抗丙型肝炎病毒药物研究进展

丙型肝炎病毒(HCV)是导致慢性肝病和肝细胞癌的主要原因,越来越多的人感染HCV已成为严重的社会和公共卫生问题。由于HCV具有很强的变异性,目前尚无有效的疫苗。虽然新上市的telaprevir和boceprevir联合pegIFN(聚乙二醇-干扰素)和ribavirin治疗方法具有较强的抗HCV能力,可以有效的治疗部分HCV患者,但是仍具有较大的副作用和较差的药物耐受性,而二代直接抗病毒药物和宿主靶向药物的发现为治愈HCV患者提供了新的方向。     

丙型病毒性肝炎直接抗病毒挽救治疗药物——索磷维伏

索磷维伏是由3种不同靶点强效抗丙型肝炎病毒药物组成的复方片剂,其主要成分为索磷布韦、维帕他韦、伏西瑞韦。大量研究表明,该药不良反应少、疗效和耐受性良好,为直接抗病毒药物治疗失败的丙型病毒性肝炎患者提供了泛基因型、高治愈率的挽救治疗方案。本文就其药理作用及机制、药物代谢动力学、临床疗效评价、安全性评价等方面进行综述,旨在为其临床合理用药提供参考。     

抗丙型肝炎病毒药物研究的新进展

丙肝是一种全球流行性疾病,是导致慢性肝病和肝细胞癌的主要原因之一。近年来,国际上对丙肝的治疗方法发生了巨大变化,干扰素、利巴韦林联合蛋白酶抑制剂的三联治疗方案已成为国际上治疗丙肝的标准用药方案。不仅如此,一些基于新机制的抗丙肝药物也开始涌现出来,如:第二代直接抗病毒药物和靶向宿主的抗病毒药物。这些新药的出现为丙肝患者带来了新的希望,也为我国抗丙肝药物的开发提供了新思路。     

药师对直接抗病毒药物治疗患者的管理与实践

目的 介绍我院药师对直接抗病毒药物（DAA）治疗患者的管理流程和实践成果,为国内药师对丙肝患者开展药学服务提供参考。方法 我院建立医师将DAA治疗患者向药师转诊的流程,由药师协作完成对患者DAA治疗的药学监护。服务重点内容包括：识别并处理与DAA相关的药物相互作用和药物不良反应,开展用药依从性及丙肝再感染风险的教育、提醒和管理患者化验检查。结果2020年5月至2021年4月药师为189例转诊患者提供药学服务,服务过程中回答并解决患者用药问题443个,主要是药物不良反应（20.09%）以及药物相互作用（18.28%）。100%的患者对药师的服务感到非常满意。结论 药师对DAA治疗患者开展药学服务可行有效,药师能够解决患者的用药问题并取得较高的患者满意度,体现了药师的专业价值。     

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。     

抗丙型肝炎病毒药物的研究进展

丙型肝炎（hepatitis C,HC）是一种发病率高、病死率高的传染病,全球约1.8亿人感染丙型肝炎病毒（hepatitis Cvirus,HCV）,至今无法治愈.本文概述了近几年来抗HCV药物,包括干扰素及利巴韦林、特殊靶向治疗药物和免疫调节剂等的研究进展.     

抗丙型肝炎病毒药Celgosivir

目前,尽管抗病毒疗法取得很大进展,丙型肝炎病毒（HCV）感染仍为一个世界关注的主要健康问题.人们一直在致力于寻找具新的作用机制,如作用于病毒特异性酶的抗HCV新药,因为α-葡糖苷酶Ⅰ参与病毒表面糖蛋白的生物合成,而这种糖蛋白是病毒与宿主间相互作用所必需的,因此抑制α-葡糖苷酶Ⅰ被认为是一种极具吸引力的抗HCV战略手段.     

丙型肝炎直接抗病毒药物的治疗现状

丙型肝炎病毒感染是一种全球流行性疾病,是导致肝硬化、肝细胞癌等终末期肝病的重要原因。早期丙型肝炎采用的乙二醇-干扰素与利巴韦林联合治疗方案,效果差且不良反应多。2014年以来,新型直接抗病毒药物的上市使慢性丙型肝炎的治疗有了突破性进展,慢性丙型肝炎的治疗进入了高效、口服、短疗程的新时代。本文对丙型肝炎以及丙肝病毒的基本情况进行了介绍,并对当前抗丙肝病毒药物研究热点以及应用进行了总结。     

抗丙型肝炎病毒药——Boceprevir

波西普韦(Boceprevir)为新上市的抗丙型肝炎病毒药,是一种口服有效的丙型肝炎病毒NS3/4A蛋白酶抑制药, 适用于治疗基因1型的慢性丙型肝炎,临床需与聚乙二醇干扰素α和利巴韦林联用. 该文对波西普韦适应症、剂量与用法、用药注意事项、不良反应、非临床药理毒理学、临床药理毒理学、临床研究及知识产权状态与国内外研究进展等进行介绍.     

The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is correlated with cerebrovascular and cardiovascular disease (CVD). This study aimed to assess the effect of treatment with DAAs on vascular endothelial function in cirrhotic and non-cirrhotic HCV infected patients without any CVD risk factors. Fifty chronic HCV genotype 4 infected patients, without cardiovascular risks who have been listed to receive sofosbuvir/daclatasvir with ribavirin combination as triple therapy for 3 months were prospectively recruited. Endothelial dysfunction markers as soluble vascular cell adhesion molecule-1 (sVCAM-1) and Von willebrand factor (vWf) and inflammation marker (IL6) were estimated at baseline and 3 months post the end of therapy (SVR). All patients achieved SVR. VCAM1 level was significantly improved after HCV clearance with DAA in cirrhotic HCV patients (P = 0.002) compared to patients with mild liver fibrosis (P = 0.006). Levels of vWF also decreased significantly in cirrhosis and non-cirrhosis groups after SVR (P < 0.001 and P = 0.011, respectively). Systemic inflammatory marker (IL6) showed significant decrease in cirrhotic patients (P = 0.001). While, IL6 level did not change significantly in non-cirrhotic group (P = 0.061). Also at SVR, noninvasive liver fibrosis indices have been reduced significantly in the two groups (P < 0.001). HCV clearance by new DAA treatment improves the vascular endothelial dysfunction in Egyptian HCV infected patients with different levels of liver fibrosis and with no risk factors for endothelial dysfunction or CVD.     

Occurrence of hepatocellular carcinoma after direct-acting antiviral therapy for hepatitis C virus infection: literature review and risk analysis

Introduction: Concerns were raised about a high occurrence of hepatocellular carcinoma (HCC) after successful treatment of chronic hepatitis C (CHC) by direct-acting antivirals (DAAs).

Areas covered: The authors summarize the clinical studies reporting the occurrence rate and risk factors of HCC after DAAs in CHC.

Expert opinion: The recent introduction of all-oral DAAs has substantially changed the scenario of CHC, achieving a sustained virological response (SVR) in >90% of cases. Earlier concerns raised about an increasing incidence of HCC post-DAAs were flawed by large heterogeneity of patients, the limited number of well-designed prospective studies (only nine, up to date) and the inclusion of a large number of patients with advanced liver disease, previously excluded from interferon-based studies. Current data on DAAs have shown a lower risk of HCC development; however, they were unable to identify patients at greater risk for HCC occurrence after SVR. Surveillance strategy, likely lifelong, is mandatory in these patients according to general expert opinion.     

New antiviral agents for the treatment of hepatitis C: ABT-450

In pulmonary medicine, there are two major international meetings held annually: the annual meeting of the American Thoracic Society (ATS), and that of the European Respiratory Society (ERS). The 2006 ERS Annual Congress was held in Munich, Germany. Both meetings provide an annual forum for scientists and clinical investigators from academia, non-university institutions (including private practices) and pharmaceutical companies to share information on many aspects of pulmonary and critical-care medicine, sleep disorders, pulmonary infectious diseases, malignancies of the chest, and numerous aspects of diagnostic and interventional procedures in these fields. With > 5000 abstracts and ~ 17,000 participants, the 2006 ERS-congress outnumbered even the 2006 ATS meeting. Research areas covered all aspects of pulmonary diseases, although this year (as in previous years) obstructive pulmonary diseases such as COPD (chronic obstructive pulmonary disease) and asthma were clearly the main focus.     

Dasabuvir: a new direct antiviral agent for the treatment of hepatitis C

Introduction: Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) has revolutionized the care of infected patients. Among these novel compounds are non-nucleoside analogs, which bind viral RNA-dependent RNA polymerase resulting in a conformational change inhibiting RNA synthesis.

Areas covered: Efficacy and tolerability of treatment regimens containing the non-nucleoside analog polymerase inhibitor dasabuvir (ABT-333).

Expert opinion: Dasabuvir-containing regimens achieve high rates of sustained virologic response in HCV genotype 1a and 1b–infected patients when combined with other DAAs, namely paritaprevir (ABT-450), ritonavir and ombitasvir (ABT-267). In the populations studied, dasabuvir seems to be well tolerated and safe. The major limitations of this novel drug are its genotype-restricted activity, the necessity to include ribavirin for HCV genotype 1a and the emergence of resistance if not combined with other DDAs.     

Applications of computer-aided approaches in the development of hepatitis C antiviral agents

Introduction: Hepatitis C virus (HCV) is a global health problem that causes several chronic life-threatening liver diseases. The numbers of people affected by HCV are rising annually. Since 2011, the FDA has approved several anti-HCV drugs; while many other promising HCV drugs are currently in late clinical trials.

Areas covered: This review discusses the applications of different computational approaches in HCV drug design.

Expert opinion: Molecular docking and virtual screening approaches have emerged as a low-cost tool to screen large databases and identify potential small-molecule hits against HCV targets. Ligand-based approaches are useful for filtering-out compounds with rich physicochemical properties to inhibit HCV targets. Molecular dynamics (MD) remains a useful tool in optimizing the ligand-protein complexes and understand the ligand binding modes and drug resistance mechanisms in HCV. Despite their varied roles, the application of in-silico approaches in HCV drug design is still in its infancy. A more mature application should aim at modelling the whole HCV replicon in its active form and help to identify new effective druggable sites within the replicon system. With more technological advancements, the roles of computer-aided methods are only going to increase several folds in the development of next-generation HCV drugs.     

丙型肝炎抗病毒药物治疗的现状与研究进展

干扰素(IFN)是丙型肝炎抗病毒治疗中一种非常重要的药物,单药治疗以及与利巴韦林联合用药都表现出较好的抗病毒疗效。IFN与利巴韦林联合用药已成为丙型肝炎的标准治疗方案,对丙型肝炎病毒(HCV)基因型和应答指标的研究有助于个体化给药。本文对聚乙二醇IFN、人血清清蛋白融合IFN以及特异性靶向HCV治疗药物的研究进展做一综述。     

Paritaprevir/ritonavir/ombitasvir and dasabuvir for the treatment of chronic hepatitis C virus infection

Introduction: The use of direct-acting antiviral (DAA) agents against chronic hepatitis C virus (HCV) infections can result in the successful treatment of nearly all patients. Effective antiviral treatments can prevent the progression to cirrhosis and hepatocellular malignancy, and decrease liver-related morbidity and mortality.

Areas covered: Paritaprevir–ritonavir–ombitasvir and dasabuvir (PrOD), with or without ribavirin, is an all-oral regimen approved for the treatment of HCV genotype 1 infections, including patients with compensated cirrhosis. Phase 2 and 3 clinical trials demonstrated the safety and efficacy of this regimen in HCV genotype 1-infected patients who are treatment-naïve and those who have failed peginterferon/ribavirin therapy. Additional studies evaluated the use of PrOD with or without ribavirin among special populations, including patients co-infected with human immunodeficiency virus-1 and HCV, liver transplant recipients with HCV recurrence, and patients with severe renal impairment. Additionally, the combination of paritaprevir-ritonavir-ombitasvir plus ribavirin is found to be highly efficacious, and is now approved in the US, for the treatment of HCV genotype 4 infections.

Expert opinion: The availability and use of interferon-free DAA combination regimens has resulted in a major paradigm shift in the treatment of HCV. PrOD, with or without ribavirin, is an effective, safe and tolerable treatment option.