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研究業績詳細

大久保 裕直(オオクボ ヒロナオ)

研究テーマ 肝炎・肝癌の臨床、肝疾患の臨床薬理学
研究業績(論文) Saeki M, Okubo H (Corresponding author), Takasaki Y, Nakadera E, Fukuo Y, Fukada H, Hotchi Y, Maruyama H, Kokubu S, Shiina S, Nagahara A, Ikejima K. The impact of partial splenic embolization on portal hypertensive gastropathy in cirrhotic patients with portal hypertension. J. Clin. Med. 2023, 12(7), 2662

Jing Z, Iba T, Naito H, Xu P, Morishige J, Nagata N, Okubo H, Ando H.
L-Carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy. Front Pharmacol. 2023 Apr 6;14:1182788.

Tanaka H, Sugo H, Iwanaga N, Machida M, Watanobe I, Okubo H, Hotchi S, Ogura K. Mixed neuroendocrine carcinoma and hepatocellular carcinoma in the liver. Cancer Reports. Cancer Rep (Hoboken). 2023 Jan;6(1):e1772.

Atsukawa M, Tsubota A, Kondo C, Shioda-Koyano K, Ishikawa T, Toyoda H, Takaguchi K, Watanabe T, Matsuura K, Ogawa C, Hiraoka A, Okubo H, Tateyama M, Uojima H, Nozaki A, Chuma M, Kato K, Mikami S, Tani J, Morishita A, Kawata K, Tada T, Furuichi Y, Okubo T, Kawano T, Arai T, Kawabe N, Kawamura N, Ikegami T, Nakamuta M, Iwasa M, Tanaka Y, Hatano M, Iwakiri K. Risk factors for portopulmonary hypertension in patients with cirrhosis: A prospective, multicenter study. Hepatol Int. 2023 Feb;17(1):139-149.

Okubo H, Ando H, Takasaki Y, Nakadera E, Fukuo Y, Shiina S, Ikejima K. Impact of Cabozantinib Exposure on Proteinuria and Muscle Toxicity in Patients with Unresectable Hepatocellular Carcinoma. Pharmaceuticals. 2022, 15(12), 1460

Hayama K, Atsukawa M, Tsubota A, Kondo C, Iwasa M, Hasegawa H, Takaguchi K, Tsutsui A, Uojima H, Hidaka H, Okubo H, Suzuki T, Matsuura K, Tada T, Kawabe N, Tani J, Morishita A, Ishikawa T, Arase Y, Furuichi Y, Kato K, Kawata K, Chuma M, Nozaki A, Hiraoka A, Watanabe T, Kagawa T, Toyoda H, Taniai N, Yoshida H, Tanaka Y, Iwakiri K, Ktk Liver Study Group. Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study. Hepatol Res. 2023 Jan;53(1):51-60.

Nishioki T, Koyama R, Okubo H (Corresponding author), Fukuo Y, Takasaki Y, Yae T, Banno T, Kido K, Takahashi K, Shiina S, Ikejima K. Endobronchial Watanabe Spigot Placement for Hepatic Abscess and Bronchobiliary Fistula Following Radiofrequency Ablation for Hepatocellular Carcinoma: A Case Report. Intern Med. 2023 Apr 1;62(7):999-1004.

Jing Z, Okubo H, Morishige J, Hasan N, Ando H. Lenvatinib causes reduced expression of carnitine/organic cation transporter 2 and carnitine deficiency in the skeletal muscle of rats. Toxicology Letters. Toxicol Lett. 2022 Aug 1;366:17-25.


Okubo H, Atsukawa M, Okubo T, Ando H, Nakadera E, Ikejima K, Nagahara A.
Gadoxetic acid-enhanced magnetic resonance imaging predicts hyperbilirubinemia induced by glecaprevir during hepatitis C virus treatment.
Sci Rep. 2022 May 12;12(1):7847.

Kawano T, Atsukawa M, Tsubota A, Shimada N, Toyoda H, Takaguchi K, Tani J, Morishita A, Hiraoka A, Mikami S, Ishikawa T, Okubo H, Watanabe T, Okubo T, Arai T, Hayama K, Itokawa N, Kondo C, Iwakiri K. Shorter pruritus period and milder disease stage are associated with response to nalfurafine hydrochloride in patients with chronic liver disease.
Sci Rep. 2022 May 4;12(1):7311.

Okubo H, Ando H, Ishizuka K, Morishige J, Ikejima K, Shiina S, Nagahara A. Impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of lenvatinib in patients with hepatocellular carcinoma. J Pharmacol Sci. 2022;148:6-13.

Okubo H, Ando H, Nakadera E, Ikejima K, Shiina S, Nagahara A. Levocarnitine Supplementation Suppresses Lenvatinib-Related Sarcopenia in Hepatocellular Carcinoma Patients: Results of a Propensity Score Analysis. Nutrients 2021, 13(12), 4428; https://doi.org/10.3390/nu13124428

Atsukawa M, Tsubota A, Kondo C, Toyoda H, Nakamuta M, Takaguchi K, Watanabe T, Hiraoka A, Uojima H, Ishikawa T, Iwasa M, Tada T, Nozaki A, Chuma M, Fukunishi S, Asano T, Ogawa C, Abe H, Kato K, Hotta N, Shima T, Matsuura K, Mikami S, Tachi Y, Fujioka S, Okubo H, Shimada N, Tani J, Morishita A, Hidaka I, Moriya A, Tsuji K, Akahane T, Okubo T, Arai T, Kitamura M, Morita K, Kawata K, Tanaka Y, Kumada T, Iwakiri K; KTK49 Liver Study Group. Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis. Hepatol Res. 2021 Dec 3. doi: 10.1111/hepr.13739. Online ahead of print.

Fukuo Y, Shibuya T, Ashizawa K, Ito K, Saeki M, Fukushima H, Takahashi M, Nomura K, Okahara K, Haga K, Akazawa Y, Nomura O, Ogura K, Okubo H, Nagahara A. Plasmablastic lymphoma of the small intestine in an HIV- and EBV-negative patient.
Intern Med. 2021 Mar 29. doi: 10.2169/internalmedicine.6837-20. Online ahead of print.

Ishii S, Fujisawa T, Isayama H, Asahara S, Ogiwara S, Okubo H, Yamagata H, Ushio M, Takahashi S, Okawa H, Yamagata W, Okawa Y, Suzuki A, Takasaki Y, Ochiai K, Tomishima K, Saito H, Shiina S, Ikari T. Clinical evaluation of a newly developed guidewire for pancreatobiliary endoscopy. J Clin Med. 2020 Dec 16;9(12):4059.

Atsukawa M, Tsubota A, Kondo C, Toyoda H, Nakamuta M, Takaguchi K, Watanabe T, Hiraoka A, Uojima H, Ishikawa T, Iwasa M, Tada T, Nozaki A, Chuma M, Fukunishi S, Asai A, Asano T, Ogawa C, Abe H, Hotta N, Shima T, Iio E, Mikami S, Tachi Y, Fujioka S, Okubo H, Shimada N, Tani J, Hidaka I, Moriya A, Tsuji K, Akahane T, Yamashita N, Okubo T, Arai T, Morita K, Kawata K, Tanaka Y, Okanoue T, Maeda S, Kumada T, Iwakiri K; KTK49 Liver Study Group. Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study. Infect Dis Ther. 2020 Dec;9(4):851-866.

Nozaki A, Atsukawa M, Kondo C, Toyoda H, Chuma M, Nakamuta M, Uojima H, Takaguchi K, Ikeda H, Watanabe T, Ogawa S, Itokawa N, Arai T, Hiraoka A, Asano T, Fujioka S, Ikegami T, Shima T, Ogawa C, Akahane T, Shimada N, Fukunishi S, Abe H, 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; KTK49 Liver Study Group. 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. Hepatol Int. 2020 Mar;14(2):225-238.

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, Hattori N, Tsutsui A, Senoh T, Yoshida Y, Okubo T, Itokawa N , Nakagawa-Iwashita A, Kondo C, Arai T, Michitaka K, Iio E, Kumada T, Tanaka Y, Takei Y, Katsuhiko, Iwakiri K. Analysis of Factors Associated With the Prognosis of Cirrhotic Patients Who Were Treated With Tolvaptan for Hepatic Edema. J Gastroenterol Hepatol. 2020;35(7):1229-1237.

Okubo H, Ando H, Ishizuka K, Kitagawa R, Okubo S, Saito H, Kokubu S, Miyazaki A, Ikejima K, Shiina S, Nagahara A. Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma. PLoS One. 2020 Mar 3;15(3):e0229772.

Toyoda H, Atsukawa M, Watanabe T, Nakamuta M, Uojima H, Nozaki A, Takaguchi K, Fujioka S, Iio E, Shima T, Akahane T, Fukunishi S, Asano T, Michitaka K, Tsuji K, Abe H, Mikami S, Okubo H, Okubo T, Shimada N, Ishikawa T, Moriya A, Tani J, Morishita A, Ogawa C, Tachi Y, Ikeda H, Yamashita N, Yasuda S, Chuma M, Tsutsui A, Hiraoka A, Ikegami T, Genda T, Tsubota A, Masaki T, Iwakiri K, Kumada T, Tanaka Y, Okanoue T. Marked heterogeneity in the diagnosis of compensated cirrhosis of patients with chronic HCV infection in a real-word setting: a large, multicenter study from Japan. J Gastroenterol Hepatol. 2020 Aug;35(8):1420-1425

Toyoda H, Atsukawa M, Watanabe T, Nakamuta M, Uojima H, Nozaki A, Takaguchi K, Fujioka S, Iio E, Shima T, Akahane T, Fukunishi S, Asano T, Michitaka K, Tsuji K, Abe H, Mikami S, Okubo H, Okubo T, Shimada N, Ishikawa T, Moriya A, Tani J, Morishita A, Ogawa C, Tachi Y, Ikeda H, Yamashita N, Yasuda S, Chuma M, Tsutsui A, Hiraoka A, Ikegami T, Genda T, Tsubota A, Masaki T, Tanaka Y, Iwakiri K, Kumada T. Real-world experience of 12-week DAA regimen of glecaprevir and pibrentasvir in patients with chronic HCV infection.  J Gastroenterol Hepatol. 2020 May;35(5):855-861.

Ikeda H, Watanabe T, Atsukawa M, Toyoda H, Takaguchi K, Nakamuta M, Matsumoto N, Okuse C, Tada T, Tsutsui A, Yamashita N, Kondo C, Hayama K, Kato K, Itokawa N, Arai T, Shimada N, Asano T, Uojima H, Ogawa C, Mikami S, Ikegami T, Fukunishi S, Asai A, 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.  Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan. J Viral Hepat. 2019 Nov;26(11):1266-1275.

Takaguchi K, Toyoda H, Tsutsui A, Suzuki Y, Nakamuta M, Imamura M, Senoh T, Nagano T, Tada T, Tachi Y, Hiraoka A, Michitaka K, Shibata H, Joko K, Okubo H, Tsuji K, Takaki S, Watanabe T, Ogawa C, Chayama K, Kumada T, Kudo M, Kumada H. Real-world virological efficacy and safety of daclatasvir/asunaprevir/beclabuvir in patients with chronic hepatitis C virus genotype 1 infection in Japan. J Gastroenterol. 2019 Aug;54(8):742-751.

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, Ikeda H, Iio E, Fukunishi S, Asano T, Tachi Y, Ikegami T, Tsuji K, Abe H, Kato K, Mikami S, Okubo H, Shimada N, Ishikawa T, Matsumoto Y, Itokawa N, Arai T, Tsubota A, Iwakiri K, Tanaka Y, Kumada T1. 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. Open Forum Infect Dis. 2019 Apr 15;6(5):ofz185.

Sagawa E, Okubo H (Corresponding author), Ando H, Sorin Y, Kanazawa R, Nakadera E, Fukada H, Kokubu S, Miyazaki A. Plasma concentration and efficacy of tolvaptan in cirrhotic patients with refractory ascites. J Pharmacol Sci. 2019;139(4):373-376

Sato Y, Nishiofuku H, Yasumoto T, Nakatsuka A, Matsuo K, Kodama Y, Okubo H, Abo D, Takaki H, Inaba Y, Yamakado K. Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study. J Vasc Interv Radiol. 2018; 29:1061-1067.

Toyoda H, Atsukawa M, Takaguchi K, Senoh T, Michitaka K, Hiraoka A, Fujioka S, Kondo C, Okubo T, Uojima H, Tada T, Yoneyama H, Watanabe T, Asano T, Ishikawa T, Tamai H, Abe H, Kato K, Tsuji K, Ogawa C, Shimada N, Iio E, Deguchi A, Itobayashi E, Mikami S, Moriya A, Okubo H, Tani J, Tsubota A, Tanaka Y, Masaki T, Iwakiri K, Kumada T. Real-world virological efficacy and safety of elbasvir and grazoprevir in patients with chronic hepatitis C virus genotype 1 infection in Japan. J Gastroenterol. 2018;53(12):1276-1284.

Okubo H, Ando H, Sorin Y, Nakadera E, Fukada H, Morishige J, Miyazaki A, Ikejima K. Gadoxetic acid-enhanced magnetic resonance imaging to predict paritaprevir-induced hyperbilirubinemia during treatment of hepatitis C. PLoS One. 2018 Apr 30; 13(4):e0196747.

Sugo H, Sekine Y, Miyano S, Watanobe I, Machida M, Kojima K, Okubo H, Ura A, Ogura K, Matsumoto T. Hepatic Sclerosing Hemangioma with Predominance of the Sclerosed Area Mimicking a Biliary Cystadenocarcinoma. Case Reports Hepatol. 2018 Oct 4;2018:7353170.

Aoyama T, Kuwahara-Arai K, Uchiyama A, Kon K, Okubo H, Yamashina S, Ikejima K, Kokubu S, Miyazaki A, Watanabe S. Spleen-derived lipocalin-2 in the portal vein, regulates Kupffer cells activation and attenuates the development of liver fibrosis in mice. Lab Invest. 2017; 97:890-902

Sagawa E, Okubo H (Corresponding author), Sorin Y, Nakadera E, Fukada H, Igusa Y, Kokubu S, Miyazaki A, Watanobe I, Sugo H, Kojima K, Watanabe S. Use of finger-piece method for indocyanine green clearance test. Hepatol Res. 2017; 47:1235-1240.

Okubo H, Kitamura T, Ando H, Fukada H, Igusa Y, Kokubu S, Miyazaki A, Fujimura A, Shiina S, Watanabe S. Gadoxetic acid-enhanced MR imaging predicts simeprevir-induced hyperbilirubinemia during hepatitis C virus treatment: A pilot study. J Clin Pharmacol. 2017; 57:369-375.

Ito T, Sai JK, Okubo H, Saito H, Ishii S, Kanazawa R, Tomishima K, Watanabe S, Shiina S. Safety of immediate endoscopic sphincterotomy in acute suppurative cholangitis caused by choledocholithiasis. World J Gastrointest Endosc 2016; 8:180-185.

Ito T, Okubo H (Corresponding author), Kokubu S, Miyazaki A, Ando H, Fujimura A, Watanabe S. Radiofrequency ablation combined with chemolipodolization in a porcine liver: comparison of the pharmacokinetic analysis with cisplatin powder and miriplatin. Hepatology Res 2015; 45:589-594.

Okubo H, Ando H, Kokubu S, Miyazaki A, Watanabe S, Fujimura A. Polymorphisms in the organic anion transporting polypeptide genes influence liver parenchymal enhancement in gadoxetic-enhanced magnetic resonance imaging. Pharmocogenomics 2013; 14:1573-1582.

Okubo H, Mogami M, Ozaki Y, Igusa Y, Aoyama T, Amano M, Kokubu S, Miyazaki A, Watanabe S. Liver function test by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging with consideration of intrahepatic regional differences. Hepatogastroenterology 2013; 60:1547-1551.

Okubo H, Kokubu S, Komiyama M, Yamagata H, Uchiyama A, Miyazaki A, Watanabe S. Radiofrequency ablation of hepatocellular carcinoma: The feasibility of magnetic resonance imaging with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid for evaluating the ablative margin. Hepatology Res 2010; 40:1034-1041.

Okubo H, Takei Y, Serizawa N, Enomoto N, Ikejima K, Sato N. Orthotopic Hepatocellular Carcinoma Model with a Controlled and Reproducible Tumorigenicity. J Gastroenterol Hepatol 2007; 22:423-428.

Serizawa N, Takei Y, Okubo H, Yamasina S, Enomoto N, Sato N. Effect of low-molecular-weight heparin on the commitment of bone marrow cells to liver sinusoidal endothelial cells in CCL4-induced liver injury. Hepatology Res 2006; 34:207-213.

Ogawa K, Ohkubo H, Abe W, Maekawa T. Percutaneous transhepatic small-caliber choledochoscopic lithotomy: a safe and effective technique for percutaneous transhepatic common bile duct exploration in high-risk elderly patients. J Hepatobiliary Pancreat Surg 2002; 9:213-217.

Okubo H, Maekawa K, Ogawa K, Wada R, Sekigawa I, Iida N, Maekawa T, Hashimoto H, Sato N. Pseudolymphoma of the liver associated with Sjogren’s syndrome Scand J Rheumatol 2001; 30:117-119.



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