慢性丙型肝炎患者感染病毒基因型对抗病毒治疗应答的影响

目的：探讨丙型肝炎病毒基因型与抗病毒治疗后病毒学应答之间的关系。方法113例慢性丙型肝炎患者接受聚乙二醇干扰素（PEG-IFNα-2a）联合利巴韦林治疗48周。采用 Simmonds 基因分型法进行 HCV 基因分型。结果在113例患者中,基因1型88例（78.0%）,非基因1型25例（22.0%）;非基因1型患者快速病毒学应答率（RVR）明显高于基因1型患者（80%对48.8%,P＜0.05）;非基因1型患者持续病毒学应答率（SVR）明显高于基因1型患者（80.0%对64.8%,P＜0.05）;低病毒载量患者RVR 明显高于高病毒载量患者（78.9%对46.7%,P＜0.05）。结论 HCV 基因型和 HCV RNA 复制水平对 PEG-IFNα-2a 联合利巴韦林抗病毒治疗的疗效有一定的影响,提示 HCV 基因分型有重要的临床意义。     

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%(P0.05);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%(P0.05);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(P0.05);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(P0.05);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(P0.05)。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。     

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。     

大剂量普通α-干扰素与聚乙二醇化α-干扰素联合利巴韦林治疗慢性丙型肝炎患者临床疗效及安全性比较研究

目的通过与聚乙二醇化α-干扰素联合利巴韦林治疗疗效的比较,评价应用大剂量普通干扰素α2b联合利巴韦林治疗慢性丙型肝炎(CHC)患者的疗效及其安全性。方法本文采用回顾性研究方法,对2012年1月~2016年1月收治的178例CHC患者接受普通α-干扰素联合利巴韦林(n=148)或聚乙二醇化干扰素联合利巴韦林(n=30)治疗48 w的效果进行分析,使用贝克曼公司生产的全自动生化分析仪检测血生化指标,采用定量RT-PCR法检测血清HCV RNA,采用ELISA法检测血清抗-HCV。病毒学应答定义为血清HCV RNA水平低于检测下限。结果治疗前,普通干扰素治疗组血清ALT水平为(80.9±22.6)U/L,AST水平为(74.3±18.2)U/L,HCV RNA水平为(2.9±0.5)×10~5 copies/ml,与长效干扰素治疗组【(82.32±20.5)U/L、(72.9±16.7)U/L和(2.8±0.5)×105 copies/ml】比,差异无统计学意义(P0.05);在治疗4 w、12 w、24 w和48 w及随访至72 w时,普通干扰素治疗患者血清ALT复常率分别为79.7%、87.2%、90.5%、92.6%和86.5%,与长效干扰素治疗患者的76.7%、83.3%、90.0%、93.3%和90.0%比,无显著性统计学差异(P0.05);血清HCV RNA阴转率分别为66.2%、71.0%、84.5%、90.5%和69.5%,与长效干扰素治疗患者的66.7%、73.3%、80.0%、90.0%和70.0%比,也无显著性统计学差异(P0.05);长效干扰素治疗患者外周血WBC和PLT减少、脱发和食欲下降等不良反应发生率显著高于普通干扰素治疗组(P0.05)。结论应用大剂量普通干扰素α2b联合利巴韦林治疗CHC患者能获得与应用聚乙二醇化干扰素治疗方案类似的疗效,且副作用显著少于后者,但停药后长期疗效方面还需要进一步观察。     

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。     

干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者疗效观察

目的：观察普通干扰素联合利巴韦林治疗慢性丙型肝炎患者的临床疗效。方法87例慢性丙型肝炎患者被随机分成对照组44例和观察组43例,均应用重组人干扰素α-2b 联合利巴韦林治疗,分别治疗48周和72周,随访24周,观察疗效。结果在44例对照组患者中,HCV 1b型感染者28例（63.6%）,2a型感染者8例（18.2%）,在观察组43例患者中则分别为29例（67.4%）和6例（14.0%）;对照组获得快速病毒学应答率（RVR）、早期病毒学应答（EVR）、治疗结束时应答（ETR）和持续病毒学应答率（SVR）分别为40.9%、59.1%、68.2%和38.6%,而观察组则分别为39.5%、60.5%、88.4%（P＜0.05）和65.1%（P＜0.05）;根据血清HCV RNA水平是否≥1×106copies/m1,将两组患者分为高病毒载量组和低病毒载量组,结果两组低病毒载量组患者的ETR和SVR均显著高于高病毒载量组（P＜0.05）。结论延长干扰素联合利巴韦林治疗慢性丙型肝炎的疗程有助于提高SVR。     

干扰素联合利巴韦林治疗慢性丙型肝炎长期随访中的复发及其影响因素

目的 观察和分析慢性丙型肝炎患者经干扰素联合利巴韦林治疗获得应答后的复发情况及其影响因素.方法 收集长期随访资料完整的慢性丙型肝炎患者资料纳入回顾性统计分析.治疗方案为聚乙二醇干扰素或普通干扰素联合利巴韦林治疗,疗程依基因型分别为24周(非1b型)或48周(1b型).主要观察指标为血清HCV RNA载量,影响因素纳入了年龄、性别、HCV基因型、基线HCV RNA载量及干扰素类型.计量资料用t检验,计数资料用x2检验,影响因素的分析用二分类logistic回归分析.结果 146例慢性丙型肝炎患者抗病毒治疗结束后平均随访(33.5±16.4)个月,最短12个月,最长85个月,累计复发率为14.8％.随访第1～6个月内复发概率最大,为8.9‰第7～12个月为1.4％、第13～18个月为1.4％、第19～24个月为1.6％、第25～30个月为1.1,30个月后未见复发.65.0％(13/20)的复发病例发生于治疗结束后6个月内,但之后2年内仍有35.0％(7/20)病例复发.HCV基因1b型和非1b型患者复发率分别为20.4％和12.2％,两组比较,差异无统计学意义(P＞0.05).复发和未复发患者平均基线HCV RNA载量分别为(6.86±1.01)log10拷贝/ml和(6.60±1.21)log10拷贝/ml,两组比较,差异无统计学意义(P＞0.05);聚乙二醇干扰素α-2b,聚乙二醇干扰素α-2a及普通干扰素α治疗后复发率分别为12.1％、14.0％及15.0‰组间比较,差异无统计学意义(P＞0.05);复发患者的平均年龄为(46.15±11.89)岁,高于未复发患者的(37.41±10.65)岁,两组比较,差异有统计学意义(t=3.352,P=0.001).结论 接受病毒基因型指导的标准抗病毒方案的患者,只有年龄与复发显著相关,高龄患者容易复发.基因型指导的抗病毒方案基本上消除了病毒因素对治疗应答的影响.     

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。     

聚乙二醇干扰素α-2a间隔10日与间隔7日治疗慢性丙型肝炎临床观察

目的：比较聚乙二醇干扰素α-2a（PEG INFα-2a）间隔10日与间隔7日联合利巴韦林治疗慢性丙型肝炎的临床疗效及不良反应的差异性。方法：65例符合条件的患者,给予聚乙二醇干扰素α-2a间隔7日联合利巴韦林抗病毒治疗12周。随后随机分为两组,A组33人,采用聚乙二醇干扰素α-2a间隔10日联合利巴韦林治疗;B组32人,采用聚乙二醇干扰素α-2a间隔7日联合利巴韦林治疗。两组均予以48针聚乙二醇干扰素α-2a皮下注射,观察两组治疗效果及不良反应的差异。结果：两组前12针治疗方案相同,治疗12针时的HCV RNA应答率,A、B两组分别为59%、61.5%,差异无显著性意义（P〉0.05）。治疗24针时HCV RNA的阴转率A、B两组分别为87.2%、88.5%,差异无显著性意义（P〉0.05）。治疗结束时HCV RNA阴转率,A、B两组分别为89.7%、92.3%,治疗结束6个月时HCV RNA阴转率,A、B两组分别为82.1%、80.8%,差异无显著性意义（P〉0.05）。A组的重度不良反应发生率低于B组,差异有显著性意义（P〈0.01）。结论：聚乙二醇干扰素α-2a间隔10日与间隔7日联合利巴韦林治疗慢性丙型肝炎疗效无显著性差异。在治疗12周后,延长聚乙二醇干扰素α-2a的给药间隔期,改为10天1次皮下注射,可有效减轻各种不良反应的发生。     

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。     

Treatment of HCV infection with pegylated interferons

The past decade has seen advances in the treatment of chronic hepatitis C infection. Therapy with interferon alpha was disappointing, with only 15% of patients achieving longterm viral clearance. Combination therapy with interferon alpha and ribavirin therapy more than doubled sustained virologic response (SVR) rates. The pegylated interferons are a recent development that have improved the outlook for patients with chronic hepatitis C virus (HCV). Pegylated interferons are produced by the binding of polyethylene glycol to interferon alpha, which results in a compound with improved pharmacokinetic properties with increased efficacy. Combination therapy with pegylated interferon alpha and ribavirin is the optimal treatment for chronic HCV infection. Up to 80% of patients with genotype 2/3 infection and up to 50% of patients with genotype 1 infection achieve SVR with treatment. For the first time, the majority of patients with chronic HCV who are treated can anticipate a long-term cure.     

Antiviral Response of HCV Genotype 1 to Consensus Interferon and Ribavirin Versus Pegylated Interferon and Ribavirin

Achieving an antiviral response at a reasonable cost is a challenge in the treatment of patients with chronic hepatitis C. A previous study indicated that consensus interferon with ribavirin had promising activity against hepatitis C virus (HCV) genotype 1. The objective of this study was to determine the virologic response with consensus interferon or pegylated interferon α-2b plus weight-ribavirin in patients chronically infected with HCV genotype 1. Intention-to-treat analysis showed response in 37% and 41% of subjects treated with consensus interferon/ribavirin or pegylated interferon/ribavirin, respectively, with response rates of 42% and 44% observed in analysis of the per-protocol population, not a significant difference. Tolerability of the two treatment regimens was similar. In conclusion, both treatment regimens were safe and gave a similar antiviral response. It is possible that if consensus interferon is administered daily rather than three times weekly, eradication of HCV could be achieved in a larger proportion of patients infected with HCV genotype 1.     

Treatment for hepatitis C virus in human immunodeficiency virus-infected patients: clinical benefits and cost-effectiveness

BACKGROUND: Hepatitis C virus (HCV) is an important cause of liver disease in human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To assess the cost-effectiveness of alternative management strategies for chronic HCV in co-infected patients with moderate hepatitis. METHODS: A state-transition model was used to simulate a cohort of HIV-infected patients with a mean CD4 cell count of 350 cells/ micro L and moderate chronic hepatitis C stratified by genotype. Strategies included interferon alfa (48 weeks), pegylated interferon alfa (48 weeks), interferon alfa and ribavirin (24 and 48 weeks), pegylated interferon alfa and ribavirin (48 weeks), and no treatment. Outcomes included life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. RESULTS: Treatment for moderate chronic HCV with combination therapy using an interferon-based regimen reduced the incidence of cirrhosis and provided gains in quality-adjusted life expectancy ranging from 6.2 to 13.9 months, depending on genotype. Regardless of genotype, the cost-effectiveness of interferon alfa and ribavirin for patients with moderate hepatitis was lower than $50 000 per QALY vs the next best strategy. With genotype 1, pegylated interferon alfa (vs interferon alfa) and ribavirin therapy provided an additional 1.6 quality-adjusted life-months for $40 000 per QALY. Because treatment is more effective with non-1 genotypes, pegylated interferon (vs interferon alfa) and ribavirin provided only 3 additional quality-adjusted life-months for $105 300 per QALY. For patients who were intolerant of ribavirin, monotherapy with pegylated interferon was always the most cost-effective option. CONCLUSIONS: Combination therapy for moderate hepatitis in coinfected patients will increase quality-adjusted life expectancy and have a cost-effectiveness ratio comparable to that of other well-accepted clinical interventions.     

Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers

BACKGROUND: The effect of conventional interferon-based therapy of hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is controversial. Yet, no studies have been carried out into pegylated interferon treatment for chronic HBV/HCV coinfection. We aimed to evaluate the response rate and side effects of conventional or pegylated interferon combined with ribavirin on chronic HBV/HCV coinfection therapy. METHODS: The study included 36 chronic hepatitis patients (M/F: 28/8, mean age 47+/-12 years) who were positive for HBsAg and anti-HCV. They were tested for the presence of HBV-DNA by hybridisation assay, and the samples giving negative results were retested by polymerase chain reaction (PCR). All patients were tested for HCV-RNA using PCR, and the HCV genotype was determined. RESULTS: Nineteen patients were given standard interferon either alone or in combination with ribavirin, whereas 17 were given pegylated interferon and ribavirin combination therapy. None of the patients had HBV-DNA positivity; however, all had HCV-RNA detectable by PCR. All the patients had HCV genotype 1b. The mean alanine aminotransferase and aspartate aminotransferase levels were 118+/-65 U/l and 90+/-95 U/l respectively. Five patients in each group discontinued the treatment due to side effects. Only two patients (one from each group) reached sustained virological response. CONCLUSION: Neither pegylated nor conventional interferon based regimes were effective for HBV/HCV coinfection, in which the dominant virus was HCV. Pegylated interferon and ribavirin therapy was not superior to conventional interferon based regimes in the treatment of HBV/HCV coinfection.     

Interferon-λ polymorphisms and response to pegylated interferon in Iranian hepatitis C patients

AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-λ(IFNL) polymorphisms. METHODS: This study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type ofpegylated interferon. Patients were treated with 180 μg pegylated interferon alpha-2a(Pegaferon#174;) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus(HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes.RESULTS: A total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men(92.8%). The most frequent HCV genotype was type-1, infecting 93/152(61.2%) patients. Sustained virologic response(SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2%(52/57) of patients with the IFNL rs12979860 CC genotype and 82.1%(78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT(39/45; 86.7%) and non-TT(61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR(OR = 6.2; 95%CI: 1.2-31.9; P = 0.03).CONCLUSION: The rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high.     

Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin

BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. METHODS: A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone. RESULTS: Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2. CONCLUSIONS: We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.     

Safety and efficacy of treatment with pegylated interferon alpha-2a with ribavirin in chronic hepatitis C genotype 4

The hepatitis C virus (HCV) genotype is an important predictive outcome parameter for pegylated interferon plus ribavirin therapy. Most published therapeutic trials to date have enrolled mainly patients with HCV genotypes 1, 2 and 3. Limited studies have focused on genotype 4 patients, who have had a poor representation in pivotal trials. Our aim was to evaluate the efficacy and safety of treatment with standard dose pegylated interferon alfa-2a in combination with weight-based ribavirin in patients with chronic hepatitis C genotype 4. In this prospective observational study, 198 patients with HCV-4 were included in this study from February 2004 to August 2005,188 patients who received at least 1 dose of drugs were included in the ITT analysis and they were treated with pegylated interferon alfa-2a and ribavirin for 48 weeks. Baseline and demographic characteristics, response to treatment at weeks 12, 48 and 72, and the nature and frequency of adverse effects were analyzed. Virological response at week 12 was achieved in 144 patients (76.6%). Virological response at the end of treatment was present in 110 patients (58.5%). At week 72, 99 patients presented SVR (52.7%). The reported adverse events were similar to those found in the literature for treatments of similar dose and duration. In conclusion, combined treatment with pegylated interferon alfa-2a and ribavirin was well tolerated and effective in chronic hepatitis C genotype 4, yielding response rates between those reported for genotype 1 and those of genotypes 2-3.     

聚乙二醇干扰素α-2a治疗慢性丙型肝炎病毒／乙型肝炎病毒共感染临床疗效

目的研究慢性丙型肝炎（CHC）与丙型肝炎病毒/乙型肝炎病毒（HCV/HBV）共感染者用聚乙二醇干扰素α-2a（PEG-IFNα-2a）抗病毒治疗疗效的观察。方法治疗前后定期采集31例CHC、30例HCV/HBV共感染者的外周血,检测HCV RNA、HBV DNA和肝脏纤维化指标。结果治疗后CHC患者血清中HCV RNA含量51.6%〈102拷贝/ml,HCV/HBV共感染者HCV、HBV下降均不理想。结论 PEG-IFNα-2a抗病毒治疗HCV/HBV共感染者疗效较单纯丙型肝炎患者差,但对HBV、HCV有抑制作用,并部分改善机体免疫功能及肝功能。     

The Evolution of HCV Treatment in Taiwan

The treatment strategies used in Taiwan for patients with chronic hepatitis C (CHC) have evolved from conventional interferon monotherapy, consensus interferon therapy, conventional interferon/ribavirinand to pegylated interferon/ribavirin combination therapy. In the past two decades, the sustained virological response (SVR) rate in Taiwanese patients improved from 6 to 75-90 %. By following genotype-guided therapy, an SVR rate of 75-80 % and 85-95 % could be achieved in Taiwanese patients with HCV-1 and HCV-2 infections, respectively. The study of HCV viral kinetics has facilitated studies in Taiwan regarding response-guided therapy with tailored regimens. The majority of Taiwanese patients can be treated successfully with pegylated interferon/ribavirin. The application of IL-28B genetic tests and the insight provided by the viral kinetics might aid in selecting the best candidates for treatment with direct antivirals in the near future in Taiwan.     

HCV in patients with end-stage renal disease

Chronic hepatitis C virus (HCV) infection remains an important cause of liver disease in patients with end-stage renal disease (ESRD) and conversely, renal failure has a significant impact on morbidity and mortality throughout the natural history of chronic HCV and its treatment. With improved awareness within dialysis units of the potential for spread and the institution of preventative measures, the prevalence of HCV infection in the hemodialysis-dependent population has continued to decline since 1995. Use of HCV (+) donor kidneys is associated with an increase in the prevalence of liver disease, but when compared with continued hemodialysis, transplantation using these kidneys is associated with improved survival. Overall, survival in patients with chronic HCV infection appears to be better after renal transplantation when compared with maintenance hemodialysis, and transplant should be considered for these patients. Data support the use of interferon and the improved efficacy of pegylated interferon formulations for treatment of chronic HCV infection in ESRD patients, although tolerability continues to be troublesome. The newest and most promising data regarding the treatment of HCV in ESRD involve the combination of reduced dose ribavirin with interferon or pegylated interferon suggesting similar enhancements in sustained virologic response (SVR) as seen in non-ESRD patients, but caution is advised, as all studies to date used ribavirin plasma concentration monitoring in patient with ESRD. Finally, with regard to postrenal transplant treatment of HCV infection, there is no evidence to support treatment with interferon-based therapy and pretransplant treatment remains the best option whenever possible.