BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhi...BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhibitor ABT-333(dasabuvir, DSV)(OBV/PTV/r + DSV) with or without ribavirin(RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1(GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1(GT1a, GT1b or GT1a/1b). Patients were treatment-na?ve or previously failed a regimen including pegylated interferon/RBV +/-telaprevir, boceprevir, or simeprevir.One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/-RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.RESULTS Many of the patients studied had comorbidities(44.2% hypertensive, 33.7%obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority(88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue(12%), headache(10%),insomnia(9%) and diarrhea(8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all(98%) patients were treatment compliant.CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/-RBV is highly effective and tolerable and results in better mental and physical health following展开更多
We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carc...We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carcinoma(HCC). Patients were infected with hepatitis C virus(HCV) genotype 1b and were previous null responders/relapsers to interferon-alpha/ribavirin(IFN/RBV). There was a rapid suppression of HCV RNA to undetectable levels within the first two treatment weeks. SVR was achieved even after marked reduction of the RBV dose. The treatment was well tolerated. Both subjects experienced worsening of liver disease during therapy, in different patterns: severe, transient, predominantly direct hyperbilirubinemia without cytolysis(case 1) or progressive increase of aminotransferases(grade 4) without severe hyperbilirubinemia(case 2).Adverse events spontaneously resolved. The patients remained in a good clinical condition without hepatic decompensation. There was no re-occurrence of HCC. This is the first report for treatment of HCV cirrhosis after complete HCC destruction.展开更多
Hepatitis C virus genotype 4(HCV-GT4)is a risk factor for cirrhosis,hepatocellular carcinoma and liver failure.A combination of three new direct-acting antivirals ombitasvir,paritaprevir,and ritonavir has been recomme...Hepatitis C virus genotype 4(HCV-GT4)is a risk factor for cirrhosis,hepatocellular carcinoma and liver failure.A combination of three new direct-acting antivirals ombitasvir,paritaprevir,and ritonavir has been recommended for treatment of HCV-GT4 infection.The current study was aimed to assess the efficacy and safety of this combination plus ribavirin in non-cirrhotic,treatment-naive and-experienced Egyptians with HCV-GT4 infection in a real-world setting.A total of 255 Egyptians with HCV-GT4 infection were enrolled,including 82 treatment-experienced and 173 treatment-naive patients.All of them completed 12-week treatment protocol of ombitasvir,paritaprevir and ritonavir as an oral dose combination with ribavirin.Virological response(VR)was measured,as well as the biochemical parameters related to treatment efficacy and adverse events at baseline and after treatment,at 4(VR4)and 12(VR12)weeks post-treatment.The results showed that the VR4 rates were 98.8%in both groups,and VR12 rates were 97.7%and 96.3%in treatment-naive and-experienced patients,respectively,with no significant differences found between the groups concerning VR4(P=0.9)and VR 12(P=0.3).The most common adverse events were headache and fatigue,which were significantly more common(P=0.001 and 0.003,respectively)in treatment-experienced than in treatment-naive group.The quadruple regimen was well-tolerated,and the reported adverse events were generally mild to moderate.This real-world setting study confirms that the combination of ombitasvir,paritaprevir,ritonavir,and ribavirin is highly effective in the treatment of HCV-GT4 infection with a good safety and tolerability profile.展开更多
目的探讨帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性丙型肝炎病毒(hepatitis C virus,HCV)感染的疗效及安全性。方法计算机检索2014年1月至2017年6月在Medline、Pub Med、CNKI全文数据库、万方数据库等公开发表的中...目的探讨帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性丙型肝炎病毒(hepatitis C virus,HCV)感染的疗效及安全性。方法计算机检索2014年1月至2017年6月在Medline、Pub Med、CNKI全文数据库、万方数据库等公开发表的中、英文文献。采用Meta分析方法合并RR值及其95%CI。采用Q检验法分析各研究之间的异质性,对纳入的文献进行质量评价及数据提取,采用Rev Man 5.3统计软件进行Meta分析。结果共收集帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性HCV感染相关文献4篇,累计病例805例,其中PROD(帕利普韦、利托那韦、奥比他韦、达沙布韦)组共379例,PROD-R(帕利普韦、利托那韦、奥比他韦、达沙布韦、利巴韦林)组426例。对4项研究进行异质性检验,结果显示P>0.05,I2<56%,提示异质性不显著,采用固定效应模型。对比分析结果显示,PROD治疗慢性HCV感染12周可获得较高持续病毒学应答(SVR)发生率,加用利巴韦林后的疗效无显著提高(Z=0.18,P=0.85)。4项研究中共有3例发生病毒复发,均为GT1b型,均位于PROD-R组。PROD-R组治疗相关不良反应发生率与PROD组比较,差异有统计学意义(P<0.05)。普通不良事件中乏力、瘙痒、恶心、失眠、皮疹、烦躁发生率两组比较,差异有统计学意义(P<0.05)。实验室检验异常以贫血最为常见,其次是胆红素升高,差异有统计学意义(P<0.05)。结论 PROD治疗慢性HCV感染效果好,特别是GT1b型,加用利巴韦林疗效无显著提高,但不良反应明显增加;对于GT1a、GT4型慢性丙型肝炎(CHC)及肝硬化患者,由于本Meta分析所涉及病例较少,无法进行亚组分析,结果显示似乎没必要加用利巴韦林,需进一步资料积累分析。展开更多
BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of c...BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations.AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain.METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018.There were 149 patients who were treated with brand DAAs,while 140 patients were treated with generic DAAs.Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir±Dasabuvir±Ribavirin,and Sofosbuvir/Daclatasvir±Ribavirin.SVR at 12 wk post treatment was the main outcome variable.RESULTS Overall,87 patients(30.1%)had cirrhosis and 68.2%had genotype 1 HCV infection.At 12 wk post treatment,SVR was achieved by 271(93.8%)of the patients.In patients who were treated with generic medications,134(95.7%)achieved SVR at 12 wk post treatment,compared to 137(91.9%)among those treated with brand medications(P=0.19).Having cirrhosis[odds ratio(OR):9.41,95%confidence interval(CI):2.47–35.84]and having HCV genotype 3(OR:3.56,95%CI:1.03–12.38)were significant independent predictors of not achieving SVR.Alanine transaminase,gamma-glutamyl transpeptidase,and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs.CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients.Both are safe and equally effective in improving biochemical markers of hepatic inflammation.展开更多
Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicent...Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.展开更多
基金an investigatorinitiated grant from AbbVie(B15-791)
文摘BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhibitor ABT-333(dasabuvir, DSV)(OBV/PTV/r + DSV) with or without ribavirin(RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1(GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1(GT1a, GT1b or GT1a/1b). Patients were treatment-na?ve or previously failed a regimen including pegylated interferon/RBV +/-telaprevir, boceprevir, or simeprevir.One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/-RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.RESULTS Many of the patients studied had comorbidities(44.2% hypertensive, 33.7%obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority(88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue(12%), headache(10%),insomnia(9%) and diarrhea(8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all(98%) patients were treatment compliant.CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/-RBV is highly effective and tolerable and results in better mental and physical health following
文摘We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carcinoma(HCC). Patients were infected with hepatitis C virus(HCV) genotype 1b and were previous null responders/relapsers to interferon-alpha/ribavirin(IFN/RBV). There was a rapid suppression of HCV RNA to undetectable levels within the first two treatment weeks. SVR was achieved even after marked reduction of the RBV dose. The treatment was well tolerated. Both subjects experienced worsening of liver disease during therapy, in different patterns: severe, transient, predominantly direct hyperbilirubinemia without cytolysis(case 1) or progressive increase of aminotransferases(grade 4) without severe hyperbilirubinemia(case 2).Adverse events spontaneously resolved. The patients remained in a good clinical condition without hepatic decompensation. There was no re-occurrence of HCC. This is the first report for treatment of HCV cirrhosis after complete HCC destruction.
文摘Hepatitis C virus genotype 4(HCV-GT4)is a risk factor for cirrhosis,hepatocellular carcinoma and liver failure.A combination of three new direct-acting antivirals ombitasvir,paritaprevir,and ritonavir has been recommended for treatment of HCV-GT4 infection.The current study was aimed to assess the efficacy and safety of this combination plus ribavirin in non-cirrhotic,treatment-naive and-experienced Egyptians with HCV-GT4 infection in a real-world setting.A total of 255 Egyptians with HCV-GT4 infection were enrolled,including 82 treatment-experienced and 173 treatment-naive patients.All of them completed 12-week treatment protocol of ombitasvir,paritaprevir and ritonavir as an oral dose combination with ribavirin.Virological response(VR)was measured,as well as the biochemical parameters related to treatment efficacy and adverse events at baseline and after treatment,at 4(VR4)and 12(VR12)weeks post-treatment.The results showed that the VR4 rates were 98.8%in both groups,and VR12 rates were 97.7%and 96.3%in treatment-naive and-experienced patients,respectively,with no significant differences found between the groups concerning VR4(P=0.9)and VR 12(P=0.3).The most common adverse events were headache and fatigue,which were significantly more common(P=0.001 and 0.003,respectively)in treatment-experienced than in treatment-naive group.The quadruple regimen was well-tolerated,and the reported adverse events were generally mild to moderate.This real-world setting study confirms that the combination of ombitasvir,paritaprevir,ritonavir,and ribavirin is highly effective in the treatment of HCV-GT4 infection with a good safety and tolerability profile.
文摘目的探讨帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性丙型肝炎病毒(hepatitis C virus,HCV)感染的疗效及安全性。方法计算机检索2014年1月至2017年6月在Medline、Pub Med、CNKI全文数据库、万方数据库等公开发表的中、英文文献。采用Meta分析方法合并RR值及其95%CI。采用Q检验法分析各研究之间的异质性,对纳入的文献进行质量评价及数据提取,采用Rev Man 5.3统计软件进行Meta分析。结果共收集帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性HCV感染相关文献4篇,累计病例805例,其中PROD(帕利普韦、利托那韦、奥比他韦、达沙布韦)组共379例,PROD-R(帕利普韦、利托那韦、奥比他韦、达沙布韦、利巴韦林)组426例。对4项研究进行异质性检验,结果显示P>0.05,I2<56%,提示异质性不显著,采用固定效应模型。对比分析结果显示,PROD治疗慢性HCV感染12周可获得较高持续病毒学应答(SVR)发生率,加用利巴韦林后的疗效无显著提高(Z=0.18,P=0.85)。4项研究中共有3例发生病毒复发,均为GT1b型,均位于PROD-R组。PROD-R组治疗相关不良反应发生率与PROD组比较,差异有统计学意义(P<0.05)。普通不良事件中乏力、瘙痒、恶心、失眠、皮疹、烦躁发生率两组比较,差异有统计学意义(P<0.05)。实验室检验异常以贫血最为常见,其次是胆红素升高,差异有统计学意义(P<0.05)。结论 PROD治疗慢性HCV感染效果好,特别是GT1b型,加用利巴韦林疗效无显著提高,但不良反应明显增加;对于GT1a、GT4型慢性丙型肝炎(CHC)及肝硬化患者,由于本Meta分析所涉及病例较少,无法进行亚组分析,结果显示似乎没必要加用利巴韦林,需进一步资料积累分析。
文摘BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations.AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain.METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018.There were 149 patients who were treated with brand DAAs,while 140 patients were treated with generic DAAs.Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir±Dasabuvir±Ribavirin,and Sofosbuvir/Daclatasvir±Ribavirin.SVR at 12 wk post treatment was the main outcome variable.RESULTS Overall,87 patients(30.1%)had cirrhosis and 68.2%had genotype 1 HCV infection.At 12 wk post treatment,SVR was achieved by 271(93.8%)of the patients.In patients who were treated with generic medications,134(95.7%)achieved SVR at 12 wk post treatment,compared to 137(91.9%)among those treated with brand medications(P=0.19).Having cirrhosis[odds ratio(OR):9.41,95%confidence interval(CI):2.47–35.84]and having HCV genotype 3(OR:3.56,95%CI:1.03–12.38)were significant independent predictors of not achieving SVR.Alanine transaminase,gamma-glutamyl transpeptidase,and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs.CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients.Both are safe and equally effective in improving biochemical markers of hepatic inflammation.
基金This work was supported by a grant for clinical investigation from Key Projects of Guangdong Science and Technology Plan of China(2014B020212025).
文摘Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.
