慢性丙型病毒性肝炎的抗病毒治疗进展

全世界约有4千万慢性丙型病毒性肝炎(简称丙肝)患者：中国在1992年—1995年做的全国性病毒性肝炎血清流行病学调查中发现，我国一般人群丙型肝炎病毒感染率为3．2％。近20年来，丙肝的抗病毒治疗，干扰素Q(INFQ)一直是首选药物；但是，单独用IFN治疗HCVRNA阴转的患者停止治疗后，约45％—80％出现病毒复现；这种治疗在大多     

利巴韦林治疗慢性丙型病毒性肝炎副作用分析

目的 探讨我院接受利巴韦林治疗慢性丙型病毒性肝炎367例患者应用后的副作用.方法 在治疗期间,统计患者副作用的发生情况及发生率.结果 利巴韦林导致的副作用发生率为10.63%(39例),其中变态反应占53.85%,血液系统及消化系统副作用分别占28.20%、12.82%.结论 利巴韦林治疗慢性丙型病毒性肝炎时的副作用发生率较高,但一般症状较轻,药物使用具有较高的安全性.     

慢性丙型病毒性肝炎的临床表现

目的 提高对慢性丙型肝炎的认识及其防治水平。方法 回顾分析４６例慢性丙型肝炎住院存档资料。采用ＰＣＲ、ＥＬＩＳＡ方法获得病毒血清学诊断。结果 （１）发病年龄以青壮年和老年为多,占２２％和２０％;（２）以输血或应用血制品为其感染主要途径,占５４％;（３）临床表现较轻,多以乏力、纳差为主,占８７％和７６％,其他症状少见。结论 提高对该病的警惕性可望及时获取诊断,加强血源及血制品的管理和检测对阻断丙型肝     

抗病毒治疗丙型病毒性肝炎的临床治疗

目的探讨丙型病毒性肝炎的传播流行,病情的变化情况。方法选取30例丙型病毒性肝炎患者的临床资料进行回顾性分析。结果 30例中血清HCV-RNA转阴12例。结论以干扰素为基础的联合治疗,但限于其较低的病毒学应答率以及不良反应较大等原因,并未取得较为理想的抗病毒效果。     

慢性乙型和丙型病毒性肝炎的药物治疗和选择

我国是病毒性肝炎的高发区,尤其是乙型病毒性肝炎.我国的慢性无症状乙型肝炎病毒(HBV)携带者可能超过1.2亿,其中需接受抗病毒治疗的慢性乙型肝炎患者约2 000万.而我国丙型肝炎病毒(HCV)感染率占总人口的3.2%左右,总数约为4 200万,其中多数为慢性持续性感染.部分患者可进展发生肝硬化和肝癌.如何阻止疾病的进展,降低肝硬化、肝癌的发生,提高患者的生存率和生活质量已成为医生和患者关注的焦点问题.     

丙型病毒性肝炎抗病毒治疗的体会

<正>丙型肝炎病毒的感染流行非常广泛,呈全球性分布。目前全世界丙肝病毒(hepatitisc virus,HCV)感染者大约有1.7亿,我国丙肝病毒感染率约为3.2%,估计有4000万以上患者。HCV感染后因为临床症     

干扰素复合治疗慢性丙型病毒性肝炎的临床疗效观察

目的讨论干扰素复合治疗慢性丙型病毒性肝炎的临床效果。方法选择2013年5月至2015年5月在我院接受治疗的88例慢性丙型病毒性肝炎患者作为分析讨论对象,随机分为观察组和对照组两组,每组44例患者,对照组患者利用口服利巴韦林颗粒、注射聚乙二醇干扰素的方式进行治疗,观察组患者采用注射聚乙二醇干扰素、口服利巴韦林颗粒的基础上配合注射苦参素进行治疗,比较两组患者采用不同治疗方式后的临床效果。结果两组患者接受不同的治疗方式后,观察组的治疗总体有效率、不良反应发生比例、天冬氨酸转氨酶以及谷氨酸转氨酶恢复正常比例均明显优于对照组,差异性具有统计学意义(P<0.05)。结论干扰素复合治疗慢性丙型病毒性肝炎能够提高临床治疗效果,减少患者不良反应症状,值得临床使用和推广。     

干扰素α-2b联合苦参素治疗慢性丙型病毒性肝炎

目的　探讨干扰素α- 2b联合苦参素治疗慢性丙型病毒性肝炎的临床疗效。方法　慢性丙型肝炎患者76例随机分为治疗组4 0例和对照组36例。治疗组给予干扰素α-2b联合苦参素,对照组单用干扰素α-2b。观察两组临床疗效、肝纤维化指标变化、转化生长因子-β1(TGF- β1)水平和不良反应。结果　治疗组完全应答率明显高于单用干扰素治疗组,复发率低于单用干扰素治疗组(P <0 . 0 5 ) ;两组患者血清Ⅲ型前胶原肽(PⅢP)、层粘蛋白(LN)、透明质酸(HA)、Ⅳ型胶原(C Ⅳ)、TGF- β1水平与治疗前相比明显下降(P <0 . 0 1) ,治疗组优与对照组(P <0 . 0 5 ) ;未见严重不良反应。结论　干扰素α- 2b联合苦参素治疗慢性丙型病毒性肝炎能有效改善肝功能,在抗病毒方面有协同作用,并能增强抗肝纤维化的效果。     

关爱生命关注丙型病毒性肝炎威胁

丙型肝炎病毒(HCV)所致的丙型病毒性肝炎(丙肝)是导致肝硬化和肝细胞癌的一个主要原因。丙肝全球流行,全球HCV感染率约为3％,即感染人群约有1亿7千万,在美国有1.8％-2％的人口(约4百万人)抗-HCV阳性。我国人群中抗HCV阳性率高达3．2％,因此估计我国的抗-HCV阳性人群约3700万。抗-HCV阳性率随年龄的增加有增加趋势,每10岁约增加0．3％-0．1％,30—40岁年龄组抗HCV阳性率最高,HCV是我国输血后肝炎的主要病因。     

慢性丙型病毒性肝炎的药物治疗

慢性丙型肝炎治疗的重要性 全世界估计有1亿7千万例慢性丙型肝炎患者,我国约有3 000多万.1992年我国调查,在自然人群中丙型肝炎抗体阳性率是3.2%.患者感染HCV大多发生在1990年前后,源于输血或血制品感染.虽然2005年以来我国丙型肝炎报告病例数逐年增加,但这不是因为新发病的病例数越来越多,而是由于医务人员和患者对内型肝炎的认识提高和丙型肝炎高危人群主动到医院就诊,检测人数明显增加所致.     

Antiviral treatment of chronic hepatitis C

The therapy of the chronically hepatitis C virus infection is still a major challenge for the attending physician. Standard therapy regimen implements the combination of pegylated interferon alpha and ribavirin. Duration of therapy is individualized according to the infecting HCV genotype and on the viral response. However, only in 50-80% (dependent on the HCV genotype) treatment will be successful. The development of so called "direct-acting antivirals"(DAA) will provide new options and this was achieved by the approval of two inhibitors of the HCV protease. Boceprevir and telaprevir give hope especially for patients infected with the worse to treat HCV genotype 1. In order to reduce the risk of antiviral resistance these drugs are given in combination with pegylated interferon and ribavirin only.     

Daclatasvir for the treatment of chronic hepatitis C

Introduction: Following more than 20 years of Interferon (IFN)-based treatment for hepatitis C virus (HCV), the understanding of viral life cycle led to the development of new antiviral drugs directly targeting HCV replication steps. Daclatasvir (DCV) is a potent inhibitor of non-structural NS5A HCV protein with pangenotypic activity and low-moderate barrier to resistance suitable for IFN-free combination with other direct acting antivirals (DAAs).

Areas covered: The present review summarizes DCV key pharmacokinetic features and results from Phase II and III trials, discussing also NS5A resistance. Main literature articles have been identified through Pubmed and Medline search; moreover, abstracts from recent international meetings on liver disease have been scrutinized.

Expert opinion: DCV in combination with other DAAs has provided IFN-free regimens with increased efficacy and tolerability. However, suboptimal barrier to resistance and the rapid development of new second-generation NS5A inhibitors will probably make DCV a relatively short-lived drug.     

Developments in the treatment of chronic hepatitis C

Hepatitis C virus is the most common chronic, blood-bourne infection, affecting 170 million people worldwide, approximately 3% of the global population. Of those infected with hepatitis C virus, 50 – 85% will develop chronic hepatitis C. Although hepatitis C is primarily a disease of the liver, a diagnosis is currently defined by the presence of the hepatitis C virus and treatment success is defined by the clearance of the virus. IFN-α is currently the mainstay of chronic hepatitis C therapy; the antiviral and anti-inflammatory components of IFN target both the infectious and the hepatic manifestations of the disease. However, even in combination with ribavirin, interferon therapy is not fully efficacious. Recently, the search for a more effective treatment has led investigators to optimise interferon therapy by developing pegylated interferons. Challenges facing our current treatment of hepatitis C virus include lack of efficacy in patients with difficult-to-treat disease, such as patients with cirrhosis or infected with hepatitis C virus genotype 1 (who represent a majority of US hepatitis C virus infections), the toxicity of combination therapy, the expense and difficulty of therapy and the poor reception of these treatments by many patients. The development of new hepatitis C antiviral agents is critical to our management of this disease. A number of approaches are under investigation, including long-acting interferons, immunomodulators, antifibrotics, specific hepatitis C virus-derived enzyme inhibitors, drugs that either block hepatitis C virus antigen production from RNA or prevent normal processing of hepatitis C virus proteins and other molecular approaches to treating hepatitis C virus, such as ribozymes and antisense oligonucleotides.     

Taribavirin for the treatment of chronic hepatitis C

Background: The current standard therapy for chronic hepatitis C virus (HCV), combination therapy with pegylated interferon and ribavirin, is plagued by a number of side effects, most notably anemia. This anemia is typically managed with a reduction of ribavirin dosing, which may lead to reduced efficacy. Taribavirin, an oral prodrug of ribavirin, which has been shown to induce a lesser degree of anemia, is being investigated for the treatment of chronic HCV. Objective: To summarize the clinical trials involving taribavirin and its potential role in the treatment of chronic HCV. Methods: Information was obtained via searches for data related to taribavirin, as well as other current and investigational therapies for chronic HCV. Press releases discussing otherwise unpublished trial outcomes were obtained from the website of Valeant Pharmaceuticals, the producer of Viramidine^® (taribavirin). Conclusion: Taribavirin may increase adherence to therapy for chronic HCV by reducing the need for dose reduction due to anemia. A recent Phase II trial investigating early and sustained virological response showed no statistically significant differences between ribavirin 1000/1200 mg and taribavirin at 800-, 1200-, or 1600-mg dosing, while illustrating a lesser degree of anemia in 800- and 1200-mg dosing of taribavirin. Ongoing studies will continue to examine the efficacy of combination therapy with taribavirin in the place of ribavirin.     

Developments in the treatment of chronic hepatitis C

Hepatitis C virus is the most common chronic, blood-bourne infection, affecting 170 million people worldwide, approximately 3% of the global population. Of those infected with hepatitis C virus, 50 - 85% will develop chronic hepatitis C. Although hepatitis C is primarily a disease of the liver, a diagnosis is currently defined by the presence of the hepatitis C virus and treatment success is defined by the clearance of the virus. IFN-alpha is currently the mainstay of chronic hepatitis C therapy; the antiviral and anti-inflammatory components of IFN target both the infectious and the hepatic manifestations of the disease. However, even in combination with ribavirin, interferon therapy is not fully efficacious. Recently, the search for a more effective treatment has led investigators to optimise interferon therapy by developing pegylated interferons. Challenges facing our current treatment of hepatitis C virus include lack of efficacy in patients with difficult-to-treat disease, such as patients with cirrhosis or infected with hepatitis C virus genotype 1 (who represent a majority of US hepatitis C virus infections), the toxicity of combination therapy, the expense and difficulty of therapy and the poor reception of these treatments by many patients. The development of new hepatitis C antiviral agents is critical to our management of this disease. A number of approaches are under investigation, including long-acting interferons, immunomodulators, antifibrotics, specific hepatitis C virus-derived enzyme inhibitors, drugs that either block hepatitis C virus antigen production from RNA or prevent normal processing of hepatitis C virus proteins and other molecular approaches to treating hepatitis C virus, such as ribozymes and antisense oligonucleotides.     

Interleukin-12 in the treatment of chronic hepatitis B and C.

Interleukin-12 plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. In two open label, multicenter, dose-escalation phase I/II studies tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin-12 (rHuIL-12) was assessed in the treatment of chronic hepatitis B and C. Forty-six patients with chronic hepatitis B and 60 patients with chronic hepatitis C were treated for 12 and 10 consecutive weeks, respectively. rHuIL-12 was generally well tolerated, but was associated with temporary decreases in neutrophils and lymphocyte counts, and with elevations in serum transaminases and bilirubin. Serum IL-12 levels observed were higher at 0.5 microg/kg compared with 0.25 microg/kg doses, suggesting a dose-related increase in systemic exposure of IL-12. Measurable levels of interferon-gamma were also observed at the highest dose of 0.5 microg/kg. At the end of treatment HBV DNA clearance was greater in patients treated with 0.50 microg/kg (25%) or with 0.25 microg/kg (13%) compared with those given 0.03 microg/kg. In patients with chronic hepatitis C, HCV RNA remained detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3/16 patients (0.03 microg/kg), in 3/14 (0.10 microg/kg), in 6/15 (0.25 microg/kg), and in 8/15 patients of the 0.5 microg/kg dose group. In conclusion, antiviral activity of rHuIL-12 in patients with chronic hepatitis B or C does not appear to be advantageous in comparison to other currently available treatments.     

丙型肝炎治疗药物经济学评价研究综述

丙型肝炎直接抗病毒药物(direct acting antivirals,DAAs)的出现极大地提高了丙肝的治疗效果,降低了丙肝长期并发症如肝硬化、肝癌、肝移植的发生率,显著提高了患者的生活质量;但DAAs药物也带来了更高的成本,潜在的治疗需求将成为极大的财政负担。因此,对DAAs药物进行经济学评价十分必要。通过系统评价了解国内外针对丙肝治疗药物的经济学评价研究现状,纳入34篇文献。目前的评价多采用模型法进行成本效用分析,以增量成本效果比(the incremental cost-effectiveness ratio,ICERs)为主要指标,绝大多数从付费方进行评价且只考虑了直接医疗成本,评价的结果因不同国家的不同患者而异,但大部分研究得出DAAs相比传统方案是具有成本效果的。未来丙肝治疗药物的经济学评价应从更全面的社会角度出发,并可探索通过多准则决策分析(multi-criteria decision analysis,MCDA)纳入包括患者在内的多方参与,以全面而准确地评价相应药物的成本和收益。     

TMC435 for the treatment of chronic hepatitis C

INTRODUCTION: Chronic hepatitis C (CHC) virus infection affects more than 170 million people globally. The aim of treatment of CHC is to effect sustained elimination of the virus (a sustained virological response, SVR). Prior to the development of direct-acting antiviral (DAA) agents, the standard of care (SOC) for CHC comprised combined treatment with pegylated interferon (PegIFN) and ribavirin (RBV). AREAS COVERED: TMC435 (Tibotec pharmaceuticals) is a macrocyclic non-covalent NS3/NS4A protease inhibitor (DAA) that is currently in Phase III clinical development. TMC435 is being developed in treatment regimens both with and without PegIFN and RBV. In Phase IIb clinical trials, the addition of TMC435 to current SOC significantly increased the SVR rate in both treatment-naive and experienced patients with CHC. It differs, however, from the other first-generation protease inhibitors in that it is administered once daily, has a different tolerability and resistance profile and has activity against CHC genotypes 1 - 6 with the exception of genotype 3. Furthermore, the addition of TMC435 to PegIFN/RBV appears to be able to significantly shorten treatment duration in the majority of patients. This article will review the pharmacology, pharmacodynamics, safety and efficacy of TMC435 by evaluating the preclinical and clinical studies to date. ExPERT OPINION: TMC435 is a 'second-wave' protease inhibitor that has the potential to play a pivotal role in the next phase of CHC treatment. The forthcoming results of Phase III trials involving TMC435 are awaited with interest.     

Promising candidates for the treatment of chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is the cause of an emerging global pandemic of chronic liver disease. Current pegylated IFN-α/ribavirin combination therapies are merely 54 – 56% efficacious and are often poorly tolerated. Popular strategies to improve upon existing therapies include efforts to decrease the dosing regime, improve the safety profile and specifically target the liver, the site of HCV replication. A clear goal of novel therapies is to significantly improve the therapeutic response for HCV-infected patients. One popular scheme to accomplish this is to directly target the viral enzymes involved in HCV RNA replication. While peptidomimetics have been pursued as potent and specific inhibitors of the serine protease, nucleoside analogues and non-nucleoside small molecules have been explored as RNA-dependent RNA polymerase inhibitors with promising potential. Advances in the understanding of HCV replication at the molecular level that stem from the use of the subgenomic replicon system, in vitro enzyme assays and from co-crystallographic structure solutions of the replication enzymes with novel inhibitors have propelled these compounds into clinical development. As these candidates are developed further, there is great hope for a cure for all those chronically infected with HCV.     

TMC435 for the treatment of chronic hepatitis C

Introduction: Chronic hepatitis C (CHC) virus infection affects more than 170 million people globally. The aim of treatment of CHC is to effect sustained elimination of the virus (a sustained virological response, SVR). Prior to the development of direct-acting antiviral (DAA) agents, the standard of care (SOC) for CHC comprised combined treatment with pegylated interferon (PegIFN) and ribavirin (RBV).

Areas covered: TMC435 (Tibotec pharmaceuticals) is a macrocyclic non-covalent NS3/NS4A protease inhibitor (DAA) that is currently in Phase III clinical development. TMC435 is being developed in treatment regimens both with and without PegIFN and RBV. In Phase IIb clinical trials, the addition of TMC435 to current SOC significantly increased the SVR rate in both treatment-naive and experienced patients with CHC. It differs, however, from the other first-generation protease inhibitors in that it is administered once daily, has a different tolerability and resistance profile and has activity against CHC genotypes 1 – 6 with the exception of genotype 3. Furthermore, the addition of TMC435 to PegIFN/RBV appears to be able to significantly shorten treatment duration in the majority of patients. This article will review the pharmacology, pharmacodynamics, safety and efficacy of TMC435 by evaluating the preclinical and clinical studies to date.

Expert opinion: TMC435 is a ‘second-wave' protease inhibitor that has the potential to play a pivotal role in the next phase of CHC treatment. The forthcoming results of Phase III trials involving TMC435 are awaited with interest.