抗丙型肝炎病毒治疗中的病毒学应答对持续应答的预测价值

慢性HCV感染极易发展成肝硬化和肝癌,抗病毒治疗是惟一有可能延缓或阻止其进程的有效方法.目前最理想的抗病毒治疗方案为聚乙二醇干扰素(PEG-IFN)联介利巴韦林.获得持续病毒学应答(SVR)是评价其疗效的主婴指标,但多种宿主因索和病毒因素都可能影响其疗效.近年来有研究者认为治疗过程中病毒的应答情况能够综合反应这些因素的影响,可更好地预测其治疗效果~([1-2]).为了解不同基因型HCV感染者在抗病毒治疗过程中的病毒学应答情况对SVR的预测价值,为对不同基因型HCV感染者制定更加合理的个体化治疗方案提供参考,本研究对近年来在本院接受PEG-IFN联合利巴韦林治疗的慢性HCV感染者的相关资料做了回顾性分析.     

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丙型肝炎病毒(HCV)感染不仅可导致肝脏炎症坏死,而且大部分患者会形成慢性感染,发展为肝纤维化和肝硬化,甚至肝细胞肝癌(HCC).据世界卫生组织统计,全球HCV的感染率约为3%,约1.7亿人感染了HCV,每年新发丙型肝炎约3.5万例.     

丙型肝炎病毒基因6型感染的流行病学和治疗进展

正丙型肝炎呈世界性流行分布。全球丙型肝炎病毒(HCV)感染率约为2.8%,约1.85亿人感染HCV,每年因HCV感染导致的死亡病例约35万例~([1~3])。据证实HCV是导致肝脏疾病(包括肝硬化及肝癌)或肝脏疾病致死的主要原因之一~([4])。2006年全国血清流行病学调查显示,我国1~59岁人群抗HCV流行率为0.43%,再加上高危人群和高发地区的HCV感染者,约为1000万例~([5])。HCV基因组具有高度的异质性,     

丙型肝炎实验室诊断技术研究进展

丙型肝炎是一种由HCV感染引起的主要经血液传播的疾病,部分患者可发展为肝硬化甚至肝细胞肝癌（HCC）,目前尚无有效疫苗,亦无有效治愈方法,故早期、准确诊断HCV感染状况有重要意义.现将丙型肝炎实验室诊断技术的研究进展综述如下.     

乙型肝炎病毒动力学临床研究进展

尽管治疗慢性乙型肝炎的药物近年来发展迅速,但仍然只有少数患者能够获得较好的治疗效果~([1]).病毒动力学数学模型的构建拓展了我们对HCV、HIV感染及对治疗应答的理解.     

慢性丙型肝炎患者肝组织内的淋巴瘤样病变及其意义

HCV感染是导致慢性肝炎、肝硬化和肝细胞肝癌的主要原因之一.据估计全球约1.7亿人感染HCV,约70%转为慢性,其中又有约20%～30%在10～30年发展为肝硬化,进而可导致肝细胞肝癌的发生.     

丙型肝炎病毒感染至临床诊断肝癌的病程经过

目的　探讨丙型肝炎病毒 (HCV)感染发展为肝硬化、肝细胞癌的平均临床病程。方法　收集我院收治的73例感染HCV的肝癌患者病例资料 ,对其从HCV感染发展为慢性肝炎、肝硬化和肝癌病程经过进行统计学分析。结果　输血至临床诊断为肝癌的平均时间为 ( 2 0 .83± 11.63 )年 ,临床诊断慢性丙型肝炎至肝硬化平均时间为 ( 11.91± 11.0 6)年 ;慢性肝炎发展为肝癌的平均时间为 ( 12 .2 1± 11.90 )年 ,肝硬化至临床诊断肝癌 ( 3 2例 )平均病程为 ( 3 .0 3± 2 .84)年。结论　HCV感染发展为肝细胞癌的病程进展缓慢 ,有输血史的患者较无输血者平均病程短。     

丙型肝炎直接抗病毒治疗与肝癌发生及复发的关系

HCV感染后引起的慢性肝炎,是导致肝硬化和肝细胞癌的主要原因之一。近年来,直接抗病毒药物(DAA)逐渐成为治疗丙型肝炎的主流药物。研究表明DAA可能会增加HCV相关肝硬化患者发生肝癌或者导致肝癌复发的风险,给DAA的临床应用带来了巨大的争议。综述了DAA对肝癌发生和复发的影响,以期为DAA的临床应用提供更好的依据。     

国产丙型肝炎病毒核心抗原检测试剂盒的临床应用评价

丙型肝炎是由HCV感染引起的一种全球性传染病,主要通过输血和注射途径传播,在我国感染率为3％ ～ 5％[1];极易转为慢性,与肝硬化和原发性肝癌的关系十分密切.因此,丙型肝炎的早期诊断对于筛查HCV的传染源、指导临床治疗和预后判断有重要意义.     

慢性丙型肝炎抗病毒治疗研究的进展

丙型肝炎是由HCV引起的一种主要经血液传播的慢性进展性肝脏疾病.据世界卫生组织统计,全球HCV感染率约为3％,估计约1.7 ～2.0亿人感染了HCV,每年新发丙型肝炎病例约为3.5万例[1,3].HCV感染后约50％～85％转化为慢性感染[4-5].HCV慢性感染可导致肝脏慢性炎症坏死及纤维化,部分患者可发展为肝硬化甚至肝细胞癌,对患者的健康及生命危害极大,已成为严重的社会和公共卫生问题[5-7].HCV感染后的疾病进展与HCV的病毒复制活跃有密切关系,经有效的抗病毒治疗后能控制病毒的复制和肝脏的炎症活动,并阻断疾病的进展,可减少急性丙型肝炎向慢性丙型肝炎发展的概率,也可减少慢性丙型肝炎转为肝硬化和肝癌的可能性[8-10].慢性丙型肝炎抗病毒的治疗目标是清除体内HCV.治疗后能获得持续病毒学应答(sustained virological response,SVR)者,99％可达到临床治愈的目标[11,12].因此,抗病毒治疗是治疗丙型肝炎的关键措施.只要没有干扰素使用的禁忌证,所有的丙型肝炎患者均应进行抗病毒治疗.近来年,慢性丙型肝炎抗病毒治疗有较大的进展,现从三个方面介绍如下:     

Sustained Virological Response in Chronic Hepatitis C Patients after a 6- and a 36-Month Interferon-a2b Treatment Schedule. A Multicenter,Randomized, Controlled Study

With the introduction of medical treatment (chenodeoxycholic acid therapy) of cholesterol gallstones, the prediction of the gallstone type, cholesterol — non-cholesterol stones (i.e. cholesterol predominating or not), has become important. In 24 consecutive patients admitted for surgery because of gallstones, the value of various criteria for differentiation between the two types of stones was assessed. It is concluded that the combined requirements of radiolucency of the stones and a cholesterol saturation index in duodenal bile above 1.00 constitutes a fairly reliable method for selection of patients for dissolution therapy with chenodeoxycholic acid.     

Cascade of care for children and adolescents with chronic hepatitis C

Chronic hepatitis C virus (HCV) infection presents a significant global public health burden. In 2015, over 400000 deaths worldwide were attributed to HCV infection. This led the World Health Organization (WHO) in 2016 to set the ambitious goal of eliminating HCV by 2030. Adult-centered guidelines have been established in order to provide direction for healthcare professionals, allowing integration of the newest screening policies and therapeutic strategies into their practices. However, for children and adolescents, HCV is a significant, unrecognized public health problem. HCV infection rates in the United States in women of childbearing age and those who are pregnant have increased in parallel with the rising opioid epidemic. An estimated 29000 women with HCV infection gave birth each year from 2011 to 2014 in the United States, with approximately 1700 of their infants being infected with HCV. Newer HCV-specific therapeutics, namely direct acting antivirals (DAA), has brought a new and highly successful approach to treatment of hepatitis C. Recent studies have confirmed similar levels of effectiveness and safety of DAA therapies in the pediatric population. Thus, an enhanced cascade of care, which should include the population under 18 years of age, can help achieve the WHO goal by focusing on elimination in the youngest populations. This review will present an overview of the natural history, clinical features, and management of HCV in children and adolescents.     

Pilot dose-finding trial on interferon alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients not responding to interferon alone

BACKGROUND: Effectiveness of combination therapy with standard interferon alpha doses and ribavirin is far from being demonstrated in patients with hepatitis C non responders to interferon alpha monotherapy. Recent kinetic studies revealed that these doses may be suboptimal. AIMS: To find the criteria for optimisation of the interferon dose, to be used in combination with ribavirin in patients with hepatitis C non responders to interferon alpha monotherapy. PATIENTS: Sixty-three patients enrolled in a pilot controlled trial were treated for 6 months with ribavirin ([1000-1200 mg daily) and were randomised to concurrently receive interferon alpha 2b for 6 months at: 3 Million Units thrice weekly [group A (21 patients)], 5 MU thrice weekly [group B (21 patients)] and 5 million units daily [group C (21 patients)]. RESULTS: A sustained virological response was observed in: 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from group C (38%; p=0.02 vs group A; p=0.03 vs group B). Side-effects were not significantly different between the 3 groups. Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units daily were independent predictors of sustained response. CONCLUSIONS: These results suggest that higher interferon doses administered daily in combination with ribavirin could be more effective in those patients with hepatitis C who had not responded to interferon alone.     

Hepatitis C virus micro-elimination: Where do we stand?

Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviral treatments, has been promoted by the World Health Organization. This achievement is not attainable, however, particularly after the 2020 pandemic of the coronavirus disease 2019. Consequently, the more realistic objective of eliminating HCV from population segments for which targeted strategies of prevention and treatment are easily attained has been promoted in Europe, as a valid alternative. The underlying idea is that micro-elimination will ultimately lead to macro-elimination. The micro-elimination strategy may target different specific populations and at-risk groups. Different settings, including prisons and hospitals, have also been identified as micro-elimination scenarios. In addition, dedicated micro-elimination strategies have been designed that are tailored at the geographical level according to HCV epidemiology and individual country’s income. The main elements of a valid and successful micro-elimination project are reliable epidemiological data and active involvement of all the stakeholders. Community involvement represents another essential component for a successful program.     

Hepatitis C disease burden and strategies for elimination by 2030 in Brazil. A mathematical modeling approach

Introduction and aimHepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO).MethodsA mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024.ResultsAn anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025–2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality.ConclusionAchieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.     

沈阳地区650例慢性丙型肝炎病毒感染者的病毒基因型分析

HCV感染呈全球分布,不同基因型和亚型的地理分布,可能与抗HCV治疗的疗程及效果相关.本研究以核酸序列分析法对650例患者进行HCV基因型检测分析,以探讨沈阳地区感染人群中HCV的基因型特征. 一、资料与方法     

Treatment of chronic viral hepatitis with nitazoxanideand second generation thiazolides

Nitazoxanide, the first thiazolide, was originally developed for the treatment of Cryptosporidium parvum. More recently, antiviral activity of nitazoxanide against hepatitis B virus （HBV） and hepatitis C virus was recognized in in vitro systems. These basic studies led to phase Ⅱ clinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon, with or without ribavirin, in the treatment of chronic hepatitis C genotype 4. The sustained virologic response rate was 79% and 80% in two studies, which was higher than the response rate of 50% with the standard of care with peginterferon plus ribavirin. In very preliminary studies of patients with chronic hepatitis B, nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients. Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway, new second generation and controlled release thiazolides are being developed, and future studies of patients with chronic hepatitis B are planned.     

肝特异性自身抗体与丙型肝炎病毒感染的关系

本研究探讨了HCV感染时体内产生免疫应答并出现多种自身抗体的特点,试图通过检测分析HCV感染与自身抗体的相关性,对丙型肝炎的诊断及治疗提供一些实验数据.     

不同人群血清单项丙型肝炎病毒核心抗体存在状态

为调查不同人群血清单项丙型肝炎病毒核心抗体（抗－ＨＣＶｃ）存在状态，应用合成肽酶免疫分析筛选抗－ＨＣＶｃ，经重组免疫印迹和中和抑制试验鉴定。发现孕妇、供血员、慢性乙型肝炎、非甲非乙型肝炎、透析患者、原因不明肝硬化和输血后肝炎单项抗－ＨＣＶｃ阳性率分别为０．８％（１１／１４３６）、２．８％（１５／５４１）、３．１％（１５／４８４）、１３．６％（９／６６）、１１．５％（１０／８７）、２８．６％（４／１４）和３０％（３／１０）。单项抗－ＨＣＶ阳性的孕妇和供血员血清仅２６．７％～２７．３％检出ＨＣＶＲＮＡ，透析和各种肝病患者检出率高达５５．６％～１００％。８例单项抗－ＨＣＶｃ阳性肝炎患者病理检查显示不同程度的肝损害。结果提示：不同人群单项抗－ＨＣＶｃ阳性的意义有差别，检测ＨＣＶＲＮＡ对区别抗－ＨＣＶｃ存在属既往或现症感染十分重要。     

丙型肝炎的免疫学研究热点

目前,长效α干扰素和利巴韦林联合应用作为丙型肝炎治疗的"标准方案",其持久病毒学应答率只有500%,而且不良反应大,费用昂贵,停止治疗后仍有很高的复发率[1].