慢性丙型肝炎抗病毒治疗的研究进展

慢性丙型肝炎目前最为有效的治疗方法就是重组干扰素α(IFNα),但疗效不很满意.临床上应用IFNα治疗病毒性肝炎遇到2个困难,一个是IFNα在血清中的半寿期太短,只有5.1 h,决定其半寿期的因素主要是机体免疫系统对于干扰素的识别以及此后的代谢过程,因此须要不断地重复用药.另一个就是引发抗体的产生.重组蛋白药物的一个缺点就是常常因为具有抗原性而影响其疗效.当与聚乙二醇(PEG)交联以后,就不易被机体的免疫系统所识别,从而降低了重组蛋白药物的免疫原性,延长了在血液循环中存在的时间,降低其毒性,提高药物的稳定性,增加药物的可溶性,显著提高重组蛋白药物的疗效.为了改进IFNα制剂,制备了IFNα与PEG的交联物.与PEG交联,IFNα用药以后吸收很快,在血清中的清除速度显著减慢,因而可以维持长时间的有效血药浓度,提高IFN α的疗效,减少用药次数.目前临床正在试用的长效干扰素有2种,即Schering-Plough公司的PEG-Intron和Roche公司的Pegasys.     

慢性丙型肝炎的抗病毒治疗

丙型肝炎病毒(ＨＣＶ)感染是慢性肝炎肝病的重要原因,其特点是隐匿性,往往在常规生化或免疫学检查时被发现。虽然仅于半数慢性ＨＣＶ感染者血清转氨酶升高,但几乎所有病例肝活检均显示不同程度的慢性肝炎改变。约10%～20%的慢性丙型肝炎(丙肝)在20年内演变为肝硬化,少数进一步演变为肝癌[1]。在美国,接受肝移植的患者中约20%～30%是终末期慢性丙肝。慢性丙肝治疗的目的包括根除或长期抑制病毒复制,减轻肝内炎症和纤维化,最终阻抑进展为肝硬化、肝癌和肝衰竭。抗病毒是丙肝治疗的关键。曾用于抗ＨＣＶ的疗法有多种(表1),但仅有干扰素被证明有…     

慢性丙型肝炎的抗病毒治疗

198 9年首次报告丙型肝炎病毒 (ＨＣＶ)以来 ,慢性丙型肝炎的抗病毒治疗得到长足发展。大量的临床研究证实 :干扰素 (ＩＦＮ)治疗慢性丙型肝炎存在着应答和无应答两种状态。慢性丙型肝炎病程进展快 ,肝癌发生率高 ,抗病毒疗效不佳成为慢性丙型肝炎预后差的最主要原因。由于对慢性丙型肝炎的抗病毒治疗存在着不正确认识 ,造成一些医生进行慢性丙型肝炎抗病毒治疗时走入误区 ,影响抗病毒的疗效。本文将依据基础研究的结论阐述慢性丙型肝炎的抗病毒治疗。1　慢性丙型肝炎极差的预后要求抗病毒治疗通常致癌病毒将自己的基因插入宿主染色体中 ,引…     

丙型肝炎抗病毒治疗研究进展

丙型肝炎由于进展隐匿、慢性率高及预后不良而倍受关注。研究发现，约20％慢性丙型肝炎患者将进展为肝硬化，约2．5％最终罹患肝癌。据估计，全球有1．7亿丙型肝炎病毒（HCV）携带者，我国人群HCV感染率约在3％左右。以干扰素为基础的治疗在临床上一直居于主导地位，特别是聚乙二醇化干扰素（Peg—IFN）联合利巴韦林的应用使病毒学应答率明显提高。但是，疗程长、有效率低、不良反应大等问题仍未得到根本解决。     

慢性丙型肝炎抗病毒药物及其治疗方案研究进展

慢性丙型肝炎成为全球严重的公共卫生问题,近年来随着丙型肝炎的药物治疗不断发展,使丙型肝炎治愈成为可能。从丙型肝炎的流行现状,传统的标准治疗方案(聚乙二醇干扰素+利巴韦林)以及不同的口服小分子直接抗病毒药物(DAAs)的优势及副作用,总结了不同DAAs药物组合对于不同慢性丙型肝炎基因型治疗的利弊,并简要介绍了世界卫生组织对于丙型肝炎治疗的推荐意见。相信未来慢性丙型肝炎的药物治疗会不断飞跃,消灭丙型肝炎指日可待。     

慢性丙型肝炎抗病毒治疗进展

抗病毒是治疗慢性丙型肝炎最重要的手段。叙述了近年来抗病毒治疗包括聚乙二醇干扰素和利巴韦林联合治疗、特异性靶点治疗、基因治疗等的进展情况。认为未来抗HCV治疗还需要更有效的药物联用治疗方式、更短的用药疗程、更低的毒副作用以及更高的耐药阈值等。     

慢性丙型肝炎抗病毒治疗效果影响因素的研究进展

聚乙二醇干扰素联合利巴韦林是目前慢性丙型肝炎抗病毒治疗的标准治疗方案,约70％的患者能够获得持续的病毒学应答,病毒和宿主因素对治疗的结局有决定性影响。部分患者对治疗无应答或治疗后复发,称为难治性丙型肝炎。对干扰素治疗结果的预测一直是研究的热点。近年有研究报道,利用患者的基线特征以及对治疗的不同病毒学应答模式,可以对远期的治疗结果进行预测,能更好的帮助临床医生设计治疗方案。新型抗病毒药物的问世,也将为难治性丙型肝炎的治疗提供新的方案。     

慢性丙型肝炎抗病毒治疗的演变

自丙型肝炎病毒(hepatitis C virus,HCV)被发现以来,对慢性丙型肝炎(chronic hepatitis C,CHC)的认识和治疗模式均已发生巨大变化。本文总结近30年来CHC抗病毒治疗方式的演变和疗效进展,并对口服直接抗病毒药物(direct-acting antiviral agents,DAAs)的临床应用及前景进行了展望。随着新一代治疗药物的研发和应用,越来越多的患者可以获得HCV清除和疾病治愈。尽管如此,DAAs在中国大陆上市前,CHC治疗仍是一大挑战,需要开展大量培训工作使临床医师尽快掌握药物使用方法,最终造福于我国CHC患者。     

慢性丙型肝炎抗病毒治疗的进展

1丙型肝炎的流行情况 丙型肝炎病毒(HCV)感染流行广泛,呈全球性分布,全球HCV感染者约为1.7亿人。我国在1992年全国病毒性肝炎血清流行病学调查,HCV感染率为3.2％,约为3700万人。2丙型肝炎的自然史和存在的问题 HCV感染后,慢性化率极高,可达50％-85％。而慢性丙肝如不及时和合理治疗,发展为肝硬化可     

丙型肝炎直接抗病毒治疗研究进展

正目前,我国针对慢性丙型肝炎(chronic hepatitis C,CHC)的标准治疗方案(standard of care,SOC)仍然是聚乙二醇干扰素(pegylated interferon,PEGIFN)-α联合利巴韦林(ribavirin,RBV),简称PR治疗。但是近年来,针对HCV生活周期中病毒蛋白靶向特异性治疗的许多小分子化合物研究进展非常迅速,这些药物被统一命名为直接作用抗病毒药物     

Chronic hepatitis C therapy: changing the rules of duration.

Traditional durations of therapy for patients with chronic hepatitis C can potentially be modified in hopes of cost savings, diminished exposure to medication side effects, and even improved rates of sustained virologic response. Clinical and viral kinetic studies suggest that shortened treatment durations for certain patients with genotype 2 and 3 infections might be equally effective as regimens of 24 weeks; for patients achieving undetectable viremia at 4 weeks of therapy, treatment durations of 12-16 weeks are sufficient. Nevertheless, abbreviated treatment courses might be inappropriate for those patients with advanced fibrosis or for genotype 3-infected patients with high viral loads. Similarly, if a rapid virologic response is obtained in those patients with genotype 1 infection and a low viral load, a truncated treatment course of merely 24 weeks is feasible. Conversely, slow virologic responders typically seen in genotype 1-infected individuals with high viral loads might benefit from an extended course of therapy; however, this approach needs to be validated prospectively. This review focuses on the evidence supporting such treatment individualization and discusses potential treatment algorithm modifications.     

慢性丙型肝炎抗病毒失败者再治疗探讨

0 引言丙型肝炎病毒(HCV)的基础和临床各方面研究已经有了很大进展,但是在诊断、治疗、疫苗研制等方面还不尽如人意,彻底控制丙型肝炎的危害还有很远的路程要走.慢性丙型肝炎目前常用的治疗方法是普通α干扰素, 300 wu,3次/wk,疗程1 a.但是用这种方法治疗的持     

Chronic hepatitis C

Opinion statement Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin.     

Chronic hepatitis C

The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual's antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specific inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fibrosis progression, the incidence of cirrhosis, and hepatocellular carcinoma.     

Chronic hepatitis C and steatosis

Steatosis is a common finding in chronic hepatitis C infection. It is associated with increased fibrogenesis and, in nongenotype 3 infection, with a reduced response to antiviral therapy. The steatosis is multifactorial; host factors, particularly excess body mass and insulin resistance, and viral cytopathic effects each play a variable role in different genotypes. How steatosis or the accompanying metabolic changes potentiate fibrosis remains enigmatic, but evidence is emerging that implicates oxidative stress, hyperinsulinemia, enhanced hepatocyte death, or altered regeneration programs. Tumorigenesis may also be increased. By reducing steatosis, and in some instances fibrosis, weight loss or other therapies targeting insulin resistance may have a role in those patients who have failed antiviral treatment.