcomes of this disease spectrum.     

药物诱导的自身免疫性肝炎

自身免疫性肝炎（AIH）是机体自身的免疫系统破坏肝细胞导致的一种肝脏慢性炎症性疾病。一般认为，AIH的发生与遗传因素和环境因素的共同作用有关。诱发AIH的环境因素有病毒、毒素及药物等。就药物而言，米诺环素、干扰素、他汀类药物、氯美辛和英夫利昔单抗等均能诱发具有遗传易感性患者的肝细胞损伤。药物诱发的自身免疫性肝炎（DAIH）通常发生在用药后2～24个月；约80％～90％患者为女性。DAIH的临床表现为乏力、食欲不振、上腹部不适，黄疸、肝肿大，常伴有发热、皮疹及关节疼痛。DAIH的临床特征有：发病率低；与剂量无关；用药与发病之间有一长时间的间隔；出现高丙种球蛋白血症和高滴度自身抗体（如ANA、ASMA）。目前治疗DAIH的有效方法为免疫抑制。大多数患者的病情在应用糖皮质激素单独治疗或与硫唑嘌呤联合治疗后改善。     

福辛普利钠治疗期间发生自身免疫性肝炎

患者女,53岁。因肝功能异常3个月,于2003年9月16日来我院就诊。患者因高血压于2001年12月开始服用福辛普利钠片(蒙诺)治疗:剂量范围为10～40mg·d-1,单次服药,初始剂量为10mg,qd。约4周后,根据降压情况给予适当调整剂量。治疗过程中未用其他药物,疗程中每半年复查一次肝功能均为正常。2003年6月因感乏力、纳差,经北京某医院化验肝功能,发现丙氨酸转氨酶(ALT)为98U·L-1,并以“肝功异常原因待查”收住院治疗。入院后,给予一般的保肝治疗,效果不佳。于8月13日停服福辛普利钠,但ALT持续异常,9月24日复查肝功能示:ALT107U·L-1,为进一步诊…     

Introducing treat-to-target strategies of autoimmune extrahepatic manifestations of chronic hepatitis C virus infection

Introduction: The hepatitis C virus (HCV) is recognized as one of the hepatic viruses most often associated with extrahepatic manifestations (EHMs). It is currently accepted that cryoglobulinemic vasculitis (CV) is the key autoimmune extrahepatic disease associated with HCV infection. Therapeutic approaches have mainly been based on the use of old antiviral interferon (IFN)-based regimens and immunosuppressive therapies, often with an inadequate balance between therapeutic benefits and excess side effects.

Areas covered: Therapeutic management of HCV patients with EHMs, including both non-autoimmune (cardiovascular, hematological, general features) and autoimmune complications (organ-specific and systemic autoimmune diseases). Therapies included antiviral (IFN, ribavirin, direct-acting antivirals – DAAs-) and non-antiviral (immunosuppressive agents, rituximab, plasma exchanges) options. The review analyses the current evidence for proposing a treat-to-target (T2T) approach for HCV-related autoimmune EHMs based on an organ-by-organ strategy.

Expert commentary: Eradication of HCV must be considered the key T2T in the therapeutic approach to HCV-related EHMs, as there has been a disruptive change due to the appearance of direct-acting antivirals (DAAs) as game-changers in HCV therapy, with an efficacy reaching nearly 100%. In this scenario, the central role played until now by IFN and ribavirin is not currently supported and they will not be used in the future.     

Pharmacological management of autoimmune hepatitis

INTRODUCTION: Without prompt immunosuppressive treatment, autoimmune hepatitis is a devastating, albeit rare, liver disease. It affects both adults and children, being particularly aggressive in the latter. Eighty per cent of patients respond satisfactorily to treatment; the other 20% progress to end-stage liver disease and require transplantation. AREAS COVERED: This review emphasizes the importance of a timely diagnosis of autoimmune hepatitis and provides a practical guide for its treatment. The authors summarize the treatment options available for autoimmune hepatitis and stress that most patients respond successfully to standard treatment with prednisolone and azathioprine, two well-tried and inexpensive drugs. The authors also review the options for difficult-to-treat patients (non-responders and frequent relapsers), for whom newer immunosuppressive agents--usually employed as anti-rejection drugs--have been tried with variable success. EXPERT OPINION: Autoimmune hepatitis is exquisitely responsive to immunosuppression but treatment must be started as soon as possible to achieve full remission and halt progression of liver disease. New strategies aiming at treating the unresponsive patients and at specifically curbing the liver autoimmune attack, without provoking unwanted systemic side effects, are being investigated and may be available within the next 5 years.