2011 Fiscal Year Final Research Report
Loss of HB-EGF accelerates carbon tetrachloride induced liver injury in mice
Project/Area Number |
21590844
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Osaka University |
Principal Investigator |
KISO Shinichi 大阪大学, 医学系・研究科, 助教 (40335352)
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Co-Investigator(Kenkyū-buntansha) |
YOSHIA Yuichi 大阪大学, 医学系・研究科, 助教 (30457014)
WATABE Kenji 大阪大学, 医学系・研究科, 助教 (50379244)
TSUTSUI Shusaku 大阪大学, 医学系・研究科, 助教 (10359846)
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Project Period (FY) |
2009 – 2011
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Keywords | HB-EGF / 肝再生 / 肝線維化 |
Research Abstract |
Heparin-binding EGF-like growth factor(HB-EGF) is a member of EGF family of growth factors that binds to and stimulates EGF receptors(EGFR) and EerbB4. Previously, we demonstrated that the HB-EGF was induced in response to several liver injuries and also showed that transgenic expression of HB-EGF in mice accelerated proliferation of hepaocyte during liver regeneration after partial hepatectomy. However, the role of HB-EGF in acute liver injury induced by hepatotoxin remains still unclear. To clarify this issue, we generated liver specific HB-EGF knockout(KO) mice. At 24 hours after CCl4 injection, KO mice showed significant increased ALT level compared with WT mice(5486+ 1961 IU/ l vs. 2275+ 656 IU/ l, p<0. 05), indicating that hepatic HB-EGF deficiency caused acceleration of liver injury. Western blotting also showed significant reduced expression level of PCNA protein at 48 hours after CCl4injection. Consistent with this, the number of BrdU positive hepatocytes in KO mice was lower than that in WT mice at 48 and 72 hours after CCl4 injection. This impaired liver regeneration in KO mice was associated with reduced activity of ERK1/ 2 MAP kinase in injured livers. Furthermore, HB-EGF significantly suppressed apoptosis of mouse hepaocyte cell lines induced by TNFαin a dose dependent manner, indicating the possible anti-apoptotic role of HB-EGF. Conclusion : Our current study demonstrated that HB-EGF might play a protective role during acute liver injury through ERK1/ 2 activation.
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[Journal Article] Glycobiology. N-Acetylglucosaminyltransferase V regulates TGF-βresponse in hepatic stellate cells and the progression of steatohepatitis2012
Author(s)
Kamada Y, Mori K, Matsumoto H, Kiso S, Yoshida Y, Shinzaki S, Hiramatsu N, Ishii M, Moriwaki K, Kawada N, Takehara T, Miyoshi E
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Journal Title
Am J Physiol Gastrointest Liver Physiol
Volume: (In press)
Peer Reviewed
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[Journal Article] Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection2012
Author(s)
Kurokawa M, Hiramatsu N, Oze T, Yakushijin T, Miyazaki M, Hosui A, Miyagi T, Yoshida Y, Ishida H, Tatsumi T, Kiso S, Kanto T, Kasahara A, Iio S, Doi Y, Yamada A, Oshita M, Kaneko A, Mochizuki K, Hagiwara H, Mita E, Ito T, Inui Y, Katayama K, Yoshihara H,
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Journal Title
J Gastroenterol
Volume: (In press)
Peer Reviewed
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[Journal Article] Protective role of adiponectin against ethanol-induced gastric injury in mice2012
Author(s)
Shunsuke Yamamoto, Kenji Watabe, Hiroshi Araki, Yoshihiro Kamada, Motohiko Kato, Takashi Kizu, Shinichi Kiso, Shusaku Tsutsui, Masahiko Tsujii, Shinji Kihara, Tohru Funahashi, Iichiro Shimomura, Norio Hayashi, and Tetsuo Takehara
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Journal Title
Am J Physiol Gastrointest Liver Physiol
Volume: (In press)
Peer Reviewed
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[Journal Article] Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin2012
Author(s)
Oze T, Hiramatsu N, Song C, Yakushijin T, Iio S, Doi Y, Oshita M, Hagiwara H, Mita E, Ito T, Inui Y, Hijioka T, Tamura S, Yoshihara H, Inoue A, Imai Y, Hayashi E, Kato M, Miyazaki M, Hosui A, Miyagi T, Yoshida Y, Tatsumi T, Kiso S, Kanto T, Kasahara A, Hayashi N, Takehara T
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Journal Title
J Gastroenterol
Volume: 47(3)
Pages: 334-42
Peer Reviewed
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[Journal Article] Indications and limitations for aged patients with chronic hepatitis C in pegylated interferon alfa-2b plus ribavirin combination therapy2011
Author(s)
Oze T, Hiramatsu N, Yakushijin T, Mochizuki K, Oshita M, Hagiwara H, Mita E, Ito T, Fukui H, Inui Y, Hijioka T, Inada M, Kaytayama K, Tamura S, Yoshihara H, Inoue A, Imai Y, Kato M, Miyagi T, Yoshida Y, Tatsumi T, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N
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Journal Title
J Hepatol
Volume: 54(4)
Pages: 604-11
Peer Reviewed
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[Journal Article] Efficacy of re-treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan2011
Author(s)
Tsugiko Oze, Naoki Hiramatsu, Takayuki Yakushijin, Kiyoshi Mochizuki, Masahide Oshita, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Yoshiaki Inui, Hiroyuki Fukui, Taizo Hijioka, Kazuhiro Katayama, Shinji Tamura, Harumasa Yoshihara, Atsuo Inoue, Yasuharu Imai, Eijiro Hayashi, Michio Kato, Atsushi Hosui, Takuya Miyagi, Hisashi Ishida, Yuichi Yoshida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Tetsuo Takehara and Norio Hayashi
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Journal Title
Gastroenterol
Volume: 46(8)
Pages: 1031-7
Peer Reviewed
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[Journal Article] The efficacy of extended treatment with pegylated interferon plus ribavirin in patients with HCV genotype 1 and slow virologic response in Japan2011
Author(s)
Tsugiko Oze, Naoki Hiramatsu, Takayuki Yakushijin, Kiyoshi Mochizuki, Kazuho Imanaka, Akira Yamada, Masahide Oshita, Akira Kaneko, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Toshihiko Nagase, Yoshiaki Inui, Taizo Hijioka, Shinji Tamura, Harumasa , Eijiro Hayashi, Yasuharu Imai, Michio Kato, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Hisashi Ishida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Tetsuo Takehara, and Norio Hayashi
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Journal Title
J Gastroenterol
Volume: 46(7)
Pages: 944-52
Peer Reviewed
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[Journal Article] Lower serum level of adiponectin is associated with increased risk of endoscopic erosive gastritis2011
Author(s)
Yamamoto S, Watabe K, Tsutsui S, Kiso S, Hamasaki T, Kato M, Kamada Y, Yoshida Y, Kihara S, Umeda M, Furubayashi A, Kinoshita K, Kishida O, Fujimoto T, Yamada A, Tsukamoto Y, Hayashi N, Matsuzawa Y
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Journal Title
Dig Dis Sci
Volume: 56(8)
Pages: 2354-60
Peer Reviewed
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[Journal Article] Association of low serum adiponectin levels with erosive esophagitis in men ; an analysis of 2405 subjects undergoing physical check-ups2011
Author(s)
Motohiko Kato, Kenji Watabe, Toshimitsu Hamasaki, Miyuki Umeda, Aiko Furubayashi, Kazuo Kinoshita, Osamu Kishida, Takashi Fujimoto, Akira Yamada, Yoshifumi Tsukamoto, Shunsuke Yamamoto, Yoshihiro Kamada, Yuichi Yoshida, Shinichi Kiso, Shusaku Tsutsui, Shinji Kihara, Norio Hayashi, and Yuji Matsuzawa
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Journal Title
J Gastroenterology
Volume: 46(12)
Pages: 1361-7
Peer Reviewed
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[Journal Article] Estrogen deficiency worsens steatohepatitis in mice fed high fat and high cholesterol diet2011
Author(s)
Kamada Y, Kiso S, Yoshida Y, Chatani N, Kizu T, Hamano M, Tsubakio M, Takemura T, Ezaki H, Hayashi N, Takehara T
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Journal Title
Am J Physiol Gastrointest Liver Physiol
Volume: 301(6)
Pages: G1031-43
Peer Reviewed
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[Journal Article] Efficacy of pegylated interferon plus ribavirin combination therapy for hepatitis C patients with normal ALT levels : a matched case-control study2011
Author(s)
Hiramatsu N, Inoue Y, Oze T, Kurashige N, Yakushijin T, Mochizuki K, Miyagi T, Tatsumi T, Kiso S, Kanto T, Kasahara A, Takehara T, Oshita M, Mita E, Hagiwara H, Inui Y, Katayama K, Tamura S, Yoshihara H, Imai Y, Hayashi N
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Journal Title
J Gastroenterol
Volume: 46(11)
Pages: 1335-43
Peer Reviewed
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[Journal Article] Amino acid substitution in the core protein has no impact on relapse in hepatitis C genotype 1 patients treated with peginterferon and ribavirin2011
Author(s)
Inoue Y, Hiramatsu N, Oze T, Yakushijin T, Mochizuki K, Fukuda K, Mita E, Haruna Y, Inoue A, Imai Y, Hosui A, Miyagi T, Yoshida Y, Tatsumi T, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N
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Journal Title
J Med Virol
Volume: 83(3)
Pages: 419-27
Peer Reviewed
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[Journal Article] Factors affecting efficacy in patients with genotype 2 chronic hepatitis C treated by pegylated interferon alpha-2b and ribavirin : reducing drug doses has no impact on rapid and sustained virological responses2010
Author(s)
Inoue Y, Hiramatsu N, Oze T, Yakushijin T, Mochizuki K, Hagiwara H, Oshita M, Mita E, Fukui H, Inada M, Tamura S, Yoshihara H, Hayashi E, Inoue A, Imai Y, Kato M, Miyagi T, Hohsui A, Ishida H, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N
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Journal Title
J Viral Hepat
Volume: 17(5)
Pages: 336-44
Peer Reviewed
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[Journal Article] Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice2010
Author(s)
Yamada T, Araki H, Watabe K, Kamada Y, Kiso S, Ogiyama H, Nishihara T, Kihara S, Funahashi T, Shimomura I, Tsutsui S, Hayashi N
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Journal Title
J Gastroenterol
Volume: 45(7)
Pages: 742-9
Peer Reviewed
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[Journal Article] Lack of adiponectin promotes formation of cholesterol gallstones in mice2010
Author(s)
Ogiyama H, Kamada Y, Kiso S, Araki H, Yamada T, Nishihara T, Watabe K, Tochino Y, Kihara S, Funahashi T, Kanno K, Shimomura I, Tsutsui S, Tazuma S, Hayashi N
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Journal Title
Biochem Biophys Res Commun
Volume: 399(3)
Pages: 352-8
Peer Reviewed
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[Journal Article] Reduced risk of hepatocellular carcinoma after interferon therapy in aged patients with chronic hepatitis C is limited to sustained virological responders2010
Author(s)
Imai Y, Tamura S, Tanaka H, Hiramatsu N, Kiso S, Doi Y, Inada M, Nagase T, Kitada T, Imanaka K, Fukuda K, Takehara T, Kasahara A, Hayashi N
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Journal Title
J Viral Hepat
Volume: 17(3)
Pages: 185-91
Peer Reviewed
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[Journal Article] Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice2009
Author(s)
Ezaki H, Yoshida Y, Saji Y, Takemura T, Fukushima J, Matsumoto H, Kamada Y, Wada A, Igura T, Kihara S, Funahashi T, Shimomura I, Tamura S, Kiso S, Hayashi N
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Journal Title
Biochem Biophys Res Commun
Volume: 378(1)
Pages: 68-72
Peer Reviewed
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[Journal Article] Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis2009
Author(s)
Kurokawa M, Hiramatsu N, Oze T, Mochizuki K, Yakushijin T, Kurashige N, Inoue Y, Igura T, Imanaka K, Yamada A, Oshita M, Hagiwara H, Mita E, Ito T, Inui Y, Hijioka T, Yoshihara H, Inoue A, Imai Y, Kato M, Kiso S, Kanto T, Takehara T, Kasahara A, Hayashi N
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Journal Title
Hepatol Res.
Volume: 39(5)
Pages: 432-8
Peer Reviewed
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[Journal Article] Factors contributing to antiviral effect of adefovir dipivoxil therapy added to ongoing lamivudine treatment in patients with lamivudine-resistant chronic hepatitis B2009
Author(s)
Kurashige N, Hiramatsu N, Ohkawa K, Yakushijin T, Kiso S, Kanto T, Takehara T, Kasahara A, Doi Y, Yamada A, Oshita M, Mita E, Hagiwara H, Nagase T, Yoshihara H, Hayashi E, Imai Y, Kato M, Kashihara T, Hayashi N
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Journal Title
J Gastroenterol
Volume: 44(6)
Pages: 601-7
Peer Reviewed
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[Journal Article] Visceral obesity and hypoadiponectinemia are significant determinants of hepatic dysfunction : An epidemiologic study of 3827 Japanese subjects2009
Author(s)
Kamada Y, Nakamura T, Funahashi T, Ryo M, Nishizawa H, Okauchi Y, Fukushima J, Yoshida Y, Kiso S, Shimomura I, Hayashi N
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Journal Title
J Clin Gastroenterol
Volume: 43(10)
Pages: 995-1000
Peer Reviewed
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[Journal Article] A novel therapeutic strategy with anti-CD9 antibody in gastric cancers2009
Author(s)
Nakamoto T, Murayama Y, Oritani K, Boucheix C, Rubinstein E, Nishida M, Katsube F, Watabe K, Kiso S, Tsutsui S, Tamura S, Shinomura Y, Hayashi N
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Journal Title
J Gastroenterol
Volume: 44(9)
Pages: 889-96
Peer Reviewed
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[Journal Article] Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance2009
Author(s)
Kurashige N, Ohkawa K, Hiramatsu N, Yakushijin T, Mochizuki K, Oze T, Kiso S, Kanto T, Takehara T, Kasahara A, Doi Y, Yamada A, Fukuda K, Oshita M, Mita E, Fukui H, Nagase T, Yoshihara H, Imai Y, Kato M, Kashihara T, Hayashi N
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Journal Title
J Gastroenterol
Volume: 44(8)
Pages: 864-70
Peer Reviewed
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[Journal Article] Adiponectin prevents progression of steatohepatitis in mice by regulating oxidative stress and Kupffer cell phenotype polarization2009
Author(s)
Fukushima J, Kamada Y, Matsumoto H, Yoshida Y, Ezaki H, Takemura T, Saji Y, Igura T, Tsutsui S, Kihara S, Funahashi T, Shimomura I, Tamura S, Kiso S, Hayashi N
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Journal Title
Hepatol Res
Volume: 39(7)
Pages: 724-38
Peer Reviewed
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[Journal Article] Pegylated interferon alpha-2b(Peg-IFN alpha-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN alpha-2b plus ribavirin2009
Author(s)
Oze T, Hiramatsu N, Yakushijin T, Kurokawa M, Igura T, Mochizuki K, Imanaka K, Yamada A, Oshita M, Hagiwara H, Mita E, Ito T, Inui Y, Hijioka T, Tamura S, Yoshihara H, Hayashi E, Inoue A, Imai Y, Kato M, Yoshida Y, Tatsumi T, Ohkawa K, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N
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Journal Title
J Viral Hepat
Volume: 16(8)
Pages: 578-85
Peer Reviewed
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[Journal Article] Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin2009
Author(s)
Hiramatsu N, Oze T, Yakushijin T, Inoue Y, Igura T, Mochizuki K, Imanaka K, Kaneko A, Oshita M, Hagiwara H, Mita E, Nagase T, Ito T, Inui Y, Hijioka T, Katayama K, Tamura S, Yoshihara H, Imai Y, Kato M, Yoshida Y, Tatsumi T, Ohkawa K, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N
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Journal Title
J Viral Hepat
Volume: 16(8)
Pages: 586-94
Peer Reviewed
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[Presentation] Suppressive effect of pegylated interferon alfa-2B plus ribavirin combination therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis C2010
Author(s)
Tugiko Oze, Naoki Hiramatsu, Takayuki Yakushijin, Kiyoshi Mochizuki, Masahide Oshita, Hideki Hagiwara, Eiji Mita, Hiroyuki Fukui, Yoshiaki Inui, Taizo Hijioka, Masami Inada, Shinji Tamura, Harumasa Yoshihara, Atsuo Inoue, Yasuharu Imai, Michio Kato, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Tetsuo Takehara, Norio Hayashi
Organizer
AASLD(ボストン)
Place of Presentation
ボストン、米国
Year and Date
20101029-1102
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[Presentation] HB-EGF conditional loss of liver accelerates the carbon tetrachloride induced liver injury in mice2010
Author(s)
Takayo Takemura, Yuichi Yoshida, Yukiko Saji, Hisao Ezaki, Mina Hamano, Takashi Kizu, Mayumi Tsubakio, Norihiro Chatani, Yoshihiro Kamada, Shinichi Kiso, Norio Hayashi
Organizer
AASLD(ボストン)
Place of Presentation
ボストン、米国
Year and Date
20101029-1102
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[Presentation] Norio Hayashi Non-invasive evaluation of liver fibrosis by using virtual touch tissue quantification in patients with chronic hepatitis C2010
Author(s)
Changho Song, Naoki Hiramatsu, Yuko Inoue, Mika Kurokawa, Tsugiko Oze, Takayuki Yakushijin, Kiyoshi Mochizuki, Takuya Miyagi, Yuichi Yoshida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Tetsuo Takehara
Organizer
AASLD(ボストン)
Place of Presentation
ボストン、米国
Year and Date
20101029-1102
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