聚乙二醇干扰素治疗慢性丙型肝炎临床观察

目的探讨聚乙二醇干扰素-α(PEG-INF-α)联合利巴韦林(RBV)治疗慢性丙型肝炎的临床疗效及安全性。方法在76例慢性丙型肝炎患者中,37例(A组)接受PEG-INF-α2a治疗48周,39例(B组)接受PEG-INF-α2b治疗48周,两组均联合应用RBV口服。在治疗结束后随访24周。结果 76例患者在疗程结束时,肝功能全部复常,HCV RNA均低于检测下限(<5×102拷贝/毫升)。停药后随访24周,75例患者获得SVR;在PEG-INF-α治疗过程中,A组出现发热2例,肌肉酸痛2例,脱发32例,消瘦27例;B组出现发热30例,肌肉酸痛31例,脱发28例,消瘦33例。结论 PEG-INF-α联合利巴韦林治疗慢性丙型肝炎安全有效,两种药物的效果无明显差异。     

聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

丙型肝炎病毒（HCV）持续感染,可引起肝脏慢性炎症坏死和纤维化,如不积极治疗可进展至肝硬化和肝细胞癌（HCC）。聚乙二醇干扰素联合利巴韦林是目前慢性丙型肝炎（CHC）的标准治疗方案,本文对聚乙二醇干扰素联合利巴韦林治疗的58例慢性丙型肝炎患者疗效进行分析,现将结果报道如下。     

聚乙二醇干扰素治疗慢性丙型肝炎疗效及其影响因素

丙型肝炎病毒(HCV)是引起输血后肝炎和散发性非甲非乙型肝炎的主要病原，其中20％～30％的患者可进展为肝硬化甚至肝癌，对人类危害极大。10多年来，干扰素α曾被选择性地用于治疗慢性丙型肝炎(简称慢丙肝)，它对于改善患者肝功能、预防肝纤维化乃至HCV相关的肝癌具有重要意义，然而只有10％～15％的患者1能治疗成功。近年，聚乙二醇干扰素(PEG-IFN)已被用于慢性肝病和肝硬化治疗的临床研究，     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

目的评价聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效。方法使用聚乙二醇干扰素α-2a(派罗欣)联合利巴韦林(800~1200mg/d)治疗58例慢性丙型肝炎患者,疗程48周,分别于治疗12周、24周和48周及治疗结束后24周评价疗效,并观察药物副作用。结果基因1型和非基因1型患者早期应答率分别为57.1%和76.7%(P>0.05),持续应答率分别为53.6%和80.0%(P<0.05);HCV RNA高水平组和低水平组之间持续应答率分别为56.3%和80.8%,具有显著性差异(P<0.05)。结论在慢性丙型肝炎患者的治疗中,基因1型患者疗效低于非基因1型,HCV RNA低水平组的疗效优于高水平组。     

普通干扰素与聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

目的研究干扰素α-1b或聚乙二醇化干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的效果、安全性、耐受性及经济-效益比。方法 86例慢性丙型肝炎患者接受干扰素α-1b联合利巴韦林治疗48周;另26例接受聚乙二醇干扰素联合利巴韦林治疗48周。结果在治疗4周和12周时,干扰素α-1b治疗患者病毒学应答率分别为18.6%和61.6%,显著低于聚乙二醇干扰素治疗组的38.5%和84.6%(P﹤0.05);在治疗48周和治疗结束后随访48周时,干扰素α-1b治疗患者病毒学应答率分别为79.1%和76.7%,与聚乙二醇干扰素组的92.3%和84.6%比,无明显差异性(P﹥0.05);干扰素α-1b治疗组成本/效果比为13959.6,显著低于聚乙二醇干扰素组的54241.1;治疗期间两组ALT复常率无明显差异性(P﹥0.05);干扰素α-1b治疗的副作用相对轻于聚乙二醇干扰素。结论在我国目前国情下,干扰素α-1b联合利巴韦林治疗慢性丙型肝炎有效、安全。     

聚乙二醇化干扰素α-2α治疗慢性丙型肝炎的疗效与安全性

聚乙二醇化干扰素α-2α(PEG—IFNα-2α，派罗欣，罗氏)，改变了干扰素(IFN)的药代动力学。其血清半衰期增加了大约10倍，同时增加了药物的药理学活性。一次注射可维持有效的抑制病毒的血药浓度长达7d，从而提高临床疗效。国外多项临床对照研究已经证实，PEG—IFNα-2α治疗慢性丙型肝炎的疗效明显优于IFNα-2α，能显著提高患者的持续病毒学应答。     

聚乙二醇化干扰素α-2a治疗血友病艾滋病合并丙型肝炎的疗效观察

慢性丙型肝炎是血友病艾滋病患者最常见的死亡原因之一,比起单独丙型肝炎病毒(HCV)感染者,艾滋病病毒(HIV)可促使HCV复制和增殖,加快病程进展,更早进展到肝硬化期[1].     

聚乙二醇干扰素治疗丙型肝炎

干扰素目前仍是治疗丙型肝炎的主要药物。干扰素是人体内自然产生的一种细胞因子，具有广谱的抗病毒活性。其作用机制一是直接抑制病毒复制，通过激活细胞干扰素受体诱导细胞产生干扰素效应蛋白(如2′，5′-寡腺苷酸合成酶，新喋呤等)而发挥作用；二是通过增强免疫系统的功能而抑制病毒。目前临床用于治疗丙型肝炎的主要是α-干扰     

聚乙二醇化干扰素--抗丙型肝炎病毒的最佳选择

近年来聚乙二醇化干扰素α(PEG-IFNα)的研制成功使慢性丙型、乙型病毒性肝炎的治疗效果有了进一步的提高,并有可能提高慢性骨髓性白血病、实体瘤和多发性硬化症的治疗效果;因其每周给药一次,而称为长效干扰素。当前国际上已公认PEG-IFNα与利巴韦林联合疗法为抗丙型肝炎病毒的最佳选择[1,2]。     

中药联合聚乙二醇干扰素治疗慢性丙型肝炎的随机对照研究

[目的]探讨中药联合聚乙二醇干扰素+利巴韦林治疗慢性丙型肝炎的疗效。[方法]本研究采用随机、单盲和安慰剂对照临床设计试验。将合格的130例患者随机分为治疗组(68例)和对照组(62例),治疗组采用聚乙二醇干扰素+利巴韦林+中药基本方治疗,对照组予聚乙二醇干扰素+利巴韦林+中药安慰剂治疗。(聚乙二醇干扰素180ug,皮下注射,1次/周;利巴韦林900~1 200mg/d;中药开水冲服,2次/天)。[结果]治疗组中1例患者因出现神经性耳鸣出组,对照组中1例因中性粒细胞持续低于0.5×109/L出组,最后纳入统计分析共有128例,其中对照组61例,治疗组67例。治疗组和对照组患者在完全早期病毒学应答率(cEVR)、持续应答率(SVR)的差异有统计学意义(P0.05)。2组患者肝功能(ALT)在治疗前及治疗后第12w、24w、48w差异无统计学意义(P0.05),在停药后随访24w差异有统计学意义(P0.05)。2组患者均出现干扰素不良反应,治疗组在头痛、肌肉酸痛、恶心呕吐、中性粒细胞下降及血小板下降与对照组差异有统计学意义(P0.05)。[结论]中药联合聚乙二醇干扰素+利巴韦林治疗慢性丙型肝炎疗效优于聚乙二醇干扰素+利巴韦林,并能减少不良反应发生,增加远期疗效。     

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for 65-85 kg; 1200 mg/d for 85-105 kg; 1400 mg/d for 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.     

Pharmacoeconomic analysis of the treatment of chronic hepatitis C with peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin in Spain

BackgroundAn independent meta-analysis of randomized comparative trials of peginterferons alfa-2a and alfa-2b, both combined with ribavirin, analyzed the probability of achieving a sustained virological response (SVR).ObjectiveTo estimate the long-term cost-effectiveness of treatment of patients with chronic hepatitis C with peginterferon alfa-2a (180 μg/week) plus ribavirin (800–1200 mg/day) vs. alfa-2b (1.5 μg/kg/week) plus ribavirin (800–1400 mg/day), from the perspective of the Spanish National Health System.MethodsA Markov model was developed with 7 health states to simulate lifetime disease progression. SVR was calculated from the meta-analysis data. Transition probabilities and health state utilities were obtained from published literature. Direct healthcare costs were obtained from the drug catalog, while costs of disease-related complications were obtained from published studies and healthcare cost database. Costs were expressed in 2010€. The annual discount rate applied was 3.5% for both costs and benefits.ResultsSVR rate for treatment with alfa-2a was higher than with alfa-2b; the differences were 6.0%, 7.6% and 8.7% for all genotypes, genotypes 1/4 and genotypes 2/3, respectively. Each patient would gain 0.469, 0.600 and 0.685 life-years and 0.155, 0.198 and 0.227 quality-adjusted life-years with alfa-2a vs. alfa-2b, for the respective genotypes. The cost saving per patient treated with alfa-2a would be €705, €672 and €1900, for all genotypes and for genotypes 1/4 and 2/3, respectively, alfa-2a being dominant.ConclusionsAccording to the present model, treatment of patients with chronic hepatitis C with peginterferon alfa-2a is cost-effective compared with peginterferon alfa-2b, both combined with ribavirin.     

聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者疗效比较和影响疗效的预测因素分析

目的 比较聚乙二醇干扰素α-2a与普通干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者的疗效,并对影响抗病毒疗效的因素进行分析。方法 2010年5月~2014年8月我院收治的慢性丙型肝炎患者116例,随机将患者分为研究组和对照组,每组58例。给予对照组患者普通干扰素α-2b 联合利巴韦林治疗,给予研究组患者聚乙二醇α-2a干扰素联合利巴韦林治疗。采用实时荧光定量PCR法检测血清HCV RNA定量,对两组病毒学应答率以及性别、年龄、体质指数和病毒载量对治疗效果的影响进行比较分析。结果 在治疗12周、24周、48周以及停药后12周和24周,研究组患者血清HCV RNA转阴率分别为51.72%、60.34%、72.41%、68.97%和65.52%,显著高于对照组患者的31.03%、48.27%、55.17%、48.27%和41.38% （P<0.05）;研究组患者快速病毒学应答率、早期病毒学应答率、治疗结束病毒学应答率和持续病毒学应答率分别为75.86%、84.48%、86.20%和74.14%,显著高于对照组的51.72%、60.34%、63.79%和55.17%（P<0.05）;在治疗4周、12周、24周和48周,研究组患者血清HCV RNA水平分别为（4.72±1.30） IU/ml、（4.09±1.21） IU/ml、（3.79±1.18） IU/ml和（3.26±1.08） IU/ml,显著低于对照组患者的（5.27±1.52） IU/ml、（4.68±1.41） IU/ml、（4.15±1.37） IU/ml和（3.99±1.16） IU/ml（P<0.05）;两组患者在治疗过程中,均出现发热、失眠、肌肉酸痛、乏力和白细胞下降等不良反应,但差异均不具有统计学意义（P>0.05）;研究组获得SVR患者治疗前血清HCV RNA水平为（3.57±0.45） IU/ml,显著低于未获得SVR患者的（4.92±0.09） IU/ml（P<0.05）。讨论 聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎患者有效且安全,治疗前患者病毒载量低将预示疗效好。     

Efficacy of low dose peginterferon alpha-2b with ribavirin on chronic hepatitis C

INTRODUCTION The hepatitis C virus is a major cause of liver diseases affecting 170 million people worldwide[1]. In India, the estimated prevalence of hepatitis C virus infection is 1.8%. Genotypes 2 and 3 are predominant in Indian population[2]. Therapy …     

Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection

AIM: To evaluate the safety and efficacy of pegylated interferon alfa-2a and ribavirin therapy in elderly patients with chronic hepatitis C infection.METHODS: Patients characteristics, treatment results and safety profiles of 4859 patients with hepatitis c virus (HCV) infection receiving treatment with pegylated interferon alfa-2a and ribavirin were retrieved from a large ongoing German multicentre non-interventional study. Recommended treatment duration was 24 wk for GT 2 and GT 3 infection and 48 wk for GT 1 and GT 4 infection. Patients were stratified according to age (< 60 years vs ≥ 60 years). Because of limited numbers of liver biopsies for further assessment of liver fibrosis APRI (aspartate aminotransferase - platelet ratio index) was performed using pre-treatment laboratory data.RESULTS: Out of 4859 treated HCV patients 301 (6.2%) were ≥ 60 years. There were more women (55.8% vs 34.2%, P < 0.001) and predominantly GT 1 (81.4% vs 57.3%, P < 0.001) infected patients in the group of patients aged ≥ 60 years and they presented more frequently with metabolic (17.6% vs 4.5%, P < 0.001) and cardiovascular comorbidities (32.6% vs 6.7%, P < 0.001) and significant fibrosis and cirrhosis (F3/4 31.1% vs 14.0%, P = 0.0003). Frequency of dose reduction and treatment discontinuation were significantly higher in elderly patients (30.9% vs 13.7%, P < 0.001 and 47.8% vs 30.8%, P < 0.001). Main reason for treatment discontinuation was “virological non-response” (26.6% vs 13.6%). Sustained virological response (SVR) rates showed an age related difference in patients with genotype 1 (23.7% vs 43.7%, P < 0.001) but not in genotype 2/3 infections (57.7% vs 64.6%, P = 0.341). By multivariate analysis, age and stage of liver disease were independent factors of SVR.CONCLUSION: Elderly HCV patients differ in clinical characteristics and treatment outcome from younger patients and demand special attention from their practitioner.     

聚乙二醇α-2b干扰素联合利巴韦林治疗慢性丙型肝炎72周随访观察

对聚乙二醇化α-2b干扰素(PEG-IFNα-2b)、利巴韦林联合治疗慢性丙型肝炎的疗效、安全性情况进行观察、随访。一、资料与方法1.病例选择:我院2002年3月-2003年12月住院或门诊的30例慢性丙型肝炎患者,诊断符合2000年病毒性肝炎防治方案。男25例,女5例,治疗组平均年龄(40.6±10.3)岁,ALT(117±12)U/L,对照组平均年龄(41.1±6.8)岁;ALT(132±14)U/L;两组患者HCV RNA定     

Acute sensorineural hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment： Outcome after resumption of therapy

Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilateral, has been repotted as a consequence of therapy with both non-pegylated and pegylated interferon (pegIFN) but is not a well-known adverse effect. We report a 45-year-old Caucasian woman who developed acute sensorineural hearing loss 2 mo after starting therapy with peglFN-a 2b and ribavirin for the treatment of chronic HCV, genotype la. She did not report the hearing loss to the hepatitis clinic until 1 mo, later whereupon therapy was promptly discontinued. Although her serum alanine aminotransferase (ALT) normalized and her HCV-RNA became undetectable after 12 wk of peglFN and ribavirin therapy, after discontinuation, her HCV-RNA became detectable with significant elevations of serum ALT. Four months after initial discontinuation, the patient re-commenced peglFN and ribavirin combination therapy. After 44 of 48 wk of therapy, the patient's liver biochemistry has normalized and the HCV-RNA is undetectable. She has not developed worsening of her hearing loss and hearing on the left-side is unaffected. Both patients and physicians should be aware that sensorineural hearing loss may occur with peglFN therapy. Our experience suggests that re-institution of therapy is not always associated with further hearing impairment.     

Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia

AIM: to evaluate addition of boceprevir to peginterferon/ribavirin(PR) in Russian patients with chronic hepatitis C virus(HCV).METHODS: treatment-naive(t N) and treatmentexperienced(t E) patients(who had failed prior treatment with PR for ≥ 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebocontrolled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. t N patients randomized to triple therapy received boceprevir(800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8(t W8) HCV RNA levels. t E patients received boceprevir plus PR for 32 wk and then further therapy according to t W8 HCV RNA levels. treatment was discontinued for t N patients with detectable HCV RNA at t W24 and t E patients with detectable HCV RNA at t W12 because of futility. the primary efficacy end point was sustained virologic response(SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy.RESULTS: SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2%(95%CI: 16.4-41.5; P 0.0001). Rates of SVR were higher in the boceprevir arm in both t N and t E patient groups(t N 78.4% vs 56.3%; t E 69.4% vs 30.0%). Within t E patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type(null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both t N(86%) and t E(71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone(47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia( 10 g/d L) and those without anemia(71.2% vs 77.4%).CONCLUSION: Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.     

聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型肝炎的随机对照临床研究

目的评价小剂量聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型病毒性肝炎的疗效和安全性.方法192例慢性丙型肝炎患者随机分为两组：聚乙二醇干扰素α-2b 0.5μg/kg每周一次联合利巴韦林750～1050 mg/d,或普通干扰素α-2b 3 MIU每周3次联合利巴韦林750～1050 mg/d.疗程48周,治疗结束后随访24周.结果聚乙二醇干扰素α-2b联合利巴韦林治疗的持续病毒学应答率为53.8%,而普通干扰素α-2b联合利巴韦林治疗的持续病毒学应答率为58.1%,两组持续病毒学应答率相当（P=0.966）.聚乙二醇干扰素α-2b治疗组的药物相关性不良反应发生率为100%,而普通干扰素α-2b治疗组的不良反应发生率为95.2%,两组间差异有统计学意义（P=0.033）.但是没有与干扰素α-2b聚乙二醇化相关的特有的新的不良反应发生.结论小剂量聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型肝炎的疗效和安全性与普通干扰素α-2b联合利巴韦林治疗的疗效和安全性相当.