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Real‐world efficacy and safety of daclatasvir and asunaprevir therapy for hepatitis C virus‐infected cirrhosis patients 下载免费PDF全文
Kei Morio Michio Imamura Yoshiiku Kawakami Reona Morio Tomoki Kobayashi Satoe Yokoyama Yuko Nagaoki Tomokazu Kawaoka Masataka Tsuge Akira Hiramatsu Grace Naswa Makokha C Nelson Hayes Hiroshi Aikata Daiki Miki Hidenori Ochi Yoji Honda Nami Mori Shintaro Takaki Keiji Tsuji Kazuaki Chayama 《Journal of gastroenterology and hepatology》2017,32(3):645-650
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Noriaki Naeshiro Hideaki Kakizawa Hiroshi Aikata Hiromi Kan Hatsue Fujino Takayuki Fukuhara Tomoki Kobayashi Yohji Honda Daisuke Miyaki Tomokazu Kawaoka Masataka Tsuge Akira Hiramatsu Michio Imamura Yoshiiku Kawakami Hideyuki Hyogo Masaki Ishikawa Kazuo Awai Kazuaki Chayama 《Hepatology research》2014,44(7):740-749
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Tomokazu Kawaoka Shoichi Takahashi Yumiko Tatsukawa Akira Hiramatsu Nobuhiko Hiraga Daiki Miki Masataka Tsuge Michio Imamura Yoshiiku Kawakami Hiroshi Aikata Hidenori Ochi Kouhei Ishiyama Kentaro Ide Hirotaka Tashiro Hideki Ohdan Kazuaki Chayama 《Hepatology research》2014,44(12):1259-1264
It is difficult to use protease inhibitors in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) due to interaction with immunosuppressive drugs. We report our experience with two patients treated with telaprevir (TVR) combined with pegylated interferon/ribavirin (PEG IFN/RBV) for recurrent HCV genotype 1 infection after LT. The first was a 63‐year‐old man with HCV‐related liver cirrhosis, who failed to respond to IFN‐β plus RBV after LT. Treatment was switched to PEG IFN‐α‐2b plus RBV and TVR was started. The donor had TT genotype of interleukin (IL)‐28 single nucleotide polymorphisms (SNP) (rs8099917). The recipient had TT genotype of IL‐28 SNP (rs8099917). Completion of 12‐week triple therapy was followed by PEG IFN‐α‐2b plus RBV for 36 weeks. Finally, he had sustained viral response. The second was a 70‐year‐old woman with HCV‐related liver cirrhosis and hepatocellular carcinoma. She failed to respond to PEG IFN‐α‐2b plus RBV after LT, and was subsequently switched to PEG IFN‐α‐2b/RBV/TVR. Genotype analysis showed TG genotype of IL‐28 SNP for the donor, and TT genotype of IL‐28 SNP for the recipient. Serum HCV RNA titer decreased below the detection limit at 5 weeks. However, triple therapy was withdrawn at 11 weeks due to general fatigue, which resulted in HCV RNA rebound 4 weeks later. Both patients were treated with cyclosporin, starting with a small dose to avoid interactions with TVR. TVR is a potentially suitable agent for LT recipients who do not respond to PEG IFN‐α‐2b plus RBV after LT. 相似文献
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Role of 3‐D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma 下载免费PDF全文
Hatsue Fujino Tomoki Kimura Hiroshi Aikata Daisuke Miyaki Tomokazu Kawaoka Hiromi Kan Takayuki Fukuhara Tomoki Kobayashi Noriaki Naeshiro Yohji Honda Masataka Tsuge Akira Hiramatsu Michio Imamura Yoshiiku Kawakami Hideyuki Hyogo Shoichi Takahashi Rika Yoshimatsu Takuji Yamagami Masahiro Kenjo Yasushi Nagata Kazuo Awai Kazuaki Chayama 《Hepatology research》2015,45(6):607-617
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Yoshio Katamura Hiroshi Aikata Yuki Kimura Tomokazu Kawaoka Shintaro Takaki Koji Waki Akira Hiramatsu Yoshiiku Kawakami Shoichi Takahashi Masaki Ishikawa Masashi Hieda Hideaki Kakizawa Kazuaki Chayama 《Journal of gastroenterology and hepatology》2010,25(6):1117-1122
Background and Aims: We investigated the efficacy of intra‐arterial 5‐fluorouracil (5‐FU) and systemic interferon (IFN)‐α (5‐FU‐IFN) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis in the first branch or trunk (Vp3/4) and extrahepatic metastases. Methods: We examined 17 HCC patients with Vp3/4 and extrahepatic metastases (meta group) and 31 HCC patients with Vp3/4 (non‐meta group). Baseline intrahepatic tumor factors and the hepatic reserve were similar between groups. The extrahepatic metastases of the meta group were not considered prognostic factors. Following the administration of 5‐FU/IFN to all patients, we compared the survival rates, response, time to progression (TTP), and safety between groups. Results: For intrahepatic HCC, complete response, partial response, stable disease, progressive disease, and drop out were observed in no (0%), one (6%), seven (41%), nine (53%), and no (0%) patients of the meta group, and in five (16%), seven (23%), 13 (42%), five (16%) and one (3%) patient of the non‐meta group, respectively. The response rate was significantly lower in the meta group (6% vs 39%, P = 0.018). The median TTP of intrahepatic HCC and the median survival time were significantly shorter in the meta group than in the non‐meta group (1.6 vs 6.3 months, P = 0.0001, and 3.9 months vs 10.5 months, P < 0.0001, respectively). The multivariate analysis showed that the absence of extrahepatic metastases was a significant and independent determinant of both TTP of intrahepatic HCC (P < 0.001) and overall survival (P < 0.001). No patient died of extrahepatic HCC‐related disease. Conclusions: The efficacy of 5‐FU/IFN for advanced HCC with Vp3/4 and extrahepatic metastases was markedly limited. 相似文献
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Azakami T Hayes CN Sezaki H Kobayashi M Akuta N Suzuki F Kumada H Abe H Miki D Tsuge M Imamura M Kawakami Y Takahashi S Ochi H Nakamura Y Kamatani N Chayama K 《Journal of medical virology》2011,83(6):1048-1057
An association between a single nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and reduction of hemoglobin during peg‐interferon plus ribavirin combination therapy for patients with chronic hepatitis C virus (HCV) infection has been reported. However, the effect of the SNP on outcome of therapy has not been fully elucidated. Factors associated with anemia during combination therapy, including rs1127354 genotype, were analyzed in 1,002 treated patients. The effect of the SNP on outcome of therapy was analyzed in a subset of 830 patients with genotype 1. A rapid initial decrease in hemoglobin levels was observed in patients with rs1127354 genotype CC compared with a slow decrease in non‐CC patients. Cumulative reduction of ribavirin was significantly more frequent in genotype CC patients than non‐CC patients (odds ratio 1.928, P = 8.6 × 10?8). The frequency of patients who received at least the recommended 80% of scheduled ribavirin was significantly lower among genotype CC patients, especially among those who had pretreatment hemoglobin levels between 13.5 and 15 g/dl (P < 0.03), and the sustained viral response rate was significantly lower in this group of patients. Independent predictive factors for sustained virological response included a SNP in the IL28B locus (rs809991), age, fibrosis, ITPA SNP rs1127354 as well as pretreatment hemoglobin levels. Our data suggests that measures to prevent anemia should be considered for patients who have pretreatment hemoglobin levels less than 13.5 g/dl or who have rs1127354 genotype CC and pretreatment hemoglobin levels between 13.5 and 15 g/dl. J. Med. Virol. 83:1048–1057, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
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Nami Mori Michio Imamura Yoshiiku Kawakami Hiromi Saneto Tomokazu Kawaoka Shintaro Takaki Hiroshi Aikata Shoichi Takahashi Kazuaki Chayama 《Journal of medical virology》2009,81(4):640-649
The aim of this study was to compare the efficacy of high‐dose interferon (IFN)‐α‐2b with standard dose of IFN‐α‐2b in combination with ribavirin (RBV) for patients with chronic hepatitis C virus (HCV) infection, and to investigate the predictive factors associated with virological response. Two hundred Japanese patients with high HCV viral load (>100 KIU/ml) were randomized to 6 or 10 mega units (MU) of 24‐week IFN‐α‐2b with RBV. Predictive factors were investigated; including pretreatment amino acid (aa) sequences of the core region and the IFN‐sensitive determining region (ISDR). The sustained virological response rate was not different in the two groups (24% vs. 30%) but the incidence of depression was significantly higher in the 10 MU group than 6 MU group (7% vs. 0%, P = 0.02). Younger age (<60) and HCV genotype (2a/b) were significant predictors of sustained virological response. In patients infected with genotype 1b, substitutions of core aa 70 and/or 91 were predictive for non‐virological response (P < 0.001), and substitutions in the ISDR was observed frequently in virological responders. Early viral kinetics study showed that serum HCV core antigen decreased more slowly in both patients with aa 70 and/or 91 substitutions in the core and with absence of substitutions in the ISDR. In conclusion, the use of a higher dose of IFN‐α‐2b in combination with RBV did not improve virological response but resulted in higher incidence of depression. Amino acid substitutions in the core and ISDR are predictive of virological response to the therapy in patients with genotype 1b and high viral load. J. Med. Virol. 81:640–649, 2009 © 2009 Wiley‐Liss, Inc. 相似文献
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Kiminori Uka Hiroshi Aikata Shintaro Takaki Daiki Miki Soo Cheol Jeong Akira Hiramatsu Hideaki Kodama Hiroo Shirakawa Yoshiiku Kawakami Shoichi Takahashi Naoyuki Toyota Katsuhide Ito Kazuaki Chayama 《Liver international》2007,27(9):1209-1216
AIM: Intra-arterial 5-fluorouracil (5-FU) plus interferon (IFN) combination therapy is effective against advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombosis. In this study, we compared the efficiency and safety of recombinant IFN-alpha-2b with natural IFN-alpha as components of the combination therapy. METHODS: Consecutive HCC patients (n=31) with portal vein tumour thrombosis were enrolled in this prospective study. They received combination therapy of 5-FU and either recombinant IFN-alpha-2b (R group, n=15) or natural IFN-alpha (N group, n=16). We compared the two groups for the early response rate, adverse reactions, time to progression (TTP) and survival rates. In addition, we assessed the cost-effectiveness of each protocol. RESULTS: The early response rate (R: 26.7%, N: 31.2%), median TTP (R: 5.8 months, N: 5.6 months) and median survival time (R: 7.5 months, N: 6.5 months) were not significantly different between the R and N groups. There were no differences in adverse reactions between the two groups. The estimated cost-effectiveness ratio of recombinant IFN-alpha-2b was better than natural IFN-alpha. CONCLUSIONS: In our protocol of combination therapy, there were no significant differences between recombinant IFN-alpha-2b and natural IFN-alpha with regard to early response to therapy, adverse effects, TTP and survival rates. 5-FU could be combined with either recombinant IFN-alpha-2b or natural IFN-alpha, although the cost-effectiveness of the former warrants its use clinically. 相似文献
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Soo Cheol Jeong Hiroshi Aikata Yoshio Katamura Takahiro Azakami Tomokazu Kawaoka Hiromi Saneto Kiminori Uka Nami Mori Shintaro Takaki Hideaki Kodama Koji Waki Michio Imamura Hiroo Shirakawa Yoshiiku Kawakami Shoichi Takahashi Kazuaki Chayama 《World journal of gastroenterology : WJG》2007,13(40)
AIM: To assess whether a 24-wk course of interferon (IFN) could prevent hepatocellular carcinoma (HCC) recurrence and worsening of liver function in patients with hepatitis C virus (HCV)-infected patients after receiving curative treatment for primary HCC. METHODS: Outcomes in 42 patients with HCV infection treated with IFN-α, after curative treatment for primary HCC (IFN group), were compared with 42 matched curatively treated historical controls not given IFN (nonIFN group). RESULTS: Although the rate of initial recurrence did not differ significantly between IFN group and non-IFN group (0%, 44%, 61%, and 67% vs 4.8%, 53%, 81%, and 87% at 1, 3, 5, and 7 years, P = 0.153, respectively), IFN group showed a lower rate than the non-IFN group for second recurrence (0%, 10.4%, 28%, and 35% vs 0%, 30%, 59%, and 66% at 1, 3, 5 and 7 years, P = 0.022, respectively). Among the IFN group, patients with sustained virologic response (SVR) were less likely to have a second HCC recurrence than IFN patients without an SVR, or non-IFN patients. Multivariate analysis identified the lack of SVR as the only independent risk factor for a second recurrence, while SVR and Child-Pugh class A independently favored overall survival. CONCLUSION: Most intrahepatic recurrences of HCVrelated HCC occurred during persistent viral infection. Eradication of HCV is essential for the prevention of HCC recurrence and improvement of survival. 相似文献