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World Journal of Gastroenterology 2006年第42期12卷 6786-6791页

作者： Hitoshi Yoshiji Ryuichi Noguchi Hideyuki Kojima Yasuhide Ikenaka Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto masaharu yamazaki Masahisa Toyohara Akira Mitoro Hiroshi Fukui Third Department of Internal Medicine Nara Medical University Nara Japan

AIM： To evaluate the effect of combination treatment with the interferon （IFN） and angiotensin-converting enzyme inhibitor （ACE-Ⅰ） on several fibrotic indices in patients with refractory chronic hepatitis C （CHC）. METHODS： Perindopril （an ACE-Ⅰ; 4 mg/d） and/or natural IFN （3 MU/L; 3 times a week） were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. RESULTS： ACE-Ⅰ decreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-β was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. CONCLUSION： The combination therapy of an ACE-Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.

关键词： Interferon Angiotensin-converting enzyme inhibitor Liver fibrosis Chronic hepatitis C Transforming growth factor-β

Combined treatment of vitamin K_2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis

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World Journal of Gastroenterology 2007年第23期13卷 3259-3261页

作者： Hitoshi Yoshiji Ryuichi Noguchi masaharu yamazaki Yasuhide Ikenaka Masayoshi Sawai Masatoshi Ishikawa Hideto Kawaratani Tsuyoshi Mashitani Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Motoyuki Yoshida Hiroshi Fukui Third Department of Internal Medicine Nara Medical University

Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP) and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC. After oral administration of VK and ACE-I, the serum levels of both AFP and AFP-L3 gradually decreased without any marked alteration of the serum aminotransferase activity. After one-year treatment, not only the serum levels of AFP and AFP-L3 returned to the normal ranges, but also the dysplastic nodule disappeared. Since both VK and ACE-I are widely used without serious side effects, this combined regimen may become a new strategy for chemoprevention against HCC.

关键词： Vitamin K2 ACE inhibitor Hepatocellular carcinoma VEGF Angiogenesis

Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis

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World Journal of Gastroenterology 2009年第41期15卷 5193-5199页

作者： Mitsuteru Kitade Hitoshi Yoshiji Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yusaku Shirai masaharu yamazaki Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Masayoshi Sawai Motoyuki Yoshida Chie Morioka Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui Third Department of Internal Medicine Nara Medical University

AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were ***: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.

关键词： Angiogenesis Cytokeratin-18 Fatty liver Insulin resistance Non-alcoholic steatohepatitis Liver fibrosis

Eosinophilic cholecystitis along with pericarditis caused by Ascaris lumbricoides: A case report

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World Journal of Gastroenterology 2007年第27期13卷 3760-3762页

作者： Kosuke Kaji Hitoshi Yoshiji Masahide Yoshikawa masaharu yamazaki Yasuhide Ikenaka Ryuichi Noguchi Masayoshi Sawai Masatoshi Ishikawa Tsuyoshi Mashitani Mitsuteru Kitade Hideto Kawaratani Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Motoyuki Yoshida Hiroshi Fukui Third Department of Internal Medicine Nara Medical University Nara Japan Department of Parasitology Nara Medical University Nara Japan

Although the etiology of eosinophilic cholecystitis is still obscure, the postulated causes include allergies, parasites, hypereosinophilic syndrome, and eosinophilic gastroenteritis. It is sometimes accompanied by several complications, but a simultaneous onset with pericarditis is very rares. A 28-year-old woman complained of acute right hypocondrial pain and dyspnea associated with systemic eruption. Several imaging modalities revealed acute cholecystitis and pericarditis with massive pericardial effusion. A marked peripheral blood eosinophilia was observed, and the eruption was diagnosed as urticaria. Her serum had a high titer of antibody against Ascaris lumbricoides . Treatment with albendazole drastically improved all clinical manifestations along with normalization of the imaging features and eosinophilia. We report herein a rare case of simultaneous onset of acute cholecystitis and pericarditis associated with a marked eosinophilia caused by parasitic infection.

关键词： Cholecystitis Pericardititis Ascaris Parasite Eosinophilia Albendazole

A case of severe acalculous cholecystitis associated with sorafenib treatment for advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2012年第5期4卷 115-118页

作者： Yosuke Aihara Hitoshi Yoshiji masaharu yamazaki Yasuhide Ikenaka Ryuichi Noguchi Chie Morioka Kosuke Kaji Haruki Tastumi Keisuke Nakanishi Maiko Nakamura Junichi Yamao Masahisa Toyohara Akira Mitoro Masayoshi Sawai Motoyuki Yoshida Masao Fujimoto Masahito Uemura Hiroshi Fukui Third Department of Internal Medicine Nara Medical UniversityNara 634-8522Japan

Sorafenib,a multikinase inhibitor,is the first and only drug,which improves significantly the overall survival in patients with advanced hepatocellular carcinoma(HCC).However,many patients experience diverse side effects,some of them severe and *** date,acute acalculous cholecystitis has not been documented in association with a HCC patient treated with ***,we report the case of a 43-yearold woman with hepatitis C virus-related advanced *** received sorafenib,and later complained ofa sudden onset of severe right hypocondrial pain with rebound tenderness and muscle *** examination showed mild elevation of transaminases,biliary enzymes,bilirubin,inflammation markers,and a marked peripheral *** computed tomography(CT) revealed a swollen gallbladder with exudate associated with severe inflammation without stones or ***,sorafenib treatment was stopped immediately,and steroid-pulse therapy was *** therapy drastically improved all clinical manifestations along with normalization of CT findings,eosinophilia,and liver *** summary,we herein report a rare case of acute severe acalculous cholecystitis associated with sorafenib in the patient with advanced HCC.

关键词： Hepatocelluar carcinoma Sorafenib Acalculous cholecystitis