慢性丙型肝炎患者血清丙氨酸转氨酶水平、丙型肝炎病毒RNA定量对干扰素疗效的影响

目的分析慢性丙型肝炎患者血清丙氨酸转氨酶水平、丙型肝炎病毒RNA定量对干扰素疗效的影响。方法我院传染科治疗的慢性丙型肝炎患者68例,所有患者均给予干扰素和利巴韦林治疗。结果 68例患者中,血清丙氨酸转氨酶>正常值2倍的患者与血清丙氨酸转氨酶<正常值2倍的患者相比,干扰素的闻道无明显差异(P>0.05);丙型肝炎病毒RNA含量<106copes/mL的患者的干扰素疗效明显优于丙型肝炎病毒RNA含量>106copes/mL的患者(P<0.05),但两组患者随访24周时,干扰素的疗效无明显差异(P>0.05)。结论慢性丙型肝炎患者血清丙氨酸转氨酶水平与干扰素的疗效无明显关系,而丙型肝炎病毒RNA含量与干扰素的近期疗效相关,但与远期疗效无明显关系,因此可以根据慢性丙型肝炎患者的丙型肝炎病毒RNA含量选择适当的干扰素治疗。     

慢性肾功能衰竭贫血患者红细胞分布宽度与促红细胞生成素水平的相关性研究

目的 探讨慢性肾功能衰竭(CRF)贫血患者红细胞分布宽度(RDW)与其红细胞生成素(EPO)水平的相关性.方法 将76例CRF贫血患者分为RDW≥13.0％组(n=43)和RDW＜13.0％组(n=33),用免疫学方法和生物检测技术测定CRF患者EPO、血色素、白蛋白、血清铁等指标,并对结果进行统计分析.结果 RDW≥13.0％组肾性贫血患者的EPO水平较RDW＜13.0％组相对低[O/P比值:(0.351±0.12)vs.(0.167±0.57),P＜0.01],并且RDW与血清Alb、Fe水平呈负相关(r=-0.42,-0.37).结论 RDW可以作为监测CRF贫血患者EPO水平的预测指标,高水平的RDW提示CRF患者EPO水平相对较低.     

系统性红斑狼疮贫血与促红细胞生成素

目的　探讨促红细胞生成素 (EPO)与系统性红斑狼疮 (SLE)贫血的关系。方法　测定 36例SLE贫血患者血清EPO(s EPO)水平 ,分析其与血红蛋白 (Hb)的相关性。结果　SLE贫血患者s EPO水平4 4 2 ( 7 8～ 192 2 )U/L ,明显高于正常对照组 4 2 ( 0 74～ 18 4 )U/L及SLE非贫血患者 6 8( 1 2～ 2 9 7)U/L ,但低于慢性失血所致缺铁性贫血 (IDA)患者 93( 15 5～ 389 2 )U/L(P <0 0 5 )。SLE贫血组和IDA组Hb与s EPO水平呈负相关 (P <0 0 5 )。结论　SLE贫血患者s EPO水平相对降低可能是SLE贫血的原因之一。     

慢性呼吸衰竭贫血患者血清EPO、RBC水平检测及其临床意义

目的探究慢性呼吸衰竭贫血患者血清促红细胞生成素(EPO)、红细胞(RBC)水平的检测及其临床意义。方法选取30例慢性呼吸衰竭贫血患者作为观察组,另选取30例正常体验的健康人作为对照组。采集两组的血样,检测并比较两组血清EPO、RBC、红细胞压积(HCT)和血红蛋白(Hb)水平。结果观察组EPO水平为(99.68±28.92)mIU/ml,RBC水平为(3.30±0.65)×10^12/L,HCT水平为(29.20±3.69)%,Hb水平为(86.30±8.68)g/L,对照组EPO水平为(21.51±5.27)mIU/ml,RBC水平为(4.27±0.26)×10^12/L,HCT水平为(38.84±2.31)%,Hb水平为(132.47±6.92)g/L;观察组EPO水平高于对照组,RBC、HCT及Hb水平均低于对照组,差异有统计学意义(P<0.05)。结论慢性呼吸衰竭患者血清EPO明显高,RBC明显降低,要根据个体化差异制定合理的治疗方案。对慢性呼吸衰竭患者血清EPO进行动态监测,血清EPO、RBC水平检测对治疗呼吸衰竭贫血患者以及预后判断有重要的意义。     

银强化滴金免疫法HCV—IgM检测临床价值

目的探讨丙型肝炎患者抗HCV—IgM检测的价值，方法对60名正常人、20例活动期丙型肝炎患者及10例稳定期丙型肝炎患者的血清进行抗HCV—IgM、HCV-RNA检测。结果两组抗HCV—IgM的阳性率比较差异有统计学意义（P〈0．001）；慢性丙肝活动期患者的阳性率明显高于稳定期患者（P〈0．001）；HCV—IgM抗体阳性率与HCV—RNA阳性率相比无差异统计学意义（P〉0．05）。结论血清抗HCV—IgM与肝细胞损害有关，可视为慢性丙型肝炎活动、HCV复制的标志。     

慢性肾功能不全患者血清促红细胞生成素水平的观察

应用酶联免疫分析法测定慢性肾功能不全（CRI）不同时期血清促红细胞生成素（EPO）水平．结果发现，CRI患者氮质血症期、尿毒症或血清EPO浓度与正常对照组无明显差异，且与肾功能损害程度、贫血程及无显著相关．透析和体外给予重组人红细胞生成素，可改善尿毒症患者的贫血状态，但基础血清EPO浓度无明显变化．以上结果提示CRI患者不仅EPO生成缺乏，而且存在EPO生以氧依赖调控系统异常。     

1例慢性丙型肝炎肝移植术后HCV HVR1序列动态观察

病例：患者，男性、已婚、汉族、65岁、干部、籍贯山东。1977年诊断为丙型肝炎肝硬化。2004年10月在云南省第一人民医院诊断为“慢性丙型肝炎，肝硬化失代偿期”，并行背驮式肝移植。术前检查乙型肝炎病毒表面抗体阳性、抗HCV抗体阳性、HCV—RNA阳性。肝移植后随访一般健康状况良好，生活质量和精神状况稳定。术后定期检测肝功能肝胆酶谱一直保持在正常范围，抗-HCV及HCV—RNA检测均为阳性。肝移植后使用免疫抑制剂PK-506，使用剂量肝移植后1～6个月内维持血药浓度在10ng／ml，7～12个月维持在5～10ng／ml，至今仍维持在5～10ng／ml。选择患者肝移植前血清标本一份、肝移植后血清标本四份做丙肝病毒基因型及HUR1序列检测。     

促红细胞生成素的临床应用

促红细胞生素(EPO)是一种由肾脏近曲小管合成的活性糖蛋白,能刺激骨髓红系造血母细胞的增殖和分化,对红细胞发育起主要调控作用。临床研究显示,EPO除可用于慢性肾性贫血治疗外,对多种疾病如早产儿、肿瘤、AIDS、充血性心力衰竭以及丙型肝炎病毒感染等疾病所致贫血亦有较好的疗效。近年来,重组人促红细胞生成素对人体免疫系统的影响开始受到重视。     

聚乙二醇IFNα-2a联合利巴韦林治疗自身免疫抗体阳性慢性丙型肝炎的临床疗效及安全性评估

目的探讨聚乙二醇IFNα-2a联合利巴韦林对自身免疫抗体阳性慢性丙型肝炎的临床疗效。方法慢性丙型肝炎病毒(HCV)感染者102例,筛查自身抗体,分为自身抗体阳性组和阴性组,均给予IFNα-2a联合利巴韦林治疗。观察治疗前HCV RNA载量、治疗过程中血ALT和AST水平变化、病毒学应答情况及不良反应。结果 102例慢性HCV感染者中,共检出自身抗体阳性患者31例,其中,抗线粒体抗体(AMA)阳性18例,抗平滑肌抗体(SMA)阳性10例,抗1型肝肾微粒抗体(LKM1)阳性3例。治疗前,阳性组和阴性组HCV RNA载量,以及治疗后快速和持续病毒学应答率比较差异无统计学意义。治疗0~20周,两组患者ALT和AST水平比较差异无统计学意义(P>0.05),治疗24周后,阳性组高于阴性组。两组患者的不良反应发生率比较差异无统计学意义。结论聚乙二醇IFNα-2a联合利巴韦林可有效治疗自身抗体阳性和阴性慢性丙型肝炎患者,自身抗体的存在与否对治疗安全性无明显影响。     

荧光聚合酶链反应定量检测丙型肝炎患者血清中的HCV RNA及其意义

目的探讨定量检测丙型肝炎患者血清中HCV RNA与急、慢性病毒性肝炎和肝纤维化等疾病之间的关系,分析其与血清丙氨酸转氨酶(ALT)水平之间的关系。方法在本组试验中,主要采用荧光聚合酶链反应(PCR)方法,以我院收治的103例不同临床类型的丙型肝炎患者为研究对象,对其血清中的HCV RNA进行定量检验。结果无症状HCV感染者血清HCV RNA含量显著低于急性丙型肝炎、慢性丙型肝炎、肝硬化患者,差异具有统计学意义(P<0.05)。结论血液中HCV RNA的检测已成为HCV感染诊断,是丙型肝炎患者病毒药物治疗疗效监测及血液筛查的重要手段。在肝损害和肝脏疾病进展过程中,高水平HCV RNA发挥着重要的作用。     

An integrated pharmacodynamic analysis of erythropoietin,reticulocyte, and hemoglobin responses in acute anemia

Purpose. To determine by pharmacodynamic (PD) analysis physiologically relevant parameters of the cellular kinetics of erythropoiesis in acute anemia. Methods. The PD relationships among erythropoietin (EPO), reticulocyte, and RBC (Hb) responses were investigated in young adult sheep in acute anemia induced twice by two controlled phlebotomies separated by a 4-week recovery period. Results. The phlebotomies resulted in rapid increases in plasma EPO, with maximal levels occurring at 3 to 8 days, followed by a reticulocyte response with a delay of 0.5 to 1.5 days. The Hb returned to prephlebotomy base line at the end of the 4-week recovery period. The EPO, reticulocyte count, and Hb responses were well described by a PK/PD model (r = 0.975) with the following cellular kinetics parameters: the lag time between EPO activation of erythroid progenitor cells and reticulocyte formation; the reticulocyte-to-RBC maturation time; the reticulocyte and Hb formation efficacy coefficients, quantifying EPO's efficacy in stimulating the formation of reticulocytes and Hb, respectively; the C50 PK/PD transduction parameter defined as the EPO level resulting in half the maximum rate of erythropoiesis. Conclusion. Physiologically relevant cellular kinetics parameters can be obtained by an endogenous PK/PD analysis of phlebotomy data and are useful for elucidating the pathophysiologic etiology of various anemias.     

122例艾滋病患者合并乙肝病毒 丙肝病毒感染的临床流行病学研究

目的 研究在抗逆转录病毒药物治疗(HAART)状态下HIV/AIDS患者合并乙肝病毒(HBV)、丙肝病毒(HCV)的流行状况以及相关血清生化和病毒学特征。 方法 对122例正在接受HAART治疗的HIV/AIDS患者采集血标本,使用酶免法(MEIA)检测乙肝五项指标(HBs Ag、抗-HBs、HBe Ag、抗-HBe、抗-HBc)、肝功能,应用酶联免疫吸附法(ELISA)检测丙型肝炎病毒抗体,运用RT-PCR法对丙肝病毒抗体阳性标本以及表面抗原和/或核心抗体阳性标本分别进行HCV-RNA以及HBV-DNA测定。以43名单纯HCV感染者作为对照组进行研究。 结果 122名 HIV/AIDS患者,乙肝五项指标全阴性97例(78.86%),表面抗原阳性3例(2.46%),表面抗体阳性者总计19例(15.57%),单纯核心抗体阳性者3例(2.46%)。HCV 抗体阳性84例(68.85%),84例HCV抗体阳性标本中HCV-RNA 阳性58例(69.05%),HIV/HCV/HBV合并感染者为0。HIV/HCV合并感染组 HCV-RNA 水平与感染者性别,CD4⁺ 细胞数水平无明显差异(P>0.05);HIV/HCV合并感染组与单纯HCV感染组 HCV-RNA水平、肝功能异常率无明显差异(P>0.05)。 结论 HIV感染者HBsAg阳性率低于普通人群,HIV/HCV合并感染的比例显著高于普通人群。HIV/HCV合并感染与单纯HCV感染者血清生化及病毒学改变相似。     

Supra-physiological doses of anabolic androgenic steroids impact erythropoietin and blood parameters

Hematological parameters and erythropoiesis are known to be influenced by anabolic androgenic steroid (AAS) use. However, little is known in relation to supra-physiological doses of AAS. Therefore, the aim of this study was to evaluate the effect of supra-physiological doses of AAS on serum and urinary erythropoietin (EPO), and blood parameters, from self-reported AAS users. Serum EPO levels were higher in testosterone positive AAS users (11.83 mIU/mL ± 4.19) than nonpositive (6.60 mIU/mL ± 2.70, p = 0.03), while no differences in urinary EPO levels were noted. There were positive correlations between serum EPO and testosterone levels (rs = 0.46, p = 0.01) and reticulocyte percentage (rs = 0.43, p = 0.02). Individuals with AAS-induced hypogonadism (ASIH; luteinizing hormone levels <1.4 IU/L) had approximately 75% higher serum EPO (p < 0.05) and 140% higher high fluorescence reticulocyte fractions (p < 0.001), as well as other affected hematological parameters, compared with non-ASIH individuals. The results extend the knowledge of how endocrine and hematological biomarkers are affected by AAS doping.     

Application of a bridging ELISA for detection of anti-erythropoietin binding antibodies and a cell-based bioassay for neutralizing antibodies in human sera

Although erythropoietin (EPO)-related pure red-cell aplasia (PRCA) is a rare disorder, attention still needs to be paid because underline mechanism of EPO immunogenicity is various and controversial. Among several assay systems for screening of anti-EPO binding antibodies (Abs), we adopted and setup the bridging ELISA using streptavidin-coated plate. To test their neutralizing activities, cell-based neutralizing (NT) bioassay was setup. When we analyzed serum samples by using these two assays, we found two positive results in the two samples. In the sample 1, 411.9 ng/ml of anti-EPO Abs were found and neutralizing activity of 36.2% at 1:5 serum dilution was detected. In the sample 2, 40.5 ng/ml of anti-EPO Abs were found and neutralizing activity of 96.7% was detected. Our results indicate that the higher anti-EPO antibody (Ab) level in a serum does not always lead to the stronger neutralizing activity. This report gives crucial consideration to the needs of establishing clear criteria to link various assay parameters with the onset of PRCA and its progression.     

Dosing patterns,hematologic outcomes,and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia

ABSTRACT

Objective: Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting.

Methods: This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for ≥ 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24‐week study period.

Results: A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (≥ Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (≥ 11?g/dL) (?p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24‐week cumulative doses were EPO 279?336 ± 68?302 units and DARB 1084 ± 246?µg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = $3400, DARB = $4726; FSS: EPO = $1528, DARB = $2379).

Conclusions: Extended dosing (≥ Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39–56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.     

New alternatives for erythropoietin therapy in chronic renal failure

Erythropoietin (EPO) is one of the main cytokines involved in the regulation of erythropoiesis. The main site of EPO production are the kidneys. An altered EPO production leads to pathological conditions such as anemia and polycythaemia. Due to the progressive loss of renal peritubular cells, patients with chronic kidney disease (CKD) have low EPO plasma levels. This decreases erythron stimulation with the direct consequence of developing anemia. Before the introduction in the clinical practice of rHuEpo, in the late 1980s, the only solution for treating this type of anemia were blood transfusions and anabolic steroids. Even rHuEpo has proven to be safe and effective for treatment of anemias, there are some concerns about its cost, the need for frequent parenteral administration, and development of anti-EPO antibodies. These inconveniences prompted the search for novel erythropoiesis stimulating agents. Different strategies lead to isolation or chemical synthesis of such agents as darbepoetin alfa and EPO mimetics. In this review, we present some general aspects of EPO biology, with emphasis on chronic renal failure, and expose some of the alternatives to EPO used for anemia correction.     

Role of ribavirin in HCV treatment response: now and in the future

Importance of the field: Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation.

Areas covered in this review: Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted.

What the reader will gain: To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials.

Take home message: Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.     

An in vivo model to assess factors that may stimulate the generation of an immune reaction to erythropoietin

The incidence of pure red cell aplasia (PRCA) in patients with chronic kidney disease associated with the subcutaneous (s.c.) administration of epoetin alfa (EPREX) began to increase in 1998. As part of an intensive investigation into the reasons for this increase, in vivo models were developed to assess the ability of potential causative factors to stimulate an immune response to recombinant human erythropoietin (rHuEPO). It was difficult to generate anti-EPO antibodies in mice. In animals injected with rHuEPO alone, anti-EPO antibodies were either absent or present at very low levels. The addition of an adjuvant to the immunization protocol was able to increase both the frequency of occurrence and titer of the immune response and resulted in the generation of anti-EPO antibodies that, in most cases, recognized both human and mouse EPO. Some mice exhibited a reduction in hematocrit, suggesting neutralization of endogenous EPO by anti-EPO antibodies. To evaluate the primary lead identified in the technical investigation, leachates from the uncoated syringe stoppers of EPREX syringes, a surrogate antigen (chicken egg albumin, OVA) was used to avoid possible interferences that could arise from the use of an endogenous protein like EPO. These leachates yielded a positive, concentration-dependent antibody response in the OVA animal model, demonstrating their adjuvant properties and providing support for the hypothesis generated through the technical investigation that leachates were capable of enhancing the immune response to rHuEPO.     

Emerging drugs for treatment of anemia of chronic kidney disease

Introduction: Erythropoiesis-stimulating agents (ESAs) prevent transfusions among anemic patients with chronic kidney disease (CKD). Clinical trials, meta-analyses, and guidelines identify arterial and venous thromboembolism as well as myocardial event risks with the traditional ESAs, erythropoietin (EPO), and darbepoietin. Side effects of anemia treatment, considering frequency and dosage of treatment as well as targeted hemoglobin levels when utilizing ESAs, greatly impact overall well-being and the quality of life. There is a need for less frequent but equally effective ESAs in this setting.

Areas covered: The three generations of ESAs used in CKD-associated anemia are described. Cost effectiveness of the utilization of these therapies, in addition to emerging therapies, is also presented. The few clinical and controlled trials only highlight the need for clarity in molecular biology surrounding the components that control EPO levels and utilization.

Expert opinion: Anemia associated with CKD is an important area for development of newer therapies which are potentially safer and more convenient to administer.     

Methadone Maintenance Patients’ Knowledge,Attitudes, Beliefs,and Experiences Concerning Treatment for Hepatitis C Virus Infection

Hepatitis C virus (HCV) knowledge, attitudes, beliefs, and experiences (KABE) of 64 HCV antibody positive methadone maintenance treatment (MMT) patients were assessed in conjunction with acceptability of an on-site semi-structured HCV education session, HCV RNA diagnostic testing, HCV treatment motivational assessment, and initiation of HCV treatment. The KABE interviews were conducted in 2006 and 2007 in an urban New York State MMT clinic in affiliation with a NIDA-funded HCV research project. The majority had basic knowledge of HCV disease, but poor understanding of HCV testing and treatment. While the majority of participants expressed fear of HCV treatment side effects, 88%% accepted HCV RNA testing and 78%% expressed willingness to start HCV treatment with the majority of chronically infected choosing to start HCV treatment medications. Study limitations and implications are discussed.