索磷布韦维帕他韦治疗慢性丙型肝炎患者疗效和安全性观察:一项单中心真实世界回顾性分析

目的 回顾性分析索磷布韦维帕他韦(SOF/VEL)联合利巴韦林(RBV)治疗慢性丙型肝炎(CHC)患者真实世界研究(RWS)的疗效和安全。方法 2018年5月～2020年4月初治/PR经治的CHC患者32例和代偿期丙型肝炎肝硬化(CHC-CLC)患者36例,接受SOF/VEL治疗12 w,失代偿期丙型肝炎肝硬化(CHC-DLC)或合并肝细胞癌(HCC)患者31例,接受SOF/VEL联合利巴韦林(RBV)治疗12 w。部分患者合并存在高血压、糖尿病、肿瘤和慢性乙型肝炎。采用RT-PCR法检测HCV基因型(GTs)。结果 本组HCV 感染患者以GT 2a(55.6%)和GT1b(34.3%)为主;CHC、CHC-CLC和CHC-DLC患者早期病毒学应答(EVR4)分别为90.6%、86.1%、83.9%,治疗结束病毒学应答(EOT)均为100.0%,CHC组和CHC-CLC组SVR12和SVR24均为100.0%,CHC-DLC组 SVR12和SVR24均为93.5%,三组间EVR4、EOT、SVR12、SVR24均无显著性差异(P>0.05);所有患者SVR12和SVR24均为97.8%,除GT3b型外其他GTs感染患者SVR12和SVR24均为100.0%;三组血生化学应答率分别为87.5%、83.3%和74.2%;本组总体不良反应(AE)发生率为12.1%,无严重AE或因AE停药和死亡事件发生。结论 应用SOF/VEL或联合RBV治疗CHC或相关的肝硬化患者,无论何种基因型感染,均有良好的效果,且安全。     

一项索磷布韦维帕他韦治疗中国北方某县HCV感染者有效性和安全性的真实世界研究

目的:评价索磷布韦维帕他韦片（SOF/VEL）治疗中国慢性HCV感染者真实世界中的有效性和安全性。方法:在中国北方某县开展一项开放标签、单中心、前瞻性临床研究,共入组299例患者,其中慢性丙型肝炎患者161例,代偿期肝硬化73例,给予SOF/VEL12周方案治疗;失代偿期肝硬化患者65例,给予SOF/VEL加利巴韦林1...     

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.     

我国丙型肝炎肝硬化患者DAA治疗现状及短期预后的研究

目的了解丙型肝炎肝硬化患者直接抗病毒药物(DAA)治疗现状、短期预后和影响因素。方法选取2015年1月至2019年11月期间于瑞金医院感染科诊治的丙型肝炎肝硬化患者,收集其数据,研究基线特征、DAA方案及疗效和预后的关系。结果共入组161例,DAA治疗者149例;代偿组122例,失代偿组27例;两组在年龄、性别、HCV基因型及干扰素治疗史等方面无显著性差别;两组疗效与安全性均良好,其中SVR12率(99.17%比96.25%,P=0.325)和SVR24率(96.64%比92.0%,P=0.614)均无明显差异;基线肝硬化失代偿期患者中发生肝病进展的比例明显高于代偿期患者(50%vs.13.75%,P=0.000);基线肝硬化失代偿是DAA治疗后短期预后的独立危险因素(HR 6.765,95%Cl:2.866~15.969,P=0.000)。结论基线肝硬化失代偿是DAA治疗后短期预后的独立预测因素。     

索非布韦/达拉他韦加利巴韦林治疗丙型肝炎肝硬化的疗效及安全性

目的观察索非布韦/达拉他韦加利巴韦林治疗丙型肝炎肝硬化患者的疗效和安全性。方法纳入2016年5月至2017年5月就诊于昆明市第三人民医院肝病科的丙型肝炎肝硬化患者129例,给予索非布韦/达拉他韦加利巴韦林抗病毒治疗12周,治疗后随访12周,观察治疗结束12周后持续性病毒学应答(SVR12)、生化学应答、肝纤维化改善和治疗期间的不良反应。结果 129例患者HCV RNA基线水平为(5.91±1.33)lgIU/mL,治疗2周时为(1.67±1.24)lgIU/mL,治疗2周75.78%患者HCV RNA达到检测下限;治疗12周时93.44%患者HCV RNA检测不到。129例患者基线的FibroScan值为(17.57±9.86);治疗12周时的FibroScan值为(8.32±1.47)kPa(与基线相比,t=15.852,P=0.000);TBil、ALT、AST基线时分别为(24.07±18.12)μmol/L、(91.42±54.56)U/L和(81.06±40.45)U/L,治疗2周时TBil、ALT、AST均显著下降(t=2.408,P=0.017;t=11.054,P=0.000;t=12.227,P=0.000),生化学应答达100%。6例未取得SVR12的患者多因素回归分析显示,复治是独立预测因子。主要不良反应为乏力和头痛,无严重不良反应发生。结论丙型肝炎肝硬化患者索非布韦/达拉他韦加利巴韦林方案可获得较高的SVR12率和生化学应答率,肝纤维化改善明显,且具有良好的安全性。     

直接作用抗病毒药物治疗慢性HCV感染者的初步临床分析

目的观察直接作用抗病毒药物(direct-acting antiviral agents,DAAs)治疗我国慢性丙型肝炎病毒(hepatitis C virus,HCV)感染者的疗效和安全性。方法回顾性分析2015年1月至2016年1月于首都医科大学附属北京地坛医院就诊并使用DAAs抗病毒治疗的慢性丙型肝炎和丙型肝炎肝硬化患者的临床特点及治疗方案,观察治疗过程中患者HCV RNA载量、肝功能、生物化学指标及不良反应。结果共纳入64例患者,平均年龄(51.91±11.32)岁,HCV RNA载量为1.63×103~2.72×107 IU/ml。其中慢性丙型肝炎患者41例,丙型肝炎肝硬化患者23例(失代偿期肝硬化11例);初治患者28例,干扰素经治患者36例;HCV RNA基因分型1b型46例,2a型14例,3a型2例,3b型2例。治疗方案为sofosbuvir+daclatasvir+利巴韦林(ribavirin,RBV)17例、sofosbuvir+daclatasvir 10例、sofosbuvir+ledipasvir+RBV 15例、sofosbuvir+ledipasvir 11例、sofosbuvir+RBV 9例、sofosbuvir+聚乙二醇化干扰素(pegylated interferons,Peg IFN)+RBV 2例。除1例失代偿期丙型肝炎肝硬化患者在治疗过程中因消化道出血死亡外,其余63例患者均完成了治疗并已停药随访24周以上,所有患者均获得快速病毒学应答(rapid virological response,RVR)和治疗结束时病毒学应答(end of treatment virological response,ETVR),62例患者获得持续病毒学应答(sustained virologic response,SVR)。抗病毒治疗后ALT、AST和甲胎蛋白(alpha fetoprotein,AFP)水平显著下降(z=-6.10,P0.001;z=-6.15,P0.001;z=-3.18,P=0.001),白蛋白(albumin,ALB)和胆碱酯酶(cholinesterase,CHE)水平显著升高(t=-2.75,P=0.008;t=-3.20,P=0.002),肾功能无减退。不良反应轻,均可自行缓解,不影响治疗。结论 DAAs治疗我国慢性丙型肝炎及丙型肝炎肝硬化患者疗效肯定,安全性好,对失代偿期丙型肝炎肝硬化患者的远期疗效有待进一步观察。     

三种DAAs方案治疗慢性丙型肝炎患者两年随访研究

目的 分析不同直接抗病毒药物(DAAs)治疗慢性丙型肝炎(CHC)患者的疗效,随访观察两年结果。方法 2018年1月～2020年12月我院收治的CHC患者123例,其中接受索磷布韦/维帕他韦(SOF/VEL)治疗52例,接受艾尔巴韦/格拉瑞韦(EBR/GZR)治疗43例,接受来迪派韦/索磷布韦(LDV/SOF)治疗28例,均连续治疗12 w,随访24 m。采用实时荧光定量RT-PCR法检测血清HCV RNA,比较不同方案治疗患者快速病毒学应答(RVR)、早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)和持续病毒学应答(SVR)情况。结果 SOF/VEL、EBR/GZR和LDV/SOF治疗患者RVR分别为96.2%、93.0%和92.9%,EVR分别为98.1%、97.7%和96.4%,ETVR和SVR均为100.0%,组间疗效比较,差异均无统计学意义(均P>0.05);在治疗过程中,SOF/VEL、EBR/GZR和LDV/SOF治疗组出现恶心、乏力和头晕等不良反应发生率分别为13.5%、11.6%和21.4%,组间比较,差异无统计学意义(P>0.05);在三组获得...     

直接抗病毒药物治疗慢性丙型肝炎肝硬化的回顾性分析

目的探讨直接抗病毒药物(direct-acting antiviral agent,DAA)治疗慢性丙型肝炎肝硬化患者实现持续病毒学应答(sustained virologic response,SVR)后的预后及转归。方法回顾性分析2014年1月至2017年6月于天津市第二人民医院临床诊断为慢性丙型肝炎肝硬化的95例患者,其中72例应用DAA获得SVR,23例未行抗病毒治疗,比较两组患者肝细胞癌发生率、病死率的差异。统计学分析采用独立样本t检验、曼-惠特尼U检验和χ²检验。结果在3~71个月的随访结束时,DAA治疗组丙氨酸转氨酶、天冬氨酸转氨酶、白蛋白、肝硬度测定值均较入组时改善[42(23,61)U/L比18(13,28)U/L,54(37,75)U/L比23(18,28)U/L,39(33,42)g/L比45(41,48)g/L,26(18,37)kPa比15(11,26)kPa,Z=-6.005、-7.008、-6.057、-3.162,均P<0.01],但DAA治疗组与未行抗病毒治疗组患者肝细胞癌发生率[12%(9/72)比17%(4/23)]、病死率[3%(2/72)比13%(3/23)]差异均无统计学意义(均P>0.05)。应用DAA治疗和未行抗病毒治疗的慢性丙型肝炎肝硬化患者进行肝细胞癌累积发生率分析,两组差异无统计学意义(P=0.609)。慢性丙型肝炎肝硬化发生肝细胞癌患者与未发生肝细胞癌患者年龄[(60.3±3.6)岁比(54.4±9.9)岁]差异有统计学意义(t=-3.948,P<0.01);代偿期肝硬化患者应用DAA治疗后,6例发生肝细胞癌的患者中4例患糖尿病,未发生肝细胞癌的患者糖尿病患病率为17%(7/42),发生肝细胞癌较未发生肝细胞癌者空腹血糖更高[(7.3±1.9)mmol/L比(5.9±1.1)mmol/L],差异均有统计学意义(χ²=7.430,t=-2.442,P=0.019、0.019)。结论DAA可以显著改善慢性丙型肝炎肝硬化患者的肝功能、肝纤维化,但未发现可以改善其近期肝细胞癌发生率、病死率;空腹血糖升高、糖尿病可能为代偿期慢性丙型肝炎肝硬化患者发生肝细胞癌的危险因素。     

索非布韦联合α-干扰素治疗慢性丙型肝炎患者疗效比较的Meta分析

目的 评价索非布韦（SOF）联合α-干扰素（PEG-IFN）与索非布韦或干扰素治疗慢性丙型肝炎患者的疗效。 方法 检索 PubMed、Cochrane Library、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、万方数据库及中文科技期刊全文数据库（VIP）等数据库,纳入索非布韦联合干扰素与索非布韦或干扰素治疗慢性丙型肝炎患者的临床随机对照试验研究。采用Revman 5.2软件进行Meta分析。 结果 纳入9篇文献,共827例慢性丙型肝炎患者,其中5篇研究比较了SOF/PEG-IFN/利巴韦林（RBV）治疗的339例与SOF/RBV治疗的269例患者,4篇研究比较了SOF/PEG-IFN/RBV治疗的105例与PEG-IFN/RBV治疗的114例患者。Mate分析结果显示,SOF/PEG-IFN/RBV组快速病毒学应答率（RVR）显著高于SOF/RBV组（86.7% 对71.7%,P=0.002）,与PEG-IFN/RBV组比为91.7% 对32.3%（P=0.006）;SOF/PEG-IFN/RBV组持续病毒学应答率（SVR）显著高于PEG-IFN/RBV组（85.7%对44.2%,P<0.00001）,但与SOF/RBV组比,差异无统计学意义（89% 对74.1%,P=0.16）;SOF/PEG-IFN/RBV组头疼、疲劳、恶心、皮疹、肌痛、食欲减退、关节痛、发热、贫血发生率较SOF/RBV组高,且差异具有统计学意义（P<0.05）。 结论 索非布韦联合α-干扰素和利巴韦林治疗相比索非布韦联合利巴韦林或聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎患者可获得更高的快速病毒学应答率,而不良反应发生率也较索非布韦联合利巴韦林治疗组高。     

直接抗病毒药物治疗慢性丙型肝炎的效果及对肝硬度、APRI的影响

目的探讨目前直接抗病毒药物(DAA)治疗方案下,慢性丙型肝炎患者真实世界病毒应答情况及对肝硬度值和天门冬氨酸/血小板比值指数(APRI)的影响。方法连续性纳入2018年4月1日-2018年11月30日在天津市第三中心医院接受DAA治疗的慢性丙型肝炎患者,应用无干扰素方案的DAA治疗12～24周,评估治疗结束后第12周病毒学应答情况,对比基线及治疗结束后12周肝硬度值和APRI的变化。计量资料两组间比较采用Wilcoxon秩和检验。结果共纳入212例慢性丙型肝炎患者,其中肝硬化患者占35. 4%,基因1b、2a、3a、6a型分别占75. 0%、18. 4%、4. 2%及2. 4%。174例患者完成了DAA治疗疗程及治疗后12周随访。在DAA治疗结束和治疗结束后12周获得持续病毒学应答(SVR)的比例分别为98. 3%及95. 4%。基因1b型、2a型、3a型及6a型患者的SVR12分别为96. 3%、93. 1%、80. 0%及100%。治疗结束后12周肝硬度值较基线[9. 8(6. 9～16. 3) kPa vs 11. 4(7. 7～19. 1) kPa,Z=-2. 5,P=0. 012]及APRI[0. 34(0. 25～0. 64) vs 0. 76(0. 56～2. 25),Z=-6. 6,P 0. 001]均明显下降。根据基线是否存在肝硬化进行分组,结果显示治疗结束12周非肝硬化组患者肝硬度值较基线显著降低[7. 6(6. 6～10. 7) k Pa vs 8. 8(7. 2～13. 0) kPa,Z=-2. 7,P=0. 007];而肝硬化组患者治疗前后肝硬度值无明显差异[17. 4(12. 7～22. 1) k Pa vs 19. 8(12. 8～24. 9) kPa,Z=-1. 4,P=0. 152]。肝硬化组和非肝硬化组患者APRI在治疗后12周较基线均明显下降[0. 73 (0. 52～1. 34) vs1. 37(0. 80～2. 11),Z=-3. 4,P 0. 001; 0. 29(0. 21～0. 36) vs 0. 54(0. 31～0. 95),Z=-6. 8,P 0. 001]。结论在该真实世界研究中,应用DAA治疗的慢性丙型肝炎患者总体病毒学应答率较高,治疗结束后12周肝硬度及APRI明显改善。     

Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study

Background

Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan.

Methods

A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT).

Results

The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child–Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child–Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl.

Conclusions

Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.

     

Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva

IntroductionThe sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.MethodsA retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.ResultsOverall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.ConclusionTreatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.     

Management of hepatitis C patients with decompensated liver disease

Little is known about the tolerance and effectiveness of novel oral direct acting antivirals (DAA) in hepatitis C patients with decompensated cirrhosis. To examine the studies relevant to the treatment of hepatitis C virus(HCV)-related decompensated liver disease, we performed computer–based searches for English articles between 1947 and August 2015. Fourteen articles including HCV patients with decompensated cirrhosis were reviewed. The combinations of ledipasvir(LDV)/sofosbuvir(SOF)/ribavirin(RBV) for 12 weeks, or daclatasvir/SOF/RBV for 12 weeks are safe and effective for HCV genotype 1 or 4 infection, and daclatasvir/SOF/RBV for 12 weeks or SOF/RBV for 24 weeks might be effective and safe for HCV genotype 2 or 3 infection. In conclusion, current evidence supports the use of all oral DAA regimens in HCV patients with decompensated cirrhosis.     

Adjuvant ribavirin and longer direct‐acting antiviral treatment duration improve sustained virological response among hepatitis C patients at risk of treatment failure

The role of ribavirin (RBV) in the era of direct‐acting antivirals (DAA) is not clear, and DAA studies have been largely genotype‐ and regimen‐specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. We performed multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir + SOF; grazoprevir + elbasvir; paritaprevir/ritonavir + ombitasvir; simeprevir + SOF; and SOF + ledipasvir; SOF + velpatasvir ± voxilaprevir; and glecaprevir + pibrentasvir—all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12 ± 4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naïve, interferon treatment failure [TF] or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one‐month increment of treatment duration increased odds of SVR by 99% (aOR = 1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR = 5.05), previous DAA treatment failure (aOR = 5.43), and GT3 (aOR = 13.28). Among RBV‐free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. Conclusion: RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis.     

Effectiveness and safety of sofosbuvir‐based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real‐life cohort

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014‐October 2015). In total, 208 patients were included: 98 (47%) treatment‐experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.     

The tolerability of sofosbuvir/velpatasvir for 12 weeks in patients treated in the ASTRAL 1, 2 and 3 studies: A pooled safety analysis

To evaluate the safety and tolerability of the fixed-dose, single-tablet regimen sofosbuvir/velpatasvir (SOF/VEL) for the treatment of hepatitis C virus (HCV) infection in three Phase 3 studies in patients with and without compensated cirrhosis. Data from three registrational trials (ASTRAL-1, NCT02201940; ASTRAL-2, NCT02220998; ASTRAL-3, NCT02201953) were pooled by treatment regimen. Researchers assessed treatment-emergent adverse events (TEAEs) and laboratory abnormalities in patients randomized to SOF/VEL or placebo for 12 weeks in ASTRAL-1 and SOF/VEL for 12 weeks in ASTRAL-2 and ASTRAL-3. Overall, 1035 patients were treated with SOF/VEL, and 116 patients received placebo. Rates of any TEAE were generally similar between patients receiving SOF/VEL (79.4%) and those receiving placebo (76.7%). The majority of TEAEs were mild to moderate, with 23 (2.2%) treatment-emergent serious AEs in patients treated with SOF/VEL. Of these treatment-emergent serious AEs, none led to premature study discontinuation, nor were they considered related to treatment. Presence of compensated cirrhosis, greater age and mild renal impairment did not impact incidence or severity of TEAEs with SOF/VEL treatment. The most common TEAEs (incidence ≥10%) were headache, fatigue, nausea and nasopharyngitis in patients receiving SOF/VEL; similar rates were observed in placebo-treated patients. Three deaths (<1%) were reported in patients treated with SOF/VEL, all posttreatment and none assessed as related to study treatment. Similar to that of placebo, SOF/VEL treatment of HCV infection had a safety/tolerability profile that was not affected by baseline factors, such as the presence of compensated cirrhosis, mild renal impairment or advanced age.     

B.A.R.C.O.S. (Brazilian Argentine Hepatitis C Collaborative Observational Study): Effectiveness and clinical outcomes of HCV treatment with daclatasvir and sofosbuvir with or without ribavirin

Real‐world data evaluating the effectiveness of direct‐acting antivirals (DAAs) in hepatitis C virus (HCV) treatment have been reported from different regions. Our aim was to evaluate the effectiveness and clinical outcomes of daclatasvir (DCV) and sofosbuvir (SOF) ± ribavirin (RBV) in a prospective multicentre cohort study including patients from Argentina and Brazil who received DCV/SOF ± RBV for 12 or 24 weeks from 2015 to 2018. Multivariable logistic regression models were carried out to identify factors associated with failure to achieve sustained virologic response (SVR) as a primary end point, and to death, decompensation, hepatocellular carcinoma (HCC) or liver transplantation (LT) as a composite secondary end point. From a total of 1517 patients treated with DCV/SOF, 906 completed 12 weeks post‐treatment evaluation and were included in the analysis. Overall SVR12 rate was 96.1% (95% CI: 94.6%‐97.2%), and 95% (95% CI: 92.8%‐96.6%) in patients with cirrhosis. LT recipients and presence of cirrhosis were independently associated with failure to achieve SVR. During post‐SVR12 follow‐up, cumulative incidence of the secondary end point was 2.4% (95% CI: 1.5%‐3.6%); two patients died from nonliver‐related causes and two from HCC, five underwent LT, 12 developed HCC and 17 patients developed hepatic decompensation. Independent variables associated with these composite secondary end points were prior to HCV treatment and presence of cirrhosis. In conclusion, although the high pangenotypic effectiveness of DCV/SOF ± RBV was confirmed in our real‐life cohort, patients with compensated and decompensated cirrhosis showed higher risk of non‐SVR and complication appearance during treatment or after achieving SVR.     

Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience

Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles.Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed.ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree.ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.     

Efficacy and safety of treatment with sofosbuvir/velpatasvir in patients aged 6–18 years with chronic hepatitis C—Results of the PANDAA-PED study

Background and Aims

The aim of this non-commercial, open-label, real-life, non-randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6–18 years with chronic hepatitis C virus (HCV) infection.

Methods

Fifty patients qualified for the 12-week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real-time polymerase chain reaction method) at 12 weeks posttreatment (SVR12).

Results

Median age of the participants was 10 (IQR 8–12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty-seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty-three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5–13) versus 9 (IQR 8–11) years (p = 0.008).

Conclusions

Results of the PANDAA-PED study indicated a 100% effectiveness of a 12-week therapy with SOF/VEL in children aged 6–18 years with chronic HCV infection and its good safety profile, in particular in younger patients.