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。     

直接作用抗病毒药物治疗丙型肝炎肝硬化和肝移植术后丙型肝炎复发的初步临床观察

目的观察直接作用抗病毒药物(direct-acting antiviral agents,DAAs)治疗丙型肝炎(丙肝)肝硬化和肝移植术后丙肝复发的安全性和临床效果。方法入组丙肝肝硬化7例(5例失代偿)和肝移植术后丙肝复发7例(移植后时间6~44个月,中位时间17个月),年龄26~69岁(中位年龄55岁),HCV RNA分型均为基因1b型,HCV RNA载量为6.90×104~4.34×107IU/ml。DAAs治疗方案为索菲布韦(sofosbuvir)+息米普韦(simeprevir)(3例)和harvoni(sofosbuvir+ledipasvir)(11例),疗程12周。治疗过程中观察HCV RNA、肝功能、安全性指标及不良反应。结果除1例肝移植术后患者4周时HCV RNA为5.60×10 IU/ml,其余患者均获快速病毒学应答,HCV RNA最快5 d低于检测值下限。所有患者均获得治疗结束时病毒学应答和持续病毒学应答,ALT和AST下降,ALB水平升高。移植术后患者他克莫司血药浓度未见明显变化。不良反应轻,主要为头痛(1例)、乏力(2例)和关节痛(1例)。结论 DAAs治疗丙肝肝硬化和肝移植术后丙肝复发安全性好,疗效肯定。对失代偿期丙肝肝硬化的远期疗效待观察。     

DAA治疗在肝硬化患者中的应用效果

目的探讨直接抗病毒药物(directly acting antivirals,DAAs)治疗HCV肝硬化的效果。方法选取秦皇岛第三医院门诊和病房2017年1月至2018年2月收治的HCV肝硬化患者62例为研究对象。分别采用治疗方案A(n=16)、治疗方案B(n=22)和治疗方案C(n=24)治疗。治疗方案A:索菲布韦+利巴韦林;治疗方案B:Harvoni;治疗方案C:索菲布韦+达卡他韦。连续治疗24周。结果随着治疗的进展,各治疗方案的HCV RNA转阴率呈上升趋势,各时间点HCV转阴率差异有统计学意义(P0.05);62例HCV肝硬化患者ALT、AST、Scr、BUN和HCV RNA水平逐渐降低,Alb水平逐渐上升,各时间点比较差异有统计学意义(P0.05)。治疗过程中仅部分患者发生轻微不良反应,主要表现为腹泻1例、发热1例、头痛1例、皮疹2例、乏力5例、头晕2例,均可耐受,无需对症处理。结论 DAAs治疗HCV肝硬化可明显改善患者肝肾功能,疗效显著,且具有较高的安全性。     

直接抗病毒药物治疗HCV相关肝硬化的效果及安全性

肝硬化在临床上十分常见,也是包括慢性HCV感染在内的多种慢性肝病的共同临床结局。在直接抗病毒药物(DAA)出现前,基于PEG-IFN及利巴韦林(RBV)的抗HCV治疗常由于肝硬化的存在而疗效不佳,甚至失代偿期肝硬化本身即是应用PEG-IFN治疗的绝对禁忌证。DAAs已逐渐成为临床治疗HCV感染的一线药物,大量研究显示DAAs用于HCV相关肝硬化患者的治疗具有良好的疗效及耐受度。一方面,DAAs治疗代偿期肝硬化患者的疗效及安全性均要优于PEG-IFN/RBV;另一方面,肝硬化失代偿患者也可耐受DAAs治疗,虽然获得的持续病毒学应答比例可能较普通患者更低,但是DAAs仍能使肝硬化失代偿患者在多方面获益。综述了DAAs用于治疗HCV相关肝硬化患者的最新研究,以求为临床诊治提供参考。     

三磷酸次黄嘌呤核苷基因多态性对利巴韦林联合直接抗病毒药物治疗丙型肝炎致溶血性贫血的预测价值

目的探讨慢性丙型肝炎治疗过程中利巴韦林(RBV)引起溶血性贫血的影响因素,为临床早期预测利巴韦林相关溶血性贫血发生提供借鉴。方法选取2018年1月—2019年7月于河北中石油中心医院门诊及住院就诊的丙型肝炎且应用直接抗病毒药物(DAA)联合RBV方案抗病毒治疗患者。三磷酸次黄嘌呤肌苷(ITPA)基因rs1127354位点主要等位基因是C等位基因,次要等位基因为A等位基因,将AA与AC合并与CC基因型进行比较。在治疗过程中,当Hb水平100 g/L时,RBV减量至600 mg;当Hb 85 g/L时停用RBV治疗。在抗病毒治疗前进行血常规、肝功能、肝脏硬度值、HCV RNA、HCV病毒基因型及ITPA基因型检测,在2、4、8、12周对患者进行血常规检测。不符合正态分布的计量资料组间比较采用Mann-Whitney U检验。结果本研究共纳入病例49例,慢性丙型肝炎患者22例,肝硬化27例,持续病毒学应答率为95.9%。因贫血RBV减量者3例(其中AA/AC组2例,CC组1例),停药3例(其中AA/AC组1例,CC组2例),均为肝硬化患者,6例患者最终均达到持续病毒学应答。DAA+RBV抗HCV治疗过程中,RBV相关溶血的发生较轻微,AA/AC型与CC型两组患者Hb较基线下降最大值比较差异无明显统计学意义(Z=-0.18,P=0.87)。结论本研究在RBV联合DAA治疗过程中,因为贫血RBV停药和减量的均为肝硬化患者,ITPA基因型与患者Hb较基线下降最大值无明显统计学关系,故在应用RBV前进行ITPA基线检测未能增加治疗过程中的安全性,因此不建议进行常规的ITPA基因多态性检测。     

直接作用抗病毒药物的抗丙型肝炎病毒作用及对患者血清血管内皮生长因子水平的影响

目的评估直接作用抗病毒药物(DAAs)治疗慢性基因1b型HCV感染患者的疗效和安全性,并分析其对患者血清VEGF水平的影响,评估DAAs治疗诱导肿瘤复发的风险因素。方法选取2012年12月至2016年1月至本院接受治疗的58例基因1b型慢性HCV患者,根据治疗方式的不同,将所有患者分为索菲布韦(SOF)+达卡他韦(DCV)组和SOF+雷迪帕韦(LDV)组。两组患者均接受DAAs无干扰素方案,药物为患者自购,疗程均为24周,随访24周。使用荧光定量PCR法检测定量HCV RNA,比较两组DAAs无干扰素方案的抗病毒作用,并统计两组患者治疗期间不良反应发生率。分别在治疗前、治疗后4周、结束治疗当天、持续病毒学应答(SVR)4和SVR12,采集研究组患者血清,使用Randox仪器精确分析治疗前后患者血清血管内皮生长因子(vascular endothelial growth factor,VEGF)水平变化。结果 SOF+DCV组SVR24率为96.7%,SOF+LDV组SVR24率96.4%,且无患者出现严重不良反应。治疗开始后4周时,两组患者血清VEGF水平较治疗前明显增加(P0.05),且一直维持至治疗结束时;治疗结束后4周时降低至治疗前水平,而后较治疗前再次升高(P0.05)。结论两组DAAs无干扰素方案治疗基因1b型慢性HCV感染均取得良好疗效,安全性较高。DAAs给药诱导患者血清VEGF水平显著增加,可能是DAAs治疗风险因素之一。     

直接抗病毒药物治愈的慢性丙型肝炎患者NK细胞的免疫学特点分析

目的探讨直接抗病毒药物(direct-acting antivirals, DAAs)治愈的慢性丙型肝炎(chronic hepatitis C, CHC)患者NK细胞的免疫学变化。方法入组13例经达拉他韦(daclatasvir, DCV)和阿舒瑞韦(asunaprevir, ASV)治疗24周的初治型HCV 1b型CHC患者,同时入组13例健康者为健康对照(healthy controls, HC)组。采用流式细胞术分析患者治疗前,治疗第24周,治疗结束后随访第12周、24周的外周血NK细胞表型和功能特点。结果 13例CHC患者经DCV/ASV抗病毒治疗均获得持续病毒学应答即临床治愈;与HC组相比,CHC患者抗病毒治疗前外周血NK细胞表达HLA-DR、NKP46、CD38的水平显著增高(P均<0.05),分泌CD107a和TNF-α的水平增高(P均<0.05),但产生IFN-γ的能力降低(P <0.05)。抗病毒治疗后,CHC患者外周血NK细胞活化程度降低,分泌IFN-γ的能力明显增强(P均<0.05)。结论经DAAs治愈的CHC患者外周血NK细胞的表型和功能显著改善。     

丙型肝炎抗病毒治疗:口服药物改变了什么?

正慢性丙型肝炎抗病毒治疗的革命性变化是近几年来直接抗病毒药物(direct-acting antiviral agents,DAAs)进入临床,开辟了慢性丙型肝炎抗病毒治疗的新纪元。以DAA为基础的抗病毒方案包括1个DAA联合聚乙二醇干扰素alpha和利巴韦林(PR)、DAAs联合RBV,以及不同DAA联合或复合制剂的应用~([1])。三种方案基本可以涵盖所有类     

基因1型丙型肝炎抗病毒药物的初步研究

对聚乙二醇干扰素联合利巴韦林治疗没有反应的慢性丙型肝炎的患者,可能从增加多个直接作用的抗病毒药物治疗方案中受益。这种开放式模式,第2a期研究包括探索对以前治疗没有反应的1型慢性HCV的2l例患者(即,应用聚乙二醇干扰素和利巴韦林联合治疗≥12周后HCV RNA下降小于2log₁₀的患者)。我们随机分配患者接受NS5A复制复合体抑制剂daclatasvir（60mg,每天1次）和NS3蛋白酶抑制剂asunaprevir的（600 mg,每天2次）单独组（A组,11例）或联合聚乙二醇干扰素α-2a和利巴     

不同直接抗病毒药物方案对基因1b型慢性丙型肝炎及代偿期丙型肝炎肝硬化临床结局的影响

目的探讨不同直接抗病毒药物(DAAs)对基因1b型慢性丙型肝炎(CHC)及丙型肝炎代偿期肝硬化(CLC)临床结局的影响。方法以2018年1月-2018年12月就诊于山西医科大学第一医院感染科门诊的115例基因型1b型CHC(n=91)及CLC(n=24)患者为研究对象。所有患者根据病情均采用DAAs抗病毒治疗,CHC患者中28例采用索磷布韦联合维帕他韦方案,21例采用艾尔巴韦格拉瑞韦片方案,16例采用奥比帕利联合达塞布韦方案,13例采用索磷布韦联合达拉他韦方案,13例采用索磷布韦联合利巴韦林方案;CLC患者中15例采用索磷布韦联合维帕他韦方案,4例采用艾尔巴韦格拉瑞韦片方案,5例采用索磷布韦联合达拉他韦方案。分析2组患者的肝功能复常率及病毒学应答率,并观察药物的不良反应。计量资料组间比较采用t检验,计数资料组间比较采用χ^2检验。结果90.4%的患者在治疗1周时获得超快速病毒学应答,98.2%的患者在治疗4周时获得快速病毒学应答,100%的患者在治疗12周时获得完全早期病毒学应答,100%的患者在治疗结束后12周获得持续病毒学应答;不同抗病毒治疗方案在治疗1周、4周时HCV RNA阴转率差异均无统计学意义(χ^2值分别为2.83、0.07,P值均>0.05)。不同抗病毒方案均可明显改善患者肝功能(ALT和AST复常率),不同组间疗效差异均无统计学意义(χ^2值分别为0.83、1.23,P值均>0.05)。DAAs治疗12周后,2组患者肾功能指标与治疗前相比未见有明显升高或降低,差异均无统计学意义(t值分别为1.32、0.56,P值均>0.05)。不良事件的发生率较低,恶心2例(1.74%),头晕、心悸、皮疹、溶血各1例(0.87%)。结论根据病情采用相应DAAs抗病毒方案治疗1b型患者,均可取得较好的病毒学应答率,肝功能改善显著、不良事件的发生率低。     

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.     

Changes in serum lipid profiles caused by three regimens of interferon‐free direct‐acting antivirals for patients infected with hepatitis C virus

Aim

Serum low‐density lipoprotein cholesterol (LDL‐C) increases during treatment of chronic hepatitis C (CHC) with interferon‐free direct‐acting antivirals (DAAs). We sought to compare the changes of serum lipid profiles caused by three regimens.

Methods

A total of 216 CHC patients were enrolled. Among 170 patients infected with hepatitis C virus (HCV) genotype 1b, 85 received daclatasvir plus asunaprevir (DCV/ASV) and 85 received sofosbuvir plus ledipasvir (SOF/LDV). Forty‐six infected with HCV genotype 2 received sofosbuvir plus ribavirin (SOF/RBV). Serum total cholesterol (TC), LDL‐C, high‐density lipoprotein cholesterol, and triglyceride were measured at baseline and 4, 8, 12 (for all regimens), and 24 weeks (for DCV/ASV) during treatment (4w, 8w, 12w, and 24w, respectively) and 12 and 24 weeks after treatment (p12w and p24w, respectively).

Results

In 69 (81.2%) patients who received DCV/ASV and achieved a sustained virologic response at 24 weeks after the end of treatment (SVR24), TC and LDL‐C increased significantly from baseline to p24w. In 84 (98.8%) treated with SOF/LDV who achieved SVR24, TC and LDL‐C increased significantly from baseline to 8w, and TC decreased significantly from 8w to p12w. The 45 (97.8%) who received SOF/RBV and achieved SVR24 showed no significant changes. At 12w, TC and LDL‐C increased to a greater degree in patients receiving SOF/LDV than in those receiving DCV/ASV or SOF/RBV.

Conclusion

During treatment with DAAs, the serum lipid profile may reflect not only recovery from the disruption of lipid metabolism induced by HCV, but also the pharmacological effects of DAAs. Further investigations are needed to elucidate the effect of DAAs on serum lipid profiles.     

Use of a hepatitis C virus (HCV) RNA‐positive donor in a treated HCV RNA‐negative liver transplant recipient

The shortage of livers has led most transplant centers to use extended criteria donors. Hepatitis C virus (HCV) RNA‐positive donor organs are typically not given to patients who have cleared HCV. A 64‐year‐old male with chronic hepatitis C, genotype 1b was listed for LT with hepatocellular carcinoma. While on the waiting list, the patient was treated with sofosbuvir, ledipasvir, and ribavirin and achieved an HCV RNA <15 IU/mL by week 10. At week 18 of a planned 24‐week treatment course, the patient underwent deceased‐donor LT and received an organ from an anti‐HCV‐positive donor. Treatment was stopped at LT. At week 3 post LT, HCV RNA was detectable and revealed a genotype 3 HCV infection, compatible with transplantation of an organ with established infection. With retreatment with sofosbuvir, daclatasvir, and ribavirin for 12 weeks, the patient achieved a sustained virologic response. This report highlights how antiviral therapies can be used to optimize the outcomes of HCV‐infected transplant patients.     

Interferon‐free therapies for patients with chronic hepatitis C genotype 3 infection: A systematic review

Treatment of hepatitis C virus (HCV) infection with genotype 3 remains a challenge. The HCV elimination rate with direct‐acting antivirals (DAAs) is lower than the values reported for other HCV genotypes. In addition, genotype 3‐infected patients have a higher risk of disease progression and hepatocellular carcinoma. The aim of this study was to review the relevant literature concerning the treatment of HCV genotype 3 patients with interferon‐free regimens. A literature search was conducted in the PubMed/Medline, Embase and Web of Science electronic databases. Trials enrolling patients with chronic hepatitis C infection treated with DAAs with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcome was sustained virological response (SVR). In total, 323 references were identified, and 29 met the inclusion criteria: 18 general clinical trials, three general observational studies, three studies in patients with decompensated liver cirrhosis and four studies in HIV–HCV‐coinfected patients. Overall, 4068 genotype 3 patients were included. As compared with sofosbuvir and ribavirin for 24 weeks, sofosbuvir/velpatasvir for 12 weeks or sofosbuvir plus daclatasvir plus ribavirin for 12 weeks provided higher SVR rates, particularly in patients with cirrhosis. Treatment of patients with decompensated cirrhosis remains a great challenge. Sofosbuvir/ledipasvir+ribavirin for 12 weeks were associated with an SVR of 85% in these patients. In summary, treatment of HCV genotype 3 patients is improving rapidly, and this population may no longer be considered a difficult‐to‐treat subgroup in the near future.     

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.     

INF-free sofosbuvir-based treatment of post-transplant hepatitis C relapse – a Swedish real life experience

Background: Relapse of hepatitis C virus (HCV) infection after liver transplantation has been universal, and the fibrosis progression faster than in non-transplanted patients. Interferon (IFN)-free treatment with direct antiviral agents (DAA) has improved the treatment outcome dramatically. We here report on the outcome of IFN-free treatment for HCV relapse after liver transplantation in a real life setting in Sweden.

Material: In total, 93 patients with a mean age of 60 years (range 32–80) with HCV relapse after liver transplantation were given sofosbuvir-based treatment in combination with a protease inhibitor (simeprevir) or a NS5A inhibitor (daclatasvir or ledipasvir) with or without addition of ribavirin (RBV), or sofosbuvir and RBV only. Treatment was generally given during 24 weeks for advanced fibrosis or cirrhosis cases and 12 weeks for mild fibrosis with fibrosis stage 2 or less. The distribution of genotype 1, 2, 3, 4 in our patients was 58, 7.5, 26.5 and 7.5%, respectively.

Results: All recipients reached end-of-treatment response (ETR) with HCV RNA <15?IU/mL. Sustained viral response 12 weeks after treatment cessation (SVR12) was achieved in 91/93 (97.8%) recipients. The SVR12 rates for genotype 1, 2, 3 and 4 were the SVR12 rate were 96, 100, 100 and 100%, respectively (p?=?.04).

Conclusion: It is concluded that IFN-free treatment with DAAs for HCV relapse after liver transplantation is highly effective also in a real life setting and offers cure for most recipients.     

Three patients treated with sofosbuvir plus ledipasvir for recurrent hepatitis C after liver transplantation

We previously reported results of interferon (IFN)-free daclatasvir and asunaprevir for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). Here we report three patients who achieved viral response with no effect on the blood concentrations of immunosuppressive agents following sofosbuvir plus ledipasvir treatment. The first patient was a 68-year-old female with HCV-related liver cirrhosis who failed to respond to pegylated-IFN and ribavirin (PEG-IFN/RBV) after living donor LT. She had been treated with 50 mg/day of cyclosporine. The second was a 63-year-old male with HCV-related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG-IFN/RBV after living donor LT. He had been treated with 50 mg/day of cyclosporine. The third was a 63-year-old female with HCV-related liver cirrhosis. She had been treated with tacrolimus. High alanine aminotransferase levels persisted after LT. Liver biopsy examination revealed active hepatitis or chronic rejection. Therefore, sofosbuvir plus ledipasvir therapy was started. However, the combination treatment was stopped at 4 weeks due to development of interstitial pneumonia. Serum HCV RNA became negative at the time treatment was discontinued and remained negative 12 weeks after cessation of therapy in all three cases. Sofosbuvir plus ledipasvir treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.     

Treatment of chronic genotype-3 hepatitis C virus infection using direct-acting antiviral agents: An Indian experience

Background

Direct-acting antiviral drugs (DAAs) are favored for the treatment of hepatitis C virus (HCV) infection. However, the experience with the DAAs currently available in India in the treatment of genotype-3 HCV is limited. We therefore reviewed our experience with these drugs in treating patients with chronic genotype-3 HCV infection, including those with cirrhosis.

Methods

We prospectively followed adult patients with genotype-3 HCV infection who had received treatment regimens containing sofosbuvir with/without daclatasvir. Patients were categorized as chronic hepatitis C (CHC), compensated cirrhosis (CC), and decompensated cirrhosis (DC). They received either (i) sofosbuvir and ribavirin, with or without pegylated interferon (Peg-IFN) for 12 or 24 weeks, or (ii) sofosbuvir and daclatasvir, with or without ribavirin for 12 or 24 weeks. Response was assessed using HCV RNA testing after 2 or 4 weeks of treatment (rapid virological response [RVR]), at treatment completion (end-of-treatment response [ETR]) or 12 weeks after treatment completion (sustained virological response [SVR12]).

Results

Of the 160 patients (90% treatment-naïve; CHC 49%, CC 32%, and DC 19%), 39 (24%) received Peg-IFN, sofosbuvir and ribavirin, 21 (13%) received sofosbuvir and ribavirin, and 100 (63%) received sofosbuvir and daclatasvir, with or without ribavirin. On intention-to-treat basis, RVR, ETR, and SVR12 in the entire cohort were 146/160 (91.3%), 151/160 (94.4%), and 147/160 (91.9%), respectively. Seven patients died (CC 2, DC 5) during treatment; four (2 CHC, 2 DC) patients discontinued treatment; and two patients with CC relapsed.

Conclusions

Dual-DAA-based regimens were safe and highly effective in treating genotype-3 HCV infection in CHC and CC patients.

     

Multicenter Experience using Ledipasvir/Sofosbuvir ± RBV to Treat HCV GT 1 Relapsers after Simeprevir and Sofosbuvir Treatment

Introduction and aim. Approximately 10%-15% of patients with hepatitis C genotype 1 (HCV GT1) experience virological relapse after all-oral antiviral regimen using simeprevir (SMV) and sofosbuvir (SOF). The efficacy and safety of treating such relapsers using ledipasvir/sofosbuvir (LDV/SOF) with/without ribavirin (RBV) has been limited.Objective. Report the virological response and safety of LDV/SOF with/without RBV for 12-24 weeks in treating HCV GT1 relapsers after SMV + SOF.Material and methods. Patients treated with standardized clinical protocol utilizing LDV/SOF with/without RBV at three transplant centers were retrospectively reviewed.Results. Forty-five patients (29% post-LT, 82% male, 13% non-white, 73% subtype 1a, 86% IL28B CT/ TT, 78% F3-4) started LDV/SOF with/without RBV at a median of 22 weeks (range 7-55 weeks) after the last dose of SMV+SOF treatment. Thirty-seven patients received LDV/SOF for 24 weeks (24/37 patients with RBV) and eight patients received LDV/SOF for 12 weeks (5/8 patients with RBV). RBV dose was adjusted for renal function. Sixteen patients who were RBV-ineligible received LDV/SOF without RBV for 12 or 24 weeks. SVR 12 was achieved in 96% (43/45) of patients. Baseline viral load, RBV use, or GT1 subtype did not impact SVR 12. Minimal adverse events were reported in those without RBV; 45% of patients who received RBV developed significant anemia requiring RBV dose reduction and/or discontinuation. In LT recipients, minimal immunosuppression dose adjustments were required and no biopsy-proven acute rejection occurred.Conclusions. Treatment with LDV/SOF with/without RBV for 12-24 weeks was very well tolerated and resulted in high SVR 12 rates (96%) in HCV GT1 relapsers to SMV + SOF treatment.