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1. Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

Author

Suzuki F, Sezaki H, Akuta N, Suzuki Y, Kawamura Y, Hosaka T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Watahiki S, Mineta R, and Kumada H

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Fumitaka Suzuki,1,2 Hitomi Sezaki,1 Norio Akuta,1 Yoshiyuki Suzuki,1 Yusuke Kawamura,1 Tetsuya Hosaka,1 Masahiro Kobayashi,1 Satoshi Saitoh,1 Yasuji Arase,1 Kenji Ikeda,1 Mariko Kobayashi,3 Sachiyo Watahiki,3 Rie Mineta,3 Yukiko Suzuki,3 Hiromitsu Kumada1 1Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 2Okinaka Memorial Institute for Medical Research, Tokyo, Japan; 3Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan Abstract: Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV), against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt) gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out. Keywords: hepatitis B virus, resistant

Published
2014

15. Long-term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide-naïve chronic hepatitis B patients

Author

Hara, T., primary, Suzuki, F., additional, Kawamura, Y., additional, Sezaki, H., additional, Hosaka, T., additional, Akuta, N., additional, Kobayashi, M., additional, Suzuki, Y., additional, Saitoh, S., additional, Arase, Y., additional, Ikeda, K., additional, Watahiki, S., additional, Mineta, R., additional, and Kumada, H., additional

Published
2013
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16. Operational status of TAMA300 with the seismic attenuation system (SAS)

Author

Takahashi, R., Arai, K., Tatsumi, D., Fukushima, M., Yamazaki, T., Fujimoto, M.-K., Agatsuma, K., Arase, Y., Nakagawa, N., Takamori, A., Tsubono, K., DeSalvo, R., Bertolini, A., Márka, S., Saninbale, V., Takahashi, R., Arai, K., Tatsumi, D., Fukushima, M., Yamazaki, T., Fujimoto, M.-K., Agatsuma, K., Arase, Y., Nakagawa, N., Takamori, A., Tsubono, K., DeSalvo, R., Bertolini, A., Márka, S., and Saninbale, V.

Abstract

TAMA300 has been upgraded to improve the sensitivity at low frequencies after the last observation run in 2004. To avoid the noise caused by seismic activities, we installed a new seismic isolation system —- the TAMA seismic attenuation system (SAS). Four SAS towers for the test-mass mirrors were sequentially installed from 2005 to 2006. The recycled Fabry–Perot Michelson interferometer was successfully locked with the SAS. We confirmed the reduction of both length and angular fluctuations at frequencies higher than 1 Hz owing to the SAS.

Published
2008

17. Utility of Detection of Telaprevir-Resistant Variants for Prediction of Efficacy of Treatment of Hepatitis C Virus Genotype 1 Infection

Author

Akuta, N., primary, Suzuki, F., additional, Fukushima, T., additional, Kawamura, Y., additional, Sezaki, H., additional, Suzuki, Y., additional, Hosaka, T., additional, Kobayashi, M., additional, Hara, T., additional, Saitoh, S., additional, Arase, Y., additional, Ikeda, K., additional, and Kumada, H., additional

Published
2013
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20. The Japanese space gravitational wave antenna - DECIGO

Author

Kawamura, S, primary, Ando, M, additional, Nakamura, T, additional, Tsubono, K, additional, Tanaka, T, additional, Funaki, I, additional, Seto, N, additional, Numata, K, additional, Sato, S, additional, Ioka, K, additional, Kanda, N, additional, Takashima, T, additional, Agatsuma, K, additional, Akutsu, T, additional, Aoyanagi, Koh-Suke, additional, Arai, K, additional, Arase, Y, additional, Araya, A, additional, Asada, H, additional, Aso, Y, additional, Chiba, T, additional, Ebisuzaki, T, additional, Enoki, M, additional, Eriguchi, Y, additional, Fujimoto, M-K, additional, Fujita, R, additional, Fukushima, M, additional, Futamase, T, additional, Ganzu, K, additional, Harada, T, additional, Hashimoto, T, additional, Hayama, K, additional, Hikida, W, additional, Himemoto, Y, additional, Hirabayashi, H, additional, Hiramatsu, T, additional, Hong, F-L, additional, Horisawa, H, additional, Hosokawa, M, additional, Ichiki, K, additional, Ikegami, T, additional, Inoue, K T, additional, Ishidoshiro, K, additional, Ishihara, H, additional, Ishikawa, T, additional, Ishizaki, H, additional, Ito, H, additional, Itoh, Y, additional, Kamagasako, S, additional, Kawashima, N, additional, Kawazoe, F, additional, Kirihara, H, additional, Kishimoto, N, additional, Kiuchi, K, additional, Kobayashi, S, additional, Kohri, K, additional, Koizumi, H, additional, Kojima, Y, additional, Kokeyama, K, additional, Kokuyama, W, additional, Kotake, K, additional, Kozai, Y, additional, Kudoh, H, additional, Kunimori, H, additional, Kuninaka, H, additional, Kuroda, K, additional, Maeda, K-i, additional, Matsuhara, H, additional, Mino, Y, additional, Miyakawa, O, additional, Miyoki, S, additional, Morimoto, M Y, additional, Morioka, T, additional, Morisawa, T, additional, Moriwaki, S, additional, Mukohyama, S, additional, Musha, M, additional, Nagano, S, additional, Naito, I, additional, Nakagawa, N, additional, Nakamura, K, additional, Nakano, H, additional, Nakao, K, additional, Nakasuka, S, additional, Nakayama, Y, additional, Nishida, E, additional, Nishiyama, K, additional, Nishizawa, A, additional, Niwa, Y, additional, Ohashi, M, additional, Ohishi, N, additional, Ohkawa, M, additional, Okutomi, A, additional, Onozato, K, additional, Oohara, K, additional, Sago, N, additional, Saijo, M, additional, Sakagami, M, additional, Sakai, S-i, additional, Sakata, S, additional, Sasaki, M, additional, Sato, T, additional, Shibata, M, additional, Shinkai, H, additional, Somiya, K, additional, Sotani, H, additional, Sugiyama, N, additional, Suwa, Y, additional, Tagoshi, H, additional, Takahashi, K, additional, Takahashi, T, additional, Takahashi, H, additional, Takahashi, R, additional, Takamori, A, additional, Takano, T, additional, Taniguchi, K, additional, Taruya, A, additional, Tashiro, H, additional, Tokuda, M, additional, Tokunari, M, additional, Toyoshima, M, additional, Tsujikawa, S, additional, Tsunesada, Y, additional, Ueda, K-i, additional, Utashima, M, additional, Yamakawa, H, additional, Yamamoto, K, additional, Yamazaki, T, additional, Yokoyama, J, additional, Yoo, C-M, additional, Yoshida, S, additional, and Yoshino, T, additional

Published
2008
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21. Control system for the seismic attenuation system (SAS) in TAMA300

Author

Agatsuma, K, primary, Takahashi, R, additional, Arai, K, additional, Tatsumi, D, additional, Fukushima, M, additional, Yamazaki, T, additional, Fujimoto, M K, additional, Arase, Y, additional, Nakagawa, N, additional, Takamori, A, additional, Tsubono, K, additional, Kuroda, K, additional, Ohashi, M, additional, Desalvo, R, additional, Bertolini, A, additional, Márka, S, additional, and Sannibale, V, additional

Published
2008
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36. Susceptibility of TT virus to interferon therapy.

Author

Chayama, K, primary, Kobayashi, M, additional, Tsubota, A, additional, Arase, Y, additional, Suzuki, Y, additional, Saitoh, S, additional, Murashima, N, additional, Ikeda, K, additional, Okamoto, K, additional, Hashimoto, M, additional, Matsuda, M, additional, Koike, H, additional, and Kumada, H, additional

Published
1999
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37. Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection

Author

Chayama, K, primary, Tsubota, A, additional, Kobayashi, M, additional, Okamoto, K, additional, Hashimoto, M, additional, Miyano, Y, additional, Koike, H, additional, Koida, I, additional, Arase, Y, additional, Saitoh, S, additional, Suzuki, Y, additional, Murashima, N, additional, Ikeda, K, additional, and Kumada, H, additional

Published
1997
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48. Interferon lowers tumor recurrence rate after surgical resection or ablation of hepatocellular carcinoma: a pilot study of patients with hepatitis B virus-related cirrhosis.

Author

Someya T, Ikeda K, Saitoh S, Kobayashi M, Hosaka T, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Arase Y, Kumada H, Someya, Takashi, Ikeda, Kenji, Saitoh, Satoshi, Kobayashi, Masahiro, Hosaka, Tetsuya, Sezaki, Hitomi, Akuta, Norio, Suzuki, Fumitaka, and Suzuki, Yoshiyuki

Abstract

Background: Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) often recurs after surgical or medical treatment.Methods: Eighty consecutive patients with HBV-positive cirrhosis and HCC who underwent potentially curative ablation for HCC were analyzed. Eleven patients received long-term interferon (IFN) therapy. HBV DNA was quantified at the time of HCC treatment. A DNA value of <6.0 log copies/ml was considered low.Results: Initial DNA was low in 39 and high in 41 patients. HCC recurrence rates in the low DNA group and high DNA group were 46.9% and 82.6% at the fifth year, and 73.5% and 91.3% at the tenth year, respectively (P = 0.0103). Similarly, recurrence rates after treatment of HCC in the normal aspartate aminotransferase (AST) group (<38 IU/l, n = 42) and abnormal AST group (n = 38) were 50.6% and 84.0% at the fifth year, and 71.3% and 100% at the tenth year, respectively (P = 0.0003). Six of the 38 patients with abnormal AST, and 5 of 42 patients with normal AST, received IFN after confirmation of tumor ablation. In the subgroup of abnormal AST, tumor recurrence rates in the IFN and untreated groups were 16.7% and 37.9% at the end of the first year, 16.7% and 60.1% at the second year, and 16.7% and 83.4% at the third year, respectively (P = 0.0139). Multivariate analysis revealed that IFN significantly reduced the recurrence rate (hazard ratio = 0.21, P = 0.037) even after adjusting for background characteristics.Conclusions: IFN was inferred to decrease tumor recurrence after treatment of HCC in patients with HBV-related cirrhosis, especially in the subgroup with high AST. [ABSTRACT FROM AUTHOR]

Published
2006

49. High-dose interferon alpha-2b induction therapy in combination with ribavirin for Japanese patients infected with hepatitis C virus genotype 1b with a high baseline viral load.

Author

Tsubota A, Arase Y, Suzuki F, Suzuki Y, Akuta N, Hosaka T, Someya T, Kobayashi M, Saitoh S, Ikeda K, Kumada H, Tsubota, Akihito, Arase, Yasuji, Suzuki, Fumitaka, Suzuki, Yoshiyuki, Akuta, Norio, Hosaka, Tetsuya, Someya, Takashi, Kobayashi, Masahiro, and Saitoh, Satoshi

Abstract

Background: Although pegylated interferon (IFN) is now used in many countries as a standard therapy for chronic hepatitis C, the efficacy and safety of combination therapy of high-dose interferon alpha-2b induction with ribavirin are not fully evaluated, especially in Japanese patients infected with hepatitis C virus (HCV) genotype 1b with a high viral load.Methods: Patients ( n = 83) received daily, high-dose induction therapy of interferon alpha-2b (6 million units [MU] once daily for 2 weeks), followed by 6 MU three times weekly for 22 weeks. Oral ribavirin (800 or 600 mg/day) was given daily for 24 weeks, and then the patients were followed up for 24 weeks.Results: Of the 83 patients, 67 (81%) had a biochemical response (BR), and 37 (45%) achieved a sustained BR (SBR). Virologic response (VR; undetectable serum HCV RNA level by polymerase chain reaction [PCR]) was noted in 55 (66%) patients, and sustained VR (SVR) in 16 (19%) patients. Baseline viral load did not influence treatment outcome. There was no significant difference in treatment outcome among treatment-naIve patients, relapsers, and nonresponders to previous IFN monotherapy. Multivariate analyses identified serum ribavirin concentrations at week 8 of therapy (odds ratio [OR], 23.7; 95% confidence interval [CI], 1.84-61.1; P = 0.015) and negativity for serum HCV RNA at week 8 (OR, 22.5; CI, 1.76-57.5; P = 0.017, respectively) as two significant and independent predictors of SVR.Conclusions: The efficacy of 24-week combination therapy of high-dose IFN alpha-2b induction and ribavirin deserves attention in HCV genotype 1b patients with a high viral load, especially in nonresponders to previous IFN monotherapy and patients with a very high viral load. [ABSTRACT FROM AUTHOR]

Published
2004
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50. Clinical characteristics of patients infected with hepatitis B virus genotypes A, B, and C.

Author

Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, Suzuki F, Akuta N, Someya T, Matsuda M, Sato J, Kumada H, Kobayashi, Mariko, Arase, Yasuji, Ikeda, Kenji, Tsubota, Akihito, Suzuki, Yoshiyuki, Saitoh, Satoshi, Kobayashi, Masahiro, and Suzuki, Fumitaka

Abstract

Background: The aim of the present study was to evaluate the clinical characteristics at first hospital consultation, according to the genotype of hepatitis B virus (HBV), in patients with chronic liver diseases and positivity for hepatitis B surface antigen (HBsAg) in metropolitan Tokyo.Methods: The subjects consisted of 1077 patients with chronic liver diseases who were HBsAg-positive. HBV genotype was determined by an enzyme-linked immunosorbent assay (ELISA), using PreS2 monoclonal antibody, which is specific for HBV genotypes in the PreS2 region.Results: The proportion of patients with genotype A was 2% (20 patients), genotype, B 9% (101 patients), and genotype C, 88% (945 patients), while 11 patients (1.0%) had other genotypes, including 2 (0.2%) each with genotypes D and F, and 7 (0.6%) that were untypeable. Patients with genotype A were significantly (P = 0.049) more likely to be positive for Hepatitis B envelope antigen (HBeAg) at the first consultation compared with those with genotype B. Patients with genotype B were significantly more likely to be HBeAg-negative at the first consultation compared with those with genotype A (P = 0.049) and genotype C (P = 0.001), significantly more likely to show minimal hepatic fibrosis (P = 0.003), and least likely to develop liver cirrhosis (P = 0.005). Patients with genotype C were likely to be HBeAg-positive (P = 0.001) and to have a positive family history of HBV infection (P = 0.0002).Conclusions: The clinical features of patients with HBV infection in metropolitan Tokyo varied depending on the HBV genotype. [ABSTRACT FROM AUTHOR]

Published
2002
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