松浦　健太郎マツウラ　ケンタロウ

研究者基本情報

基本情報

科研費研究者番号:30580576

学歴

• 2006年04月 - 2010年03月, 名古屋市立大学, 大学院医学研究科
• 1994年04月 - 2000年03月, 名古屋市立大学, 医学部

学位

• 医学博士, 名古屋市立大学

所属学協会

• 日本臨床検査学会
• 日本臨床腫瘍学会
• 日本消化器内視鏡学会
• 日本肝臓学会
• 日本消化器病学会
• 日本内科学会

委員歴

•   2019年11月 - 現在, 日本肝臓学会, 日本肝臓学会総会 審査委員
•   2018年06月 - 現在, 日本肝臓学会, MSD Award 審査委員

経歴

•   2019年02月 - 現在, 名古屋市立大学大学院医学研究科, 消化器・代謝内科学, 講師
•   2017年04月 - 2019年01月, 名古屋市立大学病院, 肝・膵臓内科, 病院助教
•   2013年04月 - 2017年03月, 米国国立衛生研究所, 輸血医学, Visiting fellow
•   2010年04月 - 2013年03月, 名古屋市立大学病院, 肝・膵臓内科, 臨床研究医
•   2007年04月 - 2010年03月, 名古屋市立大学大学院医学研究科, 大学院生
•   2006年04月 - 2007年03月, 藤田保健衛生大学七栗サナトリウム, 内科, 助手
•   2002年04月 - 2006年03月, 名古屋第二赤十字病院, 消化器内科, 医師
•   2000年04月 - 2002年03月, 名古屋市立大学病院, 第2内科, 臨床研修医

研究活動情報

研究分野

• ライフサイエンス, 消化器内科学, 肝臓学

研究キーワード

microRNA, ヒトゲノム, ウイルス肝炎

論文

• TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus by interferon-free therapy, Iio E, Matsuura K, 54, (4) 339 - 346,   2019年04月, 査読有り
• Circulating let-7 levels in serum correlate with the severity of hepatic fibrosis in chronic hepatitis C, Matsuura K, Open Forum Infct Dis., 5, (11) ,   2018年10月, 査読有り
• Host genetic variations associated with disease progression in chronic hepatitis C virus infection, Matsuura K, Hepatol Res., 48, (2) 127 - 133,   2018年02月, 査読有り
• Efficacy of regimens combining direct acting anti-viral agents for hepatitis C virus recombinant form RF1_2 k/1b, Hepatol Res., 48, (1) 3 - 4,   2018年01月, 査読有り
• Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection, Kentaro Matsuura, Hiromi Sawai, Kazuho Ikeo, Shintaro Ogawa, Etsuko Iio, Masanori Isogawa, Noritomo Shimada, Atsumasa Komori, Hidenori Toyoda, Takashi Kumada, Tadashi Namisaki, Hitoshi Yoshiji, Naoya Sakamoto, Mina Nakagawa, Yasuhiro Asahina, Masayuki Kurosaki, Namiki Izumi, Nobuyuki Enomoto, Atsunori Kusakabe, Eiji Kajiwara, Yoshito Itoh, Tatsuya Ide, Akihiro Tamori, Misako Matsubara, Norifumi Kawada, Ken Shirabe, Eiichi Tomita, Masao Honda, Shuichi Kaneko, Sohji Nishina, Atsushi Suetsugu, Yoichi Hiasa, Hisayoshi Watanabe, Takuya Genda, Isao Sakaida, Shuhei Nishiguchi, Koichi Takaguchi, Eiji Tanaka, Junichi Sugihara, Mitsuo Shimada, Yasuteru Kondo, Yosuke Kawai, Kaname Kojima, Masao Nagasaki, Katsushi Tokunaga, Yasuhito Tanaka, GASTROENTEROLOGY, 152, (6) 1383 - 1394,   2017年05月, 査読有り, BACKGROUND & AIMS: There is still a risk for hepatocellular carcinoma (HCC) development after eradication of hepatitis C virus (HCV) infection with antiviral agents. We investigated genetic factors associated with the development of HCC in patients with a sustained virologic response (SVR) to treatment for chronic HCV infection. METHODS: We obtained genomic DNA from 457 patients in Japan with a SVR to interferon-based treatment for chronic HCV infection from 2007 through 2015. We conducted a genome-wide association study (GWAS), followed by a replication analysis of 79 candidate single nucleotide polymorphisms (SNPs) in an independent set of 486 patients in Japan. The study end point was HCC diagnosis or confirmation of lack of HCC (at follow-up examinations until December 2014 in the GWAS cohort, and until January 2016 in the replication cohort). We collected clinical and laboratory data from all patients. We analyzed expression levels of candidate gene variants in human hepatic stellate cells, rats with steatohepatitis caused by a choline-deficient L-amino acid-defined diet, and a mouse model of liver injury caused by administration of carbon tetrachloride. We also analyzed expression levels in liver tissues of patients with chronic HCV infection with different stages of fibrosis or tumors vs patients without HCV infection (controls). RESULTS: We found a strong association between the SNP rs17047200, located within the intron of the tolloid like 1 gene (TLL1) on chromosome 4, and development of HCC; there was a genome-wide level of significance when the results of the GWAS and replication study were combined (odds ratio, 2.37; P = 2.66 x 10(-8)). Multivariate analysis showed rs17047200 AT/TT to be an independent risk factor for HCC (hazard ratio, 1.78; P = .008), along with male sex, older age, lower level of albumin, advanced stage of hepatic fibrosis, presence of diabetes, and higher post-treatment level of alpha-fetoprotein. Combining the rs17047200 genotype with other factors, we developed prediction models for HCC development in patients with mild or advanced hepatic fibrosis. Levels of TLL1 messenger RNA (mRNA) in human hepatic stellate cells increased with activation. Levels of Tll1 mRNA increased in liver tissues of rodents with hepatic fibrogenesis compared with controls. Levels of TLL1 mRNA increased in liver tissues of patients with progression of fibrosis. Gene expression levels of TLL1 short variants, including isoform 2, were higher in patients with rs17047200 AT/TT. CONCLUSIONS: In a GWAS, we identified the association between the SNP rs17047200, within the intron of TLL1, and development of HCC in patients who achieved an SVR to treatment for chronic HCV infection. We found levels of Tll1/TLL1 mRNA to be increased in rodent models of liver injury and liver tissues of patients with fibrosis, compared with controls. We propose that this SNP might affect splicing of TLL1 mRNA, yielding short variants with high catalytic activity that accelerates hepatic fibrogenesis and carcinogenesis. Further studies are needed to determine how rs17047200 affects TLL1 mRNA levels, splicing, and translation, as well as the prevalence of this variant among other patients with HCC. Tests for the TLL1 SNP might be used to identify patients at risk for HCC after an SVR to treatment of HCV infection.
  DOI
• Host genetic variants influencing the clinical course of hepatitis B virus infection, Matsuura K, J Med Virol., 88, (3) 371 - 379,   2016年09月, 査読有り
• Circulating let-7 levels in plasma and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C, Kentaro Matsuura, Valeria De Giorgi, Cathy Schechterly, Richard Y. Wang, Patrizia Farci, Yasuhito Tanaka, Harvey J. Alter, HEPATOLOGY, 64, (3) 732 - 745,   2016年09月, 査読有り, The goal of this study was to determine whether an association exists between circulating microRNA (miRNA) levels and disease progression in chronic hepatitis C (CHC), whether plasma or extracellular vesicles (EVs) were optimal for miRNA measurement and their correlation with hepatic miRNA expression, and the mechanistic plausibility of this association. We studied 130 CHC patients prospectively followed over several decades. A comprehensive miRNA profile in plasma using microarray with 2578 probe sets showed 323 miRNAs differentially expressed between healthy individuals and CHC patients, but only six that distinguished patients with mild versus severe chronic hepatitis. Eventually, let-7a/7c/7d-5p and miR-122-5p were identified as candidate predictors of disease progression. Cross-sectional analyses at the time of initial liver biopsy showed that reduced levels of let-7a/7c/7d-5p (let-7s) in plasma were correlated with advanced histological hepatic fibrosis stage and other fibrotic markers, whereas miR-122-5p levels in plasma were positively correlated with inflammatory activity, but not fibrosis. Measuring let-7s levels in EVs was not superior to intact plasma for discriminating significant hepatic fibrosis. Longitudinal analyses in 60 patients with paired liver biopsies showed that let-7s levels in plasma markedly declined over time in parallel with fibrosis progression. However, circulating let-7s levels did not parallel those in the liver. Conclusion: Of all miRNAs screened, the let-7 family showed the best correlation with hepatic fibrosis in CHC. A single determination of let-7s levels in plasma did not have superior predictive value for significant hepatic fibrosis compared with that of fibrosis-4 index, but the rate of let-7s decline in paired longitudinal samples correlated well with fibrosis progression. Pathway analysis suggested that low levels of let-7 may influence hepatic fibrogenesis through activation of transforming growth factor signaling in hepatic stellate cells. (Hepatology 2016;64:732-745)
  DOI
• Host genetic variants influencing the clinical course of hepatitis C virus infection, J Med Virol., 88, (2) 185 - 195,   2016年02月, 査読有り
• Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C, Hum Genet., 134, (3) 279 - 289,   2015年03月, 査読有り
• Suppressive genes expressions of interferon signaling pathway in peripheral blood mononuclear cells associated with IL28B genetic variants and virological response to PEG-IFN, RBV plus NS3/4 protease inhibitor, PLoS One, 10, (2) ,   2015年02月, 査読有り
• Serum IP-10 concentrations and IL28B genotype associated with responses to PEG-IFN/RBV with and without telaprevir for chronic hepatitis C, Hepatol Res., 44, (12) 1208 - 1216,   2014年11月, 査読有り
• ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients with IL28B favorable type infected with HCV genotype 1, J Viral Hepatis., 21, (7) 466 - 474,   2014年06月, 査読有り
• Role of interferon-lambda (IL28B) for chronic hepatitis C treatment toward personalized medicine, J Gastroenterol Hepatol., 29, (2) 241 - 249,   2014年02月, 査読有り
• Recommendation of lamivudine-to-entecavir switching treatment in chronic hepatitis B responders: Randomized controlled trial, Kentaro Matsuura, Yasuhito Tanaka, Atsunori Kusakabe, Shuhei Hige, Jun Inoue, Masashi Komatsu, Tomoyuki Kuramitsu, Katsuharu Hirano, Tomoyoshi Ohno, Izumi Hasegawa, Haruhiko Kobashi, Keisuke Hino, Yoichi Hiasa, Hideyuki Nomura, Fuminaka Sugauchi, Shunsuke Nojiri, Takashi Joh, Masashi Mizokami, HEPATOLOGY RESEARCH, 41, (6) 505 - 511,   2011年06月, 査読有り, Aim: In the 2007-2008 guidelines of the study group (Ministry of Health, Labor and Welfare of Japan), lamivudine (LAM)-continuous treatment was recommended in patients treated with LAM for more than 3 years who maintained hepatitis B virus (HBV) DNA less than 2.6 log copies/mL, because in these patients LAM resistance might exist and switching treatment to entecavir (ETV) might cause ETV resistance. However, there was no evidence on whether switching treatment to ETV- or LAM-continuous treatment was better in those patients. In the present study, we performed a randomized controlled trial of LAM-to-ETV switching treatment. Methods: Twenty-seven patients treated with LAM for more than 3 years whose HBV DNA levels were less than 2.6 log copies/mL were enrolled and randomly divided into two groups, LAM-continued group or switching to ETV group. Then, we examined incidence of virological breakthrough (VBT) and breakthrough hepatitis (BTH) in each group. Results: There was no BTH in any of the patients. VBT was observed in six patients of the LAM group (6/15, 40%), and no patient of the ETV group (0/11, 0%) (P = 0.02). The differences of the proportion of cumulated VBT using a log-rank test with Kaplan-Meier analysis were significant between the LAM and ETV groups (P = 0.025). Conclusion: In patients treated with LAM for more than 3 years maintaining HBV DNA less than 2.6 log copies/mL, switching treatment to ETV is recommended at least during the 2 years' follow-up period.
  DOI
• Distribution of Hepatitis B Virus Genotypes among Patients with Chronic Infection in Japan Shifting toward an Increase of Genotype A, J Clin Microbiol., 47, (5) 1476 - 1483,   2009年05月, 査読有り
• Abbott RealTime hepatitis C virus (HCV) and Roche Cobas AmpliPrep/Cobas TaqMan HCV assays for prediction of sustained virological response to pegylated interferon and ribavirin in chronic hepatitis C patients., J Clin Microbiol., 47, (2) 385 - 389,   2009年02月, 査読有り

受賞

•   2018年12月, 名古屋市立大学医学会, 平成30年度名古屋市立大学医学会賞, Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection
•   2018年04月, ギリアド・サイエンシズ株式会社, 第3回ギリアド研究助成プログラム, let-7 mimicを用いた新規肝線維化治療法の確立
•   2017年11月, 日本肝臓学会, 平成29年度冠 Award, C型肝炎の病態進展に関わるmicroRNAの検討
•   2012年12月, 公益財団法人 上原記念生命科学財団, 海外留学助成リサーチフェローシップ, C型肝炎病態解明を目指した次世代基盤研究
•   2012年, 日本肝臓学会, 研究奨励賞, Recommendation of lamivudine-to-entecavir switching treatment in chronic hepatitis B responders: Randomized controlled trial
•   2010年04月, 45th EASL, Best Poster Presentation Award, Genome-wide association study identifies genetic variants in the HLA-DP locus associated with chronic hepatitis B
•   2010年04月, 45th EASL, Young Investigator Award, Identification of genetic variants of the IL28B associated with spontaneous clearance of hepatitis C virus in Japanese population
•   2010年, Liver Forum in Kyoto, 2010年度研究奨励賞, B型肝炎ウイルス感染症の病態に関わるウイルス・宿主因子の検討
•   2009年12月, ウイルス肝炎研究財団, 平成21年度 外国への日本人研究派遣事業, C型肝炎の自然治癒例、インターフェロン治療著効例における潜在性HCV感染について
•   2009年11月, The 8th JSH Single Topic Conference, Presidential Award, Identification of genetic variants associated with chronic hepatitis B or C in a genome-wide association study
•   2008年03月, The 18th Conference of the Asian Pacific Association for the Study of the Liver, Young Investigator Award, Predicting sustained virological response in chronic hepatitis C patients treated with pegylated interferon and ribavirin using a novel highly sensitive real-time detection PCR assay

競争的資金

• C型肝炎ウイルス排除治療による肝硬変患者のアウトカムに関する研究開発, AMED, 肝炎等克服実用化研究事業 肝炎等克服緊急対策研究事業,   2019年04月 - 2021年03月
• 肝線維化および肝発がんにおけるTLL1-TGFβ相互活性化機構の解明, 日本学術振興会, 科学研究費助成事業（学術研究助成基金助成金）,   2018年04月 - 2021年03月
• 肝線維化の新規診断･治療法の確立を目指したlet-7の発現･機能解析, 日本学術振興会, 科学研究費助成事業（学術研究助成基金助成金）,   2017年04月 - 2020年03月
• 難病・がん等の疾患分野の医療の実用化研究事業肝炎対策の状況を踏まえたウイルス性肝疾患患者数の動向予測に関する研究, 厚生労働省, 厚生労働科学研究費補助金,   2011年04月 - 2013年03月
• データマイニング手法を用いた効果的なC型肝炎治療法に関する研究, 厚生労働省, 1． 厚生労働省科学研究費補助金 肝炎等克服緊急対策研究事業,   2010年04月 - 2011年03月