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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 探讨应用索非布韦(SOF)联合雷迪帕韦(LDV)治疗慢性丙型肝炎(CHC)患者的疗效。方法 2017年8月~2020年8月我院诊治的CHC患者116例,给予SOF联合LDV治疗3个月。计算肝纤维化四指数(FIB-4),采用RT-PCR法检测HCV RNA,采用单因素和多因素Logistic回归分析影响CHC患者获得持续病毒学应答(SVR)的影响因素,应用受试者工作曲线(ROC)分析指标的预测效能。结果 在治疗结束后随访6个月,116例CHC患者血清ALT、AST和外周血PLT计数分别为(32.4±6.8)U/L、(36.5±9.2)U/L和(224.6±31.9)×109/L,显著低于治疗结束时【分别为(56.6±11.7)U/L、(64.7±11.8)U/L和(262.3±41.7)×109/L,P<0.05】或治疗前【分别为(204.3±41.6)U/L、(131.2±26.5)U/L和(313.7±53.6)×109/L,P<0.05】;FIB-4和HCV RNA水平分别为(0.9±0.1)和(1.1±1.2)lgU/mL,显著低于治疗结束时【分别为(1.2±0.2)和(1.9±1.1)lgU/mL,P<0.05】或治疗前【分别为(1.4±0.2)和(6.4±1.3)lgU/mL,P<0.05】;本组CHC患者获得快速病毒学应答率(RVR)为75.0%,治疗结束时病毒学应答率(ETVR)为89.7%,SVR为82.0%;多因素Logistic回归分析显示,FIB-4和血清HCV RNA是影响CHC患者获得SVR的独立影响因素(P<0.05);联合治疗前FIB-4<1.65和血清HCV RNA载量为(6.6±0.8)lgU/mL为截断点,其预测CHC患者在治疗后获得SVR的AUC为0.875,敏感性为83.2%,特异性为90.5%。结论 SOF联合LDV治疗CHC患者可获得很好的治疗效果,FIB-4水平低和血清HCV RNA载量低的患者可能获得更好的抗病毒效果。 相似文献
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Goki Suda Mineo Kudo Atsushi Nagasaka Ken Furuya Yoshiya Yamamoto Tomoe Kobayashi Keisuke Shinada Miki Tateyama Jun Konno Yoko Tsukuda Kazushi Yamasaki Megumi Kimura Machiko Umemura Takaaki Izumi Seiji Tsunematsu Fumiyuki Sato Katsumi Terashita Masato Nakai Hiromasa Horimoto Takuya Sho Mitsuteru Natsuizaka Kenichi Morikawa Koji Ogawa Naoya Sakamoto 《Journal of gastroenterology》2016,51(7):733-740
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《World journal of hepatology》2017,(11)
AIM To survey the efficacy and safety of dual therapy with daclatasvir and asunaprevir in the elderly hepatitis C virus(HCV) patients multicentricity.METHODS Interferon-ineligible/intolerant patients and non-responders to previous pegylated-interferon/ribavirin therapy with chronic HCV genotype 1b infection were enrolled. Child B, C cirrhotic patients were excluded.Patients received oral direct acting antiviral treatment consisting of 60 mg daclatasvir once daily plus 200 mg asunaprevir twice daily for 24 wk. We divided the patients into two groups of 56 elderly patients(≥ 75 years-old) and 141 non-elderly patients( 75 years old) and compared the efficacy and safety. RESULTS Ninety-one point one percent of elderly patients and 90.1% of non-elderly patients achieved sustained virological response at 24 wk(SVR24). In the former, 1.8% experienced viral breakthrough, as compared with 3.5% in the latter(not significant). Adverse events occurred in 55.4% of the former and 56.0% of the latter. In the former, 7 cases(12.5%) were discontinued due to adverse events, and in the latter 9 cases were discontinued(6.4%, not significant). CONCLUSION Dual therapy with daclatasvir and asunaprevir achieved the same high rates of SVR24 in HCV elderly patients without more adverse events than in the non-elderly patients. 相似文献
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《World journal of hepatology》2017,(3)
Chronic hepatitis C virus(HCV) infection is one of the main causes of chronic liver disease worldwide. In the last 5 years, treatment for HCV infection has experienced a marked development. In 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. However, new side effects have been associated. We report the first case of an HCV infected patient treated for 12 wk with the combination of sofosbuvir/ledipasvir plus ribavirin who developed a miliary tuberculosis(TB) infection while on therapy. The patient was a 65-year-old woman, who referred malaise, asthenia, hyporexia, 7 kg weight loss, productive cough, evening fever and night sweats, right after finishing the treatment. The chest computed tomography-scan revealed a superior mediastinal widening secondary to numerous lymphadenopathies with extensive necrosis and bilateral diffuse lung miliary pattern with little subsequent bilateral pleural effusion, highly suggestive of lymph node tuberculosis with lung miliary spread. A bronchoscopy was performed and bronchial suction showed more than 50 acid-alcohol resistant bacillus per line. A Mycobacterium tuberculosis DNA was detected in blood by polymerase chain reaction, which confirmed the diagnosis of miliary tuberculosis. Some cases of TB infection have been identified with α-interferon-based therapy and with the triple therapy of pegylated interferon, ribavirin and boceprevir or telaprevir. However, significant infection has not been reported with sofosbuvir/ledipasvir plus ribavirin.We believe that the case is relevant to increase awareness of opportunistic infections and particularly TB infection. Although the international guidelines offer no recommendation regarding TB screening, we wonder whether it would be advisable to screen for opportunistic infections prior to the introduction of HCV therapy. 相似文献
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Journal of Gastroenterology - 相似文献
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Successful achievement of sustained virological response to triple combination therapy containing simeprevir in two patients with chronic hepatitis C who had failed asunaprevir:Daclatasvir combination therapy 下载免费PDF全文
Itaru Ozeki Tomoaki Nakajima Masakatsu Yamaguchi Mutsuumi Kimura Tomohiro Arakawa Yasuaki Kuwata Takumi Ohmura Takahiro Sato Shuhei Hige Yoshiyasu Karino Joji Toyota 《Hepatology research》2016,46(11):1162-1167
Patients 1 and 2 were treatment‐naive women who had genotype 1b chronic hepatitis C. Both had IL‐28B genotype TT, and amino acid substitutions of core 70 and 91 were both wild type. Search for the presence of resistance‐associated variants (RAV) in non‐structural (NS)3 and NS5A regions confirmed wild‐type D168 and L31, along with Y93H, in both patients. These patients participated in a Japanese phase III clinical study of asunaprevir and daclatasvir at the age of 52 and 67 years, respectively, and were treated with the combination regimen for 24 weeks. However, both experienced post‐treatment relapse, and then treated with triple combination therapy with simeprevir, pegylated interferon (IFN) and ribavirin at the age of 53 and 68 years, respectively, and achieved sustained virological response. A search for RAV prior to simeprevir treatment identified multiple resistance including D168E, Y93H and L31V in both patients. It has been demonstrated that, in many cases, a treatment failure with a combination of asunaprevir and daclatasvir results in acquisition of RAV in NS3 and NS5A regions and that drug‐resistant mutants, particularly those in the NS5A region, survive for a long time. In these cases, direct‐acting antivirals targeted towards the NS5A region may have a limited efficacy. The present case report is based on an idea that a regimen containing IFN with simeprevir could be a therapeutic option particularly for those who are likely to be highly sensitive and tolerable to IFN. 相似文献
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Short‐duration treatment for chronic hepatitis C virus with daclatasvir,asunaprevir, beclabuvir and sofosbuvir (FOURward study) 下载免费PDF全文
Mark S. Sulkowski Steve Flamm Zeid Kayali Eric J. Lawitz Paul Kwo Fiona McPhee Anne Torbeyns Eric A. Hughes Eugene S. Swenson Philip D. Yin Misti Linaberry 《Liver international》2017,37(6):836-842
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Mawatari Seiichi Oda Kohei Tabu Kazuaki Ijuin Sho Kumagai Kotaro Inada Yukiko Uto Hirofumi Hiramine Yasunari Kure Takeshi Fujisaki Kunio Hashiguchi Masafumi Hori Takeshi Oshige Akihiko Imanaka Dai Saishoji Akiko Taniyama Oki Sakae Haruka Tamai Tsutomu Moriuchi Akihiro Ido Akio 《Journal of gastroenterology》2017,52(7):855-867
Journal of Gastroenterology - Daclatasvir (DCV) and asunaprevir (ASV) combination therapy has been primarily used in patients without NS5A L31 or Y93 resistance-associated substitutions (RASs)... 相似文献
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Fargion S Borzio M Maraschi A Cargnel A;Gruppo Epatologico Lombardo 《World journal of gastroenterology : WJG》2006,12(33):5293-5300
INTRODUCTIONWhile advances in the treatment of HCV chronic hepatitis have markedly improved outcomes for treatment-na?ve patients, a large number of patients still fail to eradicate HCV infection[1-4], and improving the re-treatment success rates of these… 相似文献
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Approximately 45% of patients with chronic hepatitis C infection fail to achieve a sustained virologic response when treated
with pegylated interferon (IFN) and ribavirin combination therapy. The lack of early virologic response after 12 to 24 weeks
of therapy can be a reliable indicator of those who will not benefit from continuing the treatment for 48 weeks. The presence
of genotype 1, high viral load, and advanced fibrosis are among the factors that can predict those patients who have higher
rates of nonresponse. Nonresponders to IFN monotherapy and IFN plus ribavirin combination therapy can benefit from retreatment
with pegylated IFN and ribavirin combination therapy. Treatment options for nonresponders to pegylated IFN and ribavirin are
being investigated in several trials. The role of maintenance pegylated IFN is also under investigation, although preliminary
evidence suggests that some patients may derive benefit. 相似文献
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Hoofnagle JH Ghany MG Kleiner DE Doo E Heller T Promrat K Ong J Khokhar F Soza A Herion D Park Y Everhart JE Liang TJ 《Hepatology (Baltimore, Md.)》2003,38(1):66-74
To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study. 相似文献
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Usefulness of semiquantitative PCR‐Invader assay for selecting candidates for daclatasvir plus asunaprevir combination therapy among patients with hepatitis C virus genotype 1b 下载免费PDF全文
Koichi Honda Masataka Seike Junya Oribe Mizuki Endo Mie Arakawa Masanori Tokoro Masao Iwao Tetsu Mori Junko Nishimura Yukou Takahashi Kaoru Omori Tsutomu Yamashita Toyokichi Muro Kazunari Murakami 《Hepatology research》2018,48(4):255-263