实验室检测在直接抗病毒药物治疗慢性丙型肝炎中的作用北大核心CSCD

本研究主要讨论在直接抗病毒药物(DAA)联合治疗慢性丙型肝炎(CHC)过程中涉及的实验室诊断,从病毒因素和宿主因素两方面进行阐述,病毒因素包括HCV基因型和病毒载量及耐药基因检测,在DAA类药物治疗之前检测丙型肝炎病毒(HCV)的原因,主要是确诊慢性HCV感染和确定治疗方案和最佳疗程,还要考虑患者对DAA的抵抗及基线HCV病毒载量,在DAA治疗HCV感染之前评估宿主状态也很重要,宿主因素主要从基因多态性与干扰素类治疗的关系、合并病毒感染、肝纤维化实验室分期、安全监测等方面来讲述。     

实验室检测在直接抗病毒药物治疗慢性丙型肝炎中的作用

本研究主要讨论在直接抗病毒药物(DAA)联合治疗慢性丙型肝炎(CHC)过程中涉及的实验室诊断,从病毒因素和宿主因素两方面进行阐述,病毒因素包括HCV基因型和病毒载量及耐药基因检测,在DAA类药物治疗之前检测丙型肝炎病毒(HCV)的原因,主要是确诊慢性HCV感染和确定治疗方案和最佳疗程,还要考虑患者对DAA的抵抗及基线HCV病毒载量,在DAA治疗HCV感染之前评估宿主状态也很重要,宿主因素主要从基因多态性与干扰素类治疗的关系、合并病毒感染、肝纤维化实验室分期、安全监测等方面来讲述。     

低蛋白饮食与慢性肾脏病的研究进展

慢性肾脏病(chronic kidney disease,CKD)是由于肾脏出现不可逆的损伤后出现结构或功能异常,随着疾病进展营养代谢问题日益突出,低蛋白饮食(low protein diet,LPD)作为营养治疗,是慢性肾脏病患者综合治疗的重要环节。就LPD对于CKD治疗的意义、实施中出现的问题及展望进行综述,旨在为慢性肾脏病的营养治疗与管理提供参考。     

NKF-K/DOQI和慢性肾脏病的调脂治疗

发现慢性肾脏病(CKD)常伴发血脂异常已近两个世纪。早在1811年Blackall就对两者的相关性进行过报道。但直到近20余年来,“表现为血脂异常的脂质代谢异常及调脂治疗在CKD中的重要意义”才得以认识。纵观CKD调脂治疗的进展可分为以下三个阶段:(1)基本忽略不治。(2)以维护慢性肾脏病中的“病肾”为主要出发点,积极进行调脂治疗(3)美国肾脏基金会(NKF)制定的“慢性肾脏病/透析病人生存质量指南(K/DOQI)”则提出应以防治慢性肾脏病患者的心血管疾病(CVD)及提高其生存率为主要治疗目的,从而CKD的调脂治疗进入规范性治疗时期。一、K/DO…     

2型糖尿病合并慢性肾脏病患者口服降糖药应用原则

慢性肾脏病(CKD)是严重威胁人类健康的常见慢性病,病因多种多样,由糖尿病所引发的肾脏病称为糖尿病肾脏病(DKD)。T2DM常合并CKD,高血糖是CKD发展的主要原因之一,降糖治疗至关重要。口服降糖药作为临床最常用的降糖手段,对于血糖控制具有重要意义。近年来,T2DM合并CKD患者中口服降糖药治疗证据不断丰富。     

基于logistic回归和随机森林的慢性肾脏病危险程度预测模型

目的分析慢性肾脏病(CKD)住院患者的基本特点,找出影响因素,进行针对性的预防与治疗,改善患者预后。方法选取上海市某三甲医院2011-2016年CKD住院患者病案资料,研究对象为信息完整的90746例住院患者。CKD根据GFR分期、白蛋白尿分组及实际数据各等级的分布情况,合并为正常、低危和高危,构建多分类logistic回归模型分析慢性肾脏病与危险因素的关系。应用随机森林算法对各变量的重要性进行排序,建立CKD危险程度预测模型。结果女性CKD危险程度低于男性;随着年龄的增长CKD危险程度逐步升高;罹患高血压、糖尿病、高尿酸血症CKD危险程度较高;尿检(尿红细胞、尿白蛋白肌酐比等)结果异常人群,CKD危险程度较高。结论在慢性肾脏病早期进行如控制血压、低蛋白饮食等干预及治疗,可以延缓肾脏病的损害,改善预后;另一方面,随机森林模型在分类预测方面有着精度高、稳定性好,易操作和不易过度学习等优势。     

乙型肝炎病毒和丙型肝炎病毒在合并感染者中的相互作用

目的 了解HBV和HCV在合并感染的慢性肝病患者中相互作用的特点.方法 收集2006年1月～2007年10月在我院治疗的慢性肝病(包括HBV和HCV合并感染引起的慢性肝炎或肝硬化、肝炎后肝硬化、慢性乙型肝炎、慢性丙型肝炎)患者的肝穿病理样本及其血清.所有病例均常规检测肝功能,血清HBV DNA、血清HBV标志物、血清HCV RNA、抗-HCV;所有肝活检样本均用10%中性福尔马林固定,石蜡包埋,作苏木精-伊红、Masson和网状纤维染色,并进行肝炎分级分期,HBsAg和HBcAg免疫组化,HBV DNA和HCV RNA原位杂交检测.结果 HBV和HCV合并感染的患者重型慢性肝炎(G4)发生率比HBV或HCV单独感染的患者高,分别为62.50%、27.05%和30.56%(P＜0.01).在HBV和HCV合并感染引起的慢性肝炎患者中,HBV DNA阳性率为4/32(12.5%),HCV RNA阳性率为24/32(75%),而HBV或HCV单独感染组分别为HBV DNA阳性107/122(87.7%)和HCV RNA阳性58/72(80.56%).结论 HBV和HCV合并感染可增加重型慢性肝炎的发生率.在HBV和HCV合并感染的患者中,HBV和HCV呈相互抑制的作用,主要表现为HCV对HBV的抑制.     

儿童终末期肾病的替代治疗

近年来,慢性肾脏病和终末期肾病发病率不断增加,已成为全球一大重要的公共健康问题。而我国儿童慢性肾脏病(CKD)的发病率也在逐渐上升。部分儿童慢性肾脏病会逐渐进展,最终进展为尿毒症,给孩子今后的生活、工作带来极大麻烦,需要引起社会和家长的高度重视。尿毒症在医学上的规范称呼应该叫终末期肾脏病(ESRD),是指各种类型肾脏疾病发展到最后的一个阶段。     

慢性肾脏疾病一体化防治的理念与目标

慢性肾脏疾病(CKD)近年来被视为一种静悄悄的流行病正在全球无情地蔓延,肾脏疾病业已成为我国的常见病、多发病。近年来糖尿病、高血压病发病率在我国明显上升,且随着老龄化社会到来,慢性肾功能衰竭患者相应增加。由于各类肾脏病的发病与进展机制甚为复杂,多年来其诊治问题一直是肾脏病工作者面临的最大挑战。慢性肾脏病一体化防治是肾脏病专业领域中医疗工作的新理念。这一理念的精髓在于要重视以人为本、预防为主,重视循证医学在肾脏疾病领域中的应用。期望达到有效减少慢性肾脏病的患病人群、延缓慢性肾脏病的进展、降低终末期肾脏病的发生率并改善患者临床预后的最终目标。     

徐州地区慢性肾病的多重危险因素探究北大核心CSCD

目的研究慢性肾病的相关危险因素,为慢性肾病提供有效干预措施。方法对徐州地区确诊的395例慢性肾脏病(CKD)患者和152例正常者进行病例对照研究,分析CKD发生的相关危险因素。结果有效问卷为547份,经logistic回归分析筛选出慢性肾病的危险因素为每日饮水量、熬夜、工作强度、高血压(均P<0.05)。结论对以上CKD的危险因素加以重点评估和合理控制,加强在高危人群中的筛查,做到早发现、早干预,早治疗。合理饮食,戒烟、戒酒,加强体育锻炼,养成良好生活习惯,才能降低CKD发病率,延缓CKD的进展,防止终末期肾脏病(ESRD)和心血管疾病(CVD)的发生,减轻社会及家庭的负担,减少由此产生的巨额医疗资源的消耗。     

直接抗病毒药物对儿童慢性丙型肝炎的治疗进展

聚乙二醇干扰素α-2a或α-2b联合利巴韦林是目前治疗儿童慢性丙型肝炎的标准方案。该方案最早应用于成人，对HCV的有效率仅约50%，并且对于儿童HCV的治疗有效率最高也只达70%。近年来，直接作用于HCV基因靶点的抗病毒药物（direct-acting antiviral agents, DAAs）不断被研发出来，对HCV的治疗起到质的飞跃，但该类药物在儿童HCV治疗中的应用大多处在临床试验阶段。本文通过对目前DAAs在儿童慢性丙型肝炎中的研究进展作一综述，以期为HCV患儿的临床治疗提供参考依据。     

Therapeutic vaccines against hepatitis C virus

Hepatitis C virus (HCV) is a blood-borne pathogen which has chronically infected about 130–210 million people worldwide. Current standard-of-care (SoC) therapy is an inadequate and expensive treatment with more side effects. Two direct-acting antiviral agents (DAAs) (telaprevir and boceprevir) in combination with SoC therapy have been used in patients infected with HCV genotype 1. Although these drugs result in a shortening of therapy, they also have additional side effects and are expensive. In their stead, several second-generation DAAs are being investigated. What important is that all-oral, interferon (IFN)- and ribavirin-free regimens for the treatment of HCV-infected patients are now being investigated, and will be applied in the next year. Preventive measures against HCV, including vaccine development, are also now in progress. However, no therapeutic vaccine against HCV has been produced to date. An effective vaccine should induce robust and broadly cross-reactive CD4⁺, CD8⁺T-cell and neutralising antibody (NAb) responses. Current data indicate that vaccines can usually not completely prevent HCV infection but rather prevent the progression of HCV infection to chronic and persistent infection, which may be a realistic goal. This review discusses the important roles of NAbs and CD8⁺T-cells in the development of therapeutic vaccines, and summarizes some important epitopes of HCV recognized by CD8⁺T-cells and some prospective therapeutic vaccine approaches.     

State Medicaid Reimbursement for Medications for Chronic Hepatitis C Infection from 2012 through 2015

Background

New direct-acting antivirals (DAAs) can cure chronic hepatitis C virus (HCV) infection. High DAA prices combined with a large number of patients needing treatment may pose substantial economic burden on health systems.

直接抗病毒药物在丙型肝炎病毒及合并艾滋病病毒感染中的应用进展

在过去几年中,抗丙型肝炎病毒（hepatitis C virus,HCV）治疗药物的研发取得了突破性进展。大量基础和临床研究证实,针对病毒蛋白的直接抗病毒药物（direct-acting antivirals,DAAs）能有效治疗HCV感染,获得高达90%以上的持续病毒应答（sustained viral response,SVR）。然而,由于诸多因素的影响,HCV合并人类免疫缺陷病毒（human immunodeficiency virus,HIV）感染的患者尚未得到有效的抗HCV治疗。在此将重点简述了DAAs的分类、作用机制及其临床试验效果;此外,还介绍了宿主靶向药物（host-targeting agents,HTAs）的研发情况,以及DAAs在HCV合并HIV患者中的临床应用进展。     

New therapeutic options in chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is the major etiology and the reason of chronic liver disease, liver cirrhosis, hepatic decompensation, hepatocellular cancer and liver transplantation. Less than half of patients with HCV-related chronic hepatitis achieve sustained viral clearance with current pegylated interferon and ribavirin (P+R) combination therapy. Due to the insufficient treatment success, an extended search for new, direct acting anti-HCV agents (DAAs) is ongoing, already leading to submissions of applications for marketing authorization of the protease-inhibitors boceprevir and telaprevir. Both are effective only in triple combinations with P+R. Studies demonstrate a 50% success rate advantage for triple therapies above current standards. In addition, treatment duration can be shortened, and half of the patients who failed previous therapy with P+R can be cured with triple therapies. A major concern with new DAAs is rapid development of DAA-resistant viral mutants, a reason as well as a consequence of insufficient triple therapy. Clinical studies with boceprevir and telaprevir are reviewed in this paper.     

Chronic hepatitis C virus infection

Following acute hepatitis C virus infection (HCV), a significant percentage of patients do not clear the virus and develop a chronic hepatitis C. The symptoms, when they exist, are usually unspecific. Besides, approximately one third of the patients present extrahepatic manifestations of the infection, basically due to the lymphotropism of HCV. Outstanding amongst these, due to their clear association with HCV, are mixed cryoglobulinaemia and the production of autoantibodies (autoAb). Other diseases such as non-Hodgkin lynphoma (NHL) or autoimmune thyroiditis do not have a clearly established association. Although the majority of patients with chronic hepatitis C have slight or moderately high levels and fluctuations of transaminases, as many as one third of those infected can show persistently normal levels of transaminases. The diagnosis of chronic HCV infection is based on serological tests, which detect the presence of antibodies against HCV, and on virological tests that detect RNA of the HCV, which confirm the existence of active infection. Finally, an important topic of chronic HCV infection, following diagnosis, is to ascertain the stage of fibrosis and the degree of inflammation, since both characteristics are very important for predicting the natural evolution and the need for treatment. Nowadays, this information can only be obtained through liver biopsy, which is recommended in patients with chronic HCV infection and high transaminases. Whether liver biopsy should be performed in patients with normal transaminases is still subject of controversy.     

Cost-Utility Analysis of Direct-Acting Antivirals for Treatment of Chronic Hepatitis C Genotype 1 and 6 in Vietnam

ObjectiveVery few cost-utility analyses have either evaluated direct-acting antivirals (DAAs) on hepatitis C virus (HCV) genotype 6 patients or undertaken societal perspective. Recently, DAAs have been introduced into the Vietnamese health insurance drug list for chronic hepatitis C (CHC) treatment without empirical cost-effectiveness evidence. This study was conducted to generate these data on DAAs among CHC patients with genotypes 1 and 6 in Vietnam.MethodsA hybrid decision-tree and Markov model was employed to compare costs and quality-adjusted life-years (QALYs) of available DAAs, including (1) sofosbuvir/ledipasvir, (2) sofosbuvir/velpatasvir, and (3) sofosbuvir plus daclatasvir, with pegylated-interferon plus ribavirin (PR). Primary data collection was conducted in Vietnam to identify costs and utility values. Incremental cost-effectiveness ratios were estimated from societal and payer perspectives. Uncertainty and scenario analyses and value of information analyses were performed.ResultsAll DAAs were cost-saving as compared with PR in CHC patients with genotypes 1 and 6 in Vietnam, and sofosbuvir/velpatasvir was the most cost-saving regimen, from both societal and payer perspectives. From the societal perspective, DAAs were associated with the increment of quality-adjusted life-years by 1.33 to 1.35 and decrement of costs by $6519 to $7246. Uncertainty and scenario analyses confirmed the robustness of base-case results, whereas the value of information analyses suggested the need for further research on relative treatment efficacies among DAA regimens.ConclusionsAllocating resources for DAA treatment for HCV genotype 1 and 6 is surely a rewarding public health investment in Vietnam. It is recommended that the government rapidly scale up treatment and enable financial accessibility for HCV patients.     

Clinical course and outcome of a nosocomial outbreak of hepatitis C in a urology ward

This paper describes a prospective study of the clinical course and outcome of a nosocomial outbreak of hepatitis C virus (HCV) infection in six male urology patients at a hospital in Stara Zagora, Bulgaria. These patients had been previously hospitalised in the urology ward, during which all had received intravenous therapy. Approximately three weeks later, all six were admitted to the infectious diseases unit with acute hepatitis, shown to be caused by HCV genotype 1b. The diagnosis was confirmed by polymerase chain reaction during the first week of their hospital stay. Infected patients were followed up for 30 months following diagnosis and 54 potential contacts for 6 months post-exposure. Four patients recovered completely; one developed chronic HCV infection and one died. The latter already had cirrhosis due to co-infection with hepatitis B virus. The investigation established the index case as a patient with chronic hepatitis C, who had been an in-patient on the same ward at the same time. The most likely route of transmission was intravenous heparin flushes administered with a common syringe. Contrary to the common assumption that acute HCV infection often leads to chronic disease, only one chronic case was observed during the 30-month period of investigation.     

Management of hepatitis C

Hepatitis C (HCV) infection is the most common cause of liver disease seen in clinical practice. The usual mode of acquisition of HCV is by blood, and HCV is most often seen in persons with a history of injection drug use or who received a transfusion prior to 1991 (when testing of the blood supply for HCV was introduced). Only 25% of those infected will clear the virus; the majority of patients progress to chronic infection. Many chronically infected patients remain asymptomatic for years, and it is only after decades that some patients present with clinically apparent liver disease. HCV infection is diagnosed by the detection of an antibody to HCV and confirmed by the demonsration of viremia. Liver biopsy is usually recommended to assess severity of liver damage. Treatment with pegylated interferon in combination with ribavirin results in sustained eradication of HCV in more than half the cases treated. Treatment is often limited by significant side effects. Newer treatment modalities are in clinical trials.     

Hepatitis C virus RNA in the skin eruption from patients with prurigo and chronic hepatitis C

Hepatitis C virus RNA in the skin eruption from patients with prurigo and chronic hepatitis C. Since the discovery of hepatitis C virus (HCV) in 1989, many cutaneous disorders have been observed in patients suffering from chronic HCV infection. The relationship between HCV infection and cryoglobulinemia and porphyria cutanea tarda is clearly established, however, the link between HCV and other skin diseases is still controversial. AIM: Two patients with intense pruritus and secondary prurigo in chronic C hepatitis have been presented. METHODS: The chronic hepatitis C of the patients were proved by elevated ALT and AST level, anti HCV (ELISA), HCV-PCR serological examination and liver biopsy. The skin lesions were accompanied by severe itching. According to clinical symptoms the patients suffered from prurigo simplex. RESULTS: HCV RNA in the skin specimen from the biopsy of the skin lesion was detected by RT PCR method, but the non affected skin specimen from the patients was HCV RNA negative. CONCLUSIONS: This report is a case of prurigo simplex with chronic C hepatitis proving a direct relation between the HCV infection and prurigo.