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Coagulation and Endothelial Dysfunction Associated with NAFLD:Current Status and Therapeutic Implications

Journal of Clinical and Translational Hepatology 2022年第2期10卷 339-355页

作者： Doris Ogresta Anna Mrzljak Maja Cigrovski Berkovic Ines Bilic-Curcic sanja stojsavljevic-shapeski Lucija Virovic-Jukic Department of Gastroenterology and Hepatology Sestre Milosrdnice University Hospital CenterZagrebCroatia Depart-ment of Gastroenterology and Hepatology University Hospital Center ZagrebZagrebCroatia Department of Medicine University of ZagrebSchool of MedicineZagrebCroatia Department for Endocrinology Diabetes and PharmacologyUniversity Hospital DubravaZagrebCroatia Department of Kinesiological Anthropology and Methodology Faculty of KinesiologyUniversity of Zagreb Department of Pharmacology Faculty of MedicineUniversity of JJ StrossmayerOsijekCroatia Department of Diabetes Endocrinology and Metabolism DisordersUniversity Hospital OsijekOsijekCroatia

Non-alcoholic fatty liver disease(NAFLD)is closely related to insulin resistance,type 2 diabetes mellitus,and *** is nowadays considered a multisystem disease with a strong association with cardiovascular disease and arterial hypertension,which interfere with changes in the coagulation *** disorders are common in patients with hepatic impairment and are dependent on the degree of liver *** with NAFLD may have preserved overall hemostatic profile,but many studies suggest a trend toward a procoagulant *** state in NAFLD patients may even induce progression of hepatic *** dysfunction is present in the systemic and portal vein circulation in NAFLD patients,and platelets are being recognized as modulators of liver diseases through various *** a literature review,we discuss possible disorders in the coagulation cascade and fibrinolysis,endothelial dysfunction,and platelet abnormalities in patients with *** the processes and mechanisms involved in the hemostatic abnormalities associated with NAFLD,directly related to liver disease or indirectly related through inflam-matory processes and metabolic disorders,several potential therapeutic targets have been identified and reviewed here.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Insulin resistance Coagulation Endothelial dysfunction Platelet dysfunction Thrombosis

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Liver regeneration as treatment target for severe alcoholic hepatitis

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World Journal of Gastroenterology 2022年第32期28卷 4557-4573页

作者： Lucija Virovic-Jukic Dominik Ljubas sanja stojsavljevic-shapeski Neven Ljubičić Tajana Filipec Kanizaj Ivana Mikolasevic Ivica Grgurevic Department of Gastroenterology and Hepatology Sisters of Charity University Hospital CenterZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of MedicineZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of Dental MedicineZagreb 10000Croatia Department of Gastroenterology Merkur University HospitalZagreb 10000Croatia Department of Gastroenterology Rijeka University Hospital CenterRijeka 51000Croatia Department of Internal Medicine University of Rijeka School of MedicineRijeka 10000Croatia Department of Gastroenterology Hepatology and Clinical NutritionDubrava University HospitalZagreb 10000Croatia

Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high *** medical care with corticosteroids in selected patients is the only currently available treatment option,often with poor *** on the insights into the pathogenetic mechanisms of AH,which are mostly obtained from animal studies,several new treatment options are being *** have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic *** evidence for the beneficial effects of granulocyte colony-stimulating factor(G-CSF)on liver regeneration and immunomodulation in animal models,several human studies investigated its role in the treatment of advanced alcohol-related liver disease and *** to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH,these effects were not confirmed by a recently published multicenter randomized trial,suggesting that other options should rather be *** cell transplantation represents another option for improving liver regeneration,but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing,with established lack of efficacy in patients with compensated *** this review,we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver *** lack of high-quality studies and evidence is a major obstacle in further treatment *** insights into the pathogenesis of not only liver injury,but also liver regeneration processes are mandatory for the development of new treatment options.A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing,and data obtained from animal studies are essential for future research.

关键词： Severe alcoholic hepatitis Alcohol-related liver disease Treatment Liver regeneration Granulocyte colony-stimulating factor Stem cell transplantation

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New Drugs on the Block—Emerging Treatments for Nonalcoholic Steatohepatitis

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 51-59页

作者： sanja stojsavljevic-shapeski Marko Duvnjak Lucija Virovic-Jukic Davor Hrabar Lea Smircic Duvnjak Department of Gastroenterology and Hepatology Clinical Hospital Center Sestre MilosrdniceZagrebCroatia Polyclinic Duvnjak ZagrebCroatia University of Applied Health Science ZagrebCroatia School of Medicine University of ZagrebZagrebCroatia Vuk Vrhovac University Clinic-UH Merkur ZagrebCroatia

Patients with nonalcoholic steatohepatitis(NASH)are at higher risk of progression to advanced stages of fibrosis,cirrhosis,hepatocellular carcinoma and other end-stage liver disease *** addressing treatment of NASH,we have limited approved options,and the mainstay of therapy is lifestyle *** research and revelation in the field of pathogenesis of NASH has offered new possibilities of treatment and emerging new drugs that are being tested currently in numerous preclinical and clinical *** drugs target almost all steps in the pathogenesis of NASH to improve insulin sensitivity,glucose and lipid metabolism,to inhibit de novo lipogenesis and delivery of lipids to the liver,and to influence apoptosis,inflammation and *** NASH is a multifactorial disease,in the future we could identify the predominating pathological mechanism and,by choosing the most appropriate specific medication,tailor the treatment for every patient individually.

关键词： Fatty liver Steatohepatitis Nonalcoholic fatty liver disease Treatment

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Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia

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World Journal of Gastrointestinal Surgery 2021年第12期13卷 1708-1720页

作者： sanja stojsavljevic-shapeski Lucija Virovic-Jukic Davor Tomas Marko Duvnjak Vedran Tomasic Davor Hrabar Dominik Kralj Ivan Budimir Neven Barsic Neven Ljubicic Division of Gastroenterology Department of Internal Medicine«Sestre Milosrdnice»University Hospital CenterZagreb 10000Croatia Department of Internal Medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia Ljudevit Jurak Department of Pathology «Sestre Milosrdnice»University Hospital CenterZagreb 10000Croatia Department of Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia

BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expressionof ghrelin and ghrelin receptor has been investigated in different tissues andtumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectaltumors are scarce and no data on expression of ghrelin and its receptor incolorectal adenomas has been published. Ghrelin and ghrelin receptor werehighly expressed in colon carcinoma cells while expression was decreased in lessdifferentiated tumors, presuming that ghrelin might be important in early phasesof *** investigate the expression of ghrelin and ghrelin receptor in human colorectaladenomas and adjacent colorectal *** this prospective study (conducted from June 2015 until May 2019) we included92 patients (64 male and 28 female) who underwent polypectomy for colorectaladenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopicremoval of colorectal adenoma, an additional sample of colon mucosa in theproximity of the adenoma was collected for pathohistological analysis. Adenomaswere graded according to the stage of dysplasia, and ghrelin and ghrelin receptorexpression were determined immunohistochemically in both adenoma andadjacent colon tissue using the polyclonal antibody for ghrelin (ab150514,ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAMInc, Cambridge, United States). Categorical and nominal variables were describedthrough frequencies and proportions and the difference between specific groupswere analyzed with Fisher’s and Fisher-Freeman-Halton’s method ***'s rank correlation coefficient was determined for correlation ofexpression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissuewith the grade of adenoma *** 92 patients with colorectal adenoma 43 had adenomas with high-gradedysplasia (46.7%). High expression of ghre

关键词： Ghrelin Ghrelin receptor Adipokines Colorectal adenoma Colorectal adenoma dysplasia Large intestine

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Scoring systems for peptic ulcer bleeding: which one to use?

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World Journal of Gastroenterology 2017年第41期23卷 7450-7458页

作者： Ivan Budimir sanja stojsavljevic Neven Barsic Alen Biscanin Gorana Mirosevic Sven Bohnec Lora Stanka Kirigin Tajana Pavic Neven Ljubicic Division of Gastroent-erology Department of Internal Medicine 'Sestre Milosrdnice' University Hospital Center Division of Endo-crinology Department of Internal Medicine 'Sestre Milosrdnice' University Hospital Center Gastronterologie Allgemeine Innere Medizin und Geriatrie Rems -Murr Klinik Winnenden

AIM To compare the Glasgow-Blatchford score(GBS), Rockall score(RS) and Baylor bleeding score(BBS) in predicting clinical outcomes and need for interventions in patients with bleeding peptic ulcers. METHODS Between January 2008 and December 2013, 1012consecutive patients admitted with peptic ulcer bleeding(PUB) were prospectively followed. The pre-endoscopic RS, BBS and GBS, as well as the post-endoscopic diagnostic scores(RS and BBS) were calculated for all patients according to their urgent upper endoscopy findings. Area under the receiver-operating characteristics(AUROC) curves were calculated for the prediction of lethal outcome, rebleeding, needs for blood transfusion and/or surgical intervention, and the optimal cutoff values were *** PUB accounted for 41.9% of all upper gastrointestinal tract bleeding, 5.2% patients died and 5.4% patients underwent surgery. By comparing the AUROC curves of the aforementioned pre-endoscopic scores, the RS best predicted lethal outcome(AUROC 0.82 vs 0.67 vs0.63, respectively), but the GBS best predicted need for hospital-based intervention or 30-d mortality(AUROC0.84 vs 0.57 vs 0.64), rebleeding(AUROC 0.75 vs 0.61 vs 0.53), need for blood transfusion(AUROC 0.83 vs0.63 vs 0.58) and surgical intervention(0.82 vs 0.63 vs 0.52) The post-endoscopic RS was also better than the post-endoscopic BBS in predicting lethal outcome(AUROC 0.82 vs 0.69, respectively).CONCLUSION The RS is the best predictor of mortality and the GBS is the best predictor of rebleeding, need for blood transfusion and/or surgical intervention in patients with PUB. There is no one 'perfect score' and we suggest that these two tests be used concomitantly.

关键词： Upper gastrointestinal bleeding Peptic ulcer bleeding Glasgow-Blatchford score Rockall score Baylor bleeding score

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Noninvasive markers of liver steatosis and fibrosis after liver transplantation-Where do we stand?

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World Journal of Transplantation 2021年第3期11卷 37-53页

作者： Ivana Mikolasevic sanja stojsavljevic Filip Blazic Maja Mijic Delfa Radic-Kristo Toni Juric Nadija Skenderevic Mia Klapan Andjela Lukic Tajana Filipec Kanizaj Department of Gastroenterology Clinical Hospital Centre RijekaRijekaCroatiaDepartment of GastroenterologyClinical hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of RijekaRijekaCroatia Department of Gastroenterology University Hospital Center“Sestre Milosrdnice”Zagreb 10000Croatia Department of Gastroenterology University Hospital Center RijekaRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagreb 10000Croatia Department of Hematology University Hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of ZagrebZagrebCroatia School of Medicine School of MedicineRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of ZagrebZagrebCroatia

In the last two decades,advances in immunosuppressive regimens have led to fewer complications of acute rejection crisis and consequently improved shortterm graft and patient *** parallel with this great success,long-term posttransplantation complications have become a focus of interest of doctors engaged in transplant *** syndrome(MetS)and its individual components,namely,obesity,dyslipidemia,diabetes,and hypertension,often develop in the post-transplant setting and are associated with immunosuppressive *** fatty liver disease(NAFLD)is closely related to MetS and its individual components and is the liver manifestation of ***,it is not surprising that MetS and its individual components are associated with recurrent or“de novo”NAFLD after liver transplantation(LT).Fibrosis of the graft is one of the main determinants of overall morbidity and mortality in the post-LT *** the assessment of post-LT steatosis and fibrosis,we have biochemical markers,imaging methods and liver *** of the significant economic burden of post-LT steatosis and fibrosis and its potential consequences,there is an unmet need for noninvasive methods that are efficient and *** scores can overestimate fibrosis and are not a good method for fibrosis evaluation in liver transplant recipients due to frequent post-LT *** elastography with controlled attenuation parameter is a promising noninvasive method for steatosis and *** this review,we will specifically focus on the evaluation of steatosis and fibrosis in the post-LT setting in the context of de novo or recurrent NAFLD.

关键词： Steatosis Fibrosis Noninvasive methods Transient elastography Transplantation Nonalcoholic fatty liver disease

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