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The presence of multiple NS5A RASs is associated with the outcome of sofosbuvir and ledipasvir therapy in NS5A inhibitor‐naïve patients with chronic HCV genotype 1b infection in a real‐world cohort 下载免费PDF全文
R. Kozuka H. Hai H. Motoyama A. Hagihara H. Fujii S. Uchida‐Kobayashi H. Morikawa M. Enomoto Y. Murakami N. Kawada A. Tamori 《Journal of viral hepatitis》2018,25(5):535-542
It is unclear whether multiple nonstructural (NS) 5A resistance‐associated substitutions (RASs) correlate with the outcome of sofosbuvir (SOF) and ledipasvir (LDV) therapy. We investigated the effects of multiple NS5A RASs in NS5A inhibitor‐naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF/LDV. In 313 patients treated with SOF/LDV, we assessed the effects of multiple NS5A RASs on the sustained virological response (SVR). RASs at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS5A region were examined by direct sequencing. The prevalence of RASs was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RASs. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS, 29.8%, 45.6% and 24.6% had one, two and three or more NS5A RASs, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS5A RASs compared to those with fewer than three NS5A RASs (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS5A RASs at baseline was low in NS5A inhibitor‐naïve patients, the presence of multiple NS5A RASs was associated with the effectiveness of SOF/LDV therapy. 相似文献
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Efficacy of ledipasvir/sofosbuvir with or without ribavirin for 12 weeks in genotype 1b HCV patients previously treated with a nonstructural protein 5A inhibitor‐containing regimen 下载免费PDF全文
Hiroki Ikeda Tsunamasa Watanabe Hirohito Shimizu Tetsuya Hiraishi Rena Kaneko Toshiyuki Baba Hideaki Takahashi Kotaro Matsunaga Nobuyuki Matsumoto Hiroshi Yasuda Chiaki Okuse Shogo Iwabuchi Michihiro Suzuki Fumio Itoh 《Hepatology research》2018,48(10):802-809
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目的 通过对抗病毒治疗前HIV/HCV合并感染者和HCV单纯感染者HCV NS3/4A蛋白酶、NS5A抑制剂相关耐药位点进行检测,探讨上述患者天然耐药变异的差异。方法 收集2016年1月—2020年1月在广州医科大学附属市八医院住院或门诊就诊的246例HIV/HCV合并感染者和HCV单纯感染者的血清标本,使用Illumina二代测序平台进行测序,比较已在中国获批准的NS3/4A蛋白酶、NS5A抑制剂相关耐药变异在两组患者的差异,纳入分析的药物包括阿舒瑞韦/达拉他韦(ASV/DCV,基因1b型),艾尔巴韦/格拉瑞韦(EBR/GZR,基因1b型)和格卡瑞韦/哌仑他韦(GLE/PIB,泛基因型)。符合正态分布的计量资料两组间比较采用t检验,不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ2检验或Fisher精确检验。结果 本研究纳入的246例患者的血清样本中,239例(97.2%)成功进行PCR扩增并测序,包括102例HIV/HCV合并感染者和137例HCV单纯感染者。对ASV/DCV和EBR/GZR相关耐药变异分析结果提... 相似文献
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Dong Ji Guo-Feng Chen Cheng Wang Yu-Dong Wang Qing Shao Bing Li Jun Zhao Shao-Li You Jin-Hua Hu Jia-Liang Liu Xiao-Xia Niu Jing Chen Lei Lu Vanessa Wu George Lau 《Hepatology International》2016,10(5):789-798
Background
Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis.Methods
One hundred forty treatment-experienced GT1b CHC Chinese with and without cirrhosis were included in this study. Ninety-four patients were treated with either daclatasvir (DCV, 60 mg)-sofosbuvir (SOF, 400 mg) (group 1, n = 46) or ledipasvir (LDV, 90 mg)-SOF (400 mg) (group 2, n = 48) for 12 weeks. Forty-six patients treated with pegylated interferon and RBV therapy for 72 weeks were enrolled as the control group (group 3). Patients were followed at 4-weekly intervals till 24 weeks after the end of treatment.Results
All patients in group 1 (46/46, 100 %) and 2 (48/48, 100 %) had achieved sustained virologic response at 24 weeks after the end of treatment (SVR 24), which was significantly higher than that of group 3 (13/46, 28.3 %) (p < 0.001). The SVR 24 rates of cirrhotic patients in group 1 (27/27, 100 %) and 2 (27/27, 100 %) were also significantly higher than that of group 3 (3/25, 12 %) (p < 0.001). Twelve weeks of RBV-free LDV-SOF and DCV-SOF was either cost-saving or cost-effective. Adverse events were significantly lower in group 1 and 2 compared with group 3 (p < 0.001).Conclusion
Compared with standard therapies, 12 weeks of RBV-free DAA therapies is highly effective, well tolerated and cost-effective in treatment-experienced Chinese with GT1b CHC including patients with cirrhosis.9.
A. C. W. Jenke S. Moser V. Orth M. Zilbauer P. Gerner S. Wirth 《Journal of viral hepatitis》2009,16(12):853-859
Summary. Viral genome analyses performed in adult HCV-patients yielded very inconsistent results and are not transferable to children who are often infected vertically during a state of high immune tolerance. We analysed the mutational frequency in the PKR-binding domain (PKR-BD) of NS5A and PePHD of E2 protein pre- and post-treatment with peginterferon-alfa-2b and ribavirin in children chronically infected with HCV genotype 1. Amino acid sequences of NS5A (2 209–2 274) and E2 (618–681) were determined in serum samples using standard PCR procedures. Concerning the PKR-BD a significant higher number of mutations was observed in vertically compared to horizontally infected patients (2.14 vs 1.24, P -value = 0.03). This difference was exclusively based on the increased number of mutations in responders vs non-responders in vertically infected patients (2.95 vs 1.33; P -value = 0.02). While all patients with at least four mutations ( n = 3) did respond to therapy, no other predictive parameters could be identified. In the PePHD no differences could be observed between either of these groups. These findings support the idea that viral properties, mode and therewith time of infection in terms of immune tolerance are equally important factors for predicting SVR in children. However given the low number of cases further studies are required to confirm this hypothesis. 相似文献
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Ohki Taniyama Seiichi Mawatari Kohei Oda Kazuaki Tabu Sho Ijuin Kotaro Kumagai Ai Kasai Shuzo Tashima Tsutomu Tamai Akihiro Moriuchi Akio Ido 《Hepatology research》2019,49(2):239-243
A 68‐year‐old Japanese man with decompensated cirrhosis due to hepatitis C virus (HCV) genotype 1b infection was treated with sofosbuvir (SOF; 400 mg/day), ledipasvir (LDV; 90 mg/day), and ribavirin (RBV; 400 mg/day). Before treatment, his Child–Pugh and Model for End‐Stage Liver Disease (MELD) scores were 10 (class C) and 13 points, respectively. Although RBV was initially given at two‐thirds the normal dose due to anemia, his hemoglobin level gradually declined, and RBV was reduced to 200 mg daily on day 11, and 200 mg every other day on day 14. His alanine aminotransferase level gradually decreased during combination therapy; and HCV‐RNA was undetectable on day 28. He complained of fatigue from day 49, and RBV was ceased. On day 56, he asked to discontinue treatment because of strong fatigue and insomnia. As hepatic encephalopathy occurred just after the cessation of direct‐acting antivirals, diuretics were discontinued, and treatment with synthetic disaccharides and intractable antibiotics were given, after which his consciousness returned to normal. Ascites gradually disappeared, and a sustained virologic response (SVR) was achieved. At 1.5 years after treatment, his Child–Pugh and MELD scores had improved to 6 (class A) and 10 points, respectively. Although he did not experience hepatic encephalopathy during the observation period, his blood ammonia concentration persistently increased. We reported a case of decompensated cirrhosis in a patient who achieved SVR with SOF/LDV plus RBV for 8 weeks. Although his liver function improved after treatment, careful long‐term observation is required for complications of liver cirrhosis, even after HCV elimination. 相似文献
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Masashi Mizokami Lauren J. Liu Naoto Fujiyama Marcus Littman Jason Yuan Tomoko Sekiya Charlotte Hedskog Leslie J. Ng 《Journal of viral hepatitis》2021,28(1):129-141
As patients with chronic hepatitis C virus (HCV) tend to be older and/or have advanced liver disease in Japan, real‐world data are needed to evaluate safe and effective treatment options. The study aim was to assess safety and effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in a real‐world cohort of Japanese patients with HCV genotype (GT) 1 infection overall and by patient subgroups: elderly, compensated cirrhotic, advanced fibrotic and those with hepatocellular carcinoma (HCC). A large prospective observational study was conducted, enrolling adult patients treated for HCV GT1 infection with LDV/SOF at clinical sites across Japan. Patients were observed for safety outcomes during and 4 weeks after treatment, and for sustained virologic response at 12‐weeks post‐treatment (SVR12). Incidence rates (IRs) of adverse drug reactions (ADRs) and serious ADRs (SADRs) and SVR12 rates were assessed overall and by subgroups. ADR and SADR IRs were low (2.26 and 0.17 per 100 person‐months, respectively) and did not significantly differ in elderly patients or those with presence of compensated cirrhosis, worsening fibrosis or HCC. SVR12 rates were high overall (98.5%) and across subgroups investigated (≥94%), including patients who were elderly (98.2%), treatment‐experienced (97.6%), advanced fibrotic (≥95.8%), had existing NS5A resistance‐associated substitutions reported pre‐treatment (95.0%), compensated cirrhosis (95.7%), HCC (94.0%) and other chronic liver diseases (96.1%). In this large, real‐world observational study of Japanese patients with HCV GT1 infection, LDV/SOF treatment resulted in low incidence of adverse events, with high real‐world effectiveness, even among patients with potentially higher risks of adverse safety outcomes and treatment failure. 相似文献
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《World journal of hepatology》2017,(36)
AIM To evaluate the efficacy and safety of a regimen containing sofosbuvir(SOF) and ledipasvir(LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1.METHODS This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects(AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger(aged 75 years) and elderly(aged ≥ 75 years). Virological data and AEs were analyzed by age group.RESULTS The sustained virological response(SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy. 相似文献
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Impact of ledipasvir/sofosbuvir on the work productivity of genotype 1 chronic hepatitis C patients in Asia 下载免费PDF全文
Z. M. Younossi H. L. Y. Chan Y. Y. Dan M. H. Lee Y. ‐S. Lim E. Kruger S. C. Tan 《Journal of viral hepatitis》2018,25(3):228-235
Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor clinical prognosis and a detrimental impact on patients' lives, including on work productivity. To estimate the value of productivity losses due to genotype 1 (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to estimate the potential productivity gains associated with treating patients with ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a time horizon of 1 year. Hepatitis C virus patients entered the model at 12 weeks post‐treatment, having achieved or not achieved sustained virological response (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of data from the ION 1‐3 studies. These rates were converted into hours of lost productivity, multiplied by the average wage and applied to the total employed, adult GT1 population in each country. Results were compared assuming no treatment, and assuming all patients were treated with LDV/SOF. Total productivity losses due to untreated HCV were: $11.3 million, $17.1 m, $146.0 m and $349.1 m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment resulted in economic gains of $4.5 m, $6.8 m, $58.7 m and $138 m, respectively. These gains were due to reduced presenteeism. The results were sensitive to changes in the prevalence of HCV and the average wage. In conclusion, productivity losses due to untreated HCV infection represent a substantial economic burden. By instituting universal HCV treatment with LDV/SOF (or other therapies with high SVR rates), productivity gains can be achieved. 相似文献
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Prevalence and characteristics of naturally occurring sofosbuvir resistance‐associated variants in patients with hepatitis C virus genotype 1b infection 下载免费PDF全文
Jun Ito Goki Suda Yoshiya Yamamoto Atsushi Nagasaka Ken Furuya Kenichi Kumagai Hideaki Kikuchi Takuto Miyagishima Tomoe Kobayashi Megumi Kimura Kazushi Yamasaki Machiko Umemura Takaaki Izumi Seiji Tsunematsu Fumiyuki Sato Yoko Tsukuda Katsumi Terashita Masato Nakai Takuya Sho Mitsuteru Natsuizaka Kenichi Morikawa Koji Ogawa Naoya Sakamoto for the NORTE Study Group 《Hepatology research》2016,46(13):1294-1303
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A different perspective on sofosbuvir‐ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital‐c network study 下载免费PDF全文
M. Barone A. Iannone E. Shahini A. M. Ippolito G. Brancaccio F. Morisco M. Milella V. Messina A. Smedile F. Conti P. Gatti T. Santantonio P. Tundo G. Lauletta N. Napoli C. Masetti A. P. Termite R. Francavilla A. Di Leo F. Pesce A. Andriulli 《Journal of viral hepatitis》2018,25(1):56-62
The effectiveness of a 12‐week course of sofosbuvir‐ledipasvir in treatment‐experienced HCV genotype 1b‐infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post‐treatment week 12 (SVR12) of sofosbuvir‐ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir‐ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir‐ledipasvir alone for 24 weeks) consecutive HCV genotype 1b‐infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child‐Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child‐Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir‐ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir‐ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12‐week treatment with sofosbuvir‐ledipasvir alone might be suboptimal for this setting of patients. 相似文献
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Retreatment with sofosbuvir/ledipasvir with or without lead‐in interferon‐β injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy 下载免费PDF全文
Hayato Uemura Yoshihito Uchida Jun‐ichi Kouyama Kayoko Naiki Shinpei Yamaba Akira Fuchigami Yoichi Saito Keisuke Shiokawa Yohei Fujii Hiroshi Uchiya Manabu Nakazawa Satsuki Ando Masamitsu Nakao Daisuke Motoya Kayoko Sugawara Mie Inao Yukinori Imai Nobuaki Nakayama Tomoaki Tomiya Satoshi Mochida 《Hepatology research》2018,48(4):233-243
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目的筛选人肝脏cDNA文库中与HCV NS5A的结合蛋白基因,验证其中顺乌头酸酶1与HCV NS5A的相互作用。方法应用酵母双杂交系统3筛选人肝脏cDNA文库中的HCV NS5A结合蛋白基因,应用哺乳动物双杂交及免疫共沉淀技术验证其中顺乌头酸酶1蛋白与HCV NS5A之间的相互作用。结果成功筛选出人肝脏cD-NA文库中与HCV NS5A存在相互作用的蛋白基因,哺乳动物双杂交及免疫共沉淀实验结果证实HCV NS5A与顺乌头酸酶1蛋白在HepG2细胞内存在相互作用。结论本实验成功筛选人肝脏cDNA文库中的HCV NS5A结合蛋白基因,并且在体外水平即细胞内证实HCV NS5A与其中的顺乌头酸酶1蛋白之间的相互作用,为进一步细胞内及体内的糖、脂类代谢等功能研究奠定基础。 相似文献