2013年版欧洲肝脏研究学会(EASL)丙型肝炎病毒感染管理临床实践指南解读

目的:两种蛋白酶抑制剂治疗基因1型丙型肝炎病毒(HCV)感染患者的Ⅲ期临床试验已经完成,并且在欧美等地区批准上市。欧洲肝脏研究学会(EASL)于2013年对HCV感染管理指南进行了修订更新。本文旨在对2013年版EASL丙型肝炎病毒感染管理临床实践指南进行部分解读。方法:从HCV治疗目标及终点、治疗适应证、不同基因分型HCV患者的治疗策略角度进行解读。结果与结论:聚乙二醇干扰素/利巴韦林(PegIFN/RBV)联合特拉泼维(TVR)或波赛泼维(BOC)是所批准的对基因1型HCV患者的标准治疗,PegIFN/RBV二联疗法仍然是非基因1型HCV患者的标准治疗。     

国内外慢性乙型肝炎管理指南推荐建议的比较

对美国肝病学会《慢性乙型肝炎的预防,诊断和治疗更新:AASLD 2018乙型肝炎指南》、欧洲肝病学会《EASL 2017乙型肝炎病毒感染管理临床实践指南》、亚太肝病学会《亚太地区乙型肝炎管理临床实践指南:2015年更新版》、世界卫生组织《慢性乙型肝炎感染者的预防,护理和治疗指南》以及中华医学会感染病学分会和肝病学分会联...     

慢性丙型肝炎的抗病毒治疗

慢性丙型肝炎病毒(hepatitis C virus,HCV)感染可以导致肝组织慢性炎症坏死及纤维化,部分病人可发展为肝硬化甚至原发性肝癌,不仅对患者的健康和生命危害极大,而且已成为严重的社会和公共卫生问题。最近,亚太地区肝病学会、美国国立卫生研究院、欧洲肝病学会等权威学术机构发表了有关丙型肝炎的诊疗指南或专家共识。中华医学会肝病分会和传染病分会也组织国内有关专家制定了我国的慢性丙型肝炎防治指南。以下根据国内外的最新资料及循证医学的原则,对慢性丙型肝炎的抗病毒治疗做一简介。     

治疗慢性乙型肝炎创新性药物的临床试验设计及关注要点

由乙型肝炎病毒（HBV）感染造成的疾病负担是全球、尤其是我国面临的一大难题，慢性乙型肝炎治疗药物的研发领域近年正处于快速发展阶段。本文参考了美国肝病协会（AASLD）、欧洲肝病协会（EASL）、亚太地区肝病协会（APASL）最新有关对慢性乙型肝炎治疗的共识、欧盟抗乙型肝炎病毒治疗药物临床评价指南和我国的慢性乙型肝炎防治指南，针对我国慢性乙型肝炎创新性药物临床试验设计中关注的问题和临床研究如何评价提出建议和交流。     

慢性乙、丙型肝炎治疗新策略

美国肝病学会(AASLD)近期对慢性乙、丙型肝炎治疗实践指南进行了修订，并在AASLD网站上(www．aasld．org)，公布了其完整版本和文献综述。这不仅此原方案先进，也更新了我们的观念。比如，慢性HBV感染者需终生监测，以及时发现抗病毒治疗时机和并发症。代偿性肝病初治，除有禁忌证或无应答者外，干扰素α、拉米夫定和阿德福韦疗效相似，均可应用。HBeAg(-)者宁可道选干扰素α或阿德福韦。ALT在正常值2倍以下者暂不考虑治疗。丙型肝是治疗对象是HCV RNA( )．肝活检有纤堆化，不论ALT高低都应治疗，其通用方案是聚乙二醇化干扰素α(peg-IFNα)和利巴韦林(RIB)联用，RIB的剂量应根据基因型和体重而定．基因Ⅰ型、体重小于75kg者为1．0，体重大于75kg者为1．2：基因Ⅱ、Ⅲ型的慢丙肝不论体重大小均为0．8，等等；本文结合近期资料对此作一综述。     

替诺福韦艾拉酚胺治疗慢性乙型肝炎的临床应用及研究进展

替诺福韦艾拉酚胺(Tenofovir alafenamide,TAF)是一种治疗慢性乙型肝炎的新型核苷酸类逆转录酶抑制剂,与替诺福韦酯相比,给药剂量更低,安全性更好,且治疗效果无明显差异。2017年欧洲肝病学会(EASL)更新的《2017年欧洲肝病学会临床实践指南:HBV感染的管理》也将其列为治疗慢性乙型肝炎的首选药物之一。     

丙型肝炎抗病毒新药研究进展

全球约1／3人群感染丙型肝炎病毒（HCV）。HCV感染是慢性肝炎、肝硬化和肝衰竭的主要病因之一,慢性丙型肝炎的有效治疗方法在全球均是紧迫的医疗难题之一。相当多的慢性丙型肝炎患者,特别是基因1、4型HCV感染者、原发无应答者、     

解读美国肝病研究协会2007年版慢性乙肝防治指南

此指南[LDk A S F,Mcmahon B J.Hepatology,2007,45(2):507-539]用于协助内科医师和其他卫生保健提供者识别、诊断和治疗慢性乙型肝炎病毒(HBV)感染患者.指南中推荐的乙型肝炎治疗方案分别获得了下列数据的支持:(1)对2006-02以前在Medline收集的刊物上发表的文献和2003-2005年间的会议摘要进行正规审查和分析后获得的结果; (2)美国医师协会卫生实践评估手册(Manual for Assessing Health Practices and Designing Practice Guidelines);(3)指导方针:包括美国肝病研究协会(AASLD)关于建立和使用防治指南及美国胃肠病学会(AGA)对指南的政策说明;(4)该指南的著者在乙型肝炎防治方面的经验.此外,该指南还包括了美国国立卫生研究院于2000年和2006年召开的有关乙型肝炎应对会议、欧洲肝脏研究学会(EASL)于2002年召开的乙型肝炎国际协商会议和亚太地区有关应对慢性乙型肝炎的共识(2005新版).该指南中列出了针对乙型肝炎的诊断、治疗和预防的优选方案,并指出这些方案并非是一层不变的.其中某些特定的推荐方案是以已发表的相关信息为基础的.该指南将会随着新信息的不断发表而被定期更新.     

浅析丙型肝炎病毒基因型与抗病毒治疗的关系

丙型肝炎是由丙型肝炎病毒(HCV)感染所引起的经血液传播的肝脏急慢性炎症性疾病,病毒性肝炎的治疗中最关键的环节是抗病毒治疗,影响治疗效果的因素有病毒和宿主,而病毒因素中又以病毒载量和病毒基因型为主,故HCV的基因型与丙肝病情的进展和治疗疗效有一定相关性。本文针对慢性丙型肝炎的流行现状、HCV病毒的基因分型、抗HCV药物的研究进展、HCV基因型与抗病毒治疗的关系作一简要的综述。     

基因1型HCV感染慢性丙型肝炎的抗病毒治疗(美国肝病研究学会2011年指南简介)

慢性丙型肝炎病毒(hepatitis C virus,HCV)感染的标准治疗方案(standard of care,SOC)是聚乙二醇干扰素(peginterferon,PegIFN)联合利巴韦林(ribavirin,RBV)治疗,对基因1、4、5型HCV感染者疗程为48周,2、3型感染者疗程为24周,在基因1型HCV感染者,其持续病毒学应答率为40％～50％,而在基因2型或3型HCV感染者,其持续病毒学应答率可达到80％或以上.持续病毒应答(sustainad virologic response,SVR)与病毒清除密切相关,被称为病毒学"治愈",对发病率和病死率亦有所改善.自上一版指南更新发布后,主要取得了两大进展,这也改变了对基因1型HCV感染者的优化治疗方案:一个是直接抗病毒药物的研究进展,另一个就是自发或经治疗清除病毒相关的一些寡核苷酸的多态性得以证实.     

Hepatitis B in clinical practice

Approximately 500000 individuals in Germany are chronically infected with hepatitis B of which most have been still not diagnosed or adequately treated. Patients with chronic hepatitis B are at risk to develop advanced liver fibrosis and cirrhosis and subsequently hepatocellular carcinoma. National and international guidelines should be valued as a practical help in the management of these patients. By the end of 2007 a national German hepatitis B guideline has been published, followed by a Clinical Practice Guideline of the European Association for the Study of the Liver (EASL) in 2009. An update of the National German guideline was published in the mid of 2011. The recommendations of these guidelines are delineated. Most importantly the management of hepatitis B remains complicated and needs very experienced hepatologists.     

Digestive disease week 2001. American association for the study of liver diseases. 19-23 May 2001, Atlanta, GA, USA

All aspects of hepatology were represented at this year's meeting of the American Association for the Study of Liver Diseases (AASLD), although the meeting was dominated by a proliferation of information in the arena of viral hepatitis. In an international multicenter study of over 1000 treatment-naive patients with hepatitis C virus (HCV) infection, sustained virological response was found in 56% of patients who received PEGylated interferon (IFN) alpha-2a (Pegasys; F Hoffmann-La Roche) in combination with ribavirin (Virazole; ICN Pharmaceuticals), versus 45% in patients who received IFN alpha-2b and ribavirin therapy, and 30% of patients who received PEG. This is a significant improvement on currently licensed therapy and will define practice patterns for the next decade. In other areas, novel therapies such as silymarin for cholestatic liver disease, L-dT (Novirio Pharmaceuticals Inc), herbal therapy, combination therapies including amantadine and mycophenolate mofetil (Roche Holding) for viral hepatitis, and long-acting octreotide (Sandostatin LAR Depot; Novartis) for portal hypertension, were presented. This review represents the best of AASLD at DDW 2001.     

Perspectives in therapy for hepatitis C

Background: Chronic hepatitis C virus (HCV) infection is a worldwide health problem. Response rates to current standard of treatment (pegylated IFNs and ribavirin) are low in patients with the prevailing genotype 1. Objective: To review papers published or presented at recent international meetings showing the results of trials of new anti-HCV drugs. Methods: Literature search using the terms ‘antivirals’, ‘interferon’, ‘pegylated interferon’, ‘ribavirin’, ‘polymerase inhibitors’, ‘protease inhibitors’, ‘cyclophilin inhibitors’ and ‘hepatitis C virus’. Search of abstracts containing the same terms in the title and presented at the American Association for the Study of Liver Diseases 2007 and at the European Association for the Study of the Liver 2008 meetings. Results/conclusion: Preliminary results of Phase II studies of new compounds look promising, although side effects are higher than with current standard of treatment.     

核苷类抗乙肝病毒药物研究近况

主要根据 2 0 0 1年 11月 9～ 13日在美国德州达拉斯市召开的第 5 2届美国肝病学年会的内容对新一代核苷类抗乙肝病毒的药物作一介绍。在这次会议上报告了 7种新的核苷类抗乙肝药 ,已分别进入Ⅰ期 ,Ⅱ期和Ⅲ期临床试验阶段 ,其中阿德福韦、恩替卡韦和依曲西他平已在作Ⅲ期临床。但是阿得福韦的肾毒性 ,恩替卡韦的长期安全性和依曲西他平与拉米夫定的交叉耐药性在正式批准临床应用阶段需作进一步的观察。本文还阐述了核苷类药物结构与抗病毒活性的关系 ,介绍了药物对病毒复制动力学影响在研究药物作用中的意义     

Digestive Disease Week. 16-19 May 1999, Orlando, FL, USA

This year's Digestive Disease Week (DDW) was an extensive conclave which encompassed the annual meetings of four different professional societies: the American Association for the Study of Liver Disease (AASLD); the American Gastroenterological Association (AGA); The American Society for Gastrointestinal Endoscopy (ASGE); and, the Society for Surgery of the Alimentary Tract (SSAT). The meeting offered over 5000 paper presentations and poster sessions; it also comprised postgraduate courses, exhibits, and special educational forums. More than 12,000 physicians, allied health professionals, pharmaceutical industry representatives and research scientists were in attendance, over half of whom came from outside the US. Topics covered ranged from basic physiological research on all aspects of the gastrointestinal tract, liver and pancreas, to pathology of the systems and the effects of therapeutic agents at all stages of development, to disease diagnosis and surgery. The size and scope of the meeting made for an extremely interesting and absorbing four days and provided delegates with wide-ranging opportunities for discussion on the very latest in gastrointestinal thinking.     

Systematic review: evidence-based management of hepatocellular carcinoma--an updated analysis of randomized controlled trials

The treatment strategy of hepatocellular carcinoma applied following scientific guidelines is only supported by 77 randomized controlled trials published so far, a figure that clearly pinpoints hepatocellular carcinoma as an 'orphan' cancer in terms of clinical research when compared with other high-prevalent cancers worldwide. A systematic review analysing 61 randomized controlled trials (1978-2002) showed a modest survival benefit from chemoembolization in patients with intermediate tumours, and the lack of an effective first-line treatment option for patients with advanced disease. These conclusions have been endorsed by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. The present updated evidence-based approach includes 16 randomized controlled trials published from 2002 to 2005 assessing percutaneous ablation (seven), other loco-regional therapies (three) and systemic therapies (six). Eight showed high-quality methodological profiles. Four randomized controlled trials demonstrated a better local hepatocellular carcinoma control in tumours larger than 2 cm treated by radiofrequency ablation compared with ethanol injection. No survival advantages were obtained from systemic treatments in patients with advanced hepatocellular carcinoma, an area that is an unmet need. Therefore, there is an urgent request to conduct well-designed phase III investigations in hepatocellular carcinoma patients.     

Current therapies for chronic hepatitis C

Hepatitis C virus affects more than 180 million people worldwide and as many as 4 million people in the United States. Given that most patients are asymptomatic until late in the disease progression, diagnostic screening and evaluation should be performed in patients who display high-risk behaviors associated with acquisition of hepatitis C. Chronic hepatitis C is associated with cirrhosis, hepatic failure, and death; therefore, treatment is aimed at reducing these complications, as well as improving quality of life and minimizing adverse effects. The American Association for the Study of Liver Diseases Practice Guidelines on the Diagnosis, Management, and Treatment of Hepatitis C represent the gold standard for guidance on the management of hepatitis C. Standard treatment for hepatitis C is peginterferon alpha in combination with ribavirin. Currently, two pegylated interferon products are approved by the U.S. Food and Drug Administration for the treatment of hepatitis C. The duration of therapy with peginterferon and ribavirin is dictated by viral genotype and virologic response. Additional therapies are under investigation for treatment of chronic hepatitis C and show early promise of comparative efficacy and fewer adverse effects. Special considerations in certain populations, including patients coinfected with human immunodeficiency virus, those with end-stage renal disease, injection drug users, pregnant women, and pediatric patients, should guide treatment decisions.     

《中药、天然药物治疗冠心病心绞痛临床研究指导原则》解读

<中药、天然药物治疗冠心病心绞痛临床研究指导原则>于2011年7月20日由国家食品药品监督管理局颁布.该适应证的临床研究技术要求得到了质的提高,试验设计更加科学、规范.本文从社会发展、研究与技术审评的需要等方面论述该指导原则的重要性.与2002年的指导原则作了针对性的比较,解读该指导原则的关键技术问题和基本框架,以期研究者能正确理解并执行.