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Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

World Journal of Gastroenterology 2010年第16期16卷 1943-1952页

作者： Takumi Kawaguchi michio sata Department of Digestive Disease Information & Research and Department of Medicine Kurume University School of Medicine

Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) ***,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular ***,these complications are not major causes of death in patients with HCV-associated insulin ***,insulin resistance plays a crucial role in the development of various complications and events associated with HCV *** evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic ***,HCV-associated insulin resistance is a therapeutic target at any stage of HCV *** the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been *** addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin *** order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc *** is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been *** the other hand,insulin-sensitizing agents are reported to improve sustained virologic response *** this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin ***,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitiz

关键词： Hepatitis C virus Diabetes mellitus Insulin resistance Complications Treatments Branched-chain amino acid

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Motor vehicle accidents: How should cirrhotic patients be managed?

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World Journal of Gastroenterology 2012年第21期18卷 2597-2599页

作者： Takumi Kawaguchi Eitaro Taniguchi michio sata Division of Gastroenterology Department of Medicine Kurume University School of MedicineKurume 830-0011 Japan Department of Digestive Disease Information and Research Kurume University School of MedicineKurume 830-0011 Japan

Motor vehicle accidents (MVAs) are serious social issues worldwide and driver illness is an important cause of MVAs. Minimal hepatic encephalopathy (MHE) is a com- plex cognitive dysfunction with attention deficit, which frequently occurs in cirrhotic patients independent of severity of liver disease. Although MHE is known as a risk factor for MVAs, the impact of diagnosis and treatment of MHE on MVA-related societal costs is largely unknown. Recently, Bajaj et al demonstrated valuable findings that the diagnosis of MHE by rapid screening using the inhibitory control test (ICT), and subsequent treatment with lactulose could substantially reduce the societal costs by preventing MVAs. Besides the ICT and lactulose, there are various diagnostic tools and therapeutic strategies for MHE. In this commentary, we discussed a current issue of diagnostic tools for MHE, including neuropsychological tests. We also discussed the advantages of the other therapeutic strategies for MHE, such as intake of a regular breakfast and coffee, and supplementation with zinc and branched chain amino acids, on the MVA-related societal costs.

关键词：交通事故肝硬化机动车移动增值业务电信增值服务诊断工具管理认知功能障碍

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Dipeptidyl peptidase-4: A key player in chronic liver disease

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World Journal of Gastroenterology 2013年第15期19卷 2298-2306页

作者： Minoru Itou Takumi Kawaguchi Eitaro Taniguchi michio sata Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume 830-0011Japan Division of Gastroenterology Department of Medicine and Department of Digestive Disease Information and ResearchKurume University School of MedicineKurume 830-0011Japan

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.

关键词： Incretin Viral hepatitis Insulin resistance Steatohepatitis Cancer Sitagliptin Vildagliptin Alogliptin Teneligliptin Linagliptin

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STAT3 deficiency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury

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World Journal of Gastroenterology 2017年第37期23卷 6833-6844页

作者： Mitsuhiko Abe Takafumi Yoshida Jun Akiba Yu Ikezono Fumitaka Wada Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Hideki Iwamoto Toru Nakamura michio sata Hironori Koga Akihiko Yoshimura Takuji Torimura Division of Gastroenterology Department of Medicine Kurume University School of Medi-cine Liver Cancer Division Research Center for Innovative Cancer Therapy Kurume University Kurume Clinical pharmacology Clinic Department of Diagnostic pathology Kurume University hospital Department of Microbiology Immun--ology Keio University School of Medicine

AIM To elucidate the role of STAT3 in hepatocarcinogenesis and biliary ductular proliferation following chronic liver injury. METHODS We investigated thioacetamide(TAA)-induced liver injury, compensatory hepatocyte proliferation, and hepatocellular carcinoma(HCC) development in hepatic STAT3-deficient mice. In addition, we evaluated TAAinduced biliary ductular proliferation and analyzed the activation of sex determining region Y-box9(SOX9) and Yes-associated protein(YAP), which regulate the transdifferentiation of hepatocytes to *** Both compensatory hepatocyte proliferation and HCC formation were significantly decreased in hepatic STAT3-deficient mice as compared with control mice. STAT3 deficiency resulted in augmentation of hepatic necrosis and fibrosis. On the other hand, biliary ductular proliferation increased in hepatic STAT3-deficient livers as compared with control livers. SOX9 and YAP were upregulated in hepatic STAT3-deficient *** STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.

关键词： Hepatocellular 癌 Ductular 反应表明抄写 3 的变换器和使活跃之物联系是的蛋白质决定区域 Y-box9 的性 Transdifferentiation

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Insulin resistance and chronic liver disease

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World Journal of Hepatology 2011年第5期3卷 99-107页

作者： Takumi Kawaguchi Eitaro Taniguchi Minoru Itou Masahiro Sakata Shuji Sumie michio sata Department of Disease Information & Research Kurume University School of MedicineKurume 830-0011Japan Department of Medicine Kurume University School of MedicineKurume 830-0011Japan

Increased insulin resistance is frequently associated with chronic liver disease and is a pathophysiological feature of hepatogenous *** factors including hepatic parenchymal cell damage,portalsystemic shunting and hepatitis C virus are responsible for the development of hepatogenous insulin resistance/*** it remains unclear whether insulin secretion from pancreatic beta cells is impaired as it is in type 2 diabetes,retinopathic and cardiovascular risk is low and major causes of death in cirrhotic patients with diabetes are liver failure,hepatocellular carcinoma and gastrointestinal *** A1c is an inaccurate marker for the assessment and management of hepatogenous ***,exogenous insulin or sulfonylureas may be harmful because these agents may promote ***,pathogenesis,cause of death,assessment and therapeutic strategy for hepatogenous insulin resistance/diabetes differ from those for lifestyle-related type 2 *** this article,we review features of insulin resistance in relationship to chronic liver *** also discuss the impact of anti-diabetic agents on interferon treatment and hepatocarcinogenesis.

关键词： Viral hepatitis Hyperinsulinemia Hypoglycemic drug Hepatoma

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Evaluation of endoscopic biliary stenting for obstructive jaundice caused by hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第22期20卷 6968-6973页

作者： Gen Sugiyama Yoshinobu Okabe Yusuke Ishida Fumihiko Saitou Ryuichi Kawahara Hiroto Ishikawa Hiroyuki Horiuchi Hisafumi Kinoshita Osamu Tsuruta michio sata Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume 830-0011Japan

AIM:To review the usefulness of endoscopic biliary stenting for obstructive jaundice caused by hepatocellular carcinoma and identify problems that may need to be ***:The study population consisted of 36 patients with obstructive jaundice caused by hepatocellular carcinoma(HCC)who underwent endoscopic biliary stenting(EBS)as the initial drainage procedure at our *** EBS technical success rate and drainage success rate were *** was considered effective when the serum total bilirubin level decreased by 50%or more following the procedure compared to the pre-drainage *** time after the procedure and patient background characteristics were assessed comparatively between the successful drainage group(group A)and the non-successful drainage group(group B).The EBS stent patency duration in the successful drainage group(group A)was also ***:The technical success rate was 100%for both the initial endoscopic nasobiliary drainage and EBS in all *** stenting was placed in 21 patients and multiple stenting in the remaining 15 *** drainage successful rate was 75%and the median interval to successful drainage was 40 d(2-295 d).The median survival time was 150 d in group A and 22 d in group B,with the difference between the two groups being statistically significant(P<0.0001).There were no statistically significant differences between the two groups with respect to patient background characteristics,background liver condition,or tumor factors;on the other hand,the two groups showed statistically significant differences in patients without a history of hepatectomy(P=0.009)and those that received multiple stenting(P=0.036).The median duration of stent patency was 43 d in group A(2-757 d).No early complications related to the EBS technique were *** complications occurred in 13 patients(36.1%),including stent occlusion in 7,infection in 3,and distal migration in ***:EBS is recommended

关键词： Hepatocellular carcinoma Obstructive jaun-dice Bil

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Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第29期20卷 10108-10114页

作者： Takaomi Kessoku Yuji Ogawa Masato Yoneda Kento Imajo Yoshio Sumida Yuichiro Eguchi Hideki Fujii Hideyuki Hyogo Masafumi Ono Yasuaki Suzuki Takumi Kawaguchi Kazuaki Chayama Saiyu Tanaka Kazuma Fujimoto Keizo Anzai Toshiji Saibara michio sata Yoshito Itoh Atsushi Nakajima Takeshi Okanoue Japan Study Group of NAFLD(JSG-NAFLD)[] Department of Gastroenterology Hepatology Yokohama City University Graduate School of MedicineYokohama 236-0004Japan Department of Molecular Gastroenterology Hepatology Kyoto Prefectural University of Medicine Kyoto 602-0841Japan Department of General Medicine Saga Medical School Saga 849-8501Japan Department of Hepatology Osaka City University Osaka 558-8585Japan Department of Medicine Molecular Science Graduate School of Biomedical Sciences Hiroshima University Hiroshima 730-0053 Japan Department of Gastroenterology and Hepatology Kochi Medical School Kochi 783-8505 Japan Department of Gastroenterology Nayoro City General Hospital Hokkaido 096-8511 Japan Department of Gastroenterology Kurume University School of Medicine Kurume 830-0011 Japan Department of Internal Medicine University Hospital Saga 849-8577 Japan Department of Gastroenterology Hepatology Saiseikai Suita Hospital Osaka 565-0862 Japan

AIM:To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease(NAFLD)***:A total of 1048 patients with liver-biopsyconfirmed NAFLD were enrolled from nine hepatology centers in Japan(stage 0,216;stage 1,334;stage 2,270;stage 3,190;stage 4,38).The weight and height of the patients were measured using a calibrated scale after requesting the patients to remove their shoes and any heavy *** blood samples were obtained in the morning after the patients had fasted overnight for 12 *** evaluation was performed in all *** analysis was conducted using SPSS version *** variables were expressed as mean±***:The optimal cutoff value of platelet count,serum albumin,and aminotransferase/alanine aminotransferase ratio(AAR)was set at0.9,respectively,by the receiver operating characteristic *** three variables were combined in an unweighted sum(platelet count=1 point,serum albumin=1 point,AAR=1 point)to form an easily calculated composite score for predicting cirrhosis in NAFLD patients,called the PLALA(platelet,albumin,AAR)*** diagnosis of PLALA≥2 had sufficient accuracy for detecting liver cirrhosis in NAFLD ***:The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.

关键词： Nonalcoholic fatty liver disease Cirrhosis Fibrosi

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