聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎临床观察

目的:观察聚乙二醇干扰素(PEG-INFa)联合利巴韦林治疗慢性丙型肝炎临床疗效.方法:共收集42例慢性丙型肝炎患者,其中治疗组24例,采用聚乙二醇干扰素180ug皮下注射,每周1次;对照组18例,采用IFNa-2b(赛若金)500万u皮下注射,隔日1次.两组均联合利巴韦林治疗,剂量均为800～1200mg/d口服,总疗程为48周.分别于治疗12周、24周、48周及治疗结束后24周评价疗效,并观察药物副反应.结果:所有患者均完成治疗,在治疗12周时,治疗组早期应答率83.3%,对照组应答率50.0%;在治疗24周时,治疗组应答率87.5%,对照组应答率61.1%;在治疗48周时,治疗组完全应答率87.5%,对照组完全应答率55.6%;治疗结束后24周,治疗组持续应答率75.0%,对照组持续应答率44.4%.主要副反应为不同程度发热,头痛,肌肉关节酸痛,白细胞,血红蛋白及血小板下降,部分患者出现脱发,皮疹皮肤瘙痒,失眠,抑郁等症状,予对症处理后好转,未影响治疗.结论:PEG干扰素联合利巴韦林治疗慢性丙型肝炎疗效优于普通干扰素,副反应两者无明显差别,患者可以耐受.     

干扰素抗体在慢性丙型肝炎干扰素治疗中的意义

目的:了解干扰素抗体(抗-IFN)在慢性丙型肝炎干扰素(IFN)治疗中的意义.方法:应用ELISA法对49例应用基因重组α2b干扰素(rIFNα2b)治疗的慢性丙型肝炎患者的抗-IFN进行检测.结果:疗程结束后24 49%(12/49)抗-IFN阳性.抗-IFN出现在治疗后2.95±1.25个月.抗体水平与治疗效果有关,高浓度抗体临床效果差.抗-IFN阳性者较阴性者治疗效果差,复发率高(P=0.0056).结论:抗-IFN产生可影响IFN抗病毒效果,降低临床疗效,可作为IFN治疗中预测疗效的指标之一.     

慢性丙型肝炎患者干扰素治疗前后血清自身抗体变化的临床观察

目的探讨慢性丙型肝炎患者干扰素治疗前后血清自身抗体的合并状况。方法回顾性分析2005年2月-2008年2月66例慢性丙型肝炎患者应用干扰素治疗前后的检测结果,观察治疗前后自身抗体合并状况及与干扰素疗效的关系。结果①66例慢性丙型肝炎患者中39例自身抗体阳性,阳性率59.1%（39/66）,主要为ANA;②自身抗体的产生与年龄相关,而与性别、HCVRNA定量无关;③自身抗体阳性组干扰素应答率66.7%（26/39）明显高于阴性组40.7%（11/27）,二者比较差异有统计学意义;④干扰素治疗后,自身抗体阴性组自身抗体检出率为44.4%（12/27）,但滴度均〈1∶320;治疗前抗甲状腺球蛋白抗体阳性患者会出现较高的甲状腺功能异常率。结论慢性丙型肝炎合并血清自身抗体阳性的患者干扰素应答率高于阴性组,但应注意抗甲状腺球蛋白抗体,以预测不良反应。     

聚乙二醇化干扰素α-2b联合利巴韦林治疗慢性丙型肝炎40例

目的:评价聚乙二醇化干扰素α-2b(佩乐能)联合利巴韦林治疗慢性丙型病毒性肝炎患者的疗效及安全性.方法:本试验为开放的2∶1随机化的阳性对照临床试验.治疗组每周1次皮下注射聚乙二醇化干扰素α-2b 50mg,同时口服利巴韦林750～1 050 mg/d.对照组接受甘乐能3MIU/次,每周3次皮下注射,利巴韦林的剂量和服法与治疗组相同;总疗程均为48周,治疗结束后停药观察24周.结果:两组治疗48周时,治疗组和对照组的终点应答率分别为73.08%(19/26)和71.43%(10/14);HCV阴转率分别为100.00%(26/26)和92.86%(13/14);丙氨酸氨基转移酶(ALT)复常率分别为73.08%(19/26)和78.57%(11/14);两组间差异均无显著性(P＞0.05).治疗结束后,停药随访24周结束时,治疗组和对照组的持续应答率分别为78.95%(15/19)和90%(9/10);HCV持续阴转率分别为92.31%(24/26)和92.31%(12/13);ALT持续复常率分别为84.21%(16/19)和90.91%(10/11).两组间差异均无显著性(P＜0.05).随访72周结束时,治疗组和对照组的持续应答率分别为78.95%(15/19)和70.00%(7/10);HCV持续阴转率分别为88.62%(23/26)和77.78%(10/13);ALT持续复常率分别为84.21%(16/19)和72.72%(8/11).结论:聚乙二醇化干扰素α-2b联合利巴韦林治疗慢性丙型病毒性肝炎具有很高的应答率,安全性高,为丙型肝炎抗病毒治疗提供更有效的手段.     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎临床疗效观察

目的:初步评价聚乙二醇(PEG)干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效。方法:选择15例慢性丙型肝炎患者,使用PEG干扰素α-2a(40ku),180μg,肌注,每周1次,联合利巴韦林900～1200mg/d,口服,疗程均为48周。分别于治疗中12周、24周、48周及治疗结束后24周评价疗效,并观察药物副反应。结果:在治疗12周时有13/15例出现血清ALT正常,血清HCV-RNA阴性(<80拷贝/mL),早期应答率为86.6%;在治疗结束时有13/15例患者血清ALT正常,血清HCV-RNA阴性(<80拷贝/mL),完全应答率为86.6%;在治疗结束后24周有3/13例患者出现ALT升高,血清HCV-RNA阳转,持续应答率为76.9%,复发率为23.1%;副反应主要为不同程度的血WBC、血红蛋白下降及低热、肌肉酸痛,大多不影响治疗。结论:PEG干扰素联合利巴韦林治疗慢性丙型肝炎具有较好的临床疗效,副反应较轻,患者可以耐受,值得临床进一步使用。     

干扰素-α治疗慢性丙型肝炎的疗效预测模型

目的评价普通干扰素-α联合利巴韦林治疗慢性丙型肝炎的疗效,探讨其影响因素并建立预测模型。方法采用前瞻性队列研究,对句容市人民医院慢性丙型肝炎住院患者进行普通干扰素-α联合利巴韦林治疗48周并随访至治疗结束后24周,观察治疗不良反应及应答情况。采用Logistics回归分析其影响因素,并运用分类树建立预测模型。结果 216例慢性丙型肝炎患者完成了治疗周期及随访,其持续病毒学应答率(SVR)为61.2%。SVR组与非SVR组基线病毒载量、白蛋白、血小板计数、甲胎蛋白及血糖存在显著差异。多因素Logistics回归分析显示,基线病毒载量高(≥106IU/m L)者或血糖含量较高者更不易获得SVR。血小板计数较高者容易获得SVR(OR=1.02,95%CI=1.00~1.04)。SVR预测模型显示相对基线血小板计数低(140×109/L)者,血小板计数高者获得SVR的可能性增加17.9%。高血小板计数者中,基线HCV RNA低者(106IU/m L)更易获得SVR(79.7%︰57.9%)。治疗过程中不良反应有早期感冒样症状(51.9%)、胃肠道反应(14.8%)、血象的改变(58.8%)、血糖升高(18.1%)、精神症状(8.8%)、甲状腺功能亢进(1.4%)、皮疹(14.8%)、脱发(6.5%)。结论普通干扰素联合利巴韦林治疗慢性丙型肝炎疗效尚可,不良反应的程度较轻。基线病毒载量、血糖及血小板计数可能是丙型肝炎治疗效果的影响因素。     

α-2b干扰素治疗HBeAg阳性慢性乙型肝炎临床分析

目的 观察普通α-2b干扰素（IFN）和聚乙二醇干扰素（PEG IFN）α-2b治疗HBeAg阳性慢性乙型肝炎抗病毒的临床疗效.方法 HBeAg阳性慢性乙型肝炎患者64例,36例给予普通α-2b干扰素抗病毒治疗,每次500万U,皮下注射,每周3次; 28例给予聚乙二醇干扰素α-2b 1.0 μg/kg皮下注射,每周1次.疗程均为52周.结果 治疗结束时,普通干扰素组与PEG IFN组的完全应答率分别为52.8%、60.7%;部分应答率分别为27.8%、21.4%;无应答率分别为19.4%、17.9%,两组比较差异无统计学意义（P〉0.05）.治疗结束时普通干扰素α-2b组,PEG-IFN α-2b组丙氨酸氨基转移酶（ALT）复常率分别是81.7%、85.9%,二者比较差异无统计学意义（P〉0.05）.普通干扰素α-2b组与PEG-IFN α-2b组在52周治疗结束时HBV DNA阴转率分别为49.3%、57.6%,二者比较差异无统计学意义（P〉0.05）.结论 两种不同剂型的α-2b干扰素治疗HBeAg阳性慢性乙型肝炎的应答率相似,普通干扰素具有更好的成本效益.     

聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

目的 观察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.方法 聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎50例为治疗组,普通干扰素α-2a(IFNα-2a)联合利巴韦林治疗慢性丙型肝炎46例为对照组.结果 治疗组具有较高的谷丙转氨酶(ALT)复常率(72.0%)和丙肝病毒(HCV-RNA)转阴率(56.0%),随访半年后,治疗组ALT持续复常率(56.0%)及HCV-RNA持续转阴率(46.0%)明显高于对照组,两组差异有统计学意义(P＜0.01).两药联用副反应无明显增加.结论 聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎可提高疗效,值得临床推广.     

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。     

聚乙二醇干扰素联合利巴韦林治疗31例慢性丙型肝炎临床疗效观察

选取61例慢性丙型肝炎患者,根据治疗方法不同将所有患者分为观察组31例和对照组30例。对照组患者采用普通干扰素联合利巴韦林治疗,观察组患者采用聚乙二醇干扰素α-2a联合利巴韦林治疗,两组均连续治疗12个月后观察病毒学应答情况、ALT复常率、HCV-RNA转阴率和不良反应。结果观察组早期应答率和完全应答率分别为70.97%和67.74%,显著高于对照组的46.67%和40.00%,差异有统计学意义(P<0.05);随着治疗时间的延长,两组ALT复常率和HCV-RNA转阴率均明显上升,且观察组治疗后12个月ALT复常率和HCV-RNA转阴率均显著高于对照组治疗后12个月,差异有统计学意义(P<0.05);两组患者治疗期间不良反应均较轻微,均能够耐受且顺利完成治疗。聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效确切,ALT复常率和HCV-RNA转阴率高且不良反应轻微,值得临床借鉴。     

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.     

Retinol Supplements Antiviral Action of Interferon in Patients with Chronic Hepatitis C: A Prospective Pilot Study

Sustained virologic response with peg-interferon and ribavirin combination therapy for 48 weeks is still inadequate. Our study examined whether short-term administration of retinol clinically influences the anti-viral activity of interferon early during interferon and ribavirin combination therapy. The control group received 6 MIU of interferon α-2b every day for two weeks and then 3 times a week for 22 weeks intramuscularly plus 600 mg or 800 mg per day of ribavirin orally for 24 weeks. The retinol group, in addition to above treatment, received retinol 30,000 units per day orally for 3 weeks from one week before the start of interferon α-2b plus ribavirin combination therapy. The hepatitis C virus (HCV) RNA negativity rate at 1 week after the end of interferon α-2b and ribavirin combination therapy was 46.7% (28/60) for the retinol group and 31.7% (19/60) for the control group, which was significantly higher for the retinol group. The level of serum HCV RNA in the retinol group was significantly lower at 1 week after beginning treatment as compared to the control group (p<0.01). Furthermore, serum 2,5''AS protein at 1 week after beginning treatment was significantly higher in the retinol group (p = 0.0002). The results suggest that retinol supplement increases the antiviral effect of interferon α-2b plus ribavirin only during the administration of IFN α-2b, ribavirin and retinol in patients with chronic hepatitis C.     

干扰素α-2α联合中药治疗HbeAg阳性慢性乙型肝炎的临床观察

目的:观察干扰素α-2α联合中药治疗HbeAg阳性慢性乙型肝炎的临床疗效。方法:62例HbeAg阳性慢性乙型肝炎患者随机分为两组,治疗组接受干扰素α-2α联合中药治疗,对照组单纯接受中药治疗。结果:治疗组与对照组HBV、DNA阴转率分别为82.6%和46.7%,差异具有统计学意义,同时治疗组HbeAg阴转率和ALT复常率均高于对照组(46.9%,16.7%,P<0.01;78.1%,50.0%,P<0.05)。两组不良反应发生率相近。结论:干扰素α-2α联合中药治疗HbeAg阳性慢性乙型肝炎可有效地提高HbeAg阴转率和ALT复常率,并且可以缩短干扰素α-2α治疗疗程。     

Interferon alfa-2a treatment for chronic hepatitis C without cirrhosis and its effects on the incidence of hepatocellular carcinoma

The aim of interferon treatment for chronic hepatitis C is eradication of the hepatitis C virus during the early stages of the disease to prevent progression to liver cirrhosis or hepatocellular carcinoma. However, the effects of interferon on preventing the development of hepatocellular carcinoma for chronic hepatitis C without cirrhosis remain obscure. We wished to study these effects. In this retrospective study, we followed up 66 patients with chronic hepatitis C who were treated with interferon alfa-2a (total dose 324 to 792 MIU) for an average period of 3 years after treatment. Of these 66 patients, 3 patients developed hepatocellular carcinoma during the follow-up period (range, 0.3 to 2.8 years; yearly incidence 1.5%). All 3 patients were among 27 patients who did not respond to interferon treatment. Of these 3 patients, 1 patient developed liver cirrhosis after interferon treatment, and the histologic staging of the remaining 2 patients before interferon treatment was F3, according to the new Inuyama classification. None of the 18 patients who were complete responders to interferon treatment or the 21 patients with incomplete responses developed hepatocellular carcinoma. Our results suggest that patients with chronic hepatitis C who have no response to interferon treatment and histologically advanced disease should be closely followed up after interferon treatment, although the mechanism of malignant transformation to hepatocellular carcinoma in patients with chronic hepatitis C virus infection is still obscure.     

Interferon therapy for acute hepatitis C during pregnancy

OBJECTIVE: Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome. CASE SUMMARY: A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology. DISCUSSION: The rate of transmission of hepatitis C virus from mother to infant is within the range of 1-5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations. CONCLUSIONS: Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.     

化学发光酶免疫分析法及ELISA检测抗-HCV的结果比较

目的对比化学发光酶免疫分析法及酶联免疫吸附试验(ELISA)用于丙型肝炎抗体检测的效果。方法选取丙型肝炎患者140例,抽取血液标本后分别进行丙型肝炎病毒(HCV)相关抗体的化学发光酶免疫分析法及ELISA法检测。结果化学发光酶免疫分析法检出抗-HCV阳性的检出率为98.6%,高于ELISA法的检出率(94.3%),差异有统计学意义(P0.05)。化学发光酶免疫分析法对于抗AMA-M2抗体、抗3E抗体、抗SP100抗体、抗PML抗体、抗GP210抗体的检测阳性率分别为80.0%、73.6%、37.9%、55.7%和47.9%,而ELISA法检测结果分别为12.9%、12.9%、13.6%、10.7%和6.4%,差异均有统计学意义(P0.05)。结论相对于ELISA法,化学发光酶免疫分析法在丙型肝炎中的应用有较高的检出阳性率,对于相关抗体检测有较高的敏感性,值得推广应用。     

Current antiviral combination therapy for chronic hepatitis C patients who failed to interferon alfa-based treatment

What is known and Objective: Interferon‐alfa‐based therapy is effective in the treatment of Hepatitis C. However, some patients fail to respond and others relapse, after initially responding. Our objective was to assess the efficacy, safety and predictive factors for sustained virological response (SVR) to peginterferon plus ribavirin in chronic hepatitis C patients who failed to interferon‐alfa (IFNα)‐based therapy. Methods: Seventy‐five consecutive patients who failed to IFNα‐based therapy were retreated with peginterferon plus ribavirin. Of these patients, 85% were infected by genotype 1. The primary endpoint was SVR. Results and Discussion: Of 75 non‐responder (n = 54) or relapser patients (n = 21), 50 were previously treated with IFNα‐monotherapy and 25 with IFNα plus ribavirin. Global SVR rate was 41·3%: for patients re‐treated with IFNα the response was 48% whilst for those retreated with IFNα plus ribavirin, it was 28%. For previous non‐responders the SVR rate was 37% and for relapsers it was 52·4%. What is new and Conclusion: Retreatment with peginterferon plus ribavirin is an effective option for some chronic hepatitis C non‐responder or relapser patients. Higher SVR rate was achieved in relapsers and in those patients who received IFNα monotherapy previously.     

Treatment of viral hepatitis - 2001

Chronic viral hepatitis may now be controlled and, in many cases, permanently eradicated. Rapid advances in the antiviral therapy of chronic hepatitis C infection have resulted in a greater than 50% sustained response rate, with genotypes 2 and 3 now considered ‘curable diseases.’ Current hepatitis B therapy leads to significant improvement in liver histology and overall survival. These advances, coupled with the fact that 8% of the world population is chronically infected with viral hepatitis, has sparked considerable interest in this condition on the part of the pharmaceutical industry. In 2001, the most effective therapy for chronic hepatitis C is the combination of pegylated interferon alpha and oral ribavirin. The treatment of hepatitis B consists of either interferon alpha or oral lamivudine, while newer nucleoside/nucleotide analogues, alone or in combination with existing therapy, are being explored.     

不同剂量干扰素α治疗慢性丙型肝炎疗效与安全性的系统评价

目的系统评价不同剂量干扰素α治疗慢性丙型肝炎的疗效与安全性。方法计算机检索MEDLINE、EMbase、CENTRAL、CBM、CNKI、VIP和WanFangData,查找有关不同剂量干扰素α治疗慢性丙型肝炎的随机对照试验,检索时限截至2012年8月。由2位研究者根据纳入与排除标准独立筛选文献、提取资料并评价质量后,采用RevMan5．0软件进行Meta分析。结果最终纳入13个RCT,共1442例患者。Meta分析结果显示：①干扰素a3MU组与1MU组治疗慢性丙型肝炎的完全应答率差异无统计学意义[RR=0．83,95％CI（0．52,1．32）,P=0．43],而两组持续应答率差异有统计学意义[RR=1．89,95％CI（1．00,3．59）,P=0．05];②干扰素α 3MU组与6MU组以及10MU组治疗慢性丙型肝炎的完全应答率和持续应答率差异均无统计学意义。结论干扰素α（治疗剂量3MU,1周3次）治疗慢性丙型肝炎有效,但目前尚无证据确定是否存在剂量依赖效应。在使用干扰素α治疗慢性丙型肝炎时,应根据患者的耐受性和经济情况等实施个体化给药以有效控制慢性丙型肝炎。