重组复合干扰素治疗慢性丙型肝炎的临床研究

目的 比较两种剂量的重组复合干扰素（Ｃｏｎｓｅｎｓｕｓ Ｉｎｔｅｒｆｅｒｏｎ,ＣＩＦＮ）和重组干扰素α－２α（ＩＦＮα－２α）治疗慢性丙型肝炎患者的疗效和安全性。方法 １８７例初治的慢性丙型肝炎（丙肝）患者,随机分成三组,分别接受：ＣＩＦＮ１５μｇ（Ａ组）６１例、９μｇ（Ｂ组）６５例和ＩＦＮα－２α３ＭＵ（Ｃ组）６１例,１周３次,共２４周,在完成治疗后继续随访２４周。本试验以治疗结束时和随访时丙氨     

复合α干扰素联合病毒唑治疗慢性丙型肝炎的临床研究

目的：观察复合α干扰素（CIFN）联合病毒唑治疗慢性丙型肝炎的临床效果及用药安全性,探讨临床抗慢性丙型肝炎病毒的方法。方法：选择68例慢性丙型肝炎患者并随机分成联合治疗组与对照组,联合治疗组38例,给予CIFN15μg,隔日皮下注射,加病毒唑450mg.tid口服,疗程为6个月,对照组30例,单用干扰素α-2b,3MU,隔日肌注1次,疗程6个月;两组停药后随访6个月。观察两组治疗前后的临床症状,体征改善状况,生化应答率,病毒应答率和临床副作用。结果：疗程结束时联合治疗组临床症状,体征的缓解率为89．47％,生化应答率为89．47％,病毒应答率为71．05％,对照组分别为83．34％、83．34％、66．67％（均P＞0．05）。随访6个月,联合治疗组的持续应答率为47．37％,而对照组为16．67％（P＜0．05）。两组副作用均有发热、乏力、胃肠道症状、白细胞下降、肌肉酸痛等（P＞0．05）。结论：CIFN联合病毒唑治疗慢性内型肝炎,可迅速缓解患者的症状体症,促进HCV－RNA阴转,停药6个月后的持续完全应答显著优于单干扰素。临床应用安全。     

重组复合干扰素—干复津治疗慢性丙型肝炎随机对照临床试验结果

目的为了研证美国安进公司研制生产的重组复合干扰素,比较15μg和9μg干复津与11.1μg(3MU)罗扰素治疗慢性丙型肝炎的疗效和安全性。材料和方法 67例确诊为慢性丙型肝炎的患者,随机分为A组(干复津15μg)20例,B组(干复津9μg)23例,C组(罗扰素)24例。每周32次皮下注射连用24周,停药后继续观察24周。定期检查肝、肾功能、血象、凝血酶原时间、甲状腺功能、抗HCV和HCV-RNA。结果治疗24周时A、B、C三组的ALT复常率分别为75.0％、73.9％和58.3％,HCV-RNA阴转率分别为80.0％,73.7％和61.9％,显效率(ALT正常,HCV-RNA亦阴转者)三组分别为65.0％、57.9％和33.3％。A、C组间差异显著。48周时ALT正常率分别为70.0％、63.6％和70.8％,HCV-RNA阴性率则为75.0％、61.1％和71.4％,显效率分别为50.0％、44.4％和61.9％,但无统计学差异,引起的不良反应三组间亦无差异。结论 15μg和9μg的干复津为治疗慢性丙型肝炎是有效而且安全的药物。     

复合α干扰素治疗慢性丙型肝炎研究进展

迄今为止,α干扰素(IFN-α)仍为治疗慢性丙型肝炎的主要药物,各种重组干扰素如IFN-α2a、2b、1b和淋巴母细胞干扰素对慢性丙型肝炎的疗效大致相同.最近研制成功的一种新型干扰素--复合α干扰素对治疗慢性丙型肝炎有独到之处,特别在降低血清病毒负荷和治疗对其他干扰素无效或复发的病人方面,优于其他类型的干扰素.     

慢性丙型肝炎与甲状腺疾病的关系及α-干扰素治疗的影响

有学者认为慢性丙型肝炎病人易并发甲状腺疾病,α-干扰素治疗可诱导产生自身抗体,从而加重甲状腺疾病,故临床医师对α-干扰素治疗慢性丙型肝炎心存疑虑。近来多项实验对此进行了研究。 Nduwayo L等检测了 215例慢性丙型肝炎病人血清中的抗甲状腺过氧化物酶抗体和抗甲状腺球蛋白抗体,发现其发生率和普通人群相似。Marazuela     

α—干扰素治疗慢性丙型肝炎的远期疗效

本文综述近年来国外对α－干扰素治疗后有应答的慢性丙型肝炎患者远期肝功能，病毒学标志及肝组织变化的随访结果，并对远期疗效的一些预测因素及近年来提高远期疗效的一些临床尝试作一概述。     

重组干扰素治疗慢性丙型肝炎疗效评价

本文报道了２９例慢性丙型肝炎（ＣＨＣ）患者采用重组α－干扰素（α－ＩＦＮ）每日６００万单位，疗程８周，于治疗前，治疗后即刻、３个月、６个月或１年，２年采集血清，测定丙型肝炎病毒核酸（ＨＣＶＲＮＡ）并动态观察其丙氦酸转氨酶（ＡＬＴ）的变化。结果表明：１２例（４１．４％）呈持续应答，ＨＣＶＲＮＡ持续阴转２年以上，ＡＬＴ亦持续正常；９例（３１．ｏ％）呈暂时应答；８例（２７．６％）为无应答反应。并提示血液中含有高滴度ＨＣＶＲＮＡ的ＣＨＣ患者可能对干扰素治疗较为敏感。     

慢性丙型肝炎的干扰素应用

1988年Choo等应用分子克隆技术,获得肠道外传播的非甲非乙型肝炎病毒的基因克隆,并相应地将其命名为丙型肝炎(HC)和丙型肝炎病毒(HCV)。本文简述干扰素治疗慢性丙型肝炎(CH-HC)的作用机制、用法用量及其副作用。     

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。     

Randomized controlled trial of consensus interferon with or without zinc for chronic hepatitis C patients with genotype 2

AIM:The beneficial effect of zinc supplementation onthe efficacy of interferon as a treatment for chronichepatitis C had been demonstrated in hepatitis virusgenotype 1b of high viral load.This study focusedon patients with genotype 2,which is more sensitiveto interferon than genotype 1b,and used consensusinterferon(CIFN)with or without zinc.METHODS:We randomized 83 patients with chronichepatitis C to CIFN at 18 MIU six times/wk for 4 wk,followed by CIFN at 18 MIU six times/wk for another 20wk,in combination with polaprezinc 300 mg(regimen A,n=41)or as monotherapy(regimen B,n=42).Thirty-one patients in regimen A and 33 patients in regimenB completed the clinical trial;the remaining patientswithdrew because of side effects or a transfer to anotherhospital.RESULTS:Sustained biochemical response,defined asa normal aminotransferase level at the end of the 6-mopost-treatment observation,was 68% and 69%,andsustained virological response,defined as undetectableHCV-RNA at the end of the 6-mo post-treatmentobservation,was 54% and 67% for regimens A and B,respectively.CONCLUSION:CIFN treatment combined with zinc didnot enhance the effect of CIFN as shown by biochemical,virological criteria.No side effects related to polaprezincwere noted.     

Relationship between serum HCV markers and response to interferon therapy in chronic hepatitis C

Hepatitis C virus is the most frequent cause of chronic non-A, non-B hepatitis, and the antibodies to structural and nonstructural proteins encoded by viral genome have been suggested to be markers of ongoing HCV infection. We studied the behavior of these antibodies during interferon therapy in 18 patients with chronic hepatitis C and also during a follow-up period of at least four years. A significant decrease of anti-HCV titer was found only in patients who had shown positive response to therapy and all of them were anti-HCV negative at the end of follow-up. Analysis by recombinant immunoblotting assay showed that only anti-c100 were affected by interferon therapy, whereas anti-c22 and anti-c33 were not modified. Using polymerase chain reaction to detect small amounts of HCV genome in serum, we could confirm that the behavior of HCV-RNA during and after interferon therapy is similar to that of anti-HCV and the loss of anti-c100 seems to be closely related to HCV-RNA disappearance from serum. Our patients with chronic hepatitis C were found to be of type 1b and 2, according to the recent score of Simmonds, and the clearance of serum HCV-RNA during treatment and its sustained negative status are closely related to genotype 2 and to long-term positive response to interferon.     

Current therapy for hepatitis C

Introduction Pegylated interferon alfa in combination with ribavirin has been established as standard therapy for chronic hepatitis C virus (HCV) infection with sustained virologic response rates of 54–63%. The duration of therapy depends on the HCV genotype with currently 48 weeks for genotype 1 and 24 weeks for genotypes 2 and 3. Results and discussion The probability of sustained virologic response is very low (<1–2%) in genotype-1-infected patients without a 2-log decline of HCV RNA concentration after 12 weeks of therapy, and treatment can therefore be discontinued early. Conclusion Efficient treatment of the multiple side-effects of interferon-based antiviral therapy is essential in order to improve compliance, prevent dose reduction or early discontinuation and therefore enhance the probability of sustained response. Future developments of interferon-based therapy aim at the individualisation of the duration of therapy according to the kinetics of viral reduction. Furthermore, direct antiviral drugs, which are currently under investigation in phase I/II clinical trials, will fundamentally expand the treatment options of HCV infection in the next few years.     

Hepatitis C virus genotypes and hepatic fibrosis regulate 24-h decline of serum hepatitis C virus RNA during interferon therapy in patients with chronic hepatitis C

BACKGROUND AND AIMS: Recently, hepatitis C virus (HCV) dynamics during interferon (IFN) therapy have been studied in detail. We examined factors that regulate the viral kinetics and the relationship between the viral kinetics and clinical effect of IFN therapy. METHODS: Eighty-eight patients with chronic hepatitis C entered this study. All patients had been treated with 3 MU of IFN-beta twice a day for the first 2-4 weeks, then IFN-alpha for the next 20-22 weeks (three injections per week). The levels of serum HCV RNA were determined by Amplicor HCV Monitor version 1.0, before and 24 h after the first injection of IFN; then the decline of HCV was calculated. Liver inflammation and fibrosis were scored as 0 (none), 1 (mild), 2 (moderate) or 3 (severe) using biopsy specimens. RESULTS: The decline of serum HCV RNA was 1.42 +/- 0.65 log copies/mL in genotype 1b and 1.83 +/- 0.72 in genotype 2a or 2b (P < 0.01). By a logistic regression model, genotype (1b, 2a or 2b) and hepatic fibrosis (0 or 1, 2 or 3) associated with 24-h decline of serum HCV RNA, independently. As the predictor of IFN therapy, the decline of serum HCV RNA and serum HCV RNA levels before IFN therapy were the independent significant factors (P < 0.001). CONCLUSIONS: The decline of serum HCV RNA during the first 24 h of IFN therapy was regulated by genotypes and hepatic fibrosis. The decline of serum HCV RNA and initial HCV load were independent factors that can be the predictor of the subsequent sustained viral response to IFN therapy.     

复合干扰素再治疗慢性丙型肝炎过程中HCV RNA基线载量及定量变化对疗效预测的意义

目的　观察复发及无应答慢性丙型肝炎患者干扰素治疗过程中HCVRNA定量及其变化与疗效的关系。方法　选择 3 2例干扰素治疗后复发或无应答的慢性丙型肝炎患者 ,用复合干扰素 15 μg ,每周 3次 ,皮下注射 ,疗程 2 4周 ,检测治疗前、治疗中 1、2、3天和第 1、4、8、12、2 4周及停药后随访 6个月的HCVRNA定量变化 ,判断治疗结束时应答率及随访 6月后持续应答率及其与治疗前后病毒水平动态变化的关系。结果　 3 1例患者完成治疗 ,持续应答与无应答及完全应答与无应答治疗前病毒载量有明显差异 (P <0 .0 5 ) ,获持续应答者中早期病毒血症的下降较非持续应答者明显 (P <0 .0 5 ) ,治疗前基线ALT水平不影响应答 (P <0 .0 5 ) ,主要副作用为发热及白细胞下降。结论　复发或无应答的慢性丙型肝炎干扰素治疗过程中 ,基线病毒载量及治疗后早期病毒水平的动态变化可作为治疗效果的预测指标     

Interferon treatment of two patients with quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV)

Abstract: We administered interferon (IFN) to two patients who had quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV), a recently isolated novel DNA virus. Nine mega-units of natural alpha-IFN were administered daily during the first two weeks and thrice weekly during the following 22 weeks (total dose, 720 mega-units). In both cases, serum alanine aminotransferase (ALT) levels decreased during IFN administration but increased thereafter. The concentrations of HCV, HIV, HGV, and TTV declined with the administration of IFN. However, the concentrations of these 4 viruses increased after the cessation of IFN with the except of TTV in patient 2 which disappeared during treatment and did not subsequently reappear. IFN reduced the concentrations of 4 viruses, in an apparently independent manner.     

Changes in serum lipid concentrations in patients with chronic hepatitis C virus positive hepatitis responsive or non-responsive to interferon therapy

BACKGROUND: Changes in serum lipid concentrations during the administration of interferon to patients with chronic hepatitis C virus (HCV) infection have not been fully investigated. The present study was designed to compare changes in serum lipid concentrations before, during and after interferon therapy in responders and non-responders to treatment. METHODS: In total, 101 patients with chronic HCV positive hepatitis were enrolled in this study. High dose interferon alpha was given on alternate days for 6 months. Six months after the end of treatment patients were assessed for the presence or absence of HCV RNA to determine the results of interferon treatment. The time courses of changes in serum lipid concentrations were measured in all patients. RESULTS: The total cholesterol level increased gradually during and after interferon therapy, and its pattern of change coincided with that of serum cholinesterase activity. Pretreatment serum cholesterol concentrations did not differ between responders and non-responders to interferon therapy. The serum triglyceride concentration, conversely, showed a sharp increase during interferon administration and returned to its basal level after the end of treatment. Responders to interferon therapy tended to have higher pretreatment triglyceride concentrations than did non-responders. CONCLUSIONS: We clarified that serum cholesterol and triglyceride levels showed different patterns of change during interferon therapy.     

Randomized placebo-controlled trial of interferon alpha-2b plus ribavirin with and without lactoferrin for chronic hepatitis C.

Lactoferrin (LF), an iron-binding glycoprotein, exhibits several biological activities, including anti-viral activity and immunomodulatory functions. LF has been reported to inhibit hepatitis C virus (HCV) infection in cultured human hepatocytes and HCV viremia in low pretreatment HCV RNA titers of patients with chronic hepatitis C (CHC). However, the combination of interferon (IFN) alpha-2b plus ribavirin with LF for CHC has not been previously investigated. Thirty-six CHC patients, who were positive for HCV RNA with high serum levels of HCV RNA or who did not respond to or relapsed after interferon monotherapy, were randomly assigned to two groups: IFN alpha-2b and ribavirin plus LF for 24 weeks (18 patients), and IFN alpha-2b and ribavirin plus placebo (18 patients). Treatment was discontinued in three patients (17%) in the LF group and eight patients (44%) in the placebo group. For the 25 patients who finished the 24 weeks of treatment, virological sustained response was seen in 6 (40%) patients in the LF group and in 5 (50%) patients in the placebo group and there was no statistically significant difference between the two groups (p=0.7). Serum alanine aminotransferase concentrations remained normal throughout the follow-up period in nine patients (60%) in the LF group as compared with five patients (50%) in the placebo group (p=0.7). The proportion of patients with a virological or biochemical response at the end of the treatment period did not differ between the two groups. Furthermore, there were no statistically significant differences between the two groups in hemoglobin concentration, serum iron, ferritin, Th1/Th2 ratio or ribavirin concentration throughout the treatment and follow-up periods. In conclusion, we could not demonstrate that LF in combination with IFN alpha-2b and ribavirin increases the virological and biochemical response rate for CHC patients with high serum levels of HCV RNA or for CHC patients who do not response to or relapse after IFN monotherapy.     

Efficacy of consensus interferon in the treatment of chronic hepatitis C

BACKGROUND AND AIMS: Consensus interferon (CIFN) is a newly developed type I interferon. The aim of this study was to investigate the safety and efficacy of CIFN in the treatment of patients with chronic hepatitis C and to determine the predictors for sustained response. METHODS: Patients were randomized to receive 3 micrograms or 9 micrograms CIFN three times a week for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum transaminase levels and disappearance of serum hepatitis C virus (HCV)-RNA at the end of treatment and at 24 weeks after stopping treatment. Histologic response was defined as a decrease of at least two points in the Knodell necroinflammatory score at week 48 and was compared with baseline. RESULTS: There were no serious adverse effects related to CIFN therapy. Overall, 44% of patients receiving 3 micrograms and 48% of patients receiving 9 micrograms had normalization of serum transaminase levels and disappearance of HCV viremia at the end of treatment. At 24 weeks after stopping treatment, 16% of patients in receiving 9 micrograms and 12% of patients receiving 3 micrograms had sustained responses. The histologic responses in patients receiving 9 micrograms and those receiving 3 micrograms were 60% and 36%, respectively. The necroinflammatory score was significantly reduced from baseline to week 48 in both groups. In addition, bodyweight < 60 kg and pretreatment serum HCV-RNA level < 0.5 MEq/mL can serve as predictors for sustained response to CIFN treatment. CONCLUSIONS: These findings suggest that 9 micrograms CIFN is safe and effective in the treatment of patients with chronic hepatitis C.