慢性乙型肝炎患者拉米夫定耐药的药物选择

近年来慢性乙型肝炎的抗病毒治疗进展迅速，尤其是核苷（酸）类似物的研究开发和临床应用使治疗慢性乙型肝炎进入一个新时代。随着接受核苷（酸）类似物治疗患者的增多和治疗时间延长，临床耐药及其处理日益成为突出的问题。现就临床最常见的拉米夫定耐药患者使用核苷（酸）类似物治疗中如何进行药物选择．谈谈个人看法。     

慢性乙型肝炎抗病毒治疗的新规范

随着新的抗乙型肝炎病毒药物陆续上市．抗乙型肝炎病毒治疗经验也不断丰富。有关慢性乙型肝炎的抗病毒治疗的策略亟待更新和完善。为此．美国肝病学会（AASLD）对2004年版《慢性乙型肝炎的临床实践指南》（以下简称《指南》2004）再次进行了更新。使其更具灵活性和实用性。现通过对指南2007与指南2004进行比较．     

苦参素联合干扰素治疗慢性乙型肝炎36例疗效观察

目的观察苦参素联合干扰素治疗慢性乙型肝炎的临床效果。方法用苦参素联合干：扰素治疗慢性乙型肝炎36例，与单用苦参素和单用于扰素治疗慢性乙型肝炎比较。结果联合治疗组肝：叻复常率达94.4％，单用苦参素组达80．6％，单用干扰素组达83．3％，联合治疗组优于单用对照组（P〈0．01）：联合治疗组HBeAg阴转率达58．3％，HBV—DNA阴转率达61％；单用苦参素组HBeAg阴转率达38．9％，HBV—DNA阴转率达41．7％；单用干扰素组HBeAg阴转率达41．7％．HBV—DNA阴转率达44％．联合治疗组优于单用对照组（P〈0．01）。应用干扰素者有不同程度的发热，头痛．肌肉关节痛．白细胞及血小板减少。结论苦参素联合干扰素治疗慢性乙型肝炎疗效比单用好．达到药物协同和增强作用。     

抗病毒药物治疗慢性乙型肝炎的临床疗效及对预后进展

对抗病毒药物治疗慢性乙型肝炎的临床疗效及对预后进展进行分析和研讨。通过对2009年10月至2011年10月我院收治的慢性乙型肝炎患者205例患者的治疗资料回顾,对抗病毒药物治疗的疗效进行分析和研讨。所有患者均获得较好的临床治疗,采用抗病毒药物进行治疗慢性乙型肝炎的应用相对较为广泛,但针对不同的患者应进行不同种类抗病毒药物的治疗,伴随药学水平的发展,慢性乙型肝炎的抗病毒临床治疗,获得了较好的发展。     

护肝宁片治疗慢性乙型肝炎疗效观察

目的：观察护肝宁片治疗慢性乙型肝炎的临床疗效。方法：将148例慢性乙型肝炎患者，随机分为两组：治疗组100例，给予护肝宁片治疗；对照组48例，给予护肝片治疗。治疗前后分别观察临床症状，检测肝功能、肝炎病毒标志物。结果：肝功能、临床症状改善两组之间总有效率差异无显著性（P〉0．05），但转氨酶等部分血清生化指标有显著性差异（P〈0．05）。结论：护肝宁片用于治疗慢性乙型肝炎，疗效确切，安全可靠。     

阿德福韦酯的研究进展

［摘要］阿德福韦酯在我国用于治疗慢性乙型肝炎已＞5 a。阿德福韦酯对乙型肝炎病毒（HBV） DNA复制有明显的抑制作用，特别对乙型肝炎病毒e抗原（HbeAg）阳性、阴性的拉米夫定耐药株（LAM R）的慢性乙型肝炎患者有显著疗效，且耐药突变率较低，适合于已发生拉米夫定耐药者。该药物常规剂量下安全性好，不良反应小，高剂量（＞30 mg•d 1）易出现肾功能损害。其肾毒性主要与有机阴离子转运体介导的细胞内药物累积和多药耐药相关蛋白2的药物转运有关。     

乙型肝炎病毒对拉米夫定的耐药性及其临床评价意义

1998年美国FDA批准拉米夫定用于治疗慢性乙型肝炎,是世界上第一个获准用于此适应证的抗病毒药物,至今已在50多个国家使用。本文详细论述了拉米夫定产生耐药性的机制及其对临床的意义。     

异甘草酸镁治疗慢性乙型肝炎60例疗效观察

慢性乙型肝炎是我国的常见病、多发病，慢性乙型肝炎反复活动易发展为肝硬化．甚至肝癌．抑制病毒复制、控制肝细胞炎症、预防肝纤维化是治疗的关键。甘草酸制剂是目前临床上使用比较广泛的抗炎保肝药物，具有较强的抗病毒、保护肝细胞、抗炎、预防肝纤维化、免疫调节的作用。异甘草酸镁是新一代的甘草酸制剂．我们运用异甘草酸镁治疗慢性乙型肝炎60例．取得良好的治疗效果．现报道如下。[第一段]     

YMDD变异的慢性乙型肝炎的临床与病理研究

目的探讨YMDD变异的慢性乙型肝炎的临床特点及病理改变，提高治疗YMDD变异的慢性乙型肝炎的疗效。方法将2003年6月-2006年5月住院的60例发生YMDD变异的慢性乙型肝炎资料进行分析。结果发生YMDD变异的慢性乙型肝炎患者肝损害以轻、中度为主；病理改变G1占38．880h，（7／18），G2占22．22％（4／18），G3占27．77％（5／18），G4占11．11％（2／18）；变异后采用阿德福韦、干扰素、恩替卡韦继续抗病毒治疗愈后好：肝硬化患者变异时停药易导致病情加重、不可逆转。结论发生YMDD变异的慢性乙型肝炎病情大多可逆转．继续抗病毒治疗愈后良好     

慢性乙型肝炎临床治疗现状探究

目的对入住天津市大港油田总医院的80例慢性乙型肝炎患者的治疗资料进行回顾性总结分析,旨在探讨治疗慢性乙型肝炎的最佳疗法,为临床诊治该病提供依据。方法结合天津市大港油田总医院对80例慢性乙型肝炎患者的临床诊治,比较分析目前临床应用的治疗药物和方法。结果临床应用治疗慢性乙型肝炎患者的药物种类较多,但没有形成统一规范,通过常规药物治疗后患者各项生理指标可恢复正常,但是仍有病症无法缓解。结论对于慢性乙型肝炎的治疗,中西医结合疗法可取得良好的预期效果,从而显著改善病情,大幅度提高患者生活质量。     

丙型肝炎病毒NS5A抑制剂——达卡他韦

达卡他韦(Daklinza)是由美国百时美-施贵宝公司(BMS)研制的口服丙型肝炎病毒(HCV)NS5A抑制剂。继2014年欧盟批准其与联合其他抗病毒药用于基因型1-4慢性丙型肝炎成人患者的治疗后,2015年7月美国FDA批准其与索非布韦[sofosbuvir]联合用于慢性HCV基因型3感染的治疗。达卡他韦是第一个无需同时给予干扰素或利巴韦林即可有效治疗基因型3 HCV感染的药物,为该类患者提供了一个新选择,包括那些不能耐受利巴韦林患者。笔者就达卡他韦的基本信息、作用机制、药代动力学、药物相互作用、临床试验及应用等研发动态作一概述,以期能为医院临床用药及药物研究开发提供参考。     

非核苷类抗乙型肝炎病毒药物的研究进展

目前美国FDA批准的抗乙型肝炎病毒（HBV）药物分为两类：免疫调节剂和核苷类似物。但免疫调节剂的副作用和核苷类似物耐药性病毒株的出现使得慢性乙型肝炎的临床治疗仍然面临着巨大的挑战。因而，非核苷类抗HBV药物的研究引起广泛关注。本文按照不同的结构和作用机制对此类药物的研究进展做一综述。     

2008年FDA批准的新分子实体介绍

目的：总结2008年FDA批准的21种新分子实体的专利名、通用名、规格、申请者、适应证和有关临床试验的情况,以供参考。方法：通过FDA官方网站、Pubmed数据库等搜集相关资料,进行汇总分析。结果：2008年FDA批准的新分子实体数目创下了近4年以来的最高水平,尤其是血液系统用药和造影剂。结论：新药的批准给临床治疗提供更多的选择,尤其是治疗罕见病的药物得到批准,其本身也是医学的一个进步。     

直接抗病毒药物类抗丙型肝炎病毒药物的黑框警告及预防

丙型肝炎病毒（hepatitis C virus,HCV）是引起丙型肝炎的病原体,感染后极易慢性化并导致肝纤维化、肝硬化甚至肝癌。随着直接抗病毒药物（direct-acting antiviral agents,DAA）类抗HCV药物不断发展,临床上用其治疗后持续病毒学应答率逐渐提高,药品不良反应明显减少。但近年来,DAA类抗HCV药物在国外临床应用中出现了一些严重不良反应事件,因此美国食品药品管理局在这些药物的使用说明书中加入了黑框警告。国内今年已开始陆续上市了多个DAA类抗HCV药物,但尚未大规模应用。本文阐述了此类药物的黑框警告内容（包括引起严重皮肤反应、导致心动过缓、严重肝损伤和乙型肝炎病毒再激活）及其发生机制,并提出预防及解决措施,为我国临床合理用药提供参考。     

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。     

Anticancer drug discovery from the marine environment

Discovery, isolation, biochemical/pharmacological characterization, pre-clinical and clinical trials of drugs derived from the marine environment are continuously developing and increasing. One of the most promising area is cancer therapy. Currently, there are two drugs approved by the Food and Drug Administration (FDA) and European Agency for the Evaluation of Medicinal Products (EMA) in cancer treatment, namely Cytarabine (Cytosar-U1?) and Eribulin (E7389 or Halaven?). Trabectedin (ET-743 or Yondelis1?), approved by EMA, is completing key Phase III studies in the U.S. for final approval. It was estimated that 118 marine natural products (MNPs) are currently in preclinical trials, 22 MNPs in clinical trials and 3 MNPs on the market. The characteristics and selectivity profiles of new drugs for cancer therapy, as well as drugs disclosed in related patent applications, will be the focus of this review, providing a brief and ready to use reference.     

Advancements in the treatment of psoriasis: role of biologic agents

OBJECTIVE: To evaluate the role of biologic agents as antipsoriatic therapy. SUMMARY: Mild psoriasis can generally be managed with topical therapy. Moderate-to-severe psoriasis has traditionally been treated with systemic therapies such as cyclosporine, methotrexate, retinoids, and phototherapy (ultraviolet B, psoralen plus ultraviolet A). The treatments for moderate-to-severe psoriasis often do not meet patient and physician expectations because of significant side effects (e.g., organ toxicity, skin cancer), lack of durable efficacy, and inconvenient administration schedules (e.g., daily dosing, multiple weekly exposures). The recognition of psoriasis as a T-cell.mediated disease has led to the development of biologic agents that more specifically target key steps in the pathologic process. A review of the literature was conducted to identify randomized controlled trials that have been published on the efficacy, safety, and quality-of-life effects of both approved and investigational biologics for the treatment of psoriasis. The first 2 biologic agents for the treatment of moderate-to-severe chronic plaque psoriasis were approved by the U.S. Food and Drug Administration (FDA) in 2003, alefacept in January and efalizumab in October. Both agents have demonstrated favorable safety profiles in clinical trials and significant benefits on patient quality of life. Head-to-head trials are lacking, but in placebo controlled trials, similar percentages of patients appear to respond to each of these 2 drugs. An advantage of alefacept is that it has been shown in clinical trials to provide durable off-treatment efficacy (approximately 7 months). Efalizumab has a relatively quick onset of antipsoriatic effect, but it needs to be administered once weekly continuously to maintain symptom control. Etanercept (approved by the FDA for treating moderate-to-severe plaque psoriasis in May 2004) and infliximab (not FDA-approved for psoriasis treatment) have also shown promise in randomized controlled trials, although less data are available on these agents. Case reports and pilot studies suggest that other biologics under investigation may also prove useful for the treatment of psoriasis. Patient populations that may particularly benefit from biologic therapy are discussed. CONCLUSION: Biologic agents appear to offer a safe and effective alternative to conventional systemic therapies and phototherapy for the treatment of moderate-to-severe chronic plaque psoriasis. The biologics appear to be safer than traditional therapies, although long-term safety data still need to be established.     

2011年美国FDA批准新药简析

2011年美国食品药品监督管理局(FDA)共批准30个新药。简要介绍其中的重点品种,并就新药研发的现状与趋势进行分析。在2011年FDA批准上市的新药中,有11个为首创一类新药,其中50余年来首次上市的系统性红斑狼疮治疗药物贝利单抗、30余年来首次获准上市的霍奇金淋巴瘤靶向治疗药物本图希单抗-维度汀、慢性丙型肝炎治疗药物特拉普韦和波塞普韦、肿瘤免疫治疗药物依普利单抗、基于基因学检测的肿瘤个体化治疗药物克唑替尼和维拉芬尼等药物作用独特或市场前景广阔,颇受关注。     

Antiviral drugs in chronic hepatitis B: review and meta-analysis

Many researchers have attempted to identify the drugs capable of acting on the viral replication cycle and maintaining clinical remission in chronic hepatitis B. We evaluated the efficacy of antiviral drugs in chronic hepatitis B, by examination of 20 controlled and non-controlled trials conducted between 1985 and 1996. In chronic hepatitis B, adenine arabinoside and its monophosphate did not achieve satisfactory results, even though combination therapy with cortisone seemed to achieve very good results (remission rates ranging from 45% to 66% in patients treated). Lamivudine did not seem to furnish lasting effects in chronic hepatitis B, because many patients relapse after suspension of the treatment due to the appearance of HBV variants resistant to the drug. Contrasting results were observed with famciclovir. Treatment of chronic hepatitis B, with this drug seemed capable of reducing HBV-DNA serum levels by a mean of 50% compared to pretreatment values, with normal alanine aminotransferase levels in about 30% of treated patients. Ganciclovir treatment of chronic hepatitis B seemed to furnish good, but transient, results. Even if no antiviral drug represented a valid alternative to interferon, antivirals may become the drugs of choice in chronic hepatitis B, because they are aimed at the etiology of disease.     

Review article: Nucleoside analogues for the treatment of chronic hepatitis B

Current accepted treatment for chronic hepatitis B uses either the immunomodulator interferon alpha or nucleoside analogues lamivudine or adefovir. Interferon has side effects which mean it is often poorly tolerated. Long-term use of lamivudine is associated with increasing viral resistance for each year it is taken and the rebound viraemia that can occur when the drug is stopped is also of concern to many. Adefovir appears to have less of the resistance issues of lamivudine but is still a relatively new drug and at present its use is principally limited to patients with lamivudine-resistant disease. A number of other nucleoside analogues are currently being developed with some now at the stage of early clinical trials. A proportion share the significant resistance problems of lamivudine but many appear to have more potent anti-viral effect than the drugs currently available. If some of these newer anti-viral agents are approved for use in chronic hepatitis B, the potential for prolonged suppression of hepatitis B virus replication with resultant stabilization or improvement in liver disease may be achieved.