新药资讯

Introduction to Chronic Kidney Disease (CKD)

简介 慢性肾病、慢性肾病的发病特点、慢性肾病的早期症状、慢性肾病的预防和治疗、慢性肾病的预后 慢性肾病的定义 临床中，诊断为肾小球肾炎、隐匿性肾炎、肾盂肾炎、过敏性紫癜肾炎、红斑狼疮肾炎、通风肾、iga肾病、肾病综合征、膜性肾病、肾病综合征、糖尿病肾病、高血压肾病、多囊肾，等等，当这些肾病的发病迁延难愈，时间超过三个月，病人尿液和相关的血液指标出现异常，肾脏病理学、影像学发现异常，或肾脏的肾小球有效滤过率低于60%，都可统称为“慢性肾病”。慢性肾病如未能及时有效救治，导致病情恶化进展，则随病程迁延，慢性肾病患者将发展成为慢性肾功能不全、肾衰竭，最终形成尿毒症。 发病特点 慢性肾病发病特点有“三高”、“三低”：发病率高、伴发的心血管病患病率高、病死率高；全社会对慢性肾病的知晓率低、防治率低、伴发心血关病的知晓率低。调查显示，我国40岁以上人群慢性肾病的患病率大于10%，知晓率却不足5%。在我国，发生于肾小球肾炎的慢性肾病患者最多，占40%。随我国人群饮食结构和生活习惯的改变，其他的继发性慢性肾病正不断增多。加上我国现有医疗水平尚有限，导致我国慢性肾病的防治工作形势面临严峻挑战。 早期症状 熟悉掌握慢性肾病早期可能出现的症状，可以对慢性肾病的发生起到警示作用，便于慢性肾病患者早期诊断和治疗，有效遏制病情恶化。通常，当尿液中出现大量泡沫以及尿中见血色或夜尿增多，即尿常规检查尿中出现尿蛋白和红细胞，则可能为慢性肾病早期发生的预警信号。早期慢性肾病的症状不显见，如一般的慢性肾炎患者都没有特别明显的不适症状。故有尿液异常时，建议就医检查诊断。一旦病人感觉自身有明显疲劳、贫血等非常明显的症状出现才去就医时，可能慢性肾病病情已经过了早期阶段了，这样将为慢性肾病的后期治疗带来更大的难度。 消化系统：消化系统表现出来的症状一般是最明显的了，比如恶心、呕吐、舌炎、腹泻、口有尿臭味和口腔粘膜溃烂，甚至出现消化道大出血等。 精神、神经系统：精神、神经系统最常见的症状就是疲乏、四肢麻木、记忆力减退、精神萎靡、头晕、头痛、失眠、手足灼躁、谵语、肌肉颤动、抽搐、昏迷等。 心血管系统：高血压是最容易出现的心血管疾病、心律失常、心力衰竭、心肌损害、心包炎、血管硬化、血管钙等。 造血系统：造血系统最突出的症状就是贫血。如果肾衰竭晚期可能会有出血倾向，常见有鼻衄、瘀斑，也可为呕血、便血、咯血、血尿、颅内出血、月经过多等。 呼吸系统：酸中毒时呼吸深长，晚期可有尿毒症性支气管炎、肺炎、胸膜炎等。 皮肤：慢性肾衰竭患者的皮肤会出现无光泽、干燥、脱屑的情况。常出现尿素霜、皮疹、色素沉着等。 脱水或水肿：因肾小管浓缩功能丧失及高浓度的尿素引起渗透性利尿，出现明显多尿，加之呕吐、腹泻、饮水少等，常发生脱水。进入少尿期又极易引起水量过多，出现水肿、高血压、心力衰竭、水中毒和稀释性低钠血症。 代谢紊乱：出现程度不同的糖耐量降低，血中胰高血糖素、生长激素甲状旁腺素、肾上腺皮质激素、胃泌素等升高。还可有脂肪代谢异常，出现高脂血症。 预防治疗 一旦患有慢性肾病，是很难根治的。但是，不是说患有了慢性肾病，就不可避免的发生尿毒症。早期对慢性肾病进行干预控制，阻止其恶化进展完全做的到。因此，对慢性肾病做好防治工作是慢性肾病患者身体康复的关键所在。 对慢性肾病的防治工作主要包含有以下三点： 首先，鉴于慢性肾病的发病特点——知晓率低，则需要动员全社会所有人引起对慢性肾病的重视，每个人应该积极主动的防治慢性肾病。 其次，要加强早期防治工作，防止慢性肾病的发生。这就需要，对自身已有的肾脏疾病（如慢性肾炎）及其危险因素（如蛋白尿、高血压）等进行及时有效的治疗，还要对可能引起肾脏继发损害的疾病（如糖尿病、通风、高血压等）和危险因素（如吸烟、高脂血症等）进行及时有效的治疗和控制，两方面共同作用，防止慢性肾病的发生和恶化进展。 最后，延缓甚至逆转慢性肾病的恶化进展。具体就是，不仅要对已有的慢性肾病就其进展的危险因素，如高血压、蛋白尿、血尿、贫血等，进行及时有效的治疗；而且对慢性肾病中晚期阶段患者全身各个系统的严重并发症，尤其是心脑血管并发症进行防止，从而降低肾衰、尿毒症的病死率，达到提高慢性肾病患者长期存活率的目的。从对慢性肾病的防治临床实践看，中西医结合治疗效果最显著。在以上防治慢性肾病的基础上，应用西医对并发症、肾病症状对症处理的同时，结合中医药进行对慢性肾病患者病损肾脏的功能修复，如此，方能达到慢性肾病真正的有效治疗，才能有望延缓甚至逆转慢性肾病的恶化进程。 各种慢性肾病的预后 慢性肾炎的预后怎样？ 慢性肾炎病因复杂，病程较长，症情发展轻重悬殊，快慢不等，具有进行性倾向。慢性肾炎患者的自然病程变化很大，有一部分病人的病情比较稳定，经5～6年，甚至20-30年，才发展到肾功能不全期，极少数病人可自行缓解。另一部分病人的病情持续发展或反复急性发作，2～3年内即发展到肾功能衰竭。一般认为慢性肾炎的持续性高血压及持续性肾功能减退者预后较差。总之，慢性肾炎是具有进行性倾向的肾小球疾病，预后是比较差的。因此，对慢性肾炎必须早期进行治疗，定期进行复查。 肾活检的病理学分型对预后的判断比较可靠，一般认为微小病变型肾病和单纯的系膜增殖性肾炎预后较好，膜性肾病进展较慢，其预后较膜增殖性肾炎好，后者大部分病例在数年内出现肾功能不全，局灶性节段性肾小球硬化预后亦差。近年来的研究表明，除了肾小球病变外，肾小管、肾内血管及肾间质病变的程度明显影响预后。肾小管萎缩、肾内小血管硬化、肾间质大量淋巴细胞浸润及间质纤维化则预后较差。 临床观察：①发病前有溶血性链球菌感染史者较无链球菌感染史者预后好。②患者仅有蛋白尿或伴血尿，或者仅有血尿，而无其它临床症状者，预后较好。③慢性肾炎高血压型预后相对较差。若使用降压药，血压能降至正常或正常略高者，预后相对好些。血压超过22.7／14.7千帕(170／110毫米汞柱)，使用一般降压药无效者，预后较差。④出现持续性血尿者，肾功能恶化较快。⑤肾功能减退，出现氮质血症者预后差。 间质性肾炎的预后 慢性间质性肾炎的病预后随病因及肾功能损害程度而异。病因能被彻底清除时，慢性间质性肾炎可以治愈。若已至发展慢性肾功能不全阶段，则多形成慢性肾功能衰竭，预后不良。 肾病综合征的预后 肾病综合征的预后因病因、病理类型的不同，以及是否得到合理治疗等因素而存在着很大的差异。在估计肾综的预后时，下列因素可作为参考： (1)年龄：儿童原发性肾病综合征中，微小病变病占80％，2—6岁年龄组中微小病变肾病达85％，随着年龄的增长而逐渐减少。在大于30岁成人中只占20％。因该型肾病综合征预后良好，因而有54％的儿童肾病综合征可完全缓解，成人仅21％可完全缓解。但在小儿，发病年龄越小，病死率越高。也有人对此持不同看法。英国有个统计数字表明，儿童肾病综合征约15％成年后继续有症状。 (2)血尿：血尿不明显的属肾病综合征1型，病理上多为微小病变病或轻度系膜增殖性肾炎，预后较好。明显血尿的属肾病综合征Ⅱ型，预后不佳。 (3)蛋白尿：选择性蛋白尿表明病变轻，预后较好，非选择性蛋白尿预后差。如果早期有严重蛋白尿者，肾功能衰竭出现较早，预后差。 (4)高血压及氮质血症：常见于肾病综合征Ⅱ型，对激素治疗不敏感，预后不良。 (5)血清胆固醇：血清胆固醇升高多见于微小病变病，其他疾病升高的幅度较低，而系统性红斑狼疮引起的继发性肾病综合征，血清胆固醇正常，故可认为血清胆固醇升高者，预后较好。但儿童血清胆固醇高于20.8mmol／L者，病死率高。 (6)开始治疗的时间：早确诊，早治疗，预后相对较好。成人肾病综合征起病后6个月以上才开始用皮质激素治疗者预后差。有人报告68例肾病综合征，病程在6个月以上才开始激素治疗者无1例缓解，而病程少于6个月就开始激素治疗的，有15％病例完全或部分缓解。 (7)浮肿出现的时间：有统计表明，成人肾病综合征在首次出现浮肿后的第3—4年发生终末期肾功能衰竭的人数最多。 (8)对激素的反应：肾病综合征病人如果一开始就对皮质激素治疗反应不良者，预示治疗困难，预后不良。 IGA肾病预后 Read more...

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Introduction to acute lymphoblastic leukemia

简介 急性淋巴细胞白血病（ALL）是一种起源于淋巴细胞的B系或T系细胞在骨髓内异常增生的恶性肿瘤性疾病。异常增生的原始细胞可在骨髓聚集并抑制正常造血功能，同时也可侵及骨髓外的组织，如脑膜、淋巴结、性腺、肝等。我国曾进行过白血病发病情况调查，ALL发病率约为0.67/10万。在油田、污染区发病率明显高于全国发病率。ALL儿童期（0～9岁）为发病高峰，可占儿童白血病的70%以上。ALL在成人中占成人白血病的20%左右。目前依据ALL不同的生物学特性制定相应的治疗方案已取得较好疗效，大约80%的儿童和30%的成人能够获得长期无病生存，并且有治愈的可能。 病因 (一)发病原因 白血病细胞的发生和发展起源于不同造血祖细胞或干细胞的恶性变，特定的ALL亚型可能具有特定阶段的标志，病因及发病机制尚未完全明了，但与下列危险因素有关： 1.遗传及家族因素：许多事实证明遗传因素是白血病发病的危险因素之一，5%ALL病例与遗传因素有关，一些具有遗传倾向综合征的病人白血病发病率增高，Down综合征儿童发生白血病的危险高于正常人群10～30倍，并且更容易有B细胞前体ALL，范可尼(Fanconi)贫血的病人白血病发生率也增高。 同一家庭中发生2个或3个白血病的病例比较少见，提示遗传因素在ALL发病中可能只起很小的作用，但当一个孪生兄弟发生白血病时，另一个1年内有20%几率罹患白血病，如果白血病是在1岁之内发生，另一个几乎无法避免也会发生白血病，比较典型的是在几个月内发生，非同卵双胎之一如发生白血病其同胞发生白血病的几率是正常人群的2～4倍，染色体异常合并白血病的机制尚不清楚，原因可能为受累基因所编码蛋白影响了基因的稳定性和DNA修复，或是有缺陷的染色体对致癌物的敏感性增加，因而引起控制细胞增殖和分化的基因发生突变所致。 2.环境因素： 电离辐射可以诱发动物实验性白血病，孕期暴露于诊断性X线，发生ALL的危险性稍有增高，并与暴露次数有关，遭受核辐射后人群ALL发病明显增多，电离辐射作为人类白血病的原因之一已被肯定，但机制未明，孕前和孕期接触杀虫剂，主动及被动吸烟可能与儿童ALL发病有关，儿童ALL发病率在工业化国家较高，女性饮用被三氯乙烯污染的水质以及年龄大于60岁吸烟者ALL的发生率增高，提示环境因素在白血病发病中起一定作用。 化学物质诱发动物实验性白血病已经被确认，其中苯及苯同类物，烷化剂被认为与人类白血病关系密切，和白血病有关的生物因素中，病毒占最重要的地位，病毒作为动物白血病的病因之一已经肯定，20世纪80年代从成人T细胞白血病的细胞系发现C型反转录病毒，即人T细胞白血病病毒Ⅰ型(HTLV-I)，这是发现的第一个与人白血病及淋巴瘤有关的反转录病毒，但白血病病毒与淋巴细胞白血病之间的关系尚未获得可靠的实验结果。 上述因素不能充分解释所有病例的发病原因，尽管有许多线索，但多数病例的发病因素仍然不清楚，一般认为，白血病的发生反映了多种遗传与环境因素之间的相互作用。 3.获得性基因改变：所有ALL病例的白血病细胞都有获得性基因改变，至少2/3是非随机的，包括染色体数目和结构的变化，后者包括易位(是最常见的异常)，倒位，缺失，点突变及重复，这些重排影响基因的表达，干扰正常细胞的分化，增生及存活。 (二)发病机制 白血病发生通常有两种机制，一种依赖于原癌基因或者具有原癌基因特性的混合基因的激活，由此产生的蛋白产物影响细胞功能，另一个机制是一种或多种抑癌基因的失活，如p53和INK4a，编码p16和p19ARF，p53作为一种抑癌基因，使DNA受损后无法修复的细胞走向凋亡，MDM-2原癌基因是p63基因的拮抗剂，其过度表达能够阻止野生型p53的功能，在白血病中已发现有这两种基因的异常，p16和p19ARF负性调节细胞周期，减少进入S期细胞的比例，因此，不能阻止白血病细胞增殖或是能阻止其程序化死亡，则失去肿瘤抑制功能，p15和p16同源性缺失在20%～30%的B细胞前体ALL以及60%～80%的 T-ALL中能被测到，研究证实，p15/p16缺失在ALL复发时经常可以见到，提示这种缺失基因编码的蛋白在疾病发展中作用。 ALL的基本病理变化主要表现为白血病细胞的增生与浸润，此为白血病的特异性病理变化，除造血系统外，其他组织如肝脏，脑，睾丸，肾脏等组织亦出现明显浸润和破坏。 1.骨髓，淋巴结，肝，脾 是最主要的累及器官。 骨髓大多呈明显增生，白血病细胞呈弥漫性片状增生及浸润，伴不同程度的分化成熟停滞，全身骨髓均有白血病细胞增生浸润，椎骨，胸骨，盆骨及肋骨的浸润最为明显，少数患者骨髓增生低下，可伴程度不一的纤维化。 淋巴结肿大较为多见(约70%)，一般为全身性或多发性的淋巴结肿大，淋巴结被累及的早期，淋巴结结构尚可辨认，白血病细胞往往仅累及淋巴结的某一区域，出现片状均一性幼稚细胞增生浸润，淋巴索增宽，窦变窄，初级滤泡或次级滤泡受挤压而萎缩，晚期淋巴结结构完全破坏。 脾脏均有不同程度肿大，镜下白髓有白血病细胞弥散浸润，可波及红髓及血窦，肝内白血病细胞主要浸润门脉区及门脉区周围，造成肝大。 扁桃体，胸腺也常被侵及，ALL胸腺受累占78.5%，其中以T-ALL最常见，被浸润的胸腺增大，临床表现为纵隔肿块，尤其儿童T-ALL时肿大较为显著。 2.神经系统 ：神经系统是白血病浸润的常见部位，ALL合并中枢神经系统损害较其他类型白血病多见，病理改变主要为脑膜及脑实质白血病细胞的局限性或广泛性浸润，可伴有出血，血肿，脊髓膜炎及硬膜外肿物形成的横段性脊髓炎，蛛网膜下隙受侵常见，脑实质的累及部位依次为大脑半球，基底节，脑干及小脑，病变部位白血病细胞呈弥散性或结节状浸润，浸润周围白质组织明显水肿和坏死，大约20%的中枢神经系统白血病(CNS-L)患者有脑神经麻痹，以面神经(Ⅶ)麻痹最多见，其次为外展(Ⅵ)，动眼(Ⅲ)，滑车(IV)神经，而脊髓及周围神经受累罕见。 3.泌尿生殖系统 ：ALL侵犯睾丸较为常见，特别是儿童ALL，睾丸间质中可见大量白血病细胞浸润，压迫精曲小管引起萎缩，临床表现为睾丸单侧或双侧无痛性肿大，坠胀感，白血病细胞浸润阴茎海绵体或因白血病细胞在静脉窦内淤积，栓塞，血流受阻或血栓形成时可引起阴茎持续异常勃起，ALL累及肾脏者，肾包膜下可见灰白色斑点或结节以及出血点，肾盂出血点也较常见，皮，髓质散在灰白色小结节，镜下见皮，髓质散在或灶性白血病细胞浸润，肾小球及肾小管上皮受压萎缩或变性坏死。 4.其他：肺脏为白血病常累及的脏器之一，浸润病变大多弥散，少数形成粟粒状，甚至结节状病灶，可侵及肺泡，肺小血管及间质，白血病浸润最常累及支气管旁淋巴结，可引起压迫，也可累及胸膜，呈不同程度的弥漫性浸润，出现胸腔积液;口咽部也是ALL易侵犯的部位之一，并常合并感染;白血病累及心脏以心肌浸润为主，心肌，肌束间弥漫性及灶性浸润，导致传导障碍，心力衰竭，心外膜及内膜均可累及，出现心包积液，浸润胃肠道可形成结节，溃疡，坏死及出血，以黏膜及黏膜下层为主，有时可发生黏膜剥脱和假膜形成，病变肠段可因坏死而穿孔，从贲门至直肠均可累及，侵及食管者较少，皮肤受侵典型的改变为位于血管周围，毛囊和皮脂腺的白血病细胞浸润，形成单个或多个结节，呈局灶性分布。 白血病由一个造血祖细胞或干细胞恶变而来的理由为： ①几乎所有ALL的白血病细胞均有免疫球蛋白(Ig)或T细胞受体(TCR)基因重排的克隆表达。 ②同一病人的所有白血病细胞具有同样的细胞遗传学异常，6-磷酸葡萄糖脱氢酶(G-6PD)同工酶型及免疫表型。 ③多数获完全缓解(CR)的病人复发时，其白血病细胞基因型及表型再现诊断时的克隆。 白血病细胞大量增殖和正常造血细胞抑制的确切机制尚未确定，但生长因子，正常和白血病细胞的生长因子受体，以及生长因子受体的反应性对二类细胞的增殖和抑制有重要作用，生长因子受体或从细胞膜传至细胞核的生长因子转录信号，均有白血病细胞表达的癌基因所编码，有人观察到白血病细胞可产生集落刺激因子(CSF)，此可能和白血病细胞无限增殖有关，几种正常的CSF在体外对白血病克隆细胞均有刺激作用，周围血红细胞，血小板减少，骨髓中白血病细胞占绝对优势是急性白血病常见的血液学特征，推测由于正常造血干细胞被白血病细胞排挤所致，但部分病人骨髓增生低下，难以用白血病细胞排挤解释，认为是白血病细胞通过细胞介导或体液机制抑制正常造血细胞，后证实白血病细胞浸出物或培养基中有一种抑制性活性物质，特异性地抑制处于DNA合成期的正常祖细胞集落形成单位(CFU-C)，多种淋巴细胞白血病的白血病细胞表面有大量白细胞介素-2受体(IL-2R)，其可能作为封闭因子阻断IL-2与正常活化的淋巴细胞结合，影响正常淋巴细胞的活性及淋巴因子的释放，从而有利于白血病细胞的增殖。 临床表现 各型急性白血病的临床表现主要包括骨髓组织受白血病细胞浸润所引起的造血功能障碍之表现(如贫血、感染、出血等)以及白血病细胞的全身浸润引起脏器的异常表现(如淋巴结、肝脾肿大等)两大方面。 一、起病： 多数病人起病急，进展快，常以发热、贫血或出血为首发症状。部分病例起病较缓，以进行性贫血为主要表现。 二、症状： (一)贫血：发病的均有贫血，但轻重不等。 (二)出血：多数患者在病程中均有不同程度之出血，以皮肤瘀点、瘀斑、牙龈出血、鼻衄为常见。严重者可有内脏出血，如便血、尿血、咳血及颅内出血。 (三)发热：是急性白血病常见的症状之一。 Read more...

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X-linked adrenal white matter malnutrition

Introduction X-linked adrenal leukodystrophy (ALD) is a refractory neurodegenerative disease associated with the accumulation of very long-chain saturated fatty acids (VLCFA) in tissues and body fluids. We have established a Japanese ALD diagnostic center using VLCFA measurement and mutation analysis. ABCD 1 identified 60 mutations in 69 Japanese ALD families, including 38 missense mutations, 6 nonsense mutations, 8 frame translocation mutations, 3 amino acid deletions, 2 exon mutations, and large deletions. 3 types. By reference to the current worldwide ALD mutation database, 24 mutations (40%) were found in Japanese patients. In these 69 families, there was no significant correlation between these mutations and phenotype in 81 male patients. About 12% of ALD patients Drewo performed mutation analysis on male probands and their mothers, providing useful data for genetic counseling. The only effective treatment for brain-type ALD is early hematopoietic stem cell transplantation. Therefore, we conducted extensive family screening of probands and conducted pre-tympanic diagnosis of ALD through genetic counseling, and established long-term for these patients. Follow-up system to prevent progression of brain involvement and to monitor adrenal insufficiency. Further elucidation of the pathology of ALD, especially the mechanism of brain involvement, is worth looking forward to. Introduction X-linked adrenal leukodystrophy is one of the most common peroxisome diseases involved in the oxidation of saturated long-chain fatty acids (β), leading to the accumulation of fatty acids in tissues and plasma. The pathogenic gene of ALD, ABCD 1 has been mapped to Xq 28, a gene of the peroxisome membrane protein homologous to the ATP-binding cassette transporter family, which acts as a VLCF- on the peroxisome membrane. The transporter of CoA. Clinical manifestations include childhood brain type (CCALD), adolescent brain type, adult brain type, adrenal myelinopathy (AMN), Olivo-P-cerebellar type and Addison's disease. 1CCALD is the most common phenotype characterized by progression of intellectual, psychological, visual, and gait disorders between the ages of 3 and 10. The prognosis of CCALD is generally poor, and patients are thought to die within a few years, but good comprehensive care improves the prognosis of these days. Hematopoietic stem cell transplantation (HSCT) is currently the only treatment that can prevent brain-type ALD brain involvement, but HSCT is only effective in patients with early brain symptoms. 2 Therefore, we established a rapid diagnostic system for ALD patients, combined with the detection and mutation analysis of VLCFA in serum, established a rapid diagnosis system for ALD patients. ABCD 1 gene. Even so, even now, only about one-third of CCALD patients have received HSCT in Japan (data not shown), so pre-tympanic diagnosis and early intervention are important to overcome this thorny disease. Diagnostic System and Mutation Range of ALD Patients in Japan This paper analyzed the VLCFA in serum or plasma of suspected ALD patients with clinical and brain magnetic resonance imaging (MRI) by gas chromatography/mass spectrometry. 3 These patients were diagnosed with an increase in VLCFA, and then we performed molecular analysis. ABCD 1 gene. The ratio of C24:0/C22:0, C25:0/C22:0 and C26:0/C22:0 in male ALD patients was significantly higher than that in the control group, but some female carriers had C24:0/C22:0, C25 The ratio of :0/C22:0 and C26:0/C22:0 overlaps with the control value (Figure 1). Moser et al. 4 also reported that 85% of obligate heterozygotes have abnormally high VLCFA levels, but normal results do not preclude carrying status. Therefore, male ALD patients can only be diagnosed by an increase in VLCFA, but female carriers should conduct molecular analysis. ABCD 1 in order to get an accurate diagnosis. In addition, our data showed that mutations in male probands and their mothers were analyzed in 33 families, 4 of whom found no mutations in the proband, which means approximately 12% of ALD patients There may be mutations. Drevo mutation. In the ALD database, approximately 93% of index cases are mutations that are inherited from one of the parents. Both data indicate that a significant number of male probands may not inherit mutations that cause disease from their mothers, and accurate carrier testing is necessary not only for further family analysis, but also for genetic counseling. . We analyzed the phenotypes of 142 patients in 69 families, including 52 children with brain type, 5 with adolescent brain type, 2 with adult brain type, and 7 with adult brain type, and 3 cases with adolescent or adult brain type. Amn>Adoc or amn>ac), 1 case of cerebellum, 11 cases of tympanic membrane, 60 cases of female carrier. figure 2). There was no significant correlation between these mutations and phenotype in Japanese ALD patients, which was not reported in previous reports. 1 Even in the same family, there is the same mutation ABCD 1, and there is variation in phenotype. At present, we cannot predict the further clinical course of tympanic ALD patients by analyzing family, genotype, VLCFA values, and even their expression. ABCD 1 gene and ALDP protein. HSCT and ALD pre-pulmonary diagnosis HSCT is the only treatment to prevent brain-type ALD brain involvement, but it is only effective in patients with early brain symptoms. 2 Although we have established a rapid diagnostic system for ALD in Japan, only one-third of patients with CCALD are able to receive HSCT after onset (data not shown) for the following reasons. First, for a significant number of CCALD patients, there was a gap between onset and brain MRI/VLCFA detection because they were initially diagnosed with attention deficit/hyperactivity disorder, learning disability, hearing impairment, exotropia, and vision loss. In addition, HSCT preparation will take a considerable amount of time, including finding matching donors, while HSCT surgery in advanced brain patients can accelerate neurological decline. Therefore, familial screening of probands has important clinical implications for early intervention and prevention of advanced brain symptoms. In addition, at least 70% of patients with CCALD and AMN have clinical and biochemical evidence of primary adrenal insufficiency (http://www.x-ald.nl). Therefore, pre-tympanic diagnosis is also useful for preparing adrenal hormone therapy. This is necessary to save the lives of all patients with ALD who have adrenal insufficiency. The vector is detected by genetic counseling, which can be achieved by paying attention to the increase in VLCFA in plasma and mutation analysis. The ABCD 1 gene is an important gene for identifying pre-tympanic patients and other female carriers. Elevated VLCFA levels confirm the diagnosis of carriers, but there may be C24 between 0:0/C22:0, C25:0/C22:0, and C26:0/C22:0 between healthy controls and at least 10% of carriers. The overlap between them. In addition, our data and other data indicate that approximately 10% of the probands are identified by the ABCD 1 gene, which means that the mother of these patients should not be carriers. For these reasons, the ABCD 1 gene is not only necessary for vector detection, but also a necessary condition for confirming spontaneous mutation. In summary, 32%-48% of female carriers over the age of 20 have some symptoms, mainly due to abnormalities in the spinal cord and leg nerves, similar to AMN. It seems that as you get older, the frequency of carriers with symptoms increases. Http://www.x-ald.nl). Proper medications are often recommended for these carriers to reduce leg cramps and pain in the lower back and hips. Neonatal screening may be a potential method for the widespread discovery of pre-tympanic male patients and female carriers. Hubbard et al.6 used liquid chromatography-tandem mass spectrometry to conduct a preliminary study on the quality screening of 1-hexacosanoyl-2-lyso-sn-3-glycerophosphorylcholine (26:0-lyso-PC). Early intervention and long-term follow-up of anterior tympanic patients The anterior tympanic male patients can develop into multiple phenotypes between the ages of 3 and 50, and their phenotype may differ from those of the proband. Therefore, it is very important to provide information to patients and their families through genetic counseling. For HSCT diagnosis of anterior tympanic ALD patients under 3 years of age, follow-up every 6 months for subtle neuropsychological signs, brain MRI and electrophysiological examination is beneficial to such boys. When any abnormalities are found, the HSCT should be performed as soon as possible. Lorenzo's oil is one of the choices for these pretympanic patients, because Moser et al. reported that Lorenzo oil therapy for asymptomatic ALD boys reduced the risk of MRI abnormalities in the normal MRI of the brain. 7 However, further research confirms that this validity has not been reported. In addition, it is reported that approximately 80% of asymptomatic ALD boys have impaired adrenal function, 8 therefore, all male patients should be monitored for adrenal insufficiency. Adrenal hormone replacement therapy is necessary and effective in patients with morbid adrenal insufficiency. Recently, HSC gene therapy with lentiviral vectors successfully prevented the progression of CCALD in two patients at an early stage. 11 However, the therapeutic mechanism of this therapy remains unclear, probably because of the replacement of ABCD 1 gene, normal stem cells or other factor. Further research on VLCFA regulation or prevention of brain damage in patients and their families should be expedited, and predictors of brain damage should be identified as the key to solving the problem.

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Introduction to chronic thromboembolic pulmonary hypertension (CTEPH)

简介 慢性血栓栓塞性肺动脉高压（chronic thromboembolic pulmonary hypertension ，CTEPH）是一类肺动脉梗阻性疾病。其原因主要为血栓栓塞导致肺动脉堵塞，肺血管重塑，进而产生肺动脉高压。2013年国际肺高压研讨会还将肺动脉肉瘤栓塞，肿瘤细胞栓塞，肺囊虫病，异物栓塞和先天性获得性肺动脉狭窄等导致的肺动脉堵塞或狭窄归到此类肺高压。 流行病学 慢性血栓栓塞性肺动脉高压发病率不详。在美国每年预计有50至60万人发生急性肺栓塞，而其中存活下来的患者中有接近0.1%至0.5%的人会进展为CTEPH。2004年新英格兰医学杂志发表意大利帕多瓦大学研究：既往有急性肺栓塞病史的患者中3.8%的人会发生CTEPH。2013年美国Kim总结了9个临床研究，急性肺栓塞后发生CTEPH的发病率从0.4%到9.1%。 病理生理及临床预后 引起CTEPH的发病机制仍然未知。既往认为下肢深静脉血栓是急性和慢性肺栓塞的重要原因。然而，近一半的CTEPH患者既往并没有急性栓塞发生的临床表现，临床表现为隐匿型，40%的患者未发现下肢深静脉血栓或深静脉病变。其他原因还包括系统性红斑狼疮，抗磷脂抗体综合征，VIII因子过度表达和蛋白C及蛋白S突变。其他少见性原因还包括慢性炎症性疾病，骨髓增生综合征和脾切除术后。近年来发现医源性（如永久起搏器植入）也是CTEPH的病因之一。 血栓堵塞超过40%的肺动脉血管床时，就会引起肺动脉高压，慢性或反复肺动脉栓塞导致肺血管阻力持续增高，有些学者提出肺动脉高压是因肺血管重建（小血管病变）引起，肺血管重建继发于原始的栓塞事件。CTEPH若不经治疗最终因呼吸衰竭、右心衰竭而死亡，死亡率极高。 CTEPH的治疗现状 慢性血栓栓塞性肺动脉高压包括药物治疗，外科肺动脉内膜剥脱术（PEA），介入肺动脉球囊扩张术和肺移植治疗。抗凝药物治疗是CTEPH的基础治疗方案，绝大多数患者需要终生服用口服抗凝药物。目前仅有利奥西胍这一种靶向药物对降低CTEPH患者的肺动脉压力提高生活质量有一定疗效，但由于价格昂贵且不能被大多数患者接受。1956年美国的Hollister首先报道了肺动脉内膜剥脱术用于治疗CTEPH。PEA手术经历漫长的探索过程，从20世纪50年代到1984年，圣地亚哥医学中心仅完成了84例肺动脉内膜剥脱术，到2001年，全世界共完成了1000例PEA手术，目前美国每年的PEA手术数量仅有300例左右。南加州圣地亚哥医学中心是世界最大CTEPH的手术治疗中心，已经完成3000余例的PEA手术，建立成熟的肺动脉内膜剥脱术治疗方案，术后30天死亡率已经控制在2.2%以内，近5年手术死亡率已经下降到1%。欧洲和加拿大的17个中心平均PEA手术死亡率也下降到4.7%(还包括部分年手术量小于10例的中心)。亚洲的PEA手术水平近年来也有长足的进步：韩国Soo Han Kim报道PEA手术死亡率10.8%；日本的Ishida报道PEA手术死亡率由最初14%（90年代）降到7.5%；中国医学科学院阜外医院PEA手术死亡率由早年的11%，下降到近5年手术死亡率2%以下。 PEA手术前评估 PEA手术是被认为可以治愈CTEPH的唯一方案。所有诊断CTEPH的患者都需要进行PEA手术的评估。CTEPH患者的治疗决策，应该由包括内科医师、放射科医师和专业的外科医师在内的CTEPH治疗团队通过多学科讨论制定。国际肺高压协会强调：对于即使被认定不可手术的CTEPH患者，还需要到第二家有PEA手术经验的中心进行可否手术的二次评估。 PEA手术的指征，首先是正规抗凝大于3个月；其次是患者NYHA分级II级以上，肺血管阻力＞300dyne·s/cm5；第三，肺血管影像学检查有慢性血栓的表现，患者的血流动力学损害程度与其解剖学表现符合，且预期外科手术可以剥离；还需排除影响手术的严重合并症。还有一部分患者在静息状态表现为正常肺血管阻力，他们也许不能诊断CTEPH，而称为慢性血栓栓塞性肺血管病，尤其是单侧栓塞的患者，但他们确实能从PEA手术获益。 通气/灌注扫描不仅用于诊断，而且通过区分大血管和小血管病变来评估手术可行性，前者表现为多发段水平灌注缺损，后者表现为不一致的斑点样改变，其敏感性和特异性分别大于96%和90%。高分辨率计算机断层扫描肺血管造影对CTEPH诊断和评估手术可行性的应用越来越多，但是CT表现没有近端血栓并不能排除外科可以治疗的慢性疾病，另一方面即使存在中心性血栓也不能完全确定CTEPH的诊断。右心导管肺血管造影仍然是诊断确认慢性血栓性肺疾病，评价手术可行性的金标准，对于有经验的治疗中心，CTPA可以作为替代选择。 PEA手术的禁忌症包括有严重的影响手术或限制术后生存的合并症，以及肺动脉压力与栓塞病变不匹配。另外远端病变、高肺血管阻力、高龄也是需要考虑权衡的因素。CTEPH的分型是进行PEA手术必须考虑的因素，I型和II型病例术后的肺动脉压力和肺血管阻力改善明显优于III型和IV型，文献报道：I型、II型围术期生存率98.1%明显高于III型、IV型86.7%，87.9%的I/II型患者的NYHA心功能分级改善，而7例IV型患者仅有1例心功能改善。术前肺血管阻力（PVR）高低明显与术后死亡率相关，Madani报道术前PVR＞1000dyne·s/cm5的围术期死亡率比其他病例增加两倍以上。评价手术可行性的因素还与外科医生的经验和技术、诊疗中心在诊断、决策和术后管理的水平相。圣地亚哥在2003年报告的500例手术患者中III型和IV仅占13.6%，而在2012年报告的结果显示这两型病例达到了47%，而围术期死亡率明显下降。 CTEPH病理分型 圣地亚哥医学中心根据手术中探查和剥离的血栓内膜标本将CTEPH分为4型，I型是在主肺动脉及左右肺动脉主干内存在血块，占12%；II型在大肺动脉内没有血栓，但可见叶动脉水平血管增厚的内膜，表面附着网格样纤维，占38%；III型为远端段及亚段水平，占39.4%；IV型为远端小血管病变，占7.6%。对于I型II型病变术中比较容易接近，易于处理，而且剥离后的肺动脉压力和肺血管阻力下降明显，是PEA的良好指征；但对于III型和IV型病变，病变位置远端小血管，术中不容易处理，术后肺动脉血压及肺血管阻力下降不理想，要到有经验的中心进行手术。 PEA手术方案 动脉内膜切除术最早于上世纪 60 年代开展，在随后的几年中不断得到完善。目前以南加州大学圣地亚哥医学中心的方案为主流手术方案。正中胸骨切开术，深低温停循环技术，双侧剥离到亚段水平是手术的关键。深低温、间断停循环可以避免体循环至肺循环的侧支分流，保持一个无血的视野，更完整的将肺血管树样血栓及内膜剥离到亚段水平。同时应用深低温（19℃）防止脑损害。一些医学中心已经通过使用顺行脑灌注成功的开展不需要完全循环停止的PEA。最近的一个随机研究显示，接受顺行脑灌注和接受传统方法手术患者的认知功能之间无显著差异，而部分患者因术中回血过多影响远端分支剥离而停止顺行脑灌注转为完全停循环手术。 在剥脱过程中找到正确的解剖层次尤为重要，因为这个层次决定了所有肺叶，肺段或亚段肺动脉层次。对于I型II型病变术推荐采用从主肺动脉或左右肺动脉近端内膜开始“内翻式”剥离；对于III型和IV型病变可以采用肺动脉段开口或亚段水平栓塞的直接剥离，而这种直接从段开口以下剥离的方式需要借助尖端纤细的镊子和剥离吸引器完成，同时这样的手术技术需要在熟练掌握常规“内翻式”剥离技术后再开始练习。在剥离过程中需要避免肺动脉中层的损伤。对于肺动脉血栓合并肺动脉壁钙化的病例，应避免钙化斑块剥离后肺动脉壁穿透性损伤。 双侧内膜剥脱完成后恢复循环并开始复温，这期间可同期行其他手术，如冠状动脉旁路移植、瓣膜修复置换、房间隔缺损的闭合等。继发于CTEPH的三尖瓣返流为功能性返流，多不必修复，随着术后右心室功能的恢复及右心室重构，返流会减轻。残余肺动脉压力较高的患者三尖瓣返流改善较差，这会延长住院时间，增加房颤的发生率，Ogino等推荐可能残存肺高压的患者进行三尖瓣成形术。多数中心主张对卵圆孔未闭进行闭合，当考虑术后残余压力高时建议保持卵圆孔开放。 PEA手术过程中麻醉和体外医生的配合尤其重要。手术需要在深低温停循环情况下进行，全身均匀降温、复温，脑保护脊髓保护都是不可忽视的环节。通过容量控制减低心排量进而减少肺灌注性损伤，缩血管药物控制体肺侧枝。圣地亚哥医学中心推荐使用一氧化氮控制术后残余肺动脉高压。 对于CTEPH患者，尤其是既往有深静脉血栓病史的患者，圣地亚哥医学中心常规在术前植入下腔静脉滤器来防止围术期栓塞复发。一项针对外科医生的调查发现，使用滤器的比例为50:50，多数中心选择在有近端深静脉血栓的肺栓塞高危患者放置滤器，但对于腓肠肌间静脉血栓导致的III型和IV型病变患者，下腔静脉滤器的使用仍有争议,目前没有RCT实验支持常规放置下腔静脉滤器，其使用的证据水平较低。 手术并发症 PEA手术难度高，学习曲线长，手术并发症发生率高，有与其他心外科手术类似的并发症，比如心律失常、出血、肺不张、胸腔积液、心包积液、膈肌功能障碍等，然而再灌注肺水肿和残余肺动脉高压是PEA手术独有的增加术后死亡率的严重并发症。 再灌注肺水肿主要发生于内膜剥脱后再灌注的肺部区域，血管通透性增加，表现为肺泡出血和严重低氧血症，明显增加机械通气时间和ICU停留时间，发生率大约是10%-40%。再灌注肺水肿在术后短时发生占60%，在术后48小时内发生占30%，48小时以后发生仅占10%。严重的术前肺动脉高压及术后残余肺动脉压力均增加再灌注肺水肿的风险。回顾性研究报道术前对支气管肺侧枝动脉行介入栓塞能降低再灌注肺水肿的发生率，但这项干预措施仅为单中心回顾报道，没有前瞻随机对照研究以及多中心的研究数据。另外试验表明尽量减少强心药使用和低潮气量通气可以降低再灌注肺损伤的发生率及死亡率。再灌注肺水肿的治疗主要是支持治疗，使用足够的机械通气并给予高PEEP，限水利尿以减少肺水，避免高的心输出量，降低氧耗。对于有严重呼吸窘迫综合征的患者，侧卧位给氧明显好于仰卧位。吸入NO以及ECMO支持对于严重再灌注肺水肿病例是十分必要的。 残余肺动脉高压在PEA术后的发生率大概是5-35%，是围术期死亡的常见原因，术后严重残余肺动脉压力是术后死亡的重要预测因子。不可逆性肺动脉高压是肺动脉远端慢性血栓栓塞病变或者合并了小血管病变的结果，这些病变不能用PEA手术治愈。近期英国的一项研究在术后3-6个月的随访中发现51%的患者mPAP≥25mmHg，mPAP≥30mmHg的患者应该启用肺血管扩张药物治疗，并长期密切随访，mPAP≥38mmHg和PVR≥425 dyne·s/cm5的患者远期生存率较差。另外有报道PEA术后3个月31%的患者有残余肺动脉高压，但如果不考虑患者的症状及活动耐力情况，其5年生存率与没有参与肺动脉高压患者相似。PEA术后严重的RPH以及合并右心衰竭时治疗困难，通常使用强心药物支持，利尿改善右心室前负荷。降低肺动脉压力的血管舒张药物通常不奏效，而且有导致体循环低血压的风险。术后即刻开始吸入NO或者伊洛前列素可以降低肺血管阻力且不影响外周血压。 再灌注肺水肿和残余肺动脉高压病情严重时传统的治疗无效，此时需用体外膜肺氧和（ECMO）等循环支持措施。存在血流动力学不稳定时推荐使用静脉-动脉ECMO，这更符合患者的病理生理特点。可以使用心脏插管的经中心方式，也可使用股动静脉插管的外周方式。血液通过管道转离心和肺，从而使肺动脉压下降、右心室负荷降低，同时提供心输出量和气体交换。对于血流动力学稳定的肺再灌注损伤，静脉-静脉ECMO支持比较合适。使用ECMO支持治疗的重要原则是患者能在预期的支持时间内恢复。UCSD均采取静脉-静脉ECMO，住院生存率为30%；Berman报道因血流动力学差、右心功能不全而行静脉-动脉ECMO，平均支持时间5天，院内生存率57%。目前ECMO已经推荐为PEA术后严重并发症的标准治疗措施。 术后抗凝治疗易尽早应用，推荐在手术当日夜，但应该排除出血并发症。为避免血栓复发，所有患者都要终身抗凝治疗。 手术结果 PEA手术结果：顶级肺栓塞外科手术中心已经将手术死亡率控制到1-4%。术后肺血管阻力大于500达因/s*cm5患者的死亡率（5.7%）明显高于术后肺血管阻力小于500达因/s*cm5患者的死亡率（1.2%）。圣地亚哥医学中心报道， PEA术后mPAP Read more...

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Introduction to non-small cell lung cancer (NSCLC)

概述 肺癌是世界上最常见的恶性肿瘤之一,已成为我国城市人口恶性肿瘤死亡原因的第1位。非小细胞型肺癌包括鳞状细胞癌（鳞癌）、腺癌、大细胞癌，与小细胞癌相比其癌细胞生长分裂较慢,扩散转移相对较晚。非小细胞肺癌约占所有肺癌的80%，约75%的患者发现时已处于中晚期，5年生存率很低。 病因 1.吸烟 目前认为吸烟是肺癌的最重要的高危因素，烟草中有超过3000种化学物质，其中多链芳香烃类化合物（如：苯并芘）和亚硝胺均有很强的致癌活性。多链芳香烃类化合物和亚硝胺可通过多种机制导致支气管上皮细胞DNA损伤，使得癌基因（如Ras基因）激活和抑癌基因（如p53，FHIT基因等）失活，进而引起细胞的转化，最终癌变。 2.职业和环境接触 肺癌是职业癌中最重要的一种。估约10%的肺癌患者有环境和职业接触史。现已证明以下9种职业环境致癌物增加肺癌的发生率：铝制品的副产品、砷、石棉、bis-chloromethylether、铬化合物、焦炭炉、芥子气、含镍的杂质、氯乙烯。长期接触铍、镉、硅、福尔马林等物质也会增加肺癌的发病率，空气污染，特别是工业废气均能引发肺癌。 3.电离辐射 肺脏是对放射线较为敏感的器官。日本原子弹爆炸幸存者中患肺癌者显著增加。 4.既往肺部慢性感染 如肺结核、支气管扩张症等患者，支气管上皮在慢性感染过程中可能化生为鳞状上皮致使癌变，但较为少见。 5.遗传等因素 家族聚集、遗传易感性以及免疫功能降低，代谢、内分泌功能失调等也可能在 肺癌的发生中起重要作用。许多研究证明，遗传因素可能在对环境致癌物易感的人群和/或个体中起重要作用。 6.大气污染 发达国家肺癌的发病率高，主要原因是由于工业和交通发达地区，石油，煤和内燃机等燃烧后和沥青公路尘埃产生的含有苯并芘致癌烃等有害物质污染大气有关。大气污染与吸烟对肺癌的发病率可能互相促进，起协同作用。 临床表现 1.早期症状 （1）胸部胀痛  肺癌早期胸痛症状较轻，主要表现为隐痛、闷痛、部位不一定，与呼吸的关系也不确定。如胀痛持续发生则说明癌症有累及胸膜的可能。 （2）痰血  肿瘤炎症致坏死、毛细血管破损时会有少量出血，往往与痰混合在一起，呈间歇或断续出现。很多肺癌患者因痰血而就诊。 （3）低热  肿瘤堵住支气管后往往有阻塞性肺叶存在，程度不一，轻者仅有低热，重者则有高热，用药后可暂时好转，但很快又会复发。 （4）咳嗽  肺癌因长在支气管肺组织上，通常会产生呼吸道刺激症状而发生刺激性咳嗽。 2.晚期症状 非小细胞肺癌晚期患者有疲乏、体重减轻、食欲下降等表现，出现呼吸困难、咳嗽、咯血等局部症状。 检查 1.X线检查 通过X线检查可以了解肺癌的部位和大小，可能看到由于支气管阻塞引起的局部肺气肿、肺不张或病灶邻近部位的浸润性病变或肺部炎变。 2.支气管镜检查 通过支气管镜可直接窥察支气管内膜及管腔的病变情况。可采取肿瘤组织供病理检查，或吸取支气管分泌物作细胞学检查，以明确诊断和判定组织学类型。 3.细胞学检查 痰细胞学检查是肺癌普查和诊断的一种简便有效的方法，原发性肺癌患者多数在痰液中可找到脱落的癌细胞。中央型肺癌痰细胞学检查的阳性率可达70%～90%，周围型肺癌痰检的阳性率则仅约50%。 4.剖胸探查术 肺部肿块经多种检查和短期诊断性治疗仍未能明确病变性质，肺癌的可能性又不能除外者，应作剖胸探查术。这样可避免延误病情致使肺癌患者失去早期治疗的机会。 5.ECT检查 ECT骨显像可以较早地发现骨转移灶。X线片与骨显像都有阳性发现，如病灶部成骨反应静止，代谢不活跃，则骨显像为阴性，X线片为阳性，二者互补，可以提高诊断率。需要注意的是ECT骨显像诊断肺癌骨转移的假阳性率可达20%～30%，因此ECT骨显像阳性者需要作阳性区域骨的MRI扫描。 6.纵隔镜检查 Read more...

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Introduction to overactive bladder (OAB)

概述 膀胱过度活动症（OAB）是一种以尿急症状为特征的症候群，常伴有尿频和夜尿症状，可伴或不伴有急迫性尿失禁，其明显影响患者的日常生活和社会活动，已成为困扰人们的一大疾病。近年来随着我国进入老龄化社会，以及糖尿病与神经系统损害性疾病的增长，由此继发的相关疾病——膀胱过度活动症的发生率也逐年上升。 《膀胱过度活动症诊断治疗指南》中指出，OAB是一种以尿急症状为特征的综合征，常伴有尿频和夜尿症状，可伴或不伴有急迫性尿失禁；尿动力学上可表现为逼尿肌过度活动，也可为其他形式的尿道一膀胱功能障碍。不包括由急性尿路感染或其他形式的膀胱尿道局部病变所致的症状。 病因 其病因尚不明确，目前认为有以下4种因素可能有关： 1.逼尿肌不稳定 由非神经源性因素所致，储尿期逼尿肌异常收缩引起相应的临床症状。 2.膀胱感觉过敏 在较小的膀胱容量时即出现排尿欲。 3.尿道及盆底肌功能异常。 4.其他原因 如精神行为异常，激素代谢失调等。 临床表现 典型症状主要包括尿急、日间尿频、夜尿和急迫性尿失禁。 1.尿急 是指一种突发、强烈的排尿欲望，且很难被主观抑制而延迟排尿。 2.急迫性尿失禁 是指与尿急相伴随或尿急后立即出现的尿失禁现象。 3.尿频 为一种主诉，指患者自觉每天排尿次数过于频繁。在主观感觉的基础上，成人排尿次数达到：日间不少于8次，夜间不少于2次，每次尿量低于200ml时考虑为尿频。 4.夜尿 指患者每夜2次以上的、因尿意而排尿的主诉。 检查 1.筛选性检查指 一般患者均应该完成的检查项目，包括： （1）病史  OAB是一种症状学诊断，因此对病史的询问非常重要，应涵盖到发病的典型症状，相关症状及相关病史，同时应进行排尿日记评估。 （2）体格检查  包括男性泌尿生殖系统、女性生殖系统和神经系统检查，以了解有无引起OAB的原发性因素，如对于有OAB症状的老年男性，应行直肠指诊，了解有无前列腺相关疾病等。 （3）实验室检查  0AB诊断首先应排除感染性因素，所以尿常规检查必不可少。 （4）泌尿外科特殊检查如尿流率、剩余尿的测定及经直肠前列腺彩超等，了解下尿路功能状态。 2.选择性检查 指对怀疑同时合并有泌尿或生殖系统某种病变的患者应进行选择性检查，包括泌尿或生殖系统病原学检查、尿液细胞学检查等，必要时根据情况可行KUB、IVU或者MRI检查。 诊断 膀肤过度活动症（OAB）的诊断是以临床症状作为主要诊断依据的。由于OAB的发病机制尚不明确，涉及膀胧感觉神经、排尿中枢、运动神经、逼尿肌等多方面因素，并且其他形式的储尿和排尿障碍也可引起逼尿肌的非抑制性收缩。因此，对OAB做出正确的诊断需依赖筛选性检查和选择性检查。 治疗 1.行为治疗 （1）膀胱训练  膀胱训练治疗OAB的疗效是肯定的。通过膀胱训练，抑制膀胱收缩，增加膀胱容量。训练要点是白天多饮水，尽量忍尿，延长排尿间隔时间；入夜后不再饮水，勿饮刺激性、兴奋性饮料，夜间可适量服用镇静安眠药物以安静入睡。治疗期间记录排尿日记，增强治愈信心。 Read more...

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Introduction to hepatitis C

疾病名称： 丙型肝炎 简介： 丙型病毒性肝炎(viral hepatitis type C，HC简称丙型肝炎)，系丙型肝炎病毒(HCV)感染所引起的疾病，主要经血源性传播。临床表现有发热、消化道症状及肝功能异常等。与乙型肝炎类似，但较轻。多数病例呈亚临床型，慢性化程度较为严重，也可导致暴发性肝衰竭。多见于与其他病毒合并感染者。 病因： (一)发病原因 HCV是经血源性传播的一类肝炎病毒。1989年美国的Chiron公司应用分子克隆技术率先将(HCV) cDNA克隆成功。HCV是用分子生物学技术发现的第一个人类病毒。HCV属披膜病毒科，其生物性状，基因结构与黄病毒、瘟病毒近似。目前已确认HCV为含有脂质外壳的球形颗粒，直径30～60nm。HCV基因组是一长的正链、单股RNA，长约9.5Kb。HCV基因组有一大的编码3010或3011个氨基酸的多元蛋白的开放阅读框架(ORF)。编码的多元蛋白体与黄病毒有明显的共同结构：含结构蛋白(包括核心蛋白和包膜蛋白)和非结构蛋白(NS1-NS5)。 HCV是RNA病毒，较易变异，不同地区的分离株只有68.1%～91.8%的核苷酸相同，根据HCV的基因序列差异可分成不同的基因型。目前HCV基因分型尚无统一标准、统一方法。Okamoto将HCV分为Ⅰ、Ⅱ、Ⅲ、Ⅳ四个基因型，按其分型，大部分北美、欧洲HCV株属Ⅰ型。日本主要为Ⅱ型，亦有Ⅲ型及Ⅳ型。我国据王宇报道，北方城市以Ⅱ、Ⅲ型为主，南方城市则90%以上为Ⅱ型。 (二)发病机制 1.HCV感染的直接致病作用 许多研究显示HCV感染者肝组织炎症严重程度与其病毒血症有关。慢性丙型肝炎患者肝组织炎症严重程度与肝细胞内HCV RNA水平的相关性比其与血清HCV RNA水平的相关性更强。使用干扰素治疗后，随血清中HCV RNA含量的减少，其血清中ALT水平也逐渐下降，以上结果提示HCV可能存在直接致病作用。然而，免疫组化研究未能充分证明肝组织HCV抗原的表达与肝病炎症活动有关。Groff等研究发现，肝细胞HCV抗原的存在并不表示肝细胞内一定存在。HCV颗粒，肝病炎症活动不一定与肝细胞HCV抗原表达有关，而肝组织炎症与肝细胞内HCV病毒颗粒的存在相关，也说明HCV具有直接细胞致病作用。HCV的直接致病作用推测可能与HCV在肝细胞内复制，引起肝细胞结构和功能改变，或干扰肝细胞内蛋白合成造成肝细胞变性和坏死有关，HCV无症状携带状态的存在，似乎暗示HCV无直接致病作用。但最近报告绝大多数ALT持续正常的“慢性HCV携带者”肝组织存在不同程度的病变和炎症，其肝组织炎症损伤程度与HCV复制水平有关，说明无症状携带状态较少见，并进一步支持HCV具有直接致病作用。 2.细胞介导的免疫性损伤可能是HCV致肝脏病变的主要原因 丙型肝炎肝组织病理学的重要特征之一是汇管区淋巴细胞集聚，有时可形成淋巴滤泡，对比研究认为较乙型肝炎明显，淋巴细胞浸润无疑与免疫反应有关。一些学者证明慢性丙型肝炎中浸润的淋巴细胞主要是CD8+胞，其中许多有活动性表位(epitope)，显示为激活状态。电镜下观察到淋巴细胞与肝细胞密切接触，提示它对肝细胞的毒性损伤。Mondelli等体外试验证实慢性非甲非乙型肝炎的细胞毒性T细胞对自体肝细胞的毒性增高。在慢性丙型肝炎，细胞毒作用主要由T细胞所致。相反，在自身免疫性肝炎患者，免疫效应细胞仅限于非T淋巴细胞。慢性HBV感染中，非T和T淋巴细胞都参与肝细胞损伤作用。HCV特异抗原能激活CD8+和CD56+细胞，提示CD56+细胞在慢性丙型肝炎发病机制中也起重要作用。慢性丙型肝炎患者肝内T细胞能识别HCV的C蛋白、E1和E2/NS1蛋白的多个抗原决定簇，这种识别受HLA-I类限制，也说明Tc细胞在慢性丙型肝炎发病机制中起一定作用。另有研究表明，绝大多数慢性HCV感染者外周血和肝组织内受HLA-Ⅱ类分子限制的CD4+细胞(TH-1细胞)能攻击HCV特异的免疫抗原决定簇，CD4+细胞对HCV核心抗原的反应与肝脏炎症活动有关，TH-1细胞在慢性丙型肝炎中起关键作用。HCV特异的TH细胞表面抗原决定簇能增强Tc细胞对HCV抗原的特异反应，提示TH细胞能协助和增强Tc细胞攻击破坏HCV感染的肝细胞。 HCV RNA的E1、E2/NS为高变区，在体内很容易发生变异，并可导致HCV感染者肝细胞膜的靶抗原(E1、E2/NS蛋白)决定簇的改变，Tc细胞就会再次识别新出现的抗原决定簇，并攻击破坏肝细胞，这就是HCV RNA变异率越高，其肝组织炎症越严重的原因。也说明免疫介导机制在慢性HCV感染者肝细胞损伤中起重要作用。 3.自身免疫HCV感染者常伴有以下特征 ①非特异性免疫障碍，例如混合性冷凝球蛋白血症、干燥综合征和甲状腺炎等 ②血清中可检出非特异性自身抗体，如类风湿因子、抗核抗体和抗平滑肌抗体 ③部分Ⅱ型自身免疫性肝炎[抗肝肾微粒体Ⅰ型抗体(抗C-LKM-1抗体)阳性]可出现抗-HCV阳性 ④可出现抗-GOR;⑤肝脏组织学改变与自身免疫性肝病相似，故人们推测HCV感染的发病机制可能有自身免疫因素参与。但抗-HCV、抗-LKM-1和抗-GOR三者的关系，及其致病意义等均有待进一步研究。 4.细胞凋亡在丙型肝炎发病机制中的意义 细胞凋亡是由细胞膜表面的Fas抗原所介导、Hiramats等证实Fas抗原在正常肝脏组织内无表达而在HCV感染时，Fas抗原多见于伴活动性病变的肝组织，特别是门汇区周围。HCV感染者Fas抗原的表达与肝组织坏死及炎症程度、肝细胞HCV核心抗原的表达密切相关。说明Fas介导的细胞凋亡是HCV感染肝细胞死亡的形式之一。 HCV感染的发病机制是复杂的，许多因素及其相互关系尚有待进一步研究和阐明。 与其他类型肝炎相比，丙型肝炎具有其特征性病理改变，主要有以下几点： ①汇管区淋巴细胞团状集聚和Poulsen-Christoffersen型胆管炎(胆管上皮细胞变性，周围有大量淋巴细胞浸润)是其重要特征，具诊断价值。 ②早期病例可见血窦炎性细胞浸润，但不波及窦周围的肝细胞是其区别急性乙型肝炎的重要所在。 ③肝细胞坏死较轻，范围比较局限，而且出现较晚。 ④窦周及肝细胞间隙纤维化较乙型肝炎更为明显，并且出现较早，这可能是更易发展为肝硬化的原因之一。 ⑤肝细胞脂肪变性多见，脂肪空泡可为大泡性或小泡性。⑥肝细胞嗜酸性变呈片状，出现于非炎性反应区。 症状： 【临床表现】 1.潜伏期 Read more...

By admin, ago
zh_CN简体中文

Disease name:

Hepatitis C

Introduction:

Viral hepatitis type C (HC) is a disease caused by hepatitis C virus (HCV) infection, which is mainly transmitted by blood. Clinical manifestations include fever, gastrointestinal symptoms and abnormal liver function. Similar to hepatitis B, but lighter. Most cases are subclinical and chronic, which can lead to fulminant hepatic failure. More common in people infected with other viruses.

Cause:

(1) Causes of the disease

HCV is a type of hepatitis virus that is transmitted blood. In 1989, Chiron Corporation of the United States applied molecular cloning technology to successfully clone (HCV) cDNA. HCV is the first human virus discovered using molecular biology techniques. HCV belongs to the family of togavirus, its biological traits, and its genetic structure is similar to that of flavivirus and prion. It has been confirmed that HCV is a spherical particle containing a lipid outer shell and has a diameter of 30 to 60 nm. The HCV genome is a long positive-strand, single-stranded RNA of approximately 9.5 Kb in length. The HCV genome has a large open reading frame (ORF) encoding a 3010 or 3011 amino acid polyprotein. The encoded polyprotein bodies have a distinct common structure with flaviviruses: structural proteins (including core and envelope proteins) and non-structural proteins (NS1-NS5).

HCV is an RNA virus, which is relatively easy to mutate. Only 68.1% to 91.8% of the nucleotides in different regions are identical, and can be divided into different genotypes according to the difference in HCV gene sequence. At present, there is no uniform standard and uniform method for HCV genotyping. Okamoto divides HCV into four genotypes I, II, III and IV. According to its classification, most North American and European HCV strains belong to type I. Japan is mainly type II, and there are also type III and type IV. According to Wang Yu's report in China, the northern cities are mainly type II and III, while the southern cities are more than 90% type II.

(two) pathogenesis

1. Direct pathogenic effects of HCV infection Many studies have shown that the severity of liver tissue inflammation in HCV-infected patients is associated with viremia. The correlation between the severity of liver tissue inflammation and the level of HCV RNA in hepatocytes in patients with chronic hepatitis C is more strongly correlated with serum HCV RNA levels. After treatment with interferon, serum ALT levels gradually decreased with the decrease of serum HCV RNA content. The above results suggest that HCV may have direct pathogenic effects. However, immunohistochemical studies have not fully demonstrated that the expression of HCV antigen in liver tissue is associated with inflammatory activity in liver disease. Groff and other studies have found that the presence of HCV antigen in hepatocytes does not necessarily indicate the presence of hepatocytes. HCV granules, liver disease inflammatory activity is not necessarily related to hepatocyte HCV antigen expression, and liver tissue inflammation is associated with the presence of HCV virions in hepatocytes, indicating that HCV has a direct cytopathic effect. The direct pathogenic effect of HCV may be related to the replication of HCV in hepatocytes, causing changes in the structure and function of hepatocytes, or interfering with hepatocyte degeneration and necrosis caused by protein synthesis in hepatocytes. The presence of HCV asymptomatic carriers seems to imply HCV. No direct pathogenic effects. However, most of the "chronic HCV carriers" liver tissues with normal ALTs have been reported to have different degrees of lesions and inflammation. The degree of liver tissue inflammation is related to the level of HCV replication, indicating that asymptomatic carriers are rare and further support HCV has a direct pathogenic effect.

2. Cell-mediated immune damage may be the main cause of liver disease caused by HCV. One of the important features of hepatitis C liver histopathology is the accumulation of lymphocytes in the portal area, sometimes forming lymphoid follicles. Hepatitis is obvious, and lymphocyte infiltration is undoubtedly related to immune response. Some scholars have shown that the lymphocytes infiltrated in chronic hepatitis C are mainly CD8+ cells, many of which have active epitopes, which are shown to be activated. Under the electron microscope, lymphocytes were observed to be in close contact with hepatocytes, suggesting that it is toxic to hepatocytes. In vitro tests by Mondelli et al have confirmed that cytotoxic T cells of chronic non-A, non-B hepatitis have increased toxicity to autologous hepatocytes. In chronic hepatitis C, cytotoxicity is mainly caused by T cells. In contrast, in patients with autoimmune hepatitis, immune effector cells are restricted to non-T lymphocytes. In chronic HBV infection, both non-T and T lymphocytes are involved in hepatocyte injury. HCV-specific antigens activate CD8+ and CD56+ cells, suggesting that CD56+ cells also play an important role in the pathogenesis of chronic hepatitis C. Intrahepatic T cells of patients with chronic hepatitis C can recognize multiple antigenic determinants of protein C, E1 and E2/NS1 proteins of HCV. This recognition is restricted by HLA class I and also indicates the pathogenesis of Tc cells in chronic hepatitis C. It plays a role. Other studies have shown that most of the chronic HCV-infected patients with peripheral blood and liver tissue restricted by HLA-II molecules CD4+ cells (TH-1 cells) can attack HCV-specific immune antigenic determinants, CD4+ cells to HCV core antigen The response is related to liver inflammatory activity, and TH-1 cells play a key role in chronic hepatitis C. The HCV-specific TH cell surface antigenic determinant enhances the specific response of Tc cells to HCV antigen, suggesting that TH cells can assist and enhance Tc cell attack to destroy HCV-infected hepatocytes.

The E1 and E2/NS of HCV RNA are hypervariable regions, which are easily mutated in vivo and can cause changes in the target antigen (E1, E2/NS protein) of the hepatocyte membrane of HCV-infected patients, and Tc cells will be recognized again. Emerging antigenic determinants attack and destroy liver cells, which is why the higher the HCV RNA mutation rate, the more serious the liver tissue inflammation. It also suggests that immune-mediated mechanisms play an important role in hepatocyte injury in chronic HCV-infected individuals.

3. Autoimmune HCV infection is often accompanied by the following characteristics

1 non-specific immune disorders, such as mixed condensed globulinemia, Sjogren's syndrome and thyroiditis

2 serum can detect non-specific autoantibodies, such as rheumatoid factor, antinuclear antibody and anti-smooth muscle antibody

3 part of type II autoimmune hepatitis [anti-liver kidney microsomal type I antibody (anti-C-LKM-1 antibody) positive] may have anti-HCV positive

4 anti-GOR can occur; 5 liver histological changes are similar to autoimmune liver disease, so it is speculated that the pathogenesis of HCV infection may involve autoimmune factors. However, the relationship between anti-HCV, anti-LKM-1 and anti-GOR, and its pathogenic significance need to be further studied.

4. Significance of apoptosis in the pathogenesis of hepatitis C Apoptosis is mediated by Fas antigen on the surface of cell membrane, and Hiramatsu et al. confirmed that Fas antigen is not expressed in normal liver tissue. When infected with HCV, Fas antigen is more common in Liver tissue with active lesions, especially around the portal area. The expression of Fas antigen in HCV-infected patients is closely related to the degree of liver tissue necrosis and inflammation, and the expression of hepatocyte HCV core antigen. This indicates that Fas-mediated apoptosis is one of the forms of HCV-infected hepatocyte death.

The pathogenesis of HCV infection is complex, and many factors and their interrelationships need further study and clarification.

Compared with other types of hepatitis, hepatitis C has its characteristic pathological changes, mainly the following:

1 The cluster of lymphocytes in the portal area and Poulsen-Christoffersen type cholangitis (degeneration of bile duct epithelial cells, surrounded by a large number of lymphocytes) are important features and have diagnostic value.

2 Early cases showed sinusoidal cell infiltration, but did not affect the liver cells around the sinus is the important difference between acute hepatitis B.

3 Hepatocyte necrosis is lighter, the range is limited, and it appears later.

4 sinus and hepatocyte interstitial fibrosis is more obvious than hepatitis B, and appears earlier, which may be one of the reasons for the development of cirrhosis.

5 Hepatocyte steatosis is more common, fat vacuoles can be macrobubble or vesicular. 6 Hepatocyte eosinophilic changes are flaky and appear in the non-inflammatory response zone.

symptom:

[clinical manifestations]

1. Latent period The incubation period of this disease is 2 to 26 weeks, with an average of 7.4 weeks. Hepatitis C caused by blood products has a short incubation period of 7 to 33 days, with an average of 19 days.

2. Clinical clinical manifestations are generally lighter than hepatitis B, mostly subclinical without jaundice, common single ALT is elevated, long-term persistence does not drop or repeated fluctuations, the average ALT and serum bilirubin are lower, jaundice persists The time is short. However, there are also serious illnesses, and the clinical difficulty is different from hepatitis B.

Hepatitis C virus infection is more chronic than hepatitis B virus infection. It has been observed that about 40% to 50% develop into chronic hepatitis, 25% develop into cirrhosis, and the rest is self-limiting. Most patients with acute hepatitis C develop chronically without jaundice. The long-term fluctuation of ALT does not decrease, and serum anti-HCV continues to be high titer positive. Therefore, clinical attention should be paid to the observation of changes in ALT and anti-HCV.

Although the clinical manifestations of hepatitis C are mild, the incidence of severe hepatitis can also be seen. Five hepatitis viruses, HAV, HBV, HCV, HDV and HEV, can cause severe hepatitis, but the background and frequency of occurrence are different. Statistics from Europe and the United States indicate that the causes of acute and subacute severe hepatitis are: HBV is the most common, and Japan is mostly HCV. It is speculated that the reason may be that the HCV infection rate in Japanese population is much higher than that in Europe and America, and the HCV genotype in Europe and America is different from that in Japan. There is no detailed information in China. Most of the reports are mostly HBV. HCV-induced severe hepatitis is mostly caused by chronic hepatitis B and HCV infection.

3. Pattern of viremia A follow-up study of patients with hepatitis C after transfusion showed that HCVemia has the following patterns:

(1) Acute self-limiting hepatitis with transient viremia.

(2) Acute self-limiting hepatitis with persistent viremia.

(3) persistent viremia but no hepatitis, as a symptomatic carrier of HCV.

(4) Chronic hepatitis C with intermittent viremia.

(5) Chronic hepatitis C with persistent viremia.

4. Overlap infection of HBV and HCV Because HCV has a similar transmission route to HBV, the possibility of infecting both viruses is present, but it is more common to infect HCV on the basis of persistent HBV infection. The 302 Hospital of the People's Liberation Army found that the anti-HCV positive rate in the serum of patients with HBsAg-positive chronic liver disease was 0 (0/14) in mild chronic hepatitis (slow-moving liver); 24.24% (8/33) in chronic active hepatitis; chronic heavy Hepatitis was 33.33% (3/9). It shows that the positive rate increases with the progress and evolution of hepatitis B, and the reason may be thatChronic hepatitis BIn the course of progress, the chances of receiving iatrogenic infections such as blood transfusions have increased. On the other hand, there are reports that there is a significant difference between the severe hepatitis with HBV/HCV overlap infection and the severe hepatitis with HBV infection alone, and the bilirubin, AST/ALT and mortality rates of the two groups. It indicated that hepatocyte necrosis in the overlapping infection group was much more serious than that in severe hepatitis with HBV infection alone.

It has been observed that HBV DNA and HCV RNA in HBV and HCV overlap cases are only 19% positive, and most of them are HCV RNA or HBV DNA single positive. In addition, almost all HCV RNA positive patients are e antigen negative cases, suggesting that the virus overlaps. The infection is proliferating and interfering.

5. HCV infection and hepatocellular carcinoma (HCC) The relationship between HCV infection and HCC has received increasing attention. From HCV infection to HCC on average for about 25 years, it can also be directly developed from chronic hepatitis without cirrhosis. The anti-HCV detection rate of HCC in different countries is different, and the initial report in China is 10.96%-59%. Due to the wide heterogeneity of HCV, the occurrence of HCC has a certain relationship with HCV infection of different genotypes. The prevalence of HCV in Japan and the United States is basically similar, but there are more HCCs associated with HCV in Japan and less in the United States. The results of the study indicate that type II HCV has the characteristics of high level of replication and poor response to interferon therapy, which may play an important role in the progressive development of liver disease and carcinogenesis, and also provide a molecular epidemic for the study of HCV-induced HCC mechanisms. Basis for learning.

The mechanism of HCV carcinogenesis is different from that of HBV. Studies have shown that HCV does not integrate into HBV DNA like HBV. It has been reported that the dual infection of HBV and HCV seems to increase the incidence of hepatocellular carcinoma, so attention should be paid to the role of HCV and HBV in carcinogenesis.

6. HCV infection and autoimmune hepatitis (AIH) Generally, autoimmune hepatitis is classified into four types according to autoantibodies, and type II AIH refers to anti-nuclear antibody-negative and anti-LKM-I-positive. Recently, the study classified type II AIH into two subtypes: type IIa AIH: young people are more common, female-dominated, have familial autoimmune diseases, immunosuppressive therapy is effective, and has nothing to do with HCV infection. Type IIb AIH: mostly elderly, male, no familial autoimmune disease, antiviral therapy is superior to immunosuppressive agents, associated with HCV infection, anti-HCV positive, anti-GOR positive, such patients should check HCV if necessary RNA.

diagnosis:

1. The history of close contact with epidemiology (acute hepatitis patients and contaminated items) and the history of blood transfusion or blood product injection have certain reference value for diagnosis.

2. Laboratory testing

(1) Detection of serum anti-HCV by enzyme-linked immunosorbent assay (ELISA): Various anti-HCV assays have been established using various HCV recombinant proteins in vitro, and the first generation ELISA is 5-1-1 and C-100. Antigen, the second-generation ELISA increased the C22 and C33 proteins, and its sensitivity was 10% to 30% higher than that of the first generation. Generally, anti-C22 was the earliest and most common. C22 has good immunogenicity. The detection of hepatitis C after acute blood transfusion indicates that the anti-HCV is negative in the latent and acute phase, and anti-HCV is positive in the period of 2 to 52 weeks after the elevation of ALT. A third generation ELISA has been established to detect anti-HCV, which increases NS5 protein and is more sensitive than the second generation ELISA.

Due to the late appearance of IgG antibodies, even 1 year after HCV infection, it is not possible to estimate the state of viral replication. Therefore, Quiroga is equivalent to the detection of IgM anti-HCV in 1991, and has been reported since then. It is currently believed that the detection rate of IgM anti-HCV in acute hepatitis is slightly higher than that of IgG antibody (IgM anti-HCV is 64%, IgG anti-HCV is 57%). In self-limiting cases, IgM anti-HCV disappeared, but still positive in chronic cases, suggesting that IgM anti-HCV can be used as a chronic indicator, which has certain value for guiding antiviral therapy.

(2) Recombinant immunoblotting (RIBA) detection of HCV antibodies: The first generation of ELISA was established shortly. To exclude ELISA for anti-C100 false positives, Chiron provided an immunoblot test for confirmatory testing, also known as the first generation RIBA. The specificity of RIBA is higher than that of ELISA, but the sensitivity is significantly reduced. The second and third generation RIBAs have been established, and their positive rates are significantly higher than those of the first generation RIBA.

(3) Detection of HCV antigen: Krawczynski et al. extracted IgG fraction from HCV-infected chimpanzee or patient serum, labeled with fluorescein isothiocyanate as a probe, and detected HCV antigen in liver tissue by direct immunofluorescence. The authors tested four acute and three chronic hepatitis C chimpanzee liver tissues with positive HCV antigens. Blocking tests and adsorption tests have demonstrated that HCV antigens in hepatocytes are associated with viral hepatitis caused by HCV. This antigen is a specific morphological marker of HCV infection and can be used as one of the laboratory diagnostic methods for HCV infection. In addition, immunohistochemical ABC method can be used to detect HCV antigen in liver tissue.

(4) Detection of HCV RNA: HCV infection, serum virus content is extremely low, it is difficult to detect HCV RNA by conventional molecular hybridization technology, PCR technology is currently the most sensitive detection technology in the field of molecular biology, has been used Detection of HCV RNA. This method is the most reliable indicator for determining whether or not HCV infection is contagious. It has good specificity and high sensitivity, which is conducive to the early diagnosis and evaluation of HCV infection. However, attention should also be paid to the possibility of false positives due to high sensitivity, complicated operation, and contamination.

3. Liver biopsy light microscopy and electron microscopy have certain reference value.

The disease should be associated with elevated levels of serum transaminases or serum bilirubin caused by toxic hepatitis, cholecystitis, infectious mononucleosis, leptospirosis, epidemic hemorrhagic fever, fatty liver, and amoebic liver disease. Identification. Cholestatic hepatitis should be differentiated from extrahepatic obstructive jaundice (such as pancreatic head cancer, cholelithiasis, etc.).

complication:

Common complications include arthritis (12% to 27%), glomerulonephritis (26.5%), and nodular polyarteritis. Direct immunofluorescence and electron microscopy were used to find HBV particles on the joint synovium. In patients with membranous glomerulonephritis with persistent HBsAg, HBcAg deposition was found in renal biopsy glomerular tissue. In this hospital, 180 patients with glomerulonephritis were examined by renal puncture, and 33 patients (18.3%) with HBcAg deposition in the kidney were found. Immune complex deposition of HBcAg, IgG, IgM, C3, etc. can be seen on the vessel wall of patients with nodular polyarteritis. Rare complications include diabetes, fatty liver,Aplastic anemia, polyneuritis, pleurisy, myocarditis and pericarditis, among which diabetes and fatty liver are worthy of attention. A small number of patients can have hyperbilirubinemia after hepatitis.

treatment:

(a) treatment

1. Interferon (IFN) treatment of IFN in the treatment of chronic hepatitis C after transfusion is 25%, can prevent 30% of acute hepatitis C to chronic development, so far, IFN is still recognized as a treatment of type C Hepatitis virus drugs.

Omata reported that ALT returned to normal after one year of transfusion of hepatitis C, 64% in the IFN-treated group, 7% in the control group, and 90% in the HCV RNA-negative group after transfusion, 90% in the IFN-treated group and 0% in the control group. It is generally believed that the shorter the HCV infection time, the lighter the liver histological lesions, and the lower the viral level in the blood, the better the curative effect. Therefore, for acute hepatitis C, blood ALT does not decline, should consider IFN antiviral treatment. Patients with chronic hepatitis C, with the following indicators, can also be treated with IFN: 1 serum ALT persists abnormally; 2 liver histology has chronic hepatitis characteristics; 3 has a history of injecting drugs or engaged in medical workers; Caused by liver disease, especially autoimmune liver disease; 5HCV serum index is positive.

The IFN dose is currently generally 3 to 5 mV, 3 times a week for 6 months. It has been reported that during the interferon treatment, more than 50% of patients with chronic hepatitis C have improved biochemical and histological indicators, but some patients relapse within 6 to 12 months. However, if the patient continues to be normal at 12 months after treatment and serum HCV RNA is negative, it may be cured. Extending the treatment can increase the response rate.

Factors affecting the efficacy of IFN, in addition to age and duration of disease, are mainly related to the following factors: 1 genotype: gene type II IFN treatment is poor, type III treatment is good; 2 serum HCV RNA content: generally considered, patient initial HCV RNA drop Degree is highly correlated with IFN efficacy. The initial titer of HCV RNA is low, and IFN treatment is effective; 3 virus variation: The theory of IFN sensitivity and tolerance to HCV has been proposed. Enomoto et al analyzed the full-length HCV gene sequence and amino acid sequence of each HCV-1b-infected patient, and found that the patient's response to IFN treatment was related to the change of HCV-1b quasispecies. One of the patients had two HCV quasispecies before IFN treatment, one disappeared from the patient shortly after IFN treatment, and the other quasispecies were throughout. There was no change during IFN treatment. When the difference between the two quasispecies sequences was compared, it was found that a mutation occurred mainly between the codon sequences of the hydroxyl terminus of the HCVNS5A protein (2209-2248). This region is referred to as the "IFN Sensitivity Determination Region (ISDR)", and it is considered that all of the quasispecies with the prototype HCV-1b are resistant to IFN-, while the HCV-1b quasispecies with the ISDR mutant are sensitive to IFN. The latter IFN efficacy was significantly higher than the former. 2. Ribavirin (Virazole, Ribavirin) Most scholars at home and abroad believe that ribavirin in the treatment of chronic hepatitis C, showing a certain effect in improving liver function and anti-virus, but this effect stops It can not be maintained after the drug, and can be used together with IFN or an immunomodulator to improve the therapeutic effect.

3. Liver transplantation Chronic hepatitis C can be treated with liver transplantation. However, HCV infection often occurs in newly transplanted liver, which is caused by the introduction of extrahepatic HCV, and acute severe hepatitis can also occur.

(two) prognosis

Hepatitis C virus infection is more chronic than hepatitis B virus infection, and about half of cases of acute hepatitis C have evolved into chronic hepatitis C. Follow-up observation of acute hepatitis C for 5 years, liver pathological examination confirmed that 60% developed cirrhosis. Japanese and Western data indicate that 70% of post-hepatitis cirrhosis is caused by HCV infection. The prevalence of hepatitis B in China is very serious, so hepatitis cirrhosis caused by HBV infection is still present. On the basis of cirrhosis, it can be converted into hepatocellular carcinoma. The incidence of cirrhosis after HCV infection is higher than that after cirrhosis after HBV infection. It usually takes about 20 to 25 years from hepatitis C to hepatocellular carcinoma.

prevention:

1. Anti-HCV screening of blood donors is an important measure to reduce hepatitis C after transfusion.

2. Manage the source of infection

According to the type of hepatitis patients, use disposable medical supplies; publicize the knowledge of prevention and treatment of hepatitis C, and abide by the disinfection and isolation system.

3. Cut off the route of transmission

The medical device is disinfected by one use, and the disposable medical supplies are used; the indications of blood transfusion, plasma and blood products are strictly controlled; the quality of blood and blood products is guaranteed.

4. Protect susceptible populations

It has been reported that immunoglobulin is effective in preventing hepatitis C, and its usage is 0.06 ml/kg, which is intramuscularly injected. The ultimate control of this disease depends on vaccine prevention, and the successful cloning of HCV molecules provides conditions for vaccine prevention for this disease.