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Gut microbiota in common elderly diseases affecting activities of daily living

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World Journal of Gastroenterology 2018年第42期24卷 4750-4758页

作者： yukihiro shimizu Gastroenterology center Nanto Municipal Hospital

Gut microbiota are involved in the development or prevention of various diseases such as type 2 diabetes,fatty liver, and malignancy such as colorectal cancer,breast cancer and hepatocellular carcinoma. Alzheimer'sdisease, osteoporosis, sarcopenia, atherosclerotic stroke and cardiovascular disease are major diseases associated with decreased activities of daily living(ADL), especially in elderly people. Recent analyses have revealed the importance of gut microbiota in the control of these diseases. The composition or diversity of these microbiota is different between patients with these conditions and healthy controls, and administration of probiotics or prebiotics has been shown effective in the treatment of these diseases. Gut microbiota may affect distant organs through mechanisms that include regulating the absorption of nutrients and/or the production of microbial metabolites, regulating and interacting with the systemic immune system, and translocating bacteria/bacterial products through disrupted mucosal barriers.Thus, the gut microbiota may be important regulators in the development of diseases that affect ADL. Although adequate exercise and proper diet are important for preventing these diseases, their combination with interventions that manipulate the composition and/or diversity of gut microbiota could be a promising strategy for maintaining health condition and preserving ADL. This review thus summarizes current understanding of the role of gut microbiota in the development or prevention of diseases closely associated with the maintenance of ADL.

关键词： Probiotics Prebiotics Alzheimer’s disease Osteoporosis Sarcopenia Gut microbiota Cardiovascular disease Cerebrovascular disease

Understanding the immunopathogenesis of COVID-19:Its implication for therapeutic strategy

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World Journal of Clinical Cases 2020年第23期8卷 5835-5843页

作者： yukihiro shimizu Gastroenterology Center Nanto Municipal HospitalNanto 932-0211ToyamaJapan

Although 80%of individuals infected with the severe acute respiratory syndromecoronavirus 2(SARS-CoV-2)recover without antiviral treatments,the other 20%progress to severe forms of pulmonary disease,suggesting that the host’s immune response to the virus could influence the outcome of coronavirus disease 2019(COVID-19).SARS-CoV-2 infects alveolar epithelial type 2 cells expressing angiotensin-converting enzyme 2,and these infected epithelial cells recruit dendritic cells,neutrophils and monocytes/macrophages,leading to the activation of CD4+and CD8+T cells.These cells launch an antiviral immune response,but are able to completely suppress viral replication or completely eradicate virus in a limited proportion of infected patients.In other patients,viral suppression is incomplete and the numbers of circulating B and T cells are subsequently reduced by as yet unknown mechanisms.Some patients with sustained viral replication progress to a severe condition called cytokine storm.Although antiviral drug(s)should be considered early in infection to prevent progression,there have been no antiviral therapies proven to be effective for significantly inhibiting the viral replication in vivo and suppressing the progression to cytokine storm.Blocking the action of cytokines with dexamethasone or anti-interleukin-6 could have a pivotal role in treatment of those patients.Therapeutic strategy should therefore be based on viral kinetics and the immunopathology of COVID-19.

关键词： COVID-19 SARS-CoV-2 Immune response Antibody Viral kinetics Treatment

Recent advances in the management of pruritus in chronic liver diseases

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World Journal of Gastroenterology 2017年第19期23卷 3418-3426页

作者： Kazuto Tajiri yukihiro shimizu Department of Gastroenterology Toyama University Hospital Gastroenterology Center Nanto Municipal Hospital

Pruritus is a symptom found in patients with chronic liver diseases,especially cholestatic liver diseases such as primary biliary cholangitis.This symptom impairs patient quality of life by disturbing sleep and may lead to consideration of liver transplantation.Mechanisms implicated in pruritus have been associated with the peripheral and central nervous systems,leading to the development of various therapeutic options.Little evidence for the efficacy of most of these treatments is currently available,indicating a need for further investigations.

关键词：瘙痒 Cholestasis Autotaxin Opioid 受体对手

Systemic abnormalities in liver disease

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World Journal of Gastroenterology 2009年第24期15卷 2960-2974页

作者： Masami Minemura Kazuto Tajiri yukihiro shimizu Department of Gastroenterology and Hematology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama Department of Internal Medicine Nanto Municipal Hospital

Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

关键词：肝脏疾病异常系统性肾疾病患者肝病畸形肺

Direct-acting antivirals for hepatitis C virus-infected patients with hepatocellular carcinoma

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World Journal of Hepatology 2022年第6期14卷 1190-1199页

作者： Kazuto Tajiri Hiroyuki Ito Kengo Kawai Yoshiro Kashii Yuka Hayashi Aiko Murayama Masami Minemura Terumi Takahara yukihiro shimizu Ichiro Yasuda Department of Gastroenterology Toyama University HospitalToyama 930-0194Japan Department of Gastroenterology Takaoka Municipal HospitalTakaoka 933-8550Japan Gastroenterology Center Nanto Municipal HospitalNanto 932-0211Japan Department of Gastroenterology Saiseikai Toyama HospitalToyama 931-8533Japan

BACKGROUND Hepatocellular carcinoma(HCC)in hepatitis C virus(HCV)-infected patients has a high risk of recurrence.Although eradication of HCV is expected to reduce this risk,the risk in patients with a history of HCC may be high after treatment with direct-acting antivirals(DAAs).AIM To determine the risk factors for HCC recurrence in patients with HCV and a history of HCC.METHODS The risk of HCC recurrence in patients with a history of HCC and/or of HCC occurrence in patients without a history of HCC after DAA therapy was retrospectively analyzed in 311 HCV patients treated at our institution and several neighboring hospitals.The frequency and predictors of HCC recurrence/occurrence after DAA treatment were included in these analyses.The clinical course of HCC before and after DAA treatment was also evaluated.RESULTS HCV patients with a history of HCC were older and had greater progression of liver fibrosis and diabetes than patients without a history of HCC.Median recurrence-free survival(RFS)was 1092 d in patients with a history of HCC,and post-DAA HCC recurrence/occurrence was observed in 29 patients(53.7%)with and 5(1.9%)without a history of HCC over 6 years(P<0.001).RFS in patients with a history of HCC did not differ significantly before and after DAA treatment.The frequency of HCC recurrence/occurrence in patients with a history of HCC was lower after than before DAA treatment.Multivariate analysis showed that the incidence rate of HCC recurrence/occurrence before DAA treatment was the only independent predictor of HCC recurrence/occurrence after DAA treatment.Liver function was well preserved and clinical course was good in patients with HCC recurrence/occurrence after DAA therapy.CONCLUSION DAA therapy in patients infected with HCV is also effective in patients with a history of HCC.Curative treatment for HCC is desirable before DAA therapy.The frequency of HCC recurrence/occurrence before DAA therapy was associated with a significantly increased risk of HCC recurrence after DAA therapy.Careful observat

关键词： Direct-acting antivirals Hepatitis C virus Hepatocellular carcinoma Recurrence Liver fibrosis Curative treatment

Liver in systemic disease

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World Journal of Gastroenterology 2008年第26期14卷 4111-4119页

作者： yukihiro shimizu Division of Internal Medicine Center for Gastroenterology and HepatologyKyoto Katsura Hospital17 Yamada-HiraoNishikyoKyoto 615-8256Japan

Potential causes of abnormal liver function tests include viral hepatitis,alcohol intake,nonalcoholic fatty liver disease,autoimmune liver diseases,hereditary diseases,hepatobiliary malignancies or infection,gallstones and drug-induced liver injury.Moreover,the liver may be involved in systemic diseases that mainly affect other organs.Therefore,in patients without etiology of liver injury by screening serology and diagnostic imaging,but who have systemic diseases,the abnormal liver function test results might be caused by the systemic disease.In most of these patients,the systemic disease should be treated primarily.However,some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

关键词：肝脏系统性疾病肝功能黄疸

Practical guidelines for diagnosis and early management of drug-induced liver injury

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World Journal of Gastroenterology 2008年第44期14卷 6774-6785页

作者： Kazuto Tajiri yukihiro shimizu Department of Gastroenterology and Hematology Graduate School of Medical and Pharmaceutical SciencesUniversity of ToyamaSugitani 2630ToyamaJapan Center for Gastroenterology and Hepatology Kyoto Katsura Hospital17 Yamada-HiraoNishikyoKyoto 615-8256Japan

The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The fi rst step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI,diagnostic scales,such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method (CIOMS/ RUCAM) scale,may be helpful for the fi nal diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible,according to serum levels of alanine aminotransferase (ALT),alkaline phosphatase (ALP),and total bilirubin (T-Bil). However,as DILI patients may show resolution of liver injury without discontinuation of the drug,it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.

关键词：诊断药品诱导肝损伤治疗方法病因

Branched-chain amino acids in liver diseases

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World Journal of Gastroenterology 2013年第43期19卷 7620-7629页

作者： Kazuto Tajiri yukihiro shimizu The Third Department of Internal Medicine Toyama University HospitalToyama 930-0194Japan Gastroenterology Unit Nanto Municipal HospitalToyama 932-0211Japan

Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.

关键词： Liver disease Branched chain amino acids Gene expression Hepatocyte apoptosis Hepatocyte regeneration Immunity Treatment

Gut microbiota and liver diseases

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World Journal of Gastroenterology 2015年第6期21卷 1691-1702页

作者： Masami Minemura yukihiro shimizu Third Department of Internal Medicine Faculty of Medicine University of Toyama Gastroenterology Center Nanto Municipal Hospital

Several studies revealed that gut microbiota are associated with various human diseases,e.g.,metabolic diseases,allergies,gastroenterological diseases,and liver diseases.The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein,and the liver-gut axis is important to understand the pathophysiology of several liver diseases,especially non-alcoholic fatty liver disease and hepatic encephalopathy.Moreover,gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis.Based on theseprevious findings,trials using probiotics have been performed for the prevention or treatment of liver diseases.In this review,we summarize the current understanding of the changes in gut microbiota associated with various liver diseases,and we describe the therapeutic trials of probiotics for those diseases.

关键词： Gut microbiota Immune system Liver disease Metabol