聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎的疗效及影响因素分析

目的观察并分析聚乙二醇化干扰素(Peg IFNα-2α)联合利巴韦林治疗慢性丙型肝炎的疗效及其影响因素。方法回顾性分析2010年1月至2015年1月期间收治的256例慢性丙型肝炎患者的临床资料,均予Peg IFNα-2α(180μg/周或135μg/周)联合利巴韦林900~1 200 mg/d抗病毒治疗48~72周,随访24周。比较不同基因分型病毒性学应答率;比较不同丙氨酸氨基转移酶(ALT)水平与病毒学应答率的关系;观察慢性丙型肝炎患者病毒载量与疗效之间的关系。结果 256例患者中,获得快速病毒学应答率(RVR)166例(64.8%),早期病毒学应答率(EVR)243例(94.9%)和持续病毒学应答率(SVR)218例(85.2%);基因分型结果显示,157例基因1型(61.3%)与99例非1型(38.7%)感染者中SVR分别为83.4%和81.8%,两组比较差异无统计学意义(P0.05);按治疗前ALT水平分为高ALT水平组(ALT80 U/L)与低ALT水平组(ALT≤80 U/L),两组之间RVR、EVR及SVR无显著差异(P0.05);按HCV RNA基线水平,高病毒载量组(HCV RNA4×105IU/ml)RVR、ETVR和SVR均较低病毒载量组(HCV RNA≤4×105IU/ml)低,差异均有统计学意义(P0.05,P0.01);按是否获得SVR分为SVR组与非SVR组,非SVR组的年龄及病程明显高于SVR组,差异有统计学意义(P0.01)。结论 Peg IFNα-2α联合利巴韦林治疗慢性丙型肝炎能获得较高的EVR和SVR,年龄、病程及治疗前HCV RNA水平均是影响SVR的重要因素。     

聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型肝炎疗效观察

目的以普通干扰素(IFN)α-2b联合利巴韦林为对照,观察聚乙二醇干扰素(PEG-IFN)α-2b联合利巴韦林治疗慢性丙型肝炎(CHC)的临床疗效。方法成人CHC患者96例随机分为两组,每组48例,观察组给予PEGIFNα-2b,对照组给予IFNα-2b,均联合利巴韦林口服,疗程48周。观察两组早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)、持久病毒学应答(SVR)和安全性等方面的差异。结果观察组EVR率、ETVR率、SVR率均高于对照组(χ2分别=6.27、4.17、4.44,P均<0.05)。两组不良反应发生率差异无统计学意义(χ2=0.12,P>0.05)。结论PEG-IFNα-2b联合利巴韦林治疗CHC疗效优于普通干扰素联合利巴韦林,但SVR率需要进一步提高。     

氟伐他汀对合并高胆固醇血症的慢性丙型肝炎的抗病毒疗效的影响

目的：观察氟伐他汀对合并高胆固醇血症的慢性丙型肝炎的抗病毒疗效的影响。方法选取2006年9月至2008年9月合并高胆固醇血症慢性丙型肝炎60例,观察组30例,对照组30例,所有患者均予聚乙二醇干扰素α-2a＋利巴韦林治疗;观察组患者加用氟伐地汀;用药后4、12、24、36、48周及停药后12周、24周复查病毒RNA定量。结果氟伐他汀治疗合并高LDL血症的慢性丙型肝炎的患者的早期病毒学应答（EVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答（SVR）均显著高于对照组（53.3%vs.46.7%,85.1%vs.63.3%,81.5%vs.53.3%,P＜0.05）。结论氟伐他汀有利于提高合并高胆固醇血症的慢性丙型肝炎患者的抗病毒疗效。     

慢性丙型肝炎患者第一高变区抗体的交叉反应性与抗病毒治疗早期病毒应答的关系

目的 探讨慢性丙型肝炎患者血清第一高变区( HVR1)抗体的交叉反应性与抗病毒治疗早期病毒应答(EVR)的关系.方法 用ELISA丙型肝炎病毒(HCV)HVR1抗体交叉反应性矩阵试剂检测抗HCV高变区抗体差异性,16条高变区抗原与患者血清交叉反应性比较采用Fisher精确概率检验.同时对2009年1月至12月首都医科大学附属北京佑安医院46例慢性丙型肝炎患者抗病毒治疗前基线血清标本进行分析.用荧光定量逆转录(RT)-PCR检测46例患者在治疗前、聚乙二醇干扰素联合利巴韦林治疗12周、48周的血清HCV RNA水平,并进行基因分型.结果 46例慢性丙型肝炎患者中,HCV2a型16例,1b型30例;治疗12周及结束时分别检测HCV RNA,其中,EVR组33例,非EVR组13例;2a型EVR发生率[93.8％ (15/16)]高于1b型[60.0％( 18/30),x2=4.316,P＜0.05].HCV 1b型慢性丙型肝炎患者中,EVR组平均多靶点HVR1抗原阳性反应数目为(12±4)个,明显高于非EVR组[(7±5)个,t=2.797,P＜0.01].经Fisher精确概率法检验,HVR1抗原编号分别为001、003、009、013、016的5条抗原在EVR组患者基线血清的反应阳性率明显高于非EVR组(P均＜0.05).结论 HVR1抗体的交叉反应性可能是一项抗病毒治疗疗效的预测指标.     

丙型肝炎病毒基因分型与治疗效果关系的研究

目的 分析丙型肝炎病毒（HCV）基因型与利巴韦林联合聚乙二醇干扰素α-2a治疗效果的关系,为临床抗HCV治疗提供依据.方法 选择179例慢性丙型肝炎初治患者进行利巴韦林联合聚乙二醇干扰素α-2a的标准方案进行治疗,采用实时荧光定量聚合酶链反应（PCR）进行HCV-RNA定量检测,采用基因测序检测进行HCV基因分型.治疗后评价持续病毒学应答（SVR）.结果 179例丙型肝炎患者中,HCV 1b型占79.3%,HCV 2a型占8.4%,HCV 3b型占5.0%,HCV 6a型占2.2%,HCV 1b、2a混合型占1.1%,其他型占4.0%.HCV 2a型患者获得SVR率明显高于HCV 1b型,差异有统计学意义（χ^2=4.956,P=0.026）.结论 该院HCV基因型主要为HCV 1b和HCV 2a型,HCV 1b型患者对标准治疗方案的疗效较2a型差.     

高病毒载量慢性丙型肝炎快速病毒学应答的预测因素分析

目的探讨高病毒载量慢性丙型肝炎抗病毒治疗的快速病毒学应答(RVR)预测因素。方法对55例高病毒载量(HCVRNA>1×105拷贝/ml)慢性丙型肝炎使用聚乙二醇干扰素α-2a联合利巴韦林进行抗病毒治疗者进行前瞻性研究,聚乙二醇干扰素α-2a135μg或180μg/次,皮下注射,每周1次,利巴韦林900～1200mg/d口服,于治疗前及治疗第4周检测HCVRNA定量,4周血清HCVRNA检测不到为获得RVR。采用Logistic多元回归分析RVR的影响因素,并比较治疗前不同病毒载量患者RVR的比例。结果 RVR与基线病毒载量呈负相关(B=-1.292)。基线HCVRNA≥1×105拷贝/ml且<1×107拷贝/ml者快速应答率为86.49%(32/37),基线HCVRNA≥1×107拷贝/ml者快速应答率为61.11%(11/18),两组比较有统计学差异(χ2=4.571,P=0.043)。结论基线HCVRNA水平可作为高病毒载量慢性丙型肝炎患者聚乙二醇干扰素联合利巴韦林治疗过程中RVR的预测因素,治疗前HCVRNA<1×107拷贝/ml者疗效较好。     

臭氧自血回输治疗丙型肝炎患者实验室检测分析及临床疗效评价

目的 通过观察臭氧自血回输疗法治疗丙型病毒性肝炎患者的实验室检测分析临床疗效及安全性,以分析其临床应用价值.方法 选择丙型肝炎患者133例,随机分为治疗组63例、对照组70例;两组患者均给予干扰素α-2b（Interferonα-2b）500万国际单位肌注、每周3次,并联合利巴韦林片300 mg、每日3次口服;治疗组患者加用臭氧自血回输疗法、每周3次治疗.治疗12周后,分别观察、比较其血清丙型肝炎病毒核酸（Hepatitis C virus ribonucleic acid,HCV RNA）水平的变化、血清病毒学应答率、生化学应答率及不良反应发生率.结果 治疗12周,两组患者血清HCV RNA水平中位数均较治疗前明显下降;治疗组血清HCV RNA水平下降幅度大于对照组,血清生化学指标优于对照组,差异均有统计学意义（P＜0.05）;血清病毒学应答率及生化学应答率,两组间差异无统计学意义（D0.05）.两组均未发生不良事件.结论 实验室检测结果分析得出臭氧自血回输疗法治疗丙型肝炎,可以使患者血清HCV RNA水平明显下降,并能促进患者肝功能恢复,安全性好;可用于丙型肝炎的辅助治疗.     

CXC趋化因子9在冷球蛋白血症慢性丙型病毒性肝炎患者血清中表达水平及其对抗病毒疗效的影响

目的探讨CXC趋化因子9在冷球蛋白血症慢性丙型病毒性肝炎(CHC)患者血清中表达水平及其对抗病毒疗效的影响。方法我院收治的100例冷球蛋白血症CHC患者(观察组)和60例同期我院体检正常者(对照组),观察组予聚乙二醇干扰素ɑ-2ɑ联合利巴韦林治疗,所有研究对象均进行CXC趋化因子9等相关指标的检测,分析影响CHC患者抗病毒治疗效果的相关因素。结果观察组血清CXC趋化因子9水平高于对照组(P 0. 001)。观察组快速病毒学应答率(RVR)为32%、完全早期病毒学应答率(c EVR)为66. 00%,持续病毒学应答率(SVR)为64. 00%。存在CHC家族史及总胆红素(TBIL)、CXC趋化因子9和HCV RNA水平过高为导致冷球蛋白血症CHC患者未能出现SVR的独立危险因素(P 0. 05)。结论在冷球蛋白血症CHC患者中血清CXC趋化因子9以较高水平表达,且为影响其抗病毒治疗效果的独立影响因素,可将CXC趋化因子9的检测作为临床上预测冷球蛋白血症CHC患者抗病毒治疗效果的有效指标。     

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎合并2型糖尿病疗效及对肝功能的影响

目的探究慢性丙型肝炎合并2型糖尿病采用聚乙二醇干扰素α-2a联合利巴韦林治疗的临床疗效及对肝功能的影响。方法随机选取该院2016年7月至2017年7月收治的72例慢性丙型肝炎合并2型糖尿病患者,按照数字表法将其分为对照组和观察组,每组各36例患者,对照组采用普通干扰素α-2b联合利巴韦林治疗,观察组采用聚乙二醇干扰素α-2a联合利巴韦林治疗,两组患者都给予常规口服降血糖药物和注射胰岛素。对比分析两组患者的临床疗效,血清丙型肝炎病毒(HCV)RNA、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、空腹血糖水平及用药后不良反应发生情况。结果观察组患者治疗后的RVR(80.56%)、EVR(86.11%)、ETVR(88.89%)及SVR(83.33%)明显高于对照组的RVR(52.78%)、EVR(69.44%)、(75.00%)及ETVR(55.56%),血清HCV RNA[(3.17±1.09)lgIU/mL]、ALT[(38.72±25.21)U/L]及AST[(30.85±14.78)U/L]明显低于对照组的血清HCV RNA[(3.79±1.15)lgIU/mL]、ALT[(53.36±27.32)U/L]及AST[(39.26±19.75)U/L],差异有统计学意义(P0.05)。两组患者治疗后空腹血糖值都有所降低,都出现一定程度的不良反应,两组相比,差异无统计学意义(P0.05)。结论聚乙二醇干扰素α-2a联合利巴韦林对慢性丙型肝炎合并2型糖尿病的疗效显著,肝功能恢复较好,血常规代谢指标得到改善。     

翻倍剂量长效干扰素联合利巴韦林治疗无应答慢性丙型病毒性肝炎疗效观察

目的探讨翻倍剂量长效干扰素联合利巴韦林治疗原发无应答慢性丙型病毒性肝炎(丙肝)的疗效。方法无应答慢性丙肝患者66例,入组后均行丙肝病毒(hepatitis C virus,HCV)基因型、白细胞介素(interleukin,IL)-28B基因rs12979860位点多态性检测;并给予翻倍剂量长效干扰素(360μg/次,1次/周,皮下注射)联合口服利巴韦林15mg/(kg·d),根据早期病毒学应答(early virological response,EVR)情况决定抗病毒疗程。比较不同HCV基因型、IL-28B基因位点患者持续病毒学应答(sustained virus response,SVR)率、复发率、无应答率。结果 66例中HCV基因1b型57例,HCV基因2a型9例;IL-28Brs12979860位点是CC型19例,CT型23例,TT型24例;基因1b型患者中实现SVR率为31.6%,无应答率为56.1%,复发率为12.3%,基因2a型患者中实现SVR率为22.2%,无应答率为55.6%,复发率为22.2%,不同基因型患者SVR率、复发率、无应答率比较差异均无统计学意义(P0.05);IL-28B rs12979860位点为CC型患者SVR率为63.16%、复发率为15.79%、无应答率为21.05%,IL-28Brs12979860CT型患者SVR为34.78%、复发率为8.70%,无应答率为56.52%,IL-28Brs12979860TT型患者SVR率为0,复发率为14.67%,无应答率为83.33%,IL-28Brs12979860CC组与TT组,IL-28Brs12979860CT组与TT组SVR率、无应答率比较差异有统计学意义(P0.05)。结论 IL-28B基因rs12979860位点多态性可预测翻倍剂量长效干扰素联合利巴韦林再治疗无应答慢性丙肝的疗效。     

Optimizing outcomes in patients with hepatitis C virus genotype 1 or 4

Currently, many decisions for the treatment of hepatitis C virus (HCV) are based on genotype, which is the most significant baseline predictor of response to therapy; however, it has become increasingly apparent that fixed treatment durations might not be appropriate for all patients. The use of on-treatment predictors such as rapid virological response (RVR) at week 4 and early virological response (EVR) at week 12 can be used to predict the likelihood of achieving a sustained virological response (SVR), helping to tailor treatment to the individual. Until now, EVR has been defined as achieving either undetectable HCV RNA (< 50 IU/ml) or a > 2 log drop in HCV RNA, but still detectable, at week 12. However, rates of SVR in patients achieving an EVR are heterogeneous. It has recently been suggested that by subdividing EVR into RVR (< 50 IU/ml at week 4), complete EVR (HCV RNA < 50 IU/ml at week 12) or partial EVR (HCV RNA > 2 log drop in HCV RNA but still detectable [> 50 IU/ml] at week 12), it might be possible to further improve the prediction of patients likely to achieve an SVR and may allow for tailoring of treatment duration. Genotype 1 and 4 patients achieving an RVR have high rates of SVR and may be candidates for shorter treatment duration. Patients with a complete EVR achieve high SVR rates with the current treatment duration of 48 weeks, whereas patients achieving a partial EVR have lower rates of SVR and could benefit from treatment intensification to 72 weeks. Here, we discuss the importance of baseline predictors of response and the emerging concept of response-guided therapy in genotype 1 and 4 patients.     

Rapid virological response at week 4 predicts response to pegylated interferon plus ribavirin among HIV/HCV-coinfected patients

INTRODUCTION: The clinical applicability of early viral kinetics at week 4 in predicting sustained virological response (SVR) of pegylated interferon (peg-IFN) plus ribavirin (RBV) in HIV/HCV-coinfected patients is unclear. Our objective was to determine if rapid virological response (RVR) at week 4 of therapy with peg-IFN and RBV could predict SVR among HIV/HCV-coinfected patients. METHODS: HIV/HCV-coinfected patients in whom an HCV viral load determination had been carried out at week 4 of therapy were included in the study. The positive predictive value (PPV) and the negative predictive value (NPV) of RVR (undetectable serum HCV RNA at 4 week) for SVR were calculated in the study population. Receiver operating characteristic curves were calculated to determine the best cutoff of HCV RNA decrease to predict treatment failure. RESULTS: A total of 101 HIV/HCV-coinfected patients were included. RVR and SVR were observed in 39 (39%) and in 49 (48%) individuals, respectively. Of patients with RVR, 37/39 patients achieved SVR (PPV: 95%), whereas 50/62 individuals without RVR did not show SVR (NPV: 81%). The highest NPV (96%) was reached by using a cutoff level of HCV RNA decrease of 0.6 log10. By applying this cutoff level, treatment could have been discontinued in 25 (25%) patients. CONCLUSIONS: An undetectable serum HCV RNA determination at week 4 of treatment with peg-IFN plus RBV is a reliable predictor of SVR in HIV/HCV-coinfected patients. In addition, a decrease of HCV RNA less than 0.6 log10 at this point of treatment could identify an appreciable proportion of individuals who will fail to achieve SVR.     

山东烟台地区丙型病毒性肝炎患者的基因分型及临床意义

目的：探讨山东烟台地区丙型肝炎病毒常见的HCV基因型、HCV RNA含量,HCV不同基因型与转氨酶相关性及干扰素治疗的应答关系。方法：筛选HCV-Ab及HCV RNA阳性患者作为研究对象,采用特异性PCR引物对HCVRNA5’UTR区和／或NS5B区进行扩增,PCR产物进行序列分析,通过与GenBank中参考序列的比对,对样本予以分型。同时,对其使用干扰素治疗前后分别测定HCV RNA含量、谷丙转氨酶、谷草转氨酶。结果：70份HCV—RNA阳性标本有42例可明确分型,可分型率为60．0％;检出1b、2a、3a、6a五种基因亚型,分别为30（71．4％）、10（23．8％）、1（2．4％）、1（2．4％）例。1b亚型是烟台地区HCV携带者的优势流行基因亚型,2a型携带者的ALT、AST均值明显高于1h型,使用干扰素治疗HCV RNA含量明显降低,但转氨酶高的2a患者在丙肝病毒含量降低的同时转氨酶也明显降低,而转氨酶升高不明显的1b患者经干扰素治疗后其转氨酶也无明显变化。结论：山东烟台地区HCV常见基因型为1b、2a、3a、6a,以1b亚型为主。HCV基因型别与转氨酶指标相关,丙肝病毒含量与干扰素治疗相关。     

Results of a study of prolonging treatment with pegylated interferon-alpha2a plus ribavirin in HIV/HCV-coinfected patients with no early virological response

OBJECTIVE: To assess the efficacy and safety of an extended treatment period in HIV/hepatitis C virus (HCV)-coinfected patients without early virological response (EVR). METHODS: Patients received pegylated interferon (peg-INF)-alpha2a 180 microg/week plus ribavirin 800 mg/d for 12 weeks. Patients achieving EVR at week 12 continued under therapy for an additional 12 or 36 weeks depending on genotype. Patients without EVR were randomized to complete the standard treatment or treatment lasting 72 weeks (extension arm). RESULTS: One hundred and ten patients were included (mean age 38.7 years, mean weight 68 kg, 74% males, 74% on highly active antiretroviral therapy, mean CD4+ T-cell count 564 cells/mm3). Fifty-one patients harboured genotype 1, 44 genotype 2/3, and 15 genotype 4. Fifty-three had an HCV load >800,000 IU/ml. Premature interruptions occurred in 32.7%. EVR was achieved in 63.6% (51% in genotype 1, 88.6% in genotype 2/3, 33.3% in genotype 4). End-of-treatment response was 52.7% (47.2% in genotype 1, 68.2% in genotype 2/3, 26.7% in genotype 4). Sustained virological response (SVR) was achieved in 41.8% (37.3% in genotype 1, 54.6% in genotype 2/3, 20% in genotype 4). Only one patient allocated to the extended arm achieved SVR. The rate of drop-outs in the extension arm was 68%. The negative predictive value of EVR was 97.5%. CONCLUSIONS: This study shows no benefit of extending therapy in patients without EVR at week 12. Measures to improve adherence to HCV antiviral therapy should be considered when new approaches based on extended periods of treatment are investigated.     

Optimizing outcomes in patients with hepatitis C virus genotype 2 or 3

On-treatment predictors of response could be useful in optimizing treatment for patients with hepatitis C virus (HCV) genotype 2 or 3. Early virological response (EVR) has limited value as a predictor of response in genotype 2 or 3 patients, as it is achieved by 97% of this population. However, rapid virological response (RVR) measured at week 4 is a strong predictor of sustained virological response (SVR) in this group, and patients achieving an RVR may be suitable candidates for shorter treatment durations. Several small studies investigating the efficacy of shortened treatment durations in this population have been published; however, differences in study design have made their collective interpretation difficult. We discuss these studies, followed by a comparison of the data from ACCELERATE, the largest, randomized trial carried out to investigate abbreviated therapy in genotype 2 and 3 patients. The data confirm that RVR, and its use alongside significant baseline predictors, can assist in optimizing therapy. Patients achieving an RVR have high SVR rates and might be candidates for shorter treatment duration, particularly those displaying a low viral load at baseline; however, the need to consider the increased rate of relapse versus the benefits of abbreviated therapy must also be considered. Conversely, in patients who do not achieve an RVR there is evidence to suggest they may benefit from intensified therapy (longer therapy and/or increased doses). As in genotype 1 and 4 patients, response-guided therapy aims to optimize treatment outcomes for individuals, without compromising SVR rates.     

Therapy for treatment-refractory chronic hepatitis C virus genotype 1b infection: A retrospective analysis

Background:

The most effective current therapy for hepatitis C virus (HCV) infection is the combination of pegylated interferon (peg-IFN) plus ribavirin (RBV).

Objective:

The aim of this retrospective analysis was to determine the rateof response to this therapy, and the factors affecting outcome, in patients with treatment-refractory chronic HCV genotype l b.

Methods:

The records of patients with chronic HCV infection and HCV geno-type1b who failed (nonresponse or relapse) previous treatment with standard interferon (IFN) + RSV were retrospectively analyzed for demographic data, virologic load, liver histology, biochemistry, treatment-related adverse effects (AEs), and the effects of dose reduction during treatment with peg-IFN + RBV for 48 weeks. Early virologic response (EVR) was defined as ≥2-log (copies/mL) decrease from baseline in serum HCV RNA concentration or the absence of detectable serum HCV RNA at treatment week 12. End-of-treatment response (ETR) was defined as the absence of detectable serum HCV RNA at treatment week 48. Sustained virologic response (SVR) was defined as the absence of detectable serum HCV RNA 24 weeks after treatment was discontinued. Factors affecting treatment outcome were determined using correlation analyses.

Results:

Data from the files of 17 patients (12 men, 5 women; mean [SD] age, 48 [2] years) were analyzed. EVR was achieved in 7 patients; however, viral breakthrough occurred in 2 of these patients during the treatment period, and 5 of these patients discontinued treatment because of severe treatment-related AEs (depression [1 patient] and neutropenia [4]). Seven patients achieved ETR, but HCV infection relapsed during the follow-up period. Three (18%) patients achieved SVR. Data concerning previous patterns of response to IFN + RBV therapy were available in 10 patients. Of these, 3 of 6 patients who had experienced relapse with the previous treatment achieved SVR with peg-IFN + RBV; neither of the 2 patients with nonresponse to the previous treatment achieved SVR. Major determinants of failure to reach SVR in these patients included previous nonresponder pattern, noncompliance with the therapy, and advanced-stage liver fibrosis. Tolerability was similar to that with the previous treatment.

Conclusions:

In this study in patients with chronic HCV genotype lb infectionand a history of relapse or nonresponse to standard IFN + RSV treatment, treatment with peg-IFN + RBV achieved an SVR rate of 18%. Further research is needed to determine the role of peg-IFN + RBV in the re-treatment of HCV infection.     

Retreatment of patients who do not respond to initial therapy for chronic hepatitis C

Despite improvements in the treatment of chronic hepatitis C virus (HCV) infection, nearly half of all patients do not respond to initial therapy. Retreatment of these patients with pegylated interferon and ribavirin has been successful in only a limited percentage of cases. Factors associated with sustained virologic response (SVR) following retreatment include prior treatment with interferon monotherapy, HCV genotype 2 or 3, a low serum HCV RNA level, and the absence of cirrhosis. Fewer than 6% of nonresponders who were previously treated with interferon and ribavirin and who have cirrhosis, genotype 1, and a high viral load achieve SVR following retreatment with pegylated interferon and ribavirin. No therapy has been shown to yield SVR in patients who do not respond to pegylated interferon and ribavirin. Long-term maintenance therapy with pegylated interferon is currently being evaluated in nonresponders with advanced fibrosis and cirrhosis. Its use should be considered investigational at this time.     

Role of viral kinetics under HCV therapy in HIV/HCV-coinfected patients

Patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are less responsive to anti-HCV therapies and are at a higher risk of toxicity than HCV monoinfected patients. HCV viral kinetics is the basis for the study of response to interferon-based therapy and for predicting sustained virological response (SVR). A lack of early virological response (EVR; undetectable HCV RNA or a decrease of >/=2 log(10) from baseline) after 12 weeks of pegylated interferon (peg-IFN) plus ribavirin (RBV) is an equally reliable predictor of lack of SVR in HIV/HCV-coinfected patients and in the monoinfected HCV population. Early stopping rules are particularly important in coinfected HIV/HCV patients, considering their low chances of response in the more difficult-to-treat HCV genotypes 1 and 4 (<30%). Several factors have been involved in this low efficacy, including higher baseline HCV viraemia, slower viral kinetics decay under interferon pressure and a defective immune substratum. A better understanding of HCV viral kinetics under HCV therapy may be the basis for assaying different peg-IFN plus RBV schedules, such as induction or extending strategies, and may help physicians to make tailored decisions for the management of their patients.     

丙型肝炎患者基因分型与干扰素治疗疗效分析

目的讨本地区丙型肝炎病毒基因型与干扰素疗效的关系。方法156例慢性丙型肝炎（CHC）患者,HCVRNA采用荧光定量PCR试剂盒,RFLP分析进行HCV基因分型,57例慢性丙型肝炎患者采用IFN—alb治疗,疗程24周。全自动生化分析仪检测血清ALT。结果156例抗HCV阳性患者HCVRNA检出率82．05％（128／156）,HCVⅠ型、Ⅱ型、Ⅲ型、Ⅳ型、Ⅱ＋Ⅲ型分别为0、21．15％、55．13％、0,5．78％。干扰素治疗病例中,HCVⅡ型、Ⅲ型、Ⅱ＋Ⅲ型感染的应答率分别为28．95％、53．33％、25．00％,有显著性差异（P〈0．05）。HCV基因型与血清ALT水平无相关性。结论鲁北地区HCV感染以Ⅱ、Ⅲ型感染为主,干扰素对HCVⅢ型感染的疗效优于HCVⅡ型,ALT与HCVRNA水平可作为干扰素疗效的参考指标,HCV基因分型有预测干扰素疗效的意义。