慢性丙型肝炎干扰素治疗后复发患者的干扰素再治疗

目的探讨干扰素(IFN)治疗后复发的慢性丙型肝炎患者对IFN再治疗的应答情况及影响因素。方法对聚乙二醇化干扰素(PEG-IFN)α-2a与重组人干扰素(CIFN)α-2a治疗中国慢性丙型肝炎患者疗效与安全性的随机、开放、多中心对照研究中的6O例干扰素治疗后复发患者的再治疗进行回顾性研究。其中PEG-IFN α-2a组35例和CIFN α-2a组25例,以持续病毒学应答(SVR)作为疗效的主要评价指标,分析HCV RNA载量、基因型、药物种类对IFN疗效的影响。结果 60例复发患者用IFN再治疗后,55．00％取得治疗结束时的病毒学应答(ETVR),35．00％取得SVR;其中PEG-IFN α-2a组74.29％取得ETVR,显著高于CIFN α-2a组(28．00％),P<0．01; PEG-IFN α-2a组45．71％取得SVR,高于CIFN α-2a组(20．00％), P>0．05;病毒载量高、低组间的ETVR、SVR的差异无统计学意义;对于HCV基因1型感染患者,PEG- IFN α-2a的ETVR(75．00％)和SVR(45．83％)均显著高于CIFN α-2a组(分别为22．22％和11．11％), P相似文献   

聚乙二醇干扰素联合利巴韦林治疗获极快速病毒学应答的初治基因1型慢性丙型肝炎患者疗效观察

目的观察获得极快速病毒学应答的初治基因1型慢性丙型肝炎患者,在继续接受36 w聚乙二醇干扰素α-2a联合利巴韦林治疗后的疗效。方法将基线HCV RNA水平〉400000 IU/ml、接受聚乙二醇干扰素α-2a（180μg/w）联合利巴韦林（1000～1200 mg/d）治疗2 w后HCV RNA阴转的基因1型慢性丙型肝炎初治患者,随机分为两组,分别接受36 w和48 w治疗,在停药后随访24 w,观察疗效。结果本研究共纳入40例患者,两组各20例。治疗36 w患者在治疗结束时病毒学应答（ETVR）、持续病毒学应答（SVR）和复发率分别为100%（20例）、90%（18例）和10%（2例）,治疗48 w患者ETVR、SVR和复发分别为95%（19例）、90%（18例）和5.3%（1例）,两组比较无统计学差异（P〉0.05）;在40例患者,基线HCV RNA水平与SVR呈负相关（OR=0.422,95%CI为0.05～0.29,P=0.007）;在治疗36 w患者,基线HCV RNA〈6×10^7IU/ml患者SVR显著高于HCV RNA≥6×10^7IU/ml患者（P=0.005）,但在治疗48 w患者,未发现这种差异（P=0.063）。结论对于基线HCV RNA水平〉400000 IU/ml的基因1型慢性丙型肝炎初治患者,接受聚乙二醇干扰素α-2a联合利巴韦林治疗,如在2 w时获得病毒学应答,治疗36 w疗程与48 w疗程的SVR相当。     

干扰素治疗慢性丙型肝炎的持续应答与复发相关因素的研究

目的 探讨丙型肝炎病毒（HCV）基因型、RNA含量与肝组织炎症活动的相关性，慢性丙型肝炎患者经干扰素治疗后复发的相关因素。方法 对慢性丙型肝炎患者的血清进行丙氨酸氨基转移酶（ALT）检测，采用Cobas Amplicor Monnitour Test．version 2．0试剂进行HCVRNA定量和Simmonds酶切分型方法进行HCV基因分型检测。对聚乙二醇化干扰素α-2a（PEG—IFN α-2a）与干扰素α-2a治疗24周结束时，取得病毒学应答的慢性丙型肝炎患者进行24周随访观察，对临床特征、病毒学特征、治疗药物等因素与复发的相关性进行分析。结果 208例丙型肝炎患者基础HCVRNA含量与ALT水平无相关性（r=0．093，P〉0．05），HCV基因1型与非基因1型之间ALT的水平差异无统计学意义，HCV基因型与RNA含量无相关性；在治疗结束取得病毒学应答的119例患者中，随访24周持续应答者61例（51．3％），复发58例（48．7％）。患者的性别、年龄、HCV感染途径、既往干扰素治疗史、天冬氨酸氨基转移酶／ALT比值、血小板计数和血清基础HCV载量等因素均与复发率无显著相关性。基因1型患者复发率（54．5％）显著高于非1型（32．1％）（x^2=4．265，P=0．039）。PEG-IFNα-2a组复发率（47．0％）低于IFNα-2a组（52．8％），但差异无统计学意义。结论 病毒基因型与慢性丙型肝炎干扰素治疗后的病毒复发显著相关。     

聚乙二醇干扰素α-2a与干扰素α-2a治疗慢性丙型肝炎疗效、安全性的评估

目的　以干扰素α 2a(IFNα 2a ,罗荛愫 ,罗氏 )为对照 ,评估聚乙二醇干扰素α 2a(FEG IFNα 2a ,派罗欣 ,罗氏 )治疗中国慢性丙型肝炎的效果及其安全性和耐受性。方法　采用随机、开放和对照的多中心临床试验设计 ,将 2 0 8例慢性丙型肝炎患者随机分为PEG IFNα 2a组 (10 6例 )和IFNα 2a组 (10 2例 ) ,两组治疗前HCVRNA、基因型等临床资料具有可比性 ,以病毒学应答和生化应答作为疗效的主要评价指标。同时观察患者药物治疗后的不良反应。结果　PEG IFNα 2a组持续性病毒应答率 (SVR)显著高于IFNα 2a组 (分别是 4 1.5 1%和 16 .6 7% ,P <0 .0 0 0 1)。PEG IFNα 2a治疗HCV基因 1型和非基因 1型的SVR显著高于IFNα 2a组 (P =0 .0 0 3) ,PEG IFNα 2a治疗高病毒载量慢性丙型肝炎的SVR明显高于IFNα 2a组 (P =0 .0 0 0 3) ,但是低病毒载量的SVR两组之间差异无显著性 (P =0 .0 5 9)。PEG IFNα 2a与IFNα 2a有相似的不良反应 ,不良反应间差异无显著性 ,两组患者均无发生不良事件。结论　PEG IFNα 2a对慢性丙型肝炎患者的疗效优于传统干扰素IFNα 2a ,在中国慢性丙型肝炎人群中具有较好的安全性和耐受性。     

聚乙二醇干扰素仪-2α／2b联合利巴韦林复治慢性丙型肝炎患者的疗效观察

目的探讨聚乙二醇干扰素α（PEG-IFNα）联合利巴韦林治疗复发慢性丙型肝炎（CHC）患者的应答情况及影响因素。方法 30例经IFN-α或PEG-IFNα标准RGT治疗后复发的CHC患者,均用PEG-IFNα-2a（180μg）或PEG-IFNα-2b（1.5μg/kg）联合利巴韦林（900 mg/d）再治疗,基因1型治疗48周,非基因1型治疗24周,停药随访24周,分析病毒基因型、基线HCV RNA载量、初治药物种类对联合治疗疗效的影响。结果 30例复发患者经联合再治疗后,24例（80%）获得持续病毒学应答（SVR）。18例低病毒载量（HCV RNA≤105拷贝/ml）患者中,17例（94.4%）获得SVR,与高病毒载量组（58.3%）差异有统计学意义（P=0.026）。基因1型组18例,其中14例（77.8%）获得SVR,与非基因1型组（83.3%）差异无统计学意义（P=1.000）。初治应用PEG-IFNα联合利巴韦林抗病毒的患者17例,其中13例（76.5%）经再治疗后获得SVR,与初治应用IFN-α抗病毒组（84.6%）无明显差异（P=0.672）。结论 PEG-IFNα联合利巴韦林治疗复发CHC患者的疗效较好。基线病毒载量高,再治疗效果差;病毒基因型及初治所采用的IFN类型与再治疗的疗效无显著相关性。     

慢性丙型肝炎患者胰岛素抵抗与抗病毒治疗应答的相关性分析

目的 探讨慢性丙型肝炎（CHC）患者胰岛素抵抗（IR）与抗病毒治疗应答的相关性.方法 随机选择慢性丙型肝炎患者78例,其中联合用药组43例,胰岛素抵抗指数（HOMA-IR） ＞2;对照组35例,HOMA-IR＜2.均予聚乙二醇干扰素（PEG-IFN） α-2a联合利巴韦林治疗,基因1型治疗48周,非基因1型治疗24周,随访12周,观察胰岛素抵抗与干扰素疗效的相关性.结果 （1）两组早期病毒学应答率（EVR）分别为48.8％和62.9％,差异无统计学意义（P＞0.05）,而两组治疗结束时病毒学应答率（ETVR）分别为58.1％和80.0％,持续应答率（SVR）分别为39.0％和74.3％,差异均有统计学意义（P＜0.05）.（2）经多因素Logistic回归分析发现,非基因1型（0R=46.10,P＜0.05）、HOMA-IR ＜2（OR=16.421,P＜O.05）是慢性丙型肝炎抗病毒治疗获得持续应答（SVR）的独立预测因素,而年龄、性别、血清转氨酶、丙型肝炎病毒RNA含量与是否获得SVR无明显相联.结论 胰岛素抵抗影响慢性丙型肝炎抗病毒治疗的疗效,是能否获得SVR的独立预测因子.     

聚乙二醇化干扰素-α对不同基因型慢性丙型肝炎患者治疗效果比较

目的观察应用聚乙二醇化干扰素-α(peg-ⅠFNα)治疗丙性肝炎病毒(HCV)基因Ⅰ型和非HCV Ⅰ型感染的慢性丙型肝炎(CHC)患者的疗效差异。方法 2013年10月～2016年10月在我院治疗的108例CHC患者,其中HCV Ⅰ型感染者58例,非HCV Ⅰ型感染者50例,均接受peg-ⅠFNα-2a联合利巴韦林治疗48周,停药后随访24周。采用荧光定量RT-PCR法检测血清HCV RNA,采用一步法聚合酶链式反应结合TaqMan技术和HCV分型特异性引物进行HCV基因分型。结果治疗前,两组基线年龄、性别比例、体质指数(BMⅠ)、血清ALT和HCV RNA水平比较,无显著性差异(P0.05);非HCV Ⅰ型感染者快速病毒学应答(RVR)、早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)和持续病毒学应答率(SVR)分别为74.0%、82.0%、88.0%和86.0%,均显著高于HCV Ⅰ型感染者(分别为51.7%、60.3%、63.8%和58.6%,P0.05);67例获得RVR患者SVR发生率为100.00%,显著高于41例未获得RVR患者的25.6%(P0.05),76例获得EVR患者SVR发生率为94.7%,也显著高于32例未获得EVR患者的15.6%(P0.05);在血清HCV RNA≤4×105 ⅠU/ml被认为系低病毒载量组,HCV Ⅰ型与非HCV Ⅰ型感染者各病毒学应答率无显著性相差(P0.05),而在血清HCV RNA4×105 ⅠU/ml被认为系高病毒载量组,39例非HCV Ⅰ型感染者RVR、EVR、ETVR和SVR分别为71.8%、79.5%、87.2%和84.6%,均显著高于44例HCV Ⅰ型感染者(分别为50.0%、59.1%、63.6%和74.4%,P0.05);治疗24周、48周和随访24周时,非HCV Ⅰ型感染者生化学应答率分别为70.0%、80.0%和84.0%,显著高于HCV Ⅰ型感染者的50.0%、60.3%和69.0%(P0.05)。结论聚乙二醇化干扰素-α联合利巴韦林治疗非HCV Ⅰ型CHC患者效果较好,获得RVR和EVR的患者将获得SVR,应坚定治疗,而对HCV Ⅰ型感染者、血清病毒载量较高和未获得RVR和EVR的患者,则应今早作出更改治疗方案的选择。     

聚乙二醇化干扰素-α对不同基因型慢性丙型肝炎患者治疗效果比较*

目的 观察应用聚乙二醇化干扰素-α（peg-IFNα）治疗丙性肝炎病毒（HCV）基因I型和非HCV I型感染的慢性丙型肝炎（CHC）患者的疗效差异。方法 2013年10月~2016年10月在我院治疗的108例CHC患者,其中HCV I型感染者58例,非HCV I型感染者50例,均接受peg-IFNα-2a联合利巴韦林治疗48周,停药后随访24周。采用荧光定量RT-PCR法检测血清HCV RNA,采用一步法聚合酶链式反应结合TaqMan技术和HCV分型特异性引物进行HCV基因分型。结果 治疗前,两组基线年龄、性别比例、体质指数（BMI）、血清ALT和HCV RNA水平比较,无显著性差异（P>0.05）;非HCV I型感染者快速病毒学应答（RVR）、早期病毒学应答（EVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答率（SVR）分别为74.0%、82.0%、88.0%和86.0%,均显著高于HCV I型感染者（分别为51.7%、60.3%、63.8%和58.6%,P<0.05）;67例获得RVR患者SVR发生率为100.00%,显著高于41例未获得RVR患者的25.6%（P<0.05）,76例获得EVR患者SVR发生率为94.7%,也显著高于32例未获得EVR患者的15.6%（P<0.05）;在血清HCV RNA≤4×10⁵ IU/ml被认为系低病毒载量组,HCV I型与非HCV I型感染者各病毒学应答率无显著性相差（P>0.05）,而在血清HCV RNA>4×10⁵ IU/ml被认为系高病毒载量组,39例非HCV I型感染者RVR、EVR、ETVR和SVR分别为71.8%、79.5%、87.2%和84.6%,均显著高于44例HCV I型感染者（分别为50.0%、59.1%、63.6%和74.4%,P<0.05）;治疗24周、48周和随访24周时,非HCV I型感染者生化学应答率分别为70.0%、80.0%和84.0%,显著高于HCV I型感染者的50.0%、60.3%和69.0%（P<0.05）。结论 聚乙二醇化干扰素-α联合利巴韦林治疗非HCV I型CHC患者效果较好,获得RVR和EVR的患者将获得SVR,应坚定治疗,而对HCV I型感染者、血清病毒载量较高和未获得RVR和EVR的患者,则应今早作出更改治疗方案的选择。     

慢性丙型肝炎干扰素治疗后复发患者干扰素联合利巴韦林再治疗

目的 探讨干扰素（IFN）治疗后复发的慢性丙型肝炎（CHC）患者对IFN联合利巴韦林再治疗的应答情况及影响因素。方法 100例IFN治疗后复发的CHC患者中，50例使用聚乙二醇干扰素α-2a（PEG—IFNα-2a），50例使用重组人干扰素α-1b（CIFNα—1b），均联合利巴韦林再治疗，联合治疗48周，停药随访24周，分析HCVRNA载量、病毒基因型、药物种类对联合治疗疗效的影响。结果 100例复发患者联合再治疗后，36．00％取得持续病毒学应答（SVR），其中PEG-IFNα-2a组48．00％取得SVR，显著高于CIFNα—1b组（24．00％，P〈0．05）。56例低病毒载量（HCV-RNA〈1×10^5拷贝／mL）患者中，PEG—IFNα-2a组28例，其中57．14％取得SVR，显著高于CIFNα—1b组（25．00％，P〈0．05）。HCV非基因1（2a或2b）型组29例，其中55．17％取得SVR，显著高于基因1型组（28．20％，P〈0．05）；在CIFNα—1b治疗组，病毒非基因1型17例患者，其中47．06％取得SVR，明显高于基因1型患者（12，12％，P〈0．01）；在基因1型组，PEG—IFNα-2a组38例，其中42．11％取得SVR，显著高于CIFNα—1b组（12．12％，P〈0.01）。结论 IFN治疗后复发的CHC患者IFN联合利巴韦林再治疗存在部分患者无应答；对于HCV病毒载量低、基因1型的复发患者，聚乙二醇干扰素联合利巴韦林再治疗疗效明显优于普通干扰素的联合治疗。     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎患者疗效及其影响因素分析

目的：观察聚乙二醇干扰素（PEG IFNα-2a）联合利巴韦林（RBV）治疗慢性丙型肝炎（CHC）患者的疗效及其影响因素。方法对331例慢性丙型肝炎患者予 PEG IFNα-2a（180μg/w 或135μg/w）联合利巴韦林（RBV）900~1200 mg/d 抗病毒治疗,疗程48～72 w,随访24 w;治疗前检测丙型肝炎病毒基因型,采用 PCR 法检测丙型肝炎病毒（HCV）RNA 水平及肝功能,以病毒学应答和生化学应答作为疗效的主要评价指标。结果在331例CHC 患者中,获得快速病毒学应答率（RVR）、早期病毒学应答率（EVR）和持续病毒学应答率（SVR）分别为65%（215/331）、94.9%（314/331）和84.9%（281/331）;对176例行基因分型,结果108例基因1型与68例非1型感染者SVR 分别为88.0%和79.4%,两组比较无明显差异;75例血清 HCV RNA 水平小于4×105 IU/ml 的患者 SVR 为93.3%,高于256例 HCV RNA 水平大于4×105 IU/ml 患者的82.4%（P〈0.05）;215例获得 RVR 的 CHC 患者的SVR 明显高于116例未获得 RVR 患者（92.6%对70.7%,x2=28.099,P=0.000）,314例获得 EVR 患者的 SVR 也明显高于17例未获得 EVR 组（88.5%对17.6%,x2=63.194,P=0.000）;50例未获得 SVR 的 CHC 患者年龄和感染丙型肝炎病毒的时间分别为（46±15）岁和（14.8±8.0）年,显著大或长于281例获得 SVR 患者[（38±13）岁和（11.5±7.7）年,P 均〈0.05]。结论聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效较好,预测临床疗效的关键因素是患者年龄、感染丙型肝炎的病程、治疗前 HCV RNA 水平及在治疗过程中能否及时获得 RVR 和 EVR。     

慢性丙型肝炎抗病毒治疗应答独立预测因子的研究

目的 通过对应用不同干扰素(IFN)剂型的大样本慢性丙型肝炎患者的治疗,对可能与IFN疗效相关的因子进行多因素回归分析,探讨慢性丙型肝炎IFN治疗应答的预测因子。方法 对入选聚乙二醇干扰素α-2a治疗慢性丙型肝炎的随机、开放、多中心对照研究的患者随机分组,分别应用聚乙二醇干扰素α-2a和干扰素α-2a治疗24周,停药后随访24周。在用药前对患者血清中的HCV RNA进行定量和基因分型检测,治疗和随访结束时检测血清HCV RNA含量,以HCV RNA阴转作为IFN治疗应答的主要评价指标,并对患者临床特征、病毒学特征进行多因素logistic回归分析。 结果 按意愿治疗分析人群208例,按方案分析人群197例,在对按方案分析人群的分析中,治疗24周结束时,女性、年龄<50岁、非输血感染途径、IFN治疗后复发者、天冬氨酸氨基转移酶/丙氨酸氨基转移酶(AST/ALT)<1、HCV RNA 含量<8×105U/ml,非基因1型HCV感染和聚乙二醇干扰素α-2a治疗患者的病毒应答率分别高于男性、年龄≥50岁、输血感染途径、IFN初治患者、AST/ALT比值≥1、HCV RNA含量≥8×105U/ml、基因1型HCV感染和干扰素α-2a治疗患者的应答率。但随访结束时,AST/ALT≥1和HCV RNA含量≥8×105U/ml患者的持续应答率却大于AST/ALT<1和HCV RNA含量<8 × 105U/ml患者。经多因素logis     

Treatment of recurrent hepatitis C in liver transplants: efficacy of a six versus a twelve month course of interferon alfa 2b with ribavirin

BACKGROUND/AIMS: Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis.METHODS: Fifty-seven patients (68% genotype 1b) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800mg/die for 6 or 12 months. Study end-points were the end of treatment (ETVR) and the 12-month post-therapy sustained virologic response (SVR; negative HCV-RNA).RESULTS: ETVR was induced in 9/27 (33%) and in 7/30 patients (23%) treated, respectively, for 6 and 12 months (P=0.4); a SVR was induced in six (22%) of the former and five (17%) of the latter (P=0.4). HCV genotype non-1 patients responded better than genotype 1 (SVR: 43% in genotype non-1 versus 12% in genotype 1, P: 0.02). In ETV responders the hepatitis activity index improved by >2 points in biopsies taken after therapy compared to pre-therapy biopsies. Anemia and leukopenia required reduction of therapy in 51% of the patients.CONCLUSIONS: CT is efficacious in controlling HCV disease in about 20% of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months.     

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan

Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy-proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferon alpha-2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n = 76) or 3 MU of interferon alpha-2b t.i.w. plus ribavirin (IFN group, n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but no difference was found in genotype non-1 patients (PEG vs IFN: 68.4%vs 86.8%, P = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG-IFNalpha2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNalpha2b ribavirin.     

Efficacy of interferon alpha-2b induction therapy before retreatment for chronic hepatitis C.

BACKGROUND/AIMS: Chronic hepatitis C (HCV) patients who have failed previous treatment have low sustained viral response (SVR) rates with repeat treatment. We evaluated whether interferon (IFN) induction during retreatment improves response rates. METHODS: Two randomized, controlled trials were conducted in chronic HCV patients who failed IFN. In Study 1, patients received IFN 3 MU daily plus ribavirin (RBV) 1000 mg/day for 4 weeks, followed by IFN 3 MU TIW plus RBV 1000 mg/day for 44 weeks (induction; n=232), or IFN 3 MU TIW plus RBV 1000 mg/day for 48 weeks (non-induction; n=237). In Study 2, patients received IFN 5 MU B.I.D. plus RBV 1000-1200 mg/day for 2 weeks, followed by pegylated IFN (PEG-IFN) 75-150 mug weekly plus RBV 1000-1200 mg/day for 46 weeks (induction; n=201), or PEG-IFN 75-150 mug weekly plus RBV 1000-1200 mg/day for 48 weeks (non-induction; n=206). The primary end point for both trials was SVR. RESULTS: Induction did not increase SVR compared with non-induction, but did increase the on-treatment response among genotype non-1 patients in Study 2. By intention-to-treat (ITT) analysis, SVR in Study 1 was 13% for induction vs. 9% for non-induction (P=NS). In Study 2 (ITT), SVR was 20% for induction vs. 24% for non-induction (P=NS). However, by non-ITT analysis of Study 2, genotype non-1-previous non-responders showed significantly higher response rates with induction than non-induction. CONCLUSION: For chronic HCV patients who have failed IFN, induction with retreatment does not improve SVR, but may be beneficial for patients with genotype non-1 HCV.     

An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin

Summary. Pegylated interferon (PEG‐IFN)/ribavirin combination therapy is the standard‐of‐care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG‐IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open‐labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG‐IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non‐fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non‐fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non‐fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin‐combined with PEG‐IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.     

A randomized trial to assess the efficacy of interferon alpha in combination with ribavirin in the treatment of interferon alpha nonresponders with chronic hepatitis C: superior efficacy of high daily dosage of interferon alpha in genotype 1

Summary. A randomized trial was conducted to assess the efficacy of daily (QD) or thrice weekly (TIW) administration of interferon- α (IFN) in high doses in combination with ribavirin (1.0–1.2 g/day) in patients with chronic hepatitis C (CHC) who were nonresponders to previous IFN monotherapy. Interferon was administered as 10 MU IFN (QD or TIW) for 4 weeks, followed by 5 MU IFN (QD or TIW) for 20 weeks, and then by 3 MU IFN (QD or TIW) for 24 weeks. Sustained virological response (SVR) was evaluated in 142 patients who received at least one dose of medication. One-fourth of the patients achieved SVR, 26% of those treated with IFN QD and 25% of those treated with IFN TIW ( P  = 0.85). For genotype 1 patients, SVR rates were 32.4 and 15.8% for IFN QD and IFN TIW, respectively, whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4%, respectively (test of homogeneity: P  = 0.031). This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction ( P  = 0.012) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas, among genotype non-1 patients, the two treatments were similar (odds ratio of SVR in IFN QD vs IFN TIW: 3.33 among genotype 1 patients, 95% CI: 1.00–11.14). In conclusion, re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients.     

Treatment of histologically mild hepatitis C virus infection with interferon and ribavirin: a multicentre randomized controlled trial

Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing alpha-interferon (3 MU thrice weekly) + ribavirin (1000-1200 mg/day) for 48 weeks with no treatment in treatment naive, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with alpha-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% vs 49% P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.