干扰素联合利巴韦林治疗由一名献血员所致慢性丙型肝炎62例分析

目的 应用干扰素α-2b联合利巴韦林治疗由一名献血员所致62例慢性丙型肝炎(CHC)患者,评估其疗效.方法 62例输血后CHC患者给予干扰素α-2b联合利巴韦林治疗(标准干扰素3～5MU,隔日一次注射,口服利巴韦林0.6～ 1.0g/d),疗程48周,随访96周.以持续病毒应答(SVR)率、早期病毒学应答(EVR)率、治疗结束时病毒学应答(ETVR)率、停药后生物化学应笞率为考核指标,同时观察药物不良反应.计量资料用均数±标准差(x-±s)表示,计数资料用x2检验.结果 SVR率为83.9％ (52/62),EVR率为95.2％ (59/62),ETVR率为87.1％ (54/62),停药后生物化学应答率为100.0％.不同病毒载量(x 2=10.13,P＜0.05)和不同年龄(x 2=14.58,P＜0.01)患者SVR率差异明显.干扰素所致8例甲状腺功能轻度异常者经内分泌专科协助能坚持完成抗病毒治疗.结论 干扰素α-2b联合利巴韦林治疗CHC患者疗效显著,获得SVR的52例停药后随访96周均无复发,疗效与感染HCV时较年轻、感染时间较短、多数患者病毒载量较低、治疗依从性较好等因素有关,与性别无关.只要患者血清HCV RNA阳性,均应抗病毒治疗,以清除病毒、阻断和延缓病情进展.     

白细胞介素28B基因多态性在冷球蛋白阳性与阴性丙型肝炎患者中的比较

目的 探讨冷球蛋白血症慢性丙型肝炎(CHC)患者白细胞介素(IL) 28B基因多态性的分布.方法 检测62例用聚乙二醇干扰素α-2a联合利巴韦林进行抗病毒治疗的CHC患者血清冷球蛋白性质,并检测IL-28B rs8099917、rs12979860、rs12980275的基因型.并分别检测患者血清HCV RNA在基线、治疗后4周与12周、治疗结束、治疗结束后24周时的水平.对计量资料用独立样本t检验或秩和检验进行两组间的比较,对计数资料用X2检验、Fisher's精确概率法进行组间比较.结果 27例患者血清冷球蛋白阳性,发生率为43.5％.IL-28B rs8099917 TT基因型(63.0％与94.3％,x2=9.581,P＜0.01)与T等位基因(81.5％与97.1％,x2=8.554,P＜ 0.01)、IL-28B rs12979860 C等位基因(83.3％与94.3％,x2=3.896,P＜ 0.05)在冷球蛋白阳性CHC患者中的分布频率低于冷球蛋白阴性患者.结论 IL-28B的基因型或等位基因分布在冷球蛋白阳性与阴性CHC患者间存在差异.     

应用RGT策略抗病毒获得SVR后复发的6例慢性丙型肝炎患者临床分析

聚乙二醇化干扰素（Peg IFN）联合利巴韦林（RBV）是目前CHC抗病毒治疗的标准方案[1],近年来,应答指导治疗（RGT）研究进展迅速,患者因此取得持续病毒学应答（SVR;治疗结束后随访24周,血清HCV RNA低于检测下限）的比例大幅提高。     

抗病毒治疗对慢性丙型肝炎患者HCV NS特异性T细胞应答的影响

目的探讨HCV特异性T细胞应答与慢性丙型肝炎(chronic hepatitis C,CHC)患者抗病毒治疗疗效之间的关系.方法聚乙二醇干扰素α联合利巴韦林治疗CHC患者48例,在治疗前及治疗第4周、第12周时收集患者血清和外周血单个核细胞,通过酶联免疫斑点法检测对HCV非结构蛋白(non-structural protein,NS)区合成肽的特异性T细胞应答,进行纵向比较分析.结果基线时,52%的患者可检测出HCV NS3、NS4和NS5A特异性T细胞应答,其中NS3诱导的免疫反应最强.持续病毒学应答(sustained virological response,SVR)组患者较非SVR组患者对多肽刺激的应答率高.SVR组患者在治疗第12周时仍维持较高水平的HCV特异性T细胞应答,而非SVR组患者在治疗第4周时HCV特异性T细胞应答明显下降,第12周时仅维持低水平.结论在接受抗病毒治疗的CHC患者中,HCV特异性T细胞应答与SVR相关.     

聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型慢性丙型肝炎临床观察

目的：观察聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型慢性丙型肝炎（CHC）的疗效及不良反应。方法40例基因1b 型 CHC 患者应用聚乙二醇干扰素α-2a 联合利巴韦林治疗,疗程48周,随访24周,观察病毒学应答情况及药物不良反应。结果获得快速病毒学应答（RVR）、完全早期病毒学应答（cEVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答（SVR）比例分别为65．0％、82．5％、90．0％、82．5％,获得 RVR 者均获得 SVR;合并脂肪肝者获得 SVR 的比例低于无脂肪肝者（P ＜0．05）;治疗过程中聚乙二醇干扰素α-2a 减量者8例,利巴韦林减量者6例。结论聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型 CHC 疗效良好;合并脂肪肝患者疗效低于无脂肪肝患者;治疗中不良反应普遍,但均能耐受。     

不耐受标准治疗方案慢性丙型肝炎患者的低剂量干扰素治疗

目的 针对不能耐受标准治疗方案的慢性丙型肝炎(CHC)患者,探索低剂量干扰素联合利巴韦林长期维持治疗的效果,并分析与疗效相关的可能影响因素. 方法 对于白细胞低下、甲状腺功能异常等多种原因不能耐受标准治疗方案的CHC患者46例,给予个体化低剂量干扰素(标准干扰素60万～300万IU隔日一次,聚乙二醇干扰素50 ～ 90μg/周)联合利巴韦林0.6 ～ 0.9 g/d 长期维持治疗,疗程≥72周.连续变量两组间比较采用t检验或秩和检验,计数资料采用x2检验或Fisher’s exact test检验.结果 93.5％患者(43/46)可耐受不同低剂量干扰素联合利巴韦林长期维持治疗,只有3例不能耐受而被迫停药.不同节点的病毒学应答率为:快速病毒学应答10.9％、早期病毒学应答 30.4％、24周病毒学应答45.7％、48周病毒学应答47.8％.3例患者在治疗过程中肝脏B型超声显示形态学改善.快速病毒学应答、早期病毒学应答、24周病毒学应答者均可在48周时获得较高病毒学应答,尤其24周病毒学应答对48周病毒学应答具有较好预测作用,获得24周病毒学应答者其48周病毒学应答率为95.2％,而24周未获得病毒学应答者其48周未应答率为92.0％.结论 (1)对于不能耐受标准治疗方案的CHC患者予以低剂量干扰素联合利巴韦林长期维持治疗,可以获得较高的48周病毒学应答率(47.8％);(2)24周病毒学应答对48周病毒学应答具有较好预测作用;(3)疗程中严密监测、对症治疗原发病并给予患者足够的依从性教育和心理疏导是治疗得以维持的重要保证.     

冷球蛋白血症对慢性丙型肝炎抗病毒治疗后甲状腺功能的影响

目的 探讨冷球蛋白血症（MC）对慢性丙型肝炎（CHC）抗病毒治疗后甲状腺功能的影响.方法 将102例慢性丙型肝炎患者分为冷球蛋白血症阳性组（44例）和阴性组（58例）,两组患者均予聚乙二醇干扰素（PEG-IFN） α-2a联合利巴韦林治疗,并检测治疗前、治疗后12周、24周、36周、48周及治疗结束后24周患者血清HCV RNA和甲状腺功能,观察治疗前后甲状腺功能的变化.结果 102例慢性丙型肝炎患者中冷球蛋白阳性44例,阳性率为43.1％（44/102）.冷球蛋白血症阳性组持续病毒学应答发生率（SVR）低于阴性组（59.1％比81.0％,P＜0.05）;冷球蛋白血症阳性组治疗12周、24周甲状腺功能异常新发病例均高于阴性组（P＜0.05）.以亚急性甲状腺机能减退为主要表现形式;冷球蛋白血症阳性组12周、24周时甲状腺功能异常发病率均高于阴性组（P＜0.05）.甲状腺功能异常者多数在治疗36周时恢复正常,均能完成48周疗程.结论 慢性丙型肝炎合并冷球蛋白血症阳性的患者干扰素治疗后更易出现甲状腺功能异常,但甲状腺功能改变不影响继续治疗.     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎初治与再治患者应答比较

目的评价聚乙二醇干扰素联合利巴韦林对慢性丙型肝炎(CHC)初治与复治患者的影响。方法回顾性分析研究设计,以是否为初治患者分为初治组与再治组,以快速病毒学应答(RVR)、早期病毒学应答(EVR)、治疗结束病毒学应答(ETR)、持续病毒学应答(SvR)为主要评价指标,分析两组患者病毒学应答之间的差异,并探讨两组之间病毒学应答差异的影响因素。结果与再治组相比,初治组患者获得RVR、EVR、SVR的概率明显高于再治组,差异具有统计学意义(P<(0.05);初治组与再治组复发率差异不具有统计学意义(P>0.05),但再治组CHC患者治疗结束后复发率明显高于初治组(21.1%与4.0%);既往采用聚乙二醇干扰素联合利巴韦林或普通干扰素联合利巴韦林抗病毒,经再次以聚乙二醇干扰素联合利巴韦林治疗后获得RVR、EVR、ETR、SVR的差异不具有统计学意义(P>0.05);初治组中基因1型CHC患者获得SVR的概率明显低于非1型CHC患者(P<0.05),年龄<40岁CHC患者具有容易获得SVR的趋势(β<0,OR<1,P>0.05);再治组中,女性CHC患者较男性更易获得SVR(P<(0.05),感染途径中输血导致的HCV感染较其他途径更容易获得SVR(P<0.05)。结论 CHC初治患者较再治患者可取得较高病毒学应答率,复发率较低,HCV基因型及年龄、性别、感染途径可能是CHC患者获得SVR的影响因素。而既往治疗方案采用普通干扰素或聚乙二醇干扰素对再治CHC患者获得病毒学应答无显著影响。     

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的疗效及不良反应

目的:观察聚乙二醇干扰素α-2a(PEG-IFNα-2a)联合利巴韦林治疗慢性丙型肝炎的疗效及不良反应。方法:回顾性分析在本院门诊接受抗病毒治疗的63例慢性丙型肝炎。各型患者均给予PEG-IFNα-2a和利巴韦林,疗程48周。分别在治疗前、治疗后4周、12周、24周、治疗结束时、治疗结束后24周及48周测定患者血清HCV RNA水平,观察不良反应发生率。结果:58.7%(37/63)的患者获得快速病毒学应答,68.2%(43/63)获得早期应答,73%(46/63)获得治疗结束后应答,治疗结束后随访24周时65%(41/63)HCV RNA仍为阴性,48周时有57.1%(36/63)仍为阴性。63例患者中有5例因为药物副作用终止干扰素治疗,完成治疗的患者,主要不良反应为感冒样症状、消化道症状、血常规异常、精神症状及甲状腺疾病。结论:PEG-IFNα-2a联合利巴韦林治疗慢性丙型肝炎疗效确切、安全,及时发现药物不良反应并采取适当措施,能够确保患者完成治疗疗程。     

抗病毒治疗对慢性丙型肝炎合并冷球蛋白血症患者肝功能的影响

目的：探讨抗病毒治疗对慢性丙型肝炎（ CHC）合并冷球蛋白血症患者肝功能的影响。方法：选取CHC合并冷球蛋白血症患者61例,按是否自愿接受干扰素治疗,分为治疗组33例,对照组28例,治疗组在对照组保肝治疗基础上予以聚乙二醇干扰素α-2a （PEG-IFN-α-2a）联合利巴韦林抗病毒治疗,比较两组患者治疗前、治疗48周及停药后24周各指标的变化。结果：①治疗组患者治疗48周、停药后24周HCV RNA水平低于对照组,差异均有统计学意义（P＜0.05）。②治疗组治疗结束、停药后24周ALT、 TBil低于对照组、 Alb、 PTA含量高于对照组,两组比较差异均有统计学意义（ P＜0.05）。结论：抗病毒治疗可以降低HCV RNA水平并能明显改善CHC合并冷球蛋白血症患者的肝功能。     

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.     

Twenty-four weeks of pegylated interferon plus ribavirin effectively treat patients with HCV genotype 6a

The optimal duration of treatment and expected response rate for hepatitis C virus genotype (HCV-6)-infected patients have not been determined. Our aims were to determine the treatment outcome with pegylated interferon (PEG-IFN) plus ribavirin for HCV-6a-infected patients at Southwest Hospital and assess the association of the on-treatment virological response with the sustained virological response (SVR). Medical records were reviewed retrospectively. Twenty-two HCV-6a-infected patients were treated for 24 weeks, and 21 (95.5%) achieved an early virological response (EVR), 20 (90.9%) an end-of-treatment response (ETR) and 18 (81.8%) a SVR. However, only 18 of the 22 HCV-6a-infected patients were tested for serum HCV RNA level at week 4 of treatment and 15 (83.3%) achieved a rapid virological response (RVR). The rates of SVR, RVR, EVR and ETR in these patients were all similar to those in HCV-2/3 treated for 24 weeks and higher than those in HCV-1b-infected patients treated for 48 weeks. A lower relapse rate (10.0%) was seen in HCV-6a compared with HCV-2/3 (12.5%) or HCV-1b-infected patients (23.3%). The positive predictive values of RVR and EVR for HCV-6a were comparable with those for HCV-2/3-infected patients (86.7%vs 90.9%, P = 0.683 and 85.7%vs 86.8%, P = 0.904, respectively). Of the 3 HCV-6a-infected patients who did not achieve a RVR, 2 achieved an EVR and went on to achieve a SVR. The patient who did not achieve an EVR did not achieve a SVR. In summary, our results indicate that 24 weeks of PEG-IFN plus ribavirin can effectively treat patients with HCV-6a chronic infection.     

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.     

Kinetics of hepatitis C virus RNA load during pegylated interferon plus ribavirin therapy in Treatment-naive Chinese patients

BACKGROUND/AIMS: To investigate the viral kinetics of Chinese CHC patients received pegylated interferon plus ribavirin and examine the impact of HCV genotypes and severity of liver disease. METHODOLOGY: 65 treatment-naove CHC patients who finished a 24-week therapy with peginterferon (alpha-2b (1.5 mcg/kg/week) plus ribavirin (1000-1200 mg /day) and 24 weeks of follow-up were enrolled. Hepatic fibrosis was graded by the METAVIR scoring system. Serum quantitative HCV RNA was determined by Versant HCV RNA 3.0 assay (Bayer Inc.). RESULTS: Genotype non-1 patients responded quickly and a higher percentage of them achieved undetectable HCV RNA (< 615 IU/mL) at week 4 compared with genotype 1 patients (93% vs. 69%, p = 0.018). Degree of hepatic fibrosis significantly affected end-of-treatment and sustained response (SVR). For patients who did not achieve early virological response (EVR), the negative predictive value for SVR was 100%. In genotype 1 patients, undetectable HCV RNA by week 4 was a good marker to predict treatment response, with a positive predictive value of 84% and a negative predictive value of 82%. CONCLUSIONS: EVR can be applied to Chinese patients as an early stopping rule. A 24-week duration of pegylated IFN/ribavirin might be adequate for genotype 1 patients who rapidly responded to therapy.     

The use of different Peg-interferon alpha-2b regimens plus ribavirin in HCV-1b-infected patients after rapid virological response does not affect the achievement of sustained virological response

Summary.  In patients with chronic hepatitis C, rapid virological response (RVR) at week 4 of treatment seems to be strongly associated with a high probability of achieving a sustained virological response (SVR). The aim of this study was to investigate the outcome of different pegylated interferon-α2b (Peg-IFN-α2b) dosages plus ribavirin (RBV) in patients with RVR. Forty-five naïve patients chronically infected with hepatitis C virus (HCV)-1b started Peg-IFN-α2b (1.5 μg/kg/week) in combination with weight-based RBV doses (800–1200 mg/day). Thirty-one patients (68.9%) attained RVR at week 4 of therapy, while four further patients showed negative HCV-RNA values for the first time at week 12 and were considered early virological responders (EVR). The 31 RVR patients were randomized to receive either RBV plus 1.5 μg/kg/week (17 pts) or 1.0 μg/kg/week (14 pts) of Peg-IFN-α2b for the remaining 44 weeks. The two groups were matched for age, sex, baseline alanine aminotransferase levels, viral load and fibrosis score. After 6 months of post-treatment follow-up, the prevalence of SVR was 94.1% (16/17) among RVR patients treated with 1.5 μg/kg/week and 92.8% (13/14) in RVR patients treated with 1.0 μg/kg/week ( P  = not significant). A high-baseline viral load ( P  = 0.01) and bridging fibrosis/cirrhosis ( P  = 0.02) negatively influenced the likelihood of achieving RVR. On the contrary, the ability of RVR patients to achieve SVR did not correlate with these baseline characteristics in either of the treatment group. Finally, the SVR rate among EVR patients who responded after more than 4 weeks of treatment was significantly lower than among RVR patients (1/4 = 25% vs 29/31 = 93.5%; P  = 0.0058), because of a high prevalence of post-treatment relapse among patients with EVR.     

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。     

Predictors of Pegylated Interferon Alpha and Ribavirin Efficacy and Long-Term Assessment of Relapse in Patients With Chronic Hepatitis C: A One-Center Experience From China

Background:

Sustained virological response (SVR) and virological relapse maintain pivotal roles in the management of chronic hepatitis C (CHC); however, there is little data regarding the long-term outcomes of patients with CHC in China.

Objectives:

We aimed to investigate the predictive factors of therapeutic effect and viral relapse in patients who achieved end-of-treatment response (ETR).

Patients and Methods:

We retrospectively analyzed clinical, biochemical and virological data of 169 adult patients with CHC from China who were not treated with pegylated interferon-alpha (PEG IFN-α) and ribavirin, of which 142 achieved ETR and with a follow-up period ranging from six months to six years. Statistical analysis was performed by SPSS 20.0.

Results:

Of the 169 patients, 124 (73.4%) achieved SVR and 23 (16.2%) experienced relapses post-therapy in cases of ETR patients. We considered sex, age, alanine aminotransferase, aspartate transaminase, baseline hepatitis C virus RNA level, HCV genotypes, IL28B rs12979860 genotype, rapid virological response (RVR), and early virological response (EVR). For antiviral effect in patients with CHC, HCV genotypes (2, 3) (χ² = 11.285, P = 0.001), IL28B genotype (rs12979860 CC) (χ² = 16.552, P < 0.001), RVR (χ² = 37.339, P < 0.001), and EVR (χ² = 70.265, P < 0.001) were significantly correlated with achieving SVR. For ETR patients with long-term follow-up, the relapse rate within six months was significantly higher than within other periods during six-year follow-up (χ² = 7.792, P = 0.005). Relapse was virtually not observed after therapy ceased for 48 weeks. The IL28B genotype (rs12979860 CT/TT) (OR = 0.102; 95% CI, 0.031-0.339; P < 0.001), lower RVR (OR = 0.239; 95% CI, 0.078-0.738; P = 0.013), and EVR (OR = 0.102; 95% CI, 0.016-0.661; P = 0.017) were independent risk factors for relapse.

Conclusions:

Our study comprehensively explored the predictive factors of therapeutic effect of administered drugs and analyzed viral relapse during a six-months to six-year follow-up period from China. The SVR may not be the perfect endpoint of HCV therapy in Chinese people; we recommend 48 weeks after treatment withdrawal as the suitable time point.     

老年慢性丙型肝炎患者抗病毒疗效及影响因素探讨

目的：探讨老年慢性丙型肝炎患者抗病毒疗效及影响因素。方法回顾性分析42例老年慢性丙型肝炎患者经聚乙二醇干扰素（Peg-IFNα-2a）联合利巴韦林治疗48周随访24周的病毒学应答、复发及无应答情况,分析与病毒学应答相关的影响因素。结果42例老年慢性丙型肝炎患者获得快速病毒学应答（RVR）、早期病毒学应答（EVR）、持续病毒学应答（SVR）比例分别为42．9％、78．6％、57．1％,复发率为26．2％,无应答率为21．4％。RVR组、EVR组的SVR为77．8％、72．7％,均高于非 RVR 组、非 EVR 组的41．7％、0（P 值分别为0．02、0．00）。SVR 组的病程（10．0±4．6）年、基线 HCV RNA（5．67±0．82）lg拷贝/mL、基因Ⅰ型占45．8％,显著低于非SVR组的（17．2±5．6）年、（6．39±0．92）lg拷贝/mL 和83．3％（P 值分别为0．00、0．02、0．01）;IL-28B 基因多态性 CC 等位基因为83．3％,明显高于非SVR组的50％（P＝0．02）。81％的老年慢性丙型肝炎患者感染途径是有手术史或输血史,78．6％的患者病程＞10年。结论老年慢性丙型肝炎患者可获得较高的病毒学应答率。感染 HCV 年限、基线 HCV RNA 载量、非基因Ⅰ型以及IL-28B等位基因CC型和RVR、EVR是预测抗病毒疗效的影响因素。     

聚乙二醇干扰素加利巴韦林治疗慢性丙型肝炎疗效影响因素分析

目的研究聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎（丙肝）疗效的影响因素。方法101例慢性丙肝患者均给予聚乙二醇干扰素α-2a 180μg／周联合利巴韦林10．6～15．0mg／（kg·d）,疗程48周,分析性别、体重指数（body mass index,BMI）、初始HCVRNA定量、ALT及GLU等对持续病毒学应答（sustainedvirologicresponse,SVR）的影响。结果聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙肝总的SVR率为50％,其中获得快速病毒学应答（rapid virologic response．RVR）和早期病毒学应答（early virologic response,EVR）患者实现SVR达100％,未获得RVR和EVR患者实现SVR为19．35％;高BMI值、发生脂肪肝的患者不容易达到SVR,而糖化血红蛋白、初始HCVRNA载量高、GLU、ALT及性别对SVR无影响。结论RVR、EVR可以预测SVR;BMI、是否合并脂肪肝是聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙肝获得SVR的影响因素。     

Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis C in Japan

AIM：To evaluate the efficacy of pegylated interferon α-2b（peg-IFNα-2b） plus ribavirin（RBV） therapy in Japanese patients with chronic hepatitis C（CHC） genotype Ib and a high viral load.METHODS：One hundred and twenty CHC patients（58.3% male） who received peg-IFNα-2b plus RBV therapy for 48 wk were enrolled.Sustained virological response（SVR） and clinical parameters were evaluated.RESULTS：One hundred（83.3%） of 120 patients completed 48 wk of treatment.53 patients（44.3%） achieved SVR.Early virological response（EVR） and end of treatment response（ETR） rates were 50% and 73.3%,respectively.The clinical parameters（SVR vs non-SVR） associated with SVR,ALT（108.4 IU/L vs 74.5 IU/L,P = 0.063）,EVR（76.4% vs 16.4%,P 〈 0.0001）,adherence to peg-IFN（≥ 80% of planned dose） at week 12（48.1% vs 13.6%,P = 0.00036）,adherence to peg-IFN at week 48（54.7% vs 16.2%,P 〈 0.0001） and adherence to RBV at week 48（56.1% vs 32.1%,P = 0.0102） were determined using univariate analysis,and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis.In the older patient group（〉 56 years）,SVR in females was significantly lower than that in males（17% vs 50%,P = 0.0262）.EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR.CONCLUSION：Peg-IFNα-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%.Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFNα-2b is important in improving the SVR rate.