Elucidation of the stealth mechanism of infection chronicity by hepatitis B virus and drug discovery of inhibitory molecular targets

• Project/Area Number: 19K08937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Tsubota Akihito 東京慈恵会医科大学, 医学部, 教授 (90322643)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: B型肝炎ウイルス / B型肝炎 / 肝炎慢性化 / microRNA / mRNA / miRNA / 慢性感染

Outline of Research at the Start

B型肝炎は世界に蔓延し、特に慢性化への対応が急がれる。ヒト化肝臓キメラマウスモデルにB型肝炎ウイルス(HBV)を感染させトランスクリプトームを解析した結果、感染直後より持続的に高発現する3つのmicroRNA(miRNA)とHBVのステルス性を示唆する遺伝子プロファイルを得た。(1) miRNAがHBVのステルス性にどう関与しているのか、(2) miRNAと標的mRNAが慢性化を阻止する分子になるのか、(3) 核酸アナログ体との併用でHBVを排除できるのか、を検討し慢性化の成立機序を解明する。これによりB型肝炎の慢性化阻止に向けた新たな分子標的の創薬が期待される。

Outline of Final Research Achievements

We generated an HBV-infected humanized liver chimera mouse model and performed transcriptome analysis of liver tissues. As a result, three miRNAs were persistently and highly up-regulated throughout the period from immediately after HBV infection, and a comprehensive gene profile suggested the stealth property of HBV.
When miRNAs were transfected into primary hepatocytes using lentiviral vectors, the amount of HBV in supernatant fluids/cells decreased in a dose-dependent manner. Conversely, it increased in a dose-dependent manner when those miRNA inhibitors were transfected as well. When siRNAs of target mRNAs specific to each miRNA confirmed by luciferase reporter assay were transfected into primary hepatocytes, the amount of HBV in supernatant fluids/cells showed an inversely correlated trend with the results of miRNA inhibitors. These results may help clarify the mechanism of HBV infection chronicity and drug discovery of inhibitory molecular targets.

Academic Significance and Societal Importance of the Research Achievements

B型肝炎は世界的に未だ主要な感染症であり、深刻な健康問題や経済的損失をもたらしている。特に感染の慢性化には急務な対応が必要である。肝炎が慢性化すれば、B型肝炎ウイルス（HBV）の特性上、感染肝細胞からの完全排除は困難だからである。これを克服するには、感染慢性化の機序解明と阻止が一つの戦略になる。
本研究で同定されたmicroRNA/mRNA分子がヒト肝細胞へのHBV感染効率や複製に影響を及ぼすことが明らかになった。これらの分子が免疫系に及ぼす影響やB型肝炎の慢性化阻止に向けた新たな分子標的としての有益性は今後の課題であるが、その一助になり得る研究成果と考えられ、将来的に社会還元が期待される。

Research Products

• [Journal Article] The Geriatric Nutritional Risk Index predicts sarcopenia in patients with cirrhosis (2023)
  • Author(s): Saeki Chisato、Kinoshita Akiyoshi、Kanai Tomoya、Ueda Kaoru、Nakano Masanori、Oikawa Tsunekazu、Torisu Yuichi、Saruta Masayuki、Tsubota Akihito
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 3888-3888
  • DOI: 10.1038/s41598-023-31065-1
  • Peer Reviewed / Open Access
• [Journal Article] Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study (2022)
  • Author(s): Atsukawa Masanori、Tsubota Akihito、Kondo Chisa、et al.
  • Journal Title: Hepatology International Volume: 17 Issue: 1 Pages: 139-149
  • DOI: 10.1007/s12072-022-10456-y
  • Peer Reviewed
• [Journal Article] Clinical outcomes of antithrombin?III‐based therapy for patients with portal vein thrombosis: A retrospective, multicenter study (2022)
  • Author(s): Hayama Korenobu、Atsukawa Masanori、Uojima Haruki、Hidaka Hisashi、Furuichi Yoshihiro、Kato Keizo、Kawata Kazuhito、Chuma Makoto、Nozaki Akito、Hiraoka Atsushi、Watanabe Tsunamasa、Kagawa Tatehiro、Toyoda Hidenori、Taniai Nobuhiko、Yoshida Hiroshi、Tanaka Yasuhito、Iwakiri Katsuhiko
  • Journal Title: Hepatology Research Volume: 53 Issue: 1 Pages: 51-60
  • DOI: 10.1111/hepr.13840
  • Peer Reviewed / Open Access
• [Journal Article] Antifibrotic effect and long‐term outcome of <scp>SGLT</scp> 2 inhibitors in patients with <scp>NAFLD</scp> complicated by diabetes mellitus (2022)
  • Author(s): Arai Taeang、Atsukawa Masanori、Tsubota Akihito、et al.
  • Journal Title: Hepatology Communications Volume: 6 Issue: 11 Pages: 3073-3082
  • DOI: 10.1002/hep4.2069
  • Peer Reviewed / Open Access
• [Journal Article] Serum Insulin-Like Growth Factor 1 Levels, Facture Risk Assessment Tool Scores and Bone Disorders in Patients with Primary Biliary Cholangitis (2022)
  • Author(s): Saeki Chisato、Oikawa Tsunekazu、Ueda Kaoru、Nakano Masanori、Torisu Yuichi、Saruta Masayuki、Tsubota Akihito
  • Journal Title: Diagnostics Volume: 12 Issue: 8 Pages: 1957-1957
  • DOI: 10.3390/diagnostics12081957
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of oral semaglutide in patients with non‐alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study (2022)
  • Author(s): Arai Taeang、Atsukawa Masanori、Tsubota Akihito、Ono Hirotaka、Kawano Tadamichi、Yoshida Yuji、Okubo Tomomi、Hayama Korenobu、Nakagawa‐Iwashita Ai、Itokawa Norio、Kondo Chisa、Nagao Mototsugu、Iwakiri Katsuhiko
  • Journal Title: JGH Open Volume: 6 Issue: 7 Pages: 503-511
  • DOI: 10.1002/jgh3.12780
  • Peer Reviewed / Open Access
• [Journal Article] SEB genotyping: SmartAmp-Eprimer binary code genotyping for complex, highly variable targets applied to HBV (2022)
  • Author(s): Delobel Diane、Furutani Yutaka、Nagoshi Sumiko、Tsubota Akihito、Miyasaka Akio、Watashi Koichi、Wakita Takaji、Matsuura Tomokazu、Usui Kengo
  • Journal Title: BMC Infectious Diseases Volume: 22 Issue: 1 Pages: 516-516
  • DOI: 10.1186/s12879-022-07458-4
  • Peer Reviewed
• [Journal Article] Misunderstanding of hepatitis C virus (HCV) infection status by non?specialized medical doctors in patients who achieved sustained virologic response to anti-HCV therapy (2022)
  • Author(s): Toyoda Hidenori、Yasuda Satoshi、Moriya Akio、Itobayashi Ei、Uojima Haruki、Watanabe Tsunamasa、Atsukawa Masanori、Arai Taeang、Ishikawa Toru、Mikami Shigeru、Hiraoka Atsushi、Tsuji Kunihiko、Oikawa Tsunekazu、Tsubota Akihito、Nozaki Akito、Chuma Makoto、Abe Hiroshi、Shima Toshihide、Kumada Takashi、Tanaka Junko
  • Journal Title: Journal of Infection and Chemotherapy Volume: 28 Issue: 9 Pages: 1231-1234
  • DOI: 10.1016/j.jiac.2022.04.024
  • Peer Reviewed
• [Journal Article] Shorter pruritus period and milder disease stage are associated with response to nalfurafine hydrochloride in patients with chronic liver disease (2022)
  • Author(s): Kawano Tadamichi、Atsukawa Masanori、Tsubota Akihito、Shimada Noritomo、Toyoda Hidenori、Takaguchi Koichi、Tani Joji、Morishita Asahiro、Hiraoka Atsushi、Mikami Shigeru、Ishikawa Toru、Okubo Hironao、Watanabe Tsunamasa、Okubo Tomomi、Arai Taeang、Hayama Korenobu、Itokawa Norio、Kondo Chisa、Iwakiri Katsuhiko
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 7311-7311
  • DOI: 10.1038/s41598-022-11431-1
  • Peer Reviewed / Open Access
• [Journal Article] Identification of circulating microRNAs as potential biomarkers for hepatic necroinflammation in patients with autoimmune hepatitis (2022)
  • Author(s): Saeki Chisato、Matsuzaki Juntaro、Kuroda Masahiko、Fujita Koji、Ichikawa Makiko、Takizawa Satoko、Takano Keiko、Oikawa Tsunekazu、Nakanuma Yasuni、Saruta Masayuki、Ochiya Takahiro、Tsubota Akihito
  • Journal Title: BMJ Open Gastroenterology Volume: 9 Issue: 1 Pages: e000879-e000879
  • DOI: 10.1136/bmjgast-2022-000879
  • Peer Reviewed / Open Access
• [Journal Article] Mac‐2‐binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C (2022)
  • Author(s): Kawata Kazuhito、Watanabe Tsunamasa、Tsubota Akihito
  • Journal Title: Hepatology Communications Volume: - Issue: 8 Pages: 1-15
  • DOI: 10.1002/hep4.1941
  • Peer Reviewed / Open Access
• [Journal Article] Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B (2021)
  • Author(s): Itokawa Norio, Atsukawa Masanori, Tsubota Akihito, et al. (他13名)
  • Journal Title: Internal Medicine Volume: 60 Issue: 4 Pages: 507-516
  • DOI: 10.2169/internalmedicine.5432-20
  • NAID: 130007986439
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-02-15
  • Peer Reviewed
• [Journal Article] Time‐course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis (2021)
  • Author(s): Atsukawa Masanori、Watanabe Tsunamasa、Iwakiri Katsuhiko
  • Journal Title: Hepatology Research Volume: 52 Issue: 3 Pages: 235-246
  • DOI: 10.1111/hepr.13739
  • Peer Reviewed
• [Journal Article] Clinical Usefulness of FRAX Score for Predicting Sarcopenia in Patients with Chronic Liver Disease. (2021)
  • Author(s): Saeki C, Saito M, Kanai T, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A.
  • Journal Title: J Clin Med Volume: 10 Issue: 18 Pages: 4080-4080
  • DOI: 10.3390/jcm10184080
  • Peer Reviewed / Open Access
• [Journal Article] Influencing Factors and Molecular Pathogenesis of Sarcopenia and Osteosarcopenia in Chronic Liver Disease. (2021)
  • Author(s): Saeki C, Tsubota A
  • Journal Title: Life (Basel) Volume: 11 Issue: 9 Pages: 899-899
  • DOI: 10.3390/life11090899
  • Peer Reviewed / Open Access
• [Journal Article] A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C (2021)
  • Author(s): Atsukawa M, Tsubota A, Kondo C, Uchida-Kobayashi S, Takaguchi K, Tsutsui A, Nozaki A, Chuma M, Hidaka I, Ishikawa T, Iwasa M, Tamai Y, Tobari M, Matsuura K, Nagura Y, Abe H, Kato K, Suzuki K, Okubo T, Arai T, Itokawa N, Toyoda H, Enomoto M, Tamori A, Tanaka Y, Kawada N, Takei Y, Iwakiri K.
  • Journal Title: PLOS ONE Volume: 16 Issue: 9 Pages: e0257166-e0257166
  • DOI: 10.1371/journal.pone.0257166
  • Peer Reviewed / Open Access
• [Journal Article] Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease. (2021)
  • Author(s): Arai T, Atsukawa M, Tsubota A, Kato K, Abe H, Ono H, Kawano T, Yoshida Y, Tanabe T, Okubo T, Hayama K, Nakagawa-Iwashita A, Itokawa N, Kondo C, Kaneko K, Emoto N, Nagao M, Inagaki K, Fukuda I, Sugihara H, Iwakiri K.
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 15938-15938
  • DOI: 10.1038/s41598-021-95581-8
  • Peer Reviewed / Open Access
• [Journal Article] Clinical characteristics of sarcopenia in patients with alcoholic liver cirrhosis. (2021)
  • Author(s): Saeki C, Kanai T, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A.
  • Journal Title: JGH Open Volume: 5 Issue: 7 Pages: 12582-12582
  • DOI: 10.1002/jgh3.12582
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Vitamin D Supplementation on Skeletal Muscle Volume and Strength in Patients with Decompensated Liver Cirrhosis Undergoing Branched Chain Amino Acids Supplementation: A Prospective, Randomized, Controlled Pilot Trial. (2021)
  • Author(s): Okubo T, Atsukawa M, Tsubota A, Ono H, Kawano T, Yoshida Y, Arai T, Hayama K, Itokawa N, Kondo C, Kaneko K, Iwakiri K.
  • Journal Title: Nutrients Volume: 13 Issue: 6 Pages: 1874-1874
  • DOI: 10.3390/nu13061874
  • Peer Reviewed / Open Access
• [Journal Article] Effect of sodium-glucose cotransporter 2 inhibitor in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a propensity score-matched analysis of real-world data. (2021)
  • Author(s): Arai T, Atsukawa M, Tsubota A, Mikami S, Ono H, Kawano T, Yoshida Y, Tanabe T, Okubo T, Hayama K, Nakagawa-Iwashita A, Itokawa N, Kondo C, Kaneko K, Emoto N, Nagao M, Inagaki K, Fukuda I, Sugihara H, Iwakiri K.
  • Journal Title: Ther Adv Endocrinol Metab Volume: 12 Pages: 1-13
  • DOI: 10.1177/20420188211000243
  • Peer Reviewed
• [Journal Article] Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease. (2021)
  • Author(s): Saeki C, Saito M, Kanai T, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A.
  • Journal Title: PLoS One Volume: 16 Issue: 4 Pages: e0249728-e0249728
  • DOI: 10.1371/journal.pone.0249728
  • Peer Reviewed / Open Access
• [Journal Article] Real-time breath ammonia measurement using a novel cuprous bromide sensor device in patients with chronic liver disease: a feasibility and pilot study (2021)
  • Author(s): Ishida Jinya, Oikawa Tsunekazu, ...., Tsubota Akihito (last; 他11名)
  • Journal Title: Journal of Breath Research Volume: 15 Issue: 2 Pages: 026010-026010
  • DOI: 10.1088/1752-7163/abb477
  • Peer Reviewed
• [Journal Article] Relationship between osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in patients with primary biliary cholangitis (2020)
  • Author(s): Saeki Chisato、Oikawa Tsunekazu、Kanai Tomoya、Nakano Masanori、Torisu Yuichi、Sasaki Nobuyuki、Abo Masahiro、Saruta Masayuki、Tsubota Akihito
  • Journal Title: European Journal of Gastroenterology & Hepatology Volume: 33 Issue: 5 Pages: 731-737
  • DOI: 10.1097/meg.0000000000001791
  • Peer Reviewed / Open Access
• [Journal Article] Sequential therapy from entecavir to tenofovir alafenamide versus continuous entecavir monotherapy for patients with chronic hepatitis B (2020)
  • Author(s): Itokawa Norio, Atsukawa Masanori, Tsubota Akihito, et al. (他30名)
  • Journal Title: JGH Open Volume: 5 Issue: 1 Pages: 34-40
  • DOI: 10.1002/jgh3.12443
  • Peer Reviewed / Open Access
• [Journal Article] Low Serum 25-Hydroxyvitamin D Levels Are Related to Frailty and Sarcopenia in Patients with Chronic Liver Disease (2020)
  • Author(s): Saeki Chisato、Kanai Tomoya、Nakano Masanori、Oikawa Tsunekazu、Torisu Yuichi、Saruta Masayuki、Tsubota Akihito
  • Journal Title: Nutrients Volume: 12 Issue: 12 Pages: 3810-3810
  • DOI: 10.3390/nu12123810
  • Peer Reviewed / Open Access
• [Journal Article] Low Serum Branched-chain Amino Acid and Insulin-Like Growth Factor-1 Levels Are Associated with Sarcopenia and Slow Gait Speed in Patients with Liver Cirrhosis (2020)
  • Author(s): Saeki Chisato、Kanai Tomoya、Nakano Masanori、Oikawa Tsunekazu、Torisu Yuichi、Saruta Masayuki、Tsubota Akihito
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 10 Pages: 3239-3239
  • DOI: 10.3390/jcm9103239
  • Peer Reviewed / Open Access
• [Journal Article] Effects of denosumab treatment in chronic liver disease patients with osteoporosis (2020)
  • Author(s): Saeki Chisato、Saito Mitsuru、Oikawa Tsunekazu、Nakano Masanori、Torisu Yuichi、Saruta Masayuki、Tsubota Akihito
  • Journal Title: World Journal of Gastroenterology Volume: 26 Issue: 33 Pages: 4960-4971
  • DOI: 10.3748/wjg.v26.i33.4960
  • Peer Reviewed
• [Journal Article] Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study (2020)
  • Author(s): Atsukawa Masanori、Tsubota Akihito、Kondo Chisa、Toyoda Hidenori、Nakamuta Makoto、Takaguchi Koichi、Watanabe Tsunamasa、et al.
  • Journal Title: Infectious Diseases and Therapy Volume: 9 Issue: 4 Pages: 851-866
  • DOI: 10.1007/s40121-020-00329-y
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence and characteristics of portopulmonary hypertension in cirrhotic patients who underwent both hepatic vein and pulmonary artery catheterization (2020)
  • Author(s): Atsukawa Masanori, Tsubota Akihito, et al. (他20名)
  • Journal Title: Hepatology Research Volume: 50 Issue: 11 Pages: 1244-1254
  • DOI: 10.1111/hepr.13560
  • Peer Reviewed
• [Journal Article] Relationship between Osteosarcopenia and Frailty in Patients with Chronic Liver Disease (2020)
  • Author(s): Saeki Chisato、Kanai Tomoya、Nakano Masanori、Oikawa Tsunekazu、Torisu Yuichi、Abo Masahiro、Saruta Masayuki、Tsubota Akihito
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 8 Pages: 2381-2381
  • DOI: 10.3390/jcm9082381
  • Peer Reviewed / Open Access
• [Journal Article] The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world: a comprehensive analysis of a prospective multicenter study (2020)
  • Author(s): Nozaki, A. Atsukawa, M. Ogawa, S. Itokawa, N. Arai, T. Ikegami, T. Tsubota, A. Genda, T. Okubo, H. Mikami, S. Morishita, A. Moriya, A. Tani, J. Tachi, Y. Hotta, N. Ishikawa, T. Okanoue, T. Tanaka, Y. Kumada, T. Iwakiri, K. Maeda, S. K. T. K. Liver Study Group
  • Journal Title: Hepatol Int Volume: - Issue: 2 Pages: 225-238
  • DOI: 10.1007/s12072-020-10019-z
  • Peer Reviewed / Open Access
• [Journal Article] Marked heterogeneity in the diagnosis of compensated cirrhosis of patients with chronic hepatitis C virus infection in a real-world setting: A large, multicenter study from Japan (2020)
  • Author(s): Toyoda H, Atsukawa M, Watanabe T..., Tsubota A, et al
  • Journal Title: J Gastroenterol Hepatol Volume: - Issue: 8 Pages: 1420-1425
  • DOI: 10.1111/jgh.14982
  • Peer Reviewed
• [Journal Article] Relationship between serum vitamin D level and sarcopenia in chronic liver disease (2020)
  • Author(s): Okubo T, Atsukawa M, Tsubota A, Yoshida Y, Arai T, Iwashita AN, Itokawa N, Kondo C, Iwakiri K
  • Journal Title: Hepatol Res Volume: - Issue: 5 Pages: 588-597
  • DOI: 10.1111/hepr.13485
  • Peer Reviewed
• [Journal Article] Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema (2020)
  • Author(s): Atsukawa M, Tsubota A, Takaguchi K, Toyoda H, Iwasa M, Ikegami T, Chuma M, Nozaki A, Uojima H, Hiraoka A, Fukunishi S, Yokohama K, Tada T, Kato K, Abe H, Tani J, Okubo H, Watanabe T, et al.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: - Issue: 7 Pages: 1229-1237
  • DOI: 10.1111/jgh.14965
  • Peer Reviewed
• [Journal Article] IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate (2020)
  • Author(s): Takano Keiko、Saeki Chisato、Oikawa Tsunekazu、Hidaka Akihisa、Mizuno Yusuke、Ishida Jinya、Takakura Kazuki、Nakano Masanori、Torisu Yuichi、Amano Katsushi、Ishikawa Tomohisa、Zeniya Mikio、Tsubota Akihito、Saruta Masayuki
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 35 Issue: 4 Pages: 663-672
  • DOI: 10.1111/jgh.14900
  • Peer Reviewed
• [Journal Article] Real‐world experience of 12‐week direct‐acting antiviral regimen of glecaprevir and pibrentasvir in patients with chronic hepatitis C virus infection (2019)
  • Author(s): Toyoda H, Atsukawa M, Watanabe T, et al
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: - Issue: 5 Pages: 855-861
  • DOI: 10.1111/jgh.14874
  • Peer Reviewed
• [Journal Article] Comparative assessment of sarcopenia using the JSH, AWGS, and EWGSOP2 criteria and the relationship between sarcopenia, osteoporosis, and osteosarcopenia in patients with liver cirrhosis (2019)
  • Author(s): Saeki C, Takano K, Oikawa T, Aoki Y, Kanai T, Takakura K, Nakano M, Torisu Y, Sasaki N, Abo M, Matsuura T, Tsubota A, Saruta M
  • Journal Title: BMC Musculoskelet Disord Volume: 20 Issue: 1 Pages: 615-615
  • DOI: 10.1186/s12891-019-2983-4
  • Peer Reviewed / Open Access
• [Journal Article] Factors influencing subclinical atherosclerosis in patients with biopsy-proven nonalcoholic fatty liver disease (2019)
  • Author(s): Arai T, Atsukawa M, Tsubota A, Kawano T, Koeda M, Yoshida Y, Tanabe T, Okubo T, Hayama K, Iwashita A, Itokawa N, Kondo C, Kaneko K, Kawamoto C, Hatori T, Emoto N, Iio E, Tanaka Y, Iwakiri K
  • Journal Title: PLoS One Volume: 14 Issue: 11 Pages: e0224184-e0224184
  • DOI: 10.1371/journal.pone.0224184
  • Peer Reviewed / Open Access
• [Journal Article] Single nucleotide polymorphisms associated with elevated alanine aminotransferase in patients receiving asunaprevir plus daclatasvir combination therapy for chronic hepatitis C (2019)
  • Author(s): Kato K, Shimada N, Atsukawa M, Abe H, Itokawa N, Matsumoto Y, Agata R, Tsubota A
  • Journal Title: PLoS One Volume: 14 Issue: 7 Pages: e0219022-e0219022
  • DOI: 10.1371/journal.pone.0219022
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of 8‐week glecaprevir/pibrentasvir treatment in direct‐acting antiviral‐naive noncirrhotic HCV genotype 1 and 2 infected patients in a real‐world setting in Japan (2019)
  • Author(s): Ikeda H, Watanabe T, Iio E, Tsubota A, Hiraoka A, Nozaki A, Okubo H, Tachi Y, Moriya A, Oikawa T, Matsumoto Y, Tsuruoka S, Tani J, Kikuchi K, Iwakiri K, Tanaka Y, Kumada T, et al.
  • Journal Title: Journal of Viral Hepatitis Volume: 26 Issue: 11 Pages: 1266-1275
  • DOI: 10.1111/jvh.13170
  • Peer Reviewed
• [Journal Article] Trends and Efficacy of Interferon-Free Anti-hepatitis C Virus Therapy in the Region of High Prevalence of Elderly Patients, Cirrhosis, and Hepatocellular Carcinoma: A Real-World, Nationwide, Multicenter Study of 10 688 Patients in Japan (2019)
  • Author(s): Toyoda H, Atsukawa M, Uojima H, Nozaki A, Tamai H, Takaguchi K, Fujioka S, Nakamuta M, Tada T, Yasuda S, Chuma M, Senoh T, Tsutsui A, Yamashita N, Hiraoka A, Michitaka K, Shima T, Akahane T, Itobayashi E, Watanabe T, et al.
  • Journal Title: Open Forum Infectious Diseases Volume: 6 Issue: 5
  • DOI: 10.1093/ofid/ofz185
  • Peer Reviewed / Open Access
• [Journal Article] The efficacy and safety of glecaprevir plus pibrentasvir in 141 patients with severe renal impairment: a prospective, multicenter study. (2019)
  • Author(s): Atsukawa M, Tsubota A, Toyoda H, Takaguchi K, Nakamuta M, Watanabe T, Michitaka K, Ikegami T, Nozaki A, Uojima H, Fukunishi S, Genda T, Abe H, Hotta N, Tsuji K, Ogawa C, Tachi Y, Shima T, Shimada N, Kondo C, Akahane T, Aizawa Y, Tanaka Y, Kumada T, Iwakiri K
  • Journal Title: Aliment Pharmacol Ther Volume: 49 Issue: 9 Pages: 1230-1241
  • DOI: 10.1111/apt.15218
  • Peer Reviewed
• [Journal Article] Association of vitamin D levels and vitamin D-related gene polymorphisms with liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. (2019)
  • Author(s): Arai T, Atsukawa M, Tsubota A, Koeda M, Yoshida Y, Okubo T, Nakagawa A, Itokawa N, Kondo C, Nakatsuka K, Masu T, Kato K, Shimada N, Hatori T, Emoto N, Kage M, Iwakiri K.
  • Journal Title: Dig Liver Dis. Volume: in press Issue: 7 Pages: 1036-1042
  • DOI: 10.1016/j.dld.2018.12.022
  • Peer Reviewed
• [Journal Article] Efficacy and safety of ombitasvir/paritaprevir/ritonavir and ribavirin for chronic hepatitis patients infected with genotype 2a in Japan. (2019)
  • Author(s): Atsukawa M, Tsubota A, Toyoda H, Takaguchi K, Nakamuta M, Watanabe T, Tada T, Tsutsui A, Ikeda H, Abe H, Kato K, Uojima H, Ikegami T, Asano T, Kondo C, Koeda M, Okubo T, Arai T, Iwashita-Nakagawa A, Itokawa N, Kumada T, Iwakiri K
  • Journal Title: Hepatol Res Volume: 49 Issue: 4 Pages: 369-376
  • DOI: 10.1111/hepr.13292
  • Peer Reviewed
• [Presentation] 実臨床におけるC型非代償性肝硬変患者のDAA治療後の転帰の特徴 (2022)
  • Author(s): 厚川正則, 坪田昭人, 岩切勝彦.
  • Organizer: 第108回日本消化器病学会総会
• [Presentation] 新規肝細胞癌バイオマーカーとしての血清PKCδの有用性 (2022)
  • Author(s): 及川恒一, 猿田雅之, 坪田昭人.
  • Organizer: 第58回日本肝臓学会総会
• [Presentation] 肝細胞癌のラジオ波熱凝固療法の治療支援としてのCone-beam CTの有用性 (2022)
  • Author(s): 加藤慶三, 安部 宏, 坪田昭人.
  • Organizer: 第16回肝癌治療ナビゲーション研究会
• [Presentation] 等温増幅SmartAmp法を用いたHBV genotype判別法の開発 (2022)
  • Author(s): 古谷 裕, Delobel D, 臼井 健, 松浦知和, 坪田昭人, 越智小枝.
  • Organizer: 第69回日本臨床検査医学会学術集会
• [Presentation] 肝細胞癌における新規バイオマーカー PKC deltaの有用性 (2022)
  • Author(s): 及川恒一, 上田薫, 中川千夏, 神岡洋, 中野真範, 佐伯千里, 鳥巣勇一, 猿田雅之, 坪田昭人.
  • Organizer: 第12回首都圏Liver Forum
• [Presentation] Cone-beam CTを肝細胞癌のラジオ波熱凝固療法の治療支援としたバルーン閉塞下肝動脈化学塞栓療法併用ラジオ波凝固療法の成績 (2022)
  • Author(s): 加藤慶三, 安部 宏, 坪田昭人.
  • Organizer: 第44回日本肝臓学会東部会
• [Presentation] 口頭 (Workshop 27: 消化器疾患とサルコペニア：診断, 治療と予後): 肝硬変におけるオステオサルコペニアの重要性. (2021)
  • Author(s): 佐伯千里, 猿田雅之, 坪田昭人.
  • Organizer: 第107回日本消化器病学会総会
• [Presentation] 口頭 (Panel Discussion 1：肝疾患におけるサルコペニアの診断と治療): 肝硬変における血清BCAA, IGF-1とサルコペニアの関連性. (2021)
  • Author(s): 佐伯千里, 猿田雅之, 坪田昭人.
  • Organizer: 第57回日本肝臓学会総会
• [Presentation] 口頭 (O16): 肝性浮腫に対するtolvaptan導入例におけるDAA治療が与える影響. (2021)
  • Author(s): 北村倫香,厚川正則,豊田秀徳,高口浩一,中牟田 誠,渡邊綱正,坪田昭人,熊田 卓,河野惟道,田邊智英,新井泰央,糸川典夫,金子恵子,岩切勝彦.
  • Organizer: 第57回日本肝臓学会総会
• [Presentation] テノホビル・アラフェナミド療法の新規導入における実臨床成績の検討 (2020)
  • Author(s): 糸川典夫, 厚川正則, 坪田昭人
  • Organizer: 第56回日本肝臓学会総会
• [Presentation] 高HN3血症早期発見を見据えたリアルタイム呼気NH3濃度測定の有用性の検討 (2020)
  • Author(s): 及川恒一, 石田仁也, 中川千夏, 上田 薫, 中野真範, 佐伯千里, 鳥巣勇一, 猿田雅之, 坪田昭人
  • Organizer: 第106回日本消化器病学会総会 (JDDW2020)
• [Presentation] 肝細胞癌に対する薬剤溶出性ビーズを用いた肝動脈化学塞栓術の治療経験 (2020)
  • Author(s): 加藤 慶三, 安部 宏, 井家麻紀子, 坂本雄飛, 清水晶平, 遠藤慎治, 松尾亮太, 坪田昭人
  • Organizer: 第43回日本肝臓学会東部会
• [Presentation] Efficacy and safety of glecaprevir/pibrentasvir in patients with severe renal impairment in Japan: A prospective, multicenter study (KTK 49 Liver Study Group) (2019)
  • Author(s): Atsukawa M, Tsubota A, Toyoda H, et al
  • Organizer: European Association for the Study of the Liver (EASL) 2019
  • Int'l Joint Research
• [Presentation] 肝性脳症に対するrifaximin使用例の予後の検討 (2019)
  • Author(s): 加藤慶三, 安部 宏, 坪田昭人
  • Organizer: 第105回日本消化器病学会総会
• [Presentation] NAFLD患者のvitamin D代謝の特徴～vitamin D介入試験の結果も含めて～ (2019)
  • Author(s): 河野惟道, 厚川正則, 肥田 舞, 吉田祐士, 大久保知美, 新井泰央, 岩下 愛, 糸川典夫, 近藤千紗, 加藤慶三, 島田紀朋, 坪田昭人, 岩切勝彦
  • Organizer: 第55回日本肝臓学会総会
• [Presentation] C型肝炎に対するダクラタスビル・アスナプレビルの肝障害に関連する遺伝子多型の検討 (2019)
  • Author(s): 加藤慶三, 安部 宏, 厚川正則, 島田紀朋, 井家麻紀子, 清水晶平, 塙 紀子, 米澤 健, 遠藤慎治, 松尾亮太, 坪田昭人
  • Organizer: 第55回日本肝臓学会総会
• [Presentation] 当院におけるHIV/HCV重複感染例に対するDAA治療 (2019)
  • Author(s): 中野真範, 及川恒一, 木下勇次, 木下千夏, 富田陽一, 高野啓子, 石田仁也, 高倉一樹, 鳥巣勇一, 石川智久, 猿田雅之, 坪田昭人, 李 広烈, 保科斉生, 清水昭宏, 吉田正樹, 堀 誠治
  • Organizer: 第61回日本消化器病学会大会