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Drug-induced liver injury: Do we know everything?

World Journal of hepatology 2017年第10期9卷 491-502页

作者： Tamara Alempijevic Simon Zec Tomica Milosavljevic University of Belgrade School of Medicine clinical center of serbia Clinic for Gastroenterology and Hepatology

Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.

关键词： Acute liver failure Drug-induced liver injury Hepatoxicity Acetaminophen toxicity Cholestatic injury Liver biopsy Pharmacoepidemiology Herbal-induced liver injury Hy’s law

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Gallbladder villous adenoma in a patient with acromegaly:A case report

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World Journal of gastroenterology 2007年第22期13卷 3144-3146页

作者： Miodrag Krstic Tamara Alempijevic Bojan Stimec Marjan Micev Miroslav Milicevic Dragan Micic Goran Jankovic Clinic for gastroenterology Clinical Center of Serbia Belgrade Serbia Institute for Anatomy School of Medicine University of Belgrade Serbia Department of Pathohistology Clinical Center of Serbia Belgrade Serbia Clinic for Digestive Surgery Clinical Center of Serbia Belgrade Serbia Institute of Endocrinology Diabetes and Diseases of Metabolism Clinical Center of Serbia Belgrade Serbia

Villous adenomas are benign epithelial lesions with malignant potential that can occur in any part of the gastrointestinal tract. We present a case of a middle age woman with acromegaly who was investigated for nonspecific gastrointestinal complaints. Ultrasonography and subsequent endosonography diagnosed a large （4.5 cm）, hyperechoic, sessile polyp with numerous pedicles. An open cholecystectomy was performed and revealed a villous adenoma with several foci of carcinoma in situ. Detailed investigations showed no other tumors of the gastrointestinal tract. After five years of follo up, the patient reports no complaints, and the results of laboratory testing and imaging studies are within the normal range.

关键词： Villous adenoma Gallbladder Acromegaly Endosonography

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Expression of cytokeratins in Helicobacter pylori-associated chronic gastritis of adult patients infected with cagA+strains:An immunohistochemical study

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World Journal of gastroenterology 2006年第12期12卷 1865-1873页

作者： Vera Todorovic Neda Drndarevic Olivera Mitrovic Institutefor MedicalResearch Aleksandra Sokic-Milutinovic Tomica Milosavljevic Marjan Micev Ivan Nikolic Thomas Wex Peter Malfertheiner Institute for Medical Research Department for Immunohistochemistry and Electron MicroscopyBelgradeSerbia and Montenegro Clinic for gastroenterology and hepatology Institute for Digestive DiseasesClinical Center of SerbiaBelgradeSerbia and Montenegro Pathology Department Institute for Digestive DiseasesClinical Center of SerbiaBelgradeSerbia and Montenegro Institute of Histology and Embryology Faculty of MedicineUniversity of NisSerbia and Montenegro Clinic for gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke UniversityMagdeburgGermany

AIM： To investigate the expression of different cytokeratins （CKs） in gastric epithelium of adult patients with chronic gastritis infected with Helicobacter pylori （H pylon） cagA ＋ strains. METHODS： The expression of CK 7, 8, 18, 19 and 20 was studied immunohistochemically in antral gastric biopsies of 84 patients. All the CKs were immunostained in cagA＋Hpylori gastritis （57 cases）, non-Hpylori gastritis （17 cases） and normal gastric mucosa （10 cases）. RESULTS： In cagA＋ H pylori gastritis, CK8 was expressed comparably to the normal antral mucosa from surface epithelium to deep glands. Distribution of CK18 and CK 19 was unchanged, i.e. transmucosal, but intensity of the expression was different in foveolar region in comparison to normal gastric mucosa. Cytokeratin 18 immunoreactivity was significantly higher in the foveolar epithelium of H pylori-positive gastritis compared to both Hpylori-negative gastritis and controls. On the contrary, decrease in CK19 immunoreactivity occurred in foveolar epithelium of H pylori-positive gastritis. In both normal and inflamed antral mucosa without Hpyloriinfection, CK20 was expressed stronglyl moderately and homogenously in surface epithelium and upper foveolar region, but in H pylod -induced gastritis significant decrease of expression in foveolar region was noted. Generally, in both normal antral mucosa and H pylori-negative gastritis, expression of CK7 was not observed, while in about half cagA＋ H pylori-infected patients, moderate focal CK7 immunoreactivity of the neck and coiled gland areas was registered, especially in areas with more severe inflammatory infiltrate. CONCLUSION： Alterations in expression of CK 7, 18, 19 and 20 together with normal expression of CK8 occur in antral mucosa of H pylori-associated chronic gastritis in adult patients infected with cagA＋ strains. Alterations in different cytokeratins expression might contribute to weakening of epithelial tight junctions observed in H pylori-infected gastric m

关键词： cytokeratin 7 cytokeratin 8 cytokeratin18 cytokeratin19 cytokeratin20 Helicobacter pylori Gastritis CagA

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Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study

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World Journal of hepatology 2024年第5期16卷 809-821页

作者： Yuan-Yao Zhang Sen Luo Hai Li Shu-Ning Sun Xian-Bo Wang Xin Zheng Yan Huang Bei-Ling Li Yan-Hang Gao Zhi-Ping Qian Feng Liu Xiao-Bo Lu Jun-Ping Liu Hao-Tang Ren Yu-Bao Zheng Hua-Dong Yan Guo-Hong Deng Liang Qiao Yan Zhang Wen-Yi Gu Xiao-Mei Xiang Yi Zhou Yi-Xin Hou Qun Zhang Yan Xiong Cong-Cong Zou Jun Chen Ze-Bing Huang Xiu-Hua Jiang Ting-Ting Qi Yuan-Yuan Chen Na Gao Chun-Yan Liu Wei Yuan Xue Mei Jing Li Tao Li Rong-Jiong Zheng Xin-Yi Zhou Jun Zhao Zhong-Ji Meng Department of Infectious Disease Institute of Biomedical ResearchRegulatory Mechanism and Targeted Therapy for Liver Cancer Shiyan Key LaboratoryHubei provincial Clinical Research Center for Precise Diagnosis and Treatment of Liver CancerTaihe HospitalHubei University of MedicineShiyan 442000Hubei ProvinceChina Department of gastroenterology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200120China Department of Infectious Diseases Southwest HospitalThe Third Military Medical University(Army Medical University)Chongqing 400000China center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100020China Department of Infectious Diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430020Hubei ProvinceChina Department of Infectious Diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangsha 110051Hunan ProvinceChina hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of hepatology The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Department of Liver Intensive Care Unit Shanghai Public Health Clinical CentreFudan UniversityShanghai 200093China Tianjin Institute of hepatology Nankai University Second People's HospitalTianjin 300192China Infectious Disease center The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054Xinjiang Uygur Autonomous RegionChina Department of Infectious Diseases and hepatology The Second Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseaseThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of Infectious Diseases The Thir

BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of hepatology or Infectious *** To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of *** Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this *** clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank *** A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).The most common cause of chronic liver disease(CLD)was HBV infection(71.4%).The most common precipitants of AoCLD was bacterial infection(22.8%).The 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for *** HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of *** most common clinical type of AoCLD is *** diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

关键词： Acute-on-chronic liver disease Acute-on-chronic liver failure Liver cirrhosis clinical features Prognosis

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Beneficial Effects of Traditional Chinese Medicine Fuzheng Huayu on the Occurrence of Hepatocellular Carcinoma in Patients with Compensated Chronic Hepatitis B Cirrhosis Receiving Entecavir:A Multicenter Retrospective Cohort Study

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Journal of clinical and Translational hepatology 2024年第5期12卷 505-515页

作者： Haina Fan Shujuan Lei Zhimin Zhao Yan Huang Hui Wang Xudong Liu Xiaodong Li Min Xu Wei Zhang Kewei Sun Huichun Xing Yang Mei Jiaquan Huang Chuanwu Zhu Kejun Zhang Yali Zong Xizhong Shen Qing Xie Chenghai Liu Institute of Liver Diseases Shanghai Key Laboratory of Traditional Chinese Clinical MedicineKey Laboratory of Liver and Kidney Diseases(Ministry of Education)Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Infectious Diseases Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Infectious Diseases Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanningGuangxiChina Institute of Liver Diseases Hubei Provincial Hospital of Traditional Chinese MedicineWuhanHubeiChina Department of Infectious Diseases Huaian Fourth People’s HospitalHuai’anJiangsuChina Institute of Liver Diseases Shijiazhuang Fifth HospitalShijiazhuangHebeiChina Department of Liver Diseases The First Hospital of Hunan University of Chinese MedicineChangshaHunanChina center of hepatology Capital Medical University Affiliated Beijing Ditan HospitalBeijingChina Department of hepatology The Fifth People’s Hospital of AnyangAnyangHenanChina Department and Institute of Infectious Disease Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiChina Department of hepatology The Fifth People’s Hospital of SuzhouSuzhouJiangsuChina Department of gastroenterology The First People’s Hospital of JingmenJingmenHubeiChina Department of Integrated Traditional and Western Medicine The Ninth Hospital of NanchangNanchangJiangxiChina Department of gastroenterology Zhongshan HospitalFudan UniversityShanghaiChina

Background and Aims:The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma(HCC)has not been ***,we aimed to assess the impact of the Traditional Chinese Medicine Fuzheng Huayu(FZHY)on the occurrence of HCC in patients with hepatitis B virus-related compensated cirrhosis receiving the antiviral drug entecavir(ETV).Methods:A multicenter retrospective cohort study was *** liver cirrhosis patients were divided into the ETV+FZHY group or the ETV group according to *** cumulative incidence of HCC was analyzed using Kaplan-Meier and log-rank *** score matching was used for confounding *** analysis and Cox regression were used to determine the effects of FZHY on the occurrence of HCC and liver function ***:Out of 910 chronic hepatitis B patients,458 were in the ETV+FZHY group and 452 were in the ETV *** propensity score matching,the 5-year cumulative incidence of HCC was 9.8%in the ETV+FZHY group and 21.8%in the ETV group(p36 ***,diabetes,alanine aminotransferase,􀇄-glutamyl transpeptidase,albumin,hepatitis B e-antigen,and fibrosis 4 score were associated with the occurrence of *** decreased the risk of HCC in patients aged>45 years with a hepatitis B virus DNA level of􀂕2,000 IU/***:Adjunctive FZHY treatment reduced HCC occurrence in patients with hepatitis B virus cirrhosis who were treated with ETV,possibly due to the antifibrotic properties of FZHY.

关键词： Entecavir Fuzheng Huayu Hepatitis B virus Cirrhosis Hepatocellular carcinoma Traditional Chinese Medicine

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Depression and anxiety levels in therapy-nave patients with inflammatory bowel disease and cancer of the colon

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World Journal of gastroenterology 2007年第3期13卷 438-443页

作者： Branislav R Filipovi Branka F Filipovi Mirko Kerkez Nikola Milini Tomislav Ran■elovi Institute of Anatomy School of Medicine Belgrade clinical and Hospital center "Be■anijska Kosa" Department of Gastroenterology Belgrade Serbia Department of Gastrointestinal Surgery Clinical Center of Serbia Serbia Department of Gastrointestinal Surgery Clinical and Hospital Center "Be■anijska Kosa" Belgrade Serbia

AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.

关键词： Crohn's disease Ulcerative colitis Colon cancer Mood disorder

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EUS mini probes in diagnosis of cystic dystrophy of duodenal wall in heterotopic pancreas:A case report

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World Journal of gastroenterology 2004年第17期10卷 2609-2612页

作者： Ivan Jovanovic Srbislav Knezevic Miodrag Krstic Marjan Micev Clinic of gastroenterology and hepatology Institute of Digestive DiseasesBelgradeSerbia and Montenegro First Surgical Clinic BelgradeSerbia and Montenegro clinical center of serbia BelgradeInstitute for Medical ResearchBelgradeSerbia and Montenegro

Cystic dystrophy of the duodenal wall is a rare condition characterized by the development of cysts in heterotopic pancreatic tissue localized in the duodenal wall.A 38-year- old man was admitted to the hospital for abdominal pain and vomiting after food *** diagnosis of acute pancreatitis was initially *** ultrasound examination revealed thickening of the second portion of duodenal wall within which,small cysts(diameter,less than 1 cm)were present in the vicinity of pancreatic head. The head of pancreas appeared enlarged(63 mm×42 mm) and *** endoscopy and barium X-ray series were performed revealing a severe circumferential deformation,as well as 4 cm long stenosis of the second portion of the *** examination revealed multiple cysts located in an enlarged,thickened duodenal wall with moderate to strong post-contrast *** suspected that patient had cystic dystrophy of duodenal wall developed in the heterotopic pancreas and diagnosis was confirmed by endoscopic ultrasound(EUS).Endoscopic ultrasound(EUS)revealed circular stenosis from the duodenal bulb onwards.A twenty megahertz mini-prope examination further showed diffuse(intramural)infiltration of duodenal wall limited to the submucosa and muscularis propria of the second portion of duodenum with multiple microcysts within the thickened mucosa and *** was successfully surgically treated and pancreatoduodenectomy was *** pathological examination confirmed a diagnosis of cystic dystrophy of a heterotopic pancreas. Endoscopic ultrasonography features allow preoperative diagnosis of cystic dystrophy of a heterotopic pancreas in duodenal wall,with intralumina120 MHz mini probe sonography being more efficient in cases of luminal stenosis.

关键词： Pancreas Adult Choristoma Cysts Duodenal Diseases Humans Male

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Plasma and platelet serotonin levels in patients with liver cirrhosis

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World Journal of gastroenterology 2007年第43期13卷 5750-5753页

作者： ■or■e M ulafi Duko S Mirkovi Miodrag D Vukevi Jelena S Rudi Clinic of gastroenterology and hepatology Institute of Digestive Diseases Institute of Medical Biochemistry Institute of Pulmonary Diseases clinical center of serbia Medical Faculty Belgrade

AIM: To analyze the relationship between plasma and platelet serotonin levels and the degree of liver insufficiency. METHODS: The prospective study included 30 patients with liver cirrhosis and 30 healthy controls. The degree of liver failure was assessed according to the Child-Pugh classification. Platelet and platelet poor plasma serotonin levels were determined. RESULTS: The mean plasma serotonin level was higher in liver cirrhosis patients than in healthy subjects (215.0 ± 26.1 vs 63.1 ± 18.1 nmol/L; P 0.05). Plasma serotonin levels were significantly higher in Child- Pugh grade A/B than in grade C patients (246.8 ± 35.0 vs 132.3 ± 30.7 nmol/L; P 0.05). CONCLUSION: Plasma serotonin levels are significantly higher in patients with cirrhosis than in the controls and represent the degree of liver insufficiency. In addition, platelet poor plasma serotonin estimation is a better marker for liver insufficiency than platelet serotonin content.

关键词： Serotonin Plasma Platelet Liver cirrhosis

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Biliary spontaneous dislodgement spiral stent for short-term biliary drainage in patients undergoing complete stone removal:A randomized controlled study

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Chinese Medical Journal 2024年第11期137卷 1363-1365页

作者： Liansong Ye Lifan Zhang Yi Mou Xianglei Yuan Wei Liu Chuncheng Wu Yonghong Luo Jiang Du Shuai Bai Jia Xie Qiongying Zhang Qinghua Tan Ling Liu Bing Hu Department of gastroenterology and hepatology West China HospitalMed-X Center for MaterialsSichuan UniversityChengduSichuan 610041China Digestive Endoscopy Medical Engineering Research Laboratory West China HospitalSichuan UniversityChengduSichuan 610041China West China School of Nursing Sichuan UniversityChengduSichuan 610041China

To the Editor:Endoscopic retrograde cholangiopancreatography(ERCP)is strongly recommended for stone removal of *** there is still risk of complications such as post-ERCP cholangitis(PEC)and post-ERCP pancreatitis(PEP).Biliary drainage including endoscopic nasobiliary drainage(ENBD)and biliary stent is considered to reduce the occurrence of PEC and ***,the ENBD tube will cause patient discomfort,and some patients may extract the tube by ***,additional endoscopic stent removal is required after insertion of conventional biliary stent for short-term biliary drainage,increasing medical costs.

关键词： biliary patients stent

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Role of serotonin in development of esophageal and gastric fundal varices

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World Journal of gastroenterology 2010年第48期16卷 6135-6138页

作者： Jelena S Rudi Dorde M ulafi Duko S Mirkovi Rada S Jei Miodrag N Krsti Clinic of gastroenterology Clinical Center of SerbiaFaculty of MedicineUniversity of Belgrade Centre of Medical Biochemistry Clinical Center of SerbiaSchool of PharmacyUniversity of Belgrade

AIM:To determine the effect of free serotonin concentrations in plasma on development of esophageal and gastric fundal varices. METHODS:This prospective study included 33 patients with liver cirrhosis and 24 healthy controls. Ultrasonography and measurement of serotonin concentration in plasma were carried out in both groups of subjects. The upper fiber panendoscopy was performed only in patients with liver cirrhosis. RESULTS:The mean plasma free serotonin levels were much higher in liver cirrhosis patients than in healthy controls (219.0 ± 24.2 nmol/L vs 65.4 ± 18.7 nmol/L,P 0.05). However,the correlation of plasma serotonin concentration and gastric fundal varices was highly significant (rs =-0.601,P clinical value of serotonergic receptor blockers in these patients.

关键词： Serotonin Portal hypertension Esophageal varices Fundal varices Platelets

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