Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease

Background and aimsThe advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a ‘real-world’ cohort of patients with CKD.MethodsWe performed an observational single-arm multi-centre study in a large (n = 198) cohort of patients with stage 1–3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15 IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities.ResultsThe average baseline eGFR (CKD-EPI equation) was 70.06 ± 20.1 mL/min/1.72 m²; the most common genotype was HCV 1b (n = 93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n = 40), simeprevir ± daclatasvir (n = 2), and sofosbuvir-based combinations (n = 147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures – eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n = 12), which required discontinuation or dose reduction of ribavirin in some cases (n = 6); deterioration of kidney function occurred in three (1.7%).ConclusionsAll-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a ‘real–world’ clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population.     

89例慢性乙型肝炎妊娠妇女孕期肝功能异常的临床分析

目的探讨慢性乙型肝炎孕妇孕期肝功能异常对妊娠和胎儿结局的影响及妊娠期间的治疗。方法研究对象为2012年1月1日-2012年6月30日至本院妇产科分娩的妇女共89例,孕期至少1次ALT≥2×ULN,且HBVDNA≥5log10拷贝／ml（HBeAg阴性者≥4logl0拷贝／ml）的患者,根据孕期治疗方案不同分为抗病毒治疗组和保肝对症治疗组。对这些患者孕期不良事件、肝病及妊娠的结局、胎儿发育情况以及新生儿状况进行回顾性分析。结果本研究入组病例89例,其中抗病毒组55例,保肝对症组34例,两组母亲基线资料差异无统计学意义,具有可比性。抗病毒治疗组产前48例（87-3％）患者ALT恢复正常,38例（69．1％）患者HBVDNA下降至〈500拷贝／ml．保肝对症治疗组产前Au、恢复正常者只有13例（38．2％）,HBVDNA〈500拷贝／ml的患者仅有1例（2．9％）。两组ALT复常率比较,差异具有统计学意义（x^2=23．4315,P〈0．0001）;两组HBVDNA低于检测下限的比率差异具有统计学意义（x^2=37．3468,P〈0．0001）。两组母亲发生不良事件的比例差异无统计学意义（P=0．176）;发生频率较高的5种不良事件有妊娠糖尿病、胎膜早破、产后出血、早产和羊水胎粪污染均为妊娠期常见不良事件,与治疗药物无显著相关性;两组母亲的不良事件类型及发生率排序相似,差异无统计学意义。结论拉米夫定或替比夫定能够有效地抑制慢性乙型肝炎患者HBV的复制,恢复其肝功能,明显地改善妊娠期间肝病活动患者的预后。妊娠期间使用拉米夫定或替比夫定未增加妊娠期不良事件的发生率,抗病毒治疗对妊娠妇女是安全的。     

Paranoid psychosis and cognitive impairment associated with hepatitis C antiviral therapy

Objective

To report a case of paranoid psychosis and cognitive impairment associated with Hepatitis C virus (HCV) antiviral therapy.

Methods

Case report.

Results

A 55-year-old male presented with paranoid psychosis and cognitive impairment, 4 months after initiating interferon-based HCV antiviral therapy. His psychosis resolved with discontinuation of therapy and initiation of risperidone, but his cognitive impairment persisted. His psychosis also re-emerged months later when attempting to titrate down his risperidone. Brain MRI demonstrated bilateral asymmetric subcortical and deep white matter changes, which were non-specific but may have rendered him susceptible to neuropsychiatric sequelae of antiviral therapy.

Conclusion

This case emphasizes the importance of neuropsychiatric screening and monitoring of patients being treated with interferon-based therapy for HCV, particularly if there is evidence of previous neurologic disease.     

Analytical characterization of an assay designed to detect and identify diverse agents of disseminated viral infection

BackgroundDiverse viruses often reactivate in or infect cancer patients, patients with immunocompromising infections or genetic conditions, and transplant recipients undergoing immunosuppressive therapy. These infections can disseminate, leading to death, transplant rejection, and other severe outcomes.ObjectivesTo develop and characterize an assay capable of inclusive and accurate identification of diverse potentially disseminating viruses directly from plasma specimens.Study designWe developed a PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) assay designed to simultaneously detect and identify adenovirus, enterovirus, polyomaviruses JC and BK, parvovirus B19, HSV-1, HSV-2, VZV, EBV, CMV, and herpesviruses 6–8 in plasma specimens. The assay performance was characterized analytically, and the results from clinical plasma samples were compared to the results obtained from single-analyte real time PCR tests currently used in clinical practice.ResultsThe assay demonstrated sensitivity and specificity to diverse strains of the targeted viral families and robustness to interfering substances and potentially cross reacting organisms. The assay yielded 94% sensitivity when testing clinical plasma samples previously identified as positive using standard-of-care real-time PCR tests for a single target virus (available samples included positive samples for 11 viruses targeted by the assay).ConclusionsThe assay functioned as designed, providing simultaneous broad-spectrum detection and identification of diverse agents of disseminated viral infection. Among 156 clinical samples tested, 37 detections were made in addition to the detections matching the initial clinical positive results.     

乙型肝炎相关性肝癌患者围手术期HBV DNA的变化及其影响因素

目的探讨乙型肝炎相关性肝癌患者围手术期HBV DNA水平变化的影响因素,比较抗病毒治疗与未抗病毒治疗对患者术后肝功能恢复的影响。方法选择65例未达到抗病毒治疗标准的乙型肝炎相关性肝癌患者,定量检测其术前和术后第3天的HBV DNA载量及白细胞介素(IL)-6、IL-10、IL-27的水平。根据术后HBV DNA载量,将患者分成HBV DNA升高(激活)组和不变组。升高组给予抗病毒治疗。记录所有患者术前、术后肝功能指标。用SPSS 17.0进行统计学分析。结果入组患者HBV激活率为37%(24/65),术前HBV DNA1×104 IU/ml的患者,术后HBV激活率为75%(18/24)。Logistic回归分析显示肿瘤直径(P=0.006)及肝切缘无水酒精注射(P=0.004)是引起HBV再激活的独立危险因素。ELISA结果示术后IL-10升高与HBV再激活有关(P=0.001),IL-6升高及IL-27降低与HBV不变有关(P=0.000)。术后HBV DNA升高且行抗病毒治疗的患者,术后肝功能恢复情况与其他患者比较差异无统计学意义(P0.05)。结论肝癌切除术可能引起患者HBV再激活,围手术期内应监测HBV DNA载量的变化。肿瘤直径、术中行肝切缘无水酒精注射术是HBV再激活的独立危险因素。患者术后IL-10、IL-6水平的变化可能与HBV DNA的变化有关。术后HBV再激活近期不会加重肝功能损伤,术后抗病毒治疗对患者近期肝功能的恢复无明显促进作用。     

慢性乙型肝炎患者疾病相关认知度及抗病毒治疗现状调查分析

目的调查CHB患者疾病相关知识的认知情况及其抗病毒治疗现状,分析患者对疾病相关知识的认知度与接受抗病毒治疗的相关性。方法依据CHB疾病相关知识设计调查问卷,对2011年10月至2013年10月首都医科大学附属北京地坛医院收治的CHB队列中部分患者进行问卷调查。结果本次调查共发放问卷930份,回收有效问卷881份（有效率94.73%）。将患者对疾病相关知识的认知程度分为较差、一般、较好3个层次。881例患者中,对预防知识的认知较差、一般、较好比例分别为17.71%、30.76%、51.53%,对基础知识的认知比例分别为22.02%、38.71%、39.27%,对治疗知识的认知比例分别为57.43%、15.89%、26.67%。正在进行抗病毒治疗的患者548例,占患者总数的62.20%,疾病相关综合知识认知较差组CHB患者抗病毒比例明显低于其他组CHB患者。结论目前患者对CHB疾病相关知识认知较差,医务人员应加强对患者的宣教。     

RNA干扰对乙型肝炎病毒复制的体外影响

目的:通过一种能够在细胞内表达短发卡RNA的逆转录病毒载体来研究RNA干扰对乙型肝炎病毒复制的影响.方法:首先针对HBV基因组Pol基因RT区寻找RNAi的靶位,并设计相对应的寡核苷酸链.然后再将一对碱基配对寡核苷酸链退火后连接入载体形成重组的质粒,并进行鉴定.在Huh-7细胞中,将通过鉴定的干扰质粒与HBV复制型质粒pHBV3.8共转染,分别应用ELISA方法来检测HBV相关的抗原,应用Northern印迹检测HBV RNA,以及应用实时荧光定量PCR和Southern印迹检测HBV核心颗粒DNA.结果:研究通过计算机方法协助寻找了3条RNAi靶位,并且构建了相应的基于逆转录病毒载体的RNA干扰质粒154i、312i和734i.结果发现312i对pHBV3.8表达有明显的抑制,HBsAg和HBeAg分别为阴性对照组的39%和41%,差异均有显著性(P=0.001,P=0.000).定量荧光PCR结果显示312i组核心颗粒DNA水平显著低于阴性对照组(21.3%±1.1%vs 100.0%±10.6%,P=0.0046).Southern blot和Northern blot结果均显示,312i组病毒复制及mRNA转录水平最低(10.5%,12.0%).结论:在HBV基因组RT区找到了一个可用于RNAi的靶位,并且构建了相对应的干扰质粒,此质粒可成功地抑制HBV复制型质粒在细胞中的复制和表达.     

三种抗病毒治疗方法对慢性乙型肝炎患者生活质量的影响

目的:探讨不同治疗方法治疗的慢性乙型病毒性肝炎,对生活质量的影响.方法:选择143例慢性乙型肝炎患者,随即分为序贯治疗组(拉米夫定 干扰素α2b,n= 56)、拉米夫定组(n=60)、干扰素组(n=27).应用标准化的量表(SF36中文版)评定法,对全部调查对象进行健康状况调查问卷.每名治疗对象于治疗前、治疗结束、随访结束分别接受评定3次.结果:三种不同的治疗方法对慢性乙型肝炎患者的生活质量影响不明显,同一治疗方法在治疗前、治疗后、随访后患者的生活质量也无显著性差异;治疗结束和随访结束,不同病毒载量的患者其生活质量亦没有显著性差异.结论:慢性乙型肝炎患者的生活质量与不同的抗病毒治疗方法无关,临床医师应根据患者的病情选择合理、有效的抗病毒方案并辅以积极的心理干预以最终提高患者生活质量.