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。     

慢性丙型病毒性肝炎抗病毒治疗的新进展

由丙型病毒性肝炎病毒(HCV)感染引起的慢性丙型病毒性肝炎(简称慢性丙型肝炎,CHC),聚乙二醇化干扰素(PEG-IFN)联合利巴韦林的治疗方案,持续病毒学应答(SVR)可以达到65%左右。因此,对于诊断明确而又适合抗病毒治疗的患者,应积极进行正规的抗病毒治疗。对于无应答(non-responder)     

广西百色地区老年丙型肝炎患者病毒基因型与抗病毒治疗疗效的关系

目的探讨广西百色地区丙型肝炎(HCV)老年患者病毒基因型分型的分布特点及其与抗病毒治疗疗效的关系。方法选取150例HCV老年患者,采用聚乙二醇干扰素(PEG-IFNα-2a)联合利巴韦林的抗病毒治疗方案进行治疗。实时荧光定量聚合酶链反应(PCR)进行HCVRNA定量检测,Simmonds基因分型法对HCV基因进行酶切分型。治疗后对持续病毒学应答(SVR)进行评价。结果 150例老年患者中HCV基因型以1b型为主,占54.7%(82例),其次是6a型占13.3%(20例)、1a型占10%(15例)、3b型占9.3%(14例)、2a型占6.7%(10例)、3a型占5.3%(8例)、6d型占0.7%(1例);非基因1型患者的快速病毒学应答(RVR)、早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)、(SVR)应答率均明显高于基因1型患者(P<0.05);治疗前血清HCV-RVA载量较高的患者在接受治疗后的RVR与SVR均明显低于载量较低的患者(P<0.05)。结论广西地区HCV老年患者的病毒基因分型以1型为主,且PEG-IFNα-2a联合利巴韦林抗病毒治疗的疗效与HCV基因型和HCV-RNA复制水平有十分密切的联系,因此,HCV基因分型对HCV患者抗病毒的个体化治疗具有重要的临床意义。     

干扰素治疗慢性丙型肝炎获得快速和早期病毒学应答的影响因素

目的:探讨慢性丙型肝炎患者应用聚乙二醇干扰素(pegylated interferon,PEG-IFN)联合利巴韦林治疗不同病毒学应答模式与疗效的关系及获得快速和早期病毒学应答的预测因素,为临床抗病毒治疗疗效判定和治疗方案的选择提供依据.方法:81例慢性丙型肝炎患者均给予pegylated interferon alpha-2a(PEG-IFNα-2a)135-180μg或PEG-IFNα-2b50-80μg,1次/wk皮下注射;利巴韦林800-1200mg/d,对所有患者进行治疗前、治疗4、12、24、48wk和停药后至少24wk的随访,详细记录患者的性别、年龄、丙型肝炎病毒(hepatitis C virus,HCV)RNA水平、肝硬化程度、脂肪肝、体质量指数(body mass index,BMI)、糖尿病史、饮酒史、输血史、既往抗病毒治疗史等等.根据治疗情况将患者分为快速病毒学应答(rapid virological response,RVR)组、早期病毒学应答(early virological response,EVR)组、无应答(no response,NR)组、复发(relapse,RL)组和持续病毒学应答(sustained virologic response,SVR)组.分别应用单因素分析和多因素Logistic逐步回归分析方法分析获得RVR和EVR的影响和预测因素.结果:81例患者中51例(62.9%)获得RVR,65例(80.2%)获得EVR,65例(80.2%)获得SVR,10例(12.3%)NR,6例(7.4%)FL.RVR组88.2%获得SVR,EVR组90.8%获得SVR.未获RVR和EVR的患者16人(19.8%),其中6人(37.5%)获得SVR,6人(100%)均未复发.3组SVR率的差异有统计学意义(?2=20.622,P<0.05),复发率差异无统计学意义(P>0.05).SVR、NR和RL组的RVR率分别为69.2%、0%、100.0%;EVR率分别为90.8%、0%、100.0%.3组RVR率及EVR率的差异有统计学意义.单因素分析结果显示:年龄≤40岁,HCVRNA载量<4×105,无肝硬化与快速病毒学应答有关;年龄≤40岁,HCVRNA载量<4×105,无肝硬化,BMI<24kg/m2与早期病毒学应答有关.将上述指标进行多因素Logistic逐步回归分析,结果表明:基线HCVRNA载量和肝硬化是预测RVR和EVR的独立影响因素.结论:RVR和EVR的获得是获得SVR的重要预测因素;未获得RVR和EVR的患者通过1年疗程的治疗,少部分患者仍可获得SVR;RVR和EVR不能预测复发.年龄、基线病毒载量、有无肝硬化和体质量指数与RVR和EVR的获得密切相关.基线病毒载量、有无肝硬化是预测RVR和EVR的独立因素.     

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。     

快速病毒学应答对干扰素治疗慢性丙型肝炎疗效的预测分析

目的 探讨干扰素治疗慢性丙型肝炎的快速病毒学应答(RVR)对疗效的预测及其相关因素.方法 对139例慢性丙型肝炎患者,根据其临床特点,给予标准干扰素(IFN)或聚乙二醇干扰素(PEG-IFN)治疗.IFN α3～5MU隔日注射1次;PEG-IFNα-2a 135～180 μg,或PEG-IFNα-2b 50～80 μg,每周注射1次.并根据患者的体质量给予600～1500 mg/d的利巴韦林,在治疗的0、4,12周和以后每间隔12周、治疗结束后的24周进行HCV RNA含量检测,根据患者治疗过程中的病毒学应答情况给予24～72周的疗程,以持续病毒学应答(SVR)作为疗效的评判指标.根据资料不同采用χ2检验或t检验.结果 132例患者完成了全程观察,其中4例治疗无效(3.0%),12例复发(9.1%),获得SVR有116例(87.9%).120例在治疗4周时检测了病毒学指标,101例(84.2%)获得了RVR,治疗前病毒载量为(5.883±1.246)lg拷贝/ml,19例无RVR,治疗前病毒载量为(6.502±0.693)lg拷贝/ml,两组比较,t:2.15,P=0.034,差异有统计学意义.97例完成全程观察的RVR患者中,88例(90.7%)获得SVR,17例无RVR的患者,14(82.4%)例获得了SVR,x3=0.371,P=0.543,差异无统计学意义.基因1型HCV感染患者的RVR为80.7%(46/57),非基因1型HCV感染患者的RVR率为92.6%(25/27),两组间比较,χ2=6.00,P=0.112,差异无统计学意义.初治患者的RVR率为87.8%,干扰素再治疗者的RVR率为65.0%,两组比较,χ2=4.651,P=0.031,差异有统计学意义. 结论 干扰素个体化抗病毒治疗慢性丙型肝炎,有较高的RVR获得率.RVR的获得与治疗前HCV RNA载量和患者是否为初次治疗相关,与基因型无关,RVR的获得可预测SVR的获得.     

微小RNA在丙型肝炎病毒感染中的作用的研究进展

全世界估计有超过1.3亿的HCV慢性感染者[1-4].目前仍无有效的疫苗或抗体制剂预防HCV感染,标准的治疗方案是聚乙二醇干扰素α(PEG-IFNα)与利巴韦林联合应用,但仍有约50%的患者不能达到持续病毒学应答(SVR)[1-2].     

微小RNA在丙型肝炎病毒感染中的作用的研究进展

全世界估计有超过1.3亿的HCV慢性感染者[1-4].目前仍无有效的疫苗或抗体制剂预防HCV感染,标准的治疗方案是聚乙二醇干扰素α(PEG-IFNα)与利巴韦林联合应用,但仍有约50%的患者不能达到持续病毒学应答(SVR)[1-2].     

微小RNA在丙型肝炎病毒感染中的作用的研究进展

全世界估计有超过1.3亿的HCV慢性感染者[1-4].目前仍无有效的疫苗或抗体制剂预防HCV感染,标准的治疗方案是聚乙二醇干扰素α(PEG-IFNα)与利巴韦林联合应用,但仍有约50%的患者不能达到持续病毒学应答(SVR)[1-2].     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎患者效果的影响因素

目的 分析聚乙二醇干扰素(PEG-IFN)联合利巴韦林(RBV)治疗慢性丙型肝炎患者的病毒学应答情况及其影响因素.方法 入组对象为接受PEG-IFNα-2a或PEG-IFNα-2b联合RBV治疗的慢性丙型肝炎患者130例,收集患者基线、治疗4、12、48周和停药24周的资料,包括年龄、性别、体质指数(BMI)、脾指数(SPI)、门静脉内径(PV)、HCV基因型、HCV RNA载量等.比较获得持续性病毒学应答( SVR)与未获得持续性病毒学应答(NSVR)的情况,对SVR的影响因素进行相关分析.数据处理采用t检验、x2检验和Logistic回归分析.结果 总SVR率为84％ (109/130),其中快速病毒学应答(RVR)率为21％(27/130),早期病毒学应答(EVR)率为72％ (94/130),治疗结束时病毒学应答(ETVR)率为93％(121/130).HCV基因1型患者SVR率为82％(45/55),非基因1型SVR率为87％(13/15);患者年龄、基线HCV RNA载量、BMI、SPI与SVR负相关(回归系数＜0,均OR＜1,均P＜0.05),EVR与RBV总量和SVR呈正相关(回归系数＞0,均OR＞1,均P＜0.05),而RVR、PV及PEG-IFN总量与SVR不相关(均P＞0.05).结论 PEG-IFN联合RBV治疗慢性丙型肝炎患者的SVR率较高,超过80％患者可治愈;年龄大于35岁、既往治疗失败、基线病毒载量高于6×105 IU/mL、BMI＞26 kg/m2、SPI＞40 cm2、RBV累计量不超过标准量80％的患者SVR率较低.     

Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin

BACKGROUND AND AIM: The therapeutic effect of pegylated interferon (peg-IFN)-alpha-2a combination with ribavirin on patients with chronic hepatitis C virus (HCV) infection is dependent on the rapidity of the virological response. The aim of this study was to investigate the predictive value of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in HCV patients treated with peg-IFN-alpha-2a and ribavirin. METHODS: The HCV genotypes of 105 patients with chronic hepatitis C were detected by enzyme-immunoassay. Patients received subcutaneous 180 microg peg-IFN-alpha-2a once weekly plus daily ribavirin. Patients with genotype 1 were treated for 48 weeks and patients with genotype 2 or 3 were treated for 24 weeks. HCV RNA was assessed by qualitative PCR at pretreatment, at weeks 4 and 12 during treatment, and at week 24 of follow-up. Virological response rates at different weeks were investigated, with RVR defined as serum HCV RNA undetectable after 4 weeks and EVR defined as HCV RNA either undetectable or decrease by >or=2 log(10) after 12 weeks. The effects of virological response rates at different weeks on SVR were analyzed. RESULTS: Of the 105 patients, 44 (41.9%) were genotype 1, 46 (43.8%) were genotype 2, and 15 (14.3%) were genotype 3. RVR rates (19.5%) of patients with genotype 1 were significantly lower than those (60.7%) of genotype 2 or 3 (chi(2) = 16.836, P = 0.000); and EVR rates (73.2%) of patients with genotype 1 were significantly lower than those (96.7%) of genotype 2 or 3 (chi(2) = 12.220, P = 0.000). The SVR rates (86.7%) of patients who had achieved RVR were significantly higher than those (43.9%) of patients who had not achieved RVR (chi(2) = 19.713, P = 0.000). The positive predictive value of RVR in all patients was higher than that of EVR, but there was no significant difference between RVR and EVR. The negative predictive value of RVR in all patients or with genotype 1 was significantly lower than that of EVR. In univariate analysis, HCV RNA level (P = 0.014), genotype (P = 0.001), RVR (P = 0.000) and EVR (P = 0.000) were associated with effect of treatment. However, in stepwise regression analysis, the independent factors associated with effect of antiviral therapy were RVR (OR = 6.501, P = 0.001), EVR (OR = 2.776, P = 0.003) and genotype (OR = 3.061, P = 0.024). CONCLUSIONS: The RVR and EVR rates of patients with genotype 1 were significantly lower than those of patients with genotype 2 or 3. RVR had a similar predictive value as EVR on SVR. Genotype, HCV RNA level, RVR and EVR were associated with SVR. Genotype, RVR and EVR were independent factors for predicting the effect of antiviral therapy.     

Sustained virological response according to the type of early virological response in HCV and HCV/HIV

Background. The most important factors to predict the sustained virological response (SVR) are the genotype and the fibrosis grade, although there are other predictive factors to be considered, mainly in HCV/ HIV coinfected patients.Aim. To evaluate different prognostic factors to obtain the SVR in HCV monoin-fected and HCV/HIV coinfected genotype I patients emphasizing the type of early virological response (EVR)-complete or partial.Methods. This is a cohort study, retrospective, where the registers of HCV mo-noinfected or HCV/HIV coinfected patients, genotype I, treated with pegylated interferon + ribavirin were reviewed. The prognostic factors: age greater than 40 years, viral load higher than 600,000UI/mL, and fibrosis grade (score METAVIR) were evaluated pre-treatment, and also the EVR considering the reduction of 100 times of the basal viral load (partial EVR) or negative PCR (complete EVR) in the week 12. In the statistical analysis, multivariate analysis was used. The significance level adopted was 5%.Results. There were 323 HCV monoinfected and 59 HCV/HIV coinfected. The SVR was 35.3% in monoinfected and 23% in coinfec-ted patients. The worst results was observed in those with age greater than 40 years, high viral load, pronounced fibrosis (F4) and partial EVR, with an expected probability of 1.9% for SVR in those coinfected and 3.8% in monoinfected. In conclusion, patients with cirrhosis HCV genotype 1, age greater than 40 years, high viral load, coinfected with HIV or not, will present a low SVR if did not obtain negative PCR in week 12, and should be evaluated for discontinuation.     

Early identification of achieving a sustained virological response in chronic hepatitis C patients without a rapid virological response

Background and Aim: A number of hepatitis C virus (HCV) patients without a rapid virological response (RVR) achieved a sustained virological response (SVR) with peginterferon‐α‐2a/ribavirin. The aim of this study was to identify factors associated with SVR in non‐RVR patients. Methods: Baseline and on‐treatment factors were used to explore the prognostic factors for SVR in 113 HCV genotype‐1 (HCV‐1) and 20 HCV‐2 non‐RVR patients in two randomized trials. Results: The SVR rate in HCV‐1 patients with a complete early virological response (cEVR) and partial early virological response was 91.9% versus 45% (P < 0.001) and 21.4% versus 10% (P = 0.62), respectively, after 48 and 24 weeks of treatment. The SVR rate in HCV‐2 patients with a cEVR was 90.9% versus 57.1% (P = 0.25), respectively, after 24 and 16 weeks of treatment. Multivariate analysis showed that cEVR and standard regimen were independently associated with SVR. Viral kinetic study revealed that HCV viral loads < 10 000 IU/mL at week 4 were the best predictor of cEVR for both HCV‐1 and HCV‐2 non‐RVR patients with the accuracy of 81% and 95%, respectively, and also of SVR with the accuracy of 78% and 92%, respectively, in patients receiving standard of care. The most important independent predictors for cEVR were HCV viral loads < 10⁴ IU/mL at week 4, followed by increased ribavirin dose within 12 weeks of treatment. Conclusions: Achieving a cEVR with standard of care is the most important predictor of SVR in non‐RVR patients. Week 4 viral loads < 10 000 IU/mL could accurately predict cEVR early and following SVR in non‐SVR patients.     

Role of rapid virological response in prediction of sustained virological response to Peg-IFN plus ribavirin in HCV / HIV co-infected individuals

Summary.  The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV / HCV co-infected patients commenced HCV treatment per protocol. HIV / HCV patients with a mean CD4 count of 502 were treated for 24–48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV / HCV patients achieved SVR (35% genotype 1 / 4; 77% genotype 2 / 3). 24 HIV / HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV–HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2 / 3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2 / 3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2 / 3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR.     

Sustained virological response based on rapid virological response in genotype-3 chronic hepatitis C treated with standard interferon in the Pakistani population

AIM：To document the sustained virological response （SVR） in rapid virological responders （RVR） of genotype-3 chronic hepatitis C with standard interferon （SdIF）. METHODS：Hepatitis C genotype-3 patients during the period July 2006 and June 2007 were included. Complete blood counts, prothrombin time, ALT, albumin, qualitative HCV RNA were done. SdIF and ribavirin were given for 4 wk and qualitative HCV RNA was repeated. Those testing negative were allocated to group-A while the rest were allocated to group-B. Treatment was continued a total of 16 and 24 wk for group A and B respectively. HCV RNA was repeated after 24 wk of treatment. End virological and sustained virological responses were compared by χ^2 test. ROC of pretreatment age, ALT and albumin were plotted for failure to achieve SVR. RESULTS：Of 74 patients treated, RCV RNA after 16 wk of therapy became undetectable in 34 （45.9%） and was detectable in 40 （54.1%） and were allocated to groups A and B respectively. SVR was achieved in 58.8% and 27.8% in groups A and B respectively. SVR rates were significantly higher in patients who had RVR as compared to those who did not （P = 0.0;γ = 2）. Both groups combined ETR and SVR were 70% and 33% respectively. ROC plots of pretreatment age, ALT and albumin for SVR showed only ALT to have a significantly large area under the curve.CONCLUSION：SVR rates were higher in patients who had RVR with SdIF and high pre treatment ALT values correlated to probability of having RVR.     

Platelet count and sustained virological response in hepatitis C treatment

AIM: To examine the epidemiological data, hematological safety and treatment responses of peginterferon-alpha 2a plus ribavirin therapy for hepatitis C. METHODS: Between March 2008 and February 2011, 196 hepatitis C virus (HCV) genotype 1 infected Japanese (127 treatment-naive and 69 treatment-experienced patients) patients treated with peginterferon-alpha 2a plus ribavirin were enrolled. We examined the epidemiological data and treatment responses were retrospectively analyzed in terms of hematological safety. HCV RNA was measured by the COBAS TaqMan HCV test. RESULTS: Overall sustained virological response (SVR) rates of treatment-naive and treatment-experienced patients were 56% and 39%, respectively. Multivariate logistic regression analysis showed that SVR was attained independently of early virological response in both treatment-naive and treatment-experienced patients. SVR rates did not differ between the pretreatment hemoglobin < 13 g/dL and ≥ 13 g/dL groups. However, in treatment-naive patients, the SVR rate of the pretreatment platelet count < 130000/µL group was significantly lower than that of the pretreatment platelet count ≥ 130000/µL group. CONCLUSION: Attention should be paid to potential thrombocytopenia in the treatment of chronic hepatitis C patients.     

Baseline predictors of virological response for chronic hepatitis B patients

AIM： To determine which baseline factors of chronic hepatitis B patients are predictive of virological response to Peginterferon α-2b therapy. METHODS： A total of 21 HBeAg-positive chronic hepatitis B （CriB） patients treated with Peginterferon α-2b were recruited. They were treated with Peginterferon α-2b （0.5-1.0 μg/kg per week） for 24 wk and followed up for 24 wk. Clinical and laboratory data of the patients were determined at pretreatment and at week 12, at 24 during treatment, and at week 48 during follow up. RESULTS： Ten patients achieved a virological response at the end of treatment. Their baseline serum alanine aminotransferase （ALT）, thyroid-stimulating hormone （TSH）, and total thyroxin （TT4） levels were significantly different from those who failed treatment. The positive predictive values （PPV） and negative predictive values （NPV） of ALT, TSH, and TT4 were 75% and 89 %, 75% and 89 %, and 75% and 75%, respectively. Moreover, combinations of the baseline ALT and TT4, ALT and TSH, TT4 and TSH levels had much higher PPV and NPV （86% and 88%, 89% and 100%, 83% and 100%, respectively）.CONCLUSION： Baseline serum ALT, TSH, and TT4 levels, especially in combination, have high predictive values of virological response to Peginterferon α-2b in HBeAg-positive CriB patients.