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Mechanisms of Hepatic Cholestatic Drug Injury

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Journal of Clinical and Translational Hepatology 2019年第1期7卷 86-92页

作者： Tea Omanovic Kolaric Vjera Nincevic robert smolic Martina smolic George Y Wu Department of Pharmacology Faculty of Medicine OsijekOsijekCroatia Department of Pharmacology Faculty of Dental Medicine and HealthOsijekCroatia Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Drug-induced cholestasis represents a form of drug-induced liver disease that can lead to severe impairment of liver *** drugs have been shown to cause cholestasis and consequently bile duct ***,there is still lack of therapeutic tools that can prevent progression to advanced stages of liver *** review focuses on the various pathological mechanisms by which drugs expresstheir hepatotoxic effects,as well as consequences of increased bile acid and toxin accumulation in the hepatocytes.

关键词： Drug-induced liver injury Bile acids Cholestasis

HCV Extrahepatic Manifestations

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Journal of Clinical and Translational Hepatology 2019年第2期7卷 172-182页

作者： Lucija Kuna Jelena Jakab robert smolic George Y Wu Martina smolic Department of Pharmacology and Biochemistry Faculty of Dental Medicine and HealthJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology and Physiology with Immunology Faculty of Dental Medicine and HealthJ.J.Strossmayer University of OsijekOsijekCroatia Department of Internal Medicine Faculty of MedicineJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pharmacology Faculty of MedicineJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Hepatitis C virus(HCV)has been shown to affect many tissues other than ***,of the many extrahepatic manifestations(EMs)that have been associated with HCV,including cryoglobulinemia,lymphoma,insulin resistance,type 2 diabetes and neurological disorders,only a few have been shown to be directly related to HCV infection of extrahepatic ***-triggered immune-mediated mechanisms account for most of the *** is estimated that up to 74%of patients with chronic hepatitis C can develop at least one *** HCV patients with EMs should be considered for antiviral therapy,although not all will resolve with sustained virological response.

关键词： Hepatitis C virus Hepatic stellate cells B cell lymphomas pancreatic B cell TGF-β-dependent signaling pathway Extrahepatic manifestations Direct-acting antivirals

An Update on Efficacy and Safety of Emerging Hepatic Antifibrotic Agents

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 60-70页

作者： Vinka Rupcic Rubin Kristina Bojanic Martina smolic Jurica Rubin Ashraf Tabll robert smolic Department of Gynaecology and Obstetrics Osijek University Hospital CentreFaculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Radiology Health Center OsijekOsijekCroatia Department of Pharmacology and Biochemistry Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pharmacology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Division of Gastroenterology/HepatologyUniversity Hospital OsijekOsijekCroatia Microbial Biotechnology Department Genetic Engineering and Biotechnology Research DivisionNational Research CentreDokkiEgypt Department of immunology Egypt Center for Research and RegenerativeMedicine(ECRRM)CairoEgypt Department of Pathophysiology Physiology and ImmunologyFaculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia

Liver fibrosis represents a response to chronic liver *** dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing ***,there is a great impetus for development of agents targeting these *** data on possible treatment options for liver fibrosis are emerging in the ***,despite extensive research and much effort in the field,approved agents for liver fibrosis are still *** this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.

关键词： Liver fibrosis MAFLD MASH Clinical trials Antifibrotic agents Efficacy Safety

Anabolic androgenic steroid-induced liver injury:An update

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World Journal of Gastroenterology 2022年第26期28卷 3071-3080页

作者： Ana Petrovic Sonja Vukadin Renata Sikora Kristina Bojanic robert smolic Davor Plavec George Y Wu Martina smolic Department of Pharmacology and Biochemistry Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Pharmacology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Dental Medicine Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Dental Medicine Health Center Osijek-Baranja CountyOsijek 31000Croatia Department of Otorhinolaryngology Neurosurgery and RadiologyFaculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Biophysics and Radiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Radiology Health Center Osijek-Baranja CountyOsijek 31000Croatia Research Department Srebrnjak Children's HospitalZagreb 10000Croatia Department of Medicine Division of Gastrenterology/HepatologyUniversity of Connecticut Health CenterFarmingtonCT 06030United States

Anabolic androgenic steroids(AASs)are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic *** properties make them therapeutically beneficial in medical conditions such as ***,they are commonly bought illegally and misused for their anabolic,skeletal muscle building,and performanceenhancing *** and long-term use of AASs affects all organs,leading to cardiovascular,neurological,endocrine,gastrointestinal,renal,and hematologic *** is one of the major concerns regarding AASs treatment and *** and its derivatives have been most often shown to induce a specific form of cholestasis,peliosis hepatis,and hepatic benign and malignant *** is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors,upregulation of bile acid synthesis,and induction of hepatocyte *** toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of ***,some long-term consequences are ***-induced liver injury should be taken in consideration in patients with liver disorders,especially with the increasing unintentional ingestion of supplements containing *** this paper,we review the most current knowledge about AAS-associated adverse effects on the liver,and their clinical presentations,prevalence,and pathophysiological mechanisms.

关键词： Androgens Steroids Cholestasis Fibrosis Liver Chemical and drug induced liver injury

Effect of COVID-19 on management of type 1 diabetes:Pushing the boundaries of telemedical healthcare

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World Journal of Diabetes 2021年第6期12卷 780-785页

作者： Ines Bilic Curcic Maja Cigrovski Berkovic Tomislav Kizivat Silvija Canecki Varzic robert smolic Martina smolic Department of Endocrinology University Hospital OsijekOsijek 31000Croatia Department of Pharmacology Faculty of Medicine OsijekOsijek 31000Croatia Department of Endocrinology DiabetesMetabolism and Clinical PharmacologyUniversity Hospital DubravaZagreb 10000Croatia Department of Kinesiological Anthropology and Methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Clinical Institute of Nuclear Medicine and Radiation Protection University Hospital OsijekOsijek 31000Croatia Department of Nuclear Medicine and Oncology Faculty of Medicine OsijekOsijek 31000Croatia Department of Internal Medicine Family Medicineand HistoryFaculty of Medicine OsijekOsijek 31000Croatia Department of Pathophysiology Faculty of Medicine OsijekOsijek 31000Croatia Department of Pathophysiology Physiology and ImmunologyFaculty of Dental Medicine and HealthOsijek 31000Croatia Department of Pharmacology and Biochemistry Faculty of Dental Medicine and HealthOsijek 31000Croatia

The new coronavirus disease 2019(COVID-19)pandemic posed a great burden on health care systems worldwide and is an enormous and real obstacle in providing needed health care to patients with chronic diseases such as *** to COVID-19,there have been great advances in technology used for management of type 1 diabetes,primarily insulin pumps,sensors,integrated and closed loop systems,ambulatory glucose profile software,and smart phone apps providing necessary essentials for telemedicine implementation right at the beginning of the COVID-19 *** results of these remote interventions are reassuring in terms of glycemic management and hemoglobin A1c ***,data on long-term outcomes and cost reductions are missing as well as proper technical infrastructure and government health policy support.

关键词： Diabetes management Telemedicine COVID-19 Diabetes type 1

Obesity Paradox in Chronic Liver Diseases:Product of Bias or a Real Thing?

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Journal of Clinical and Translational Hepatology 2019年第3期7卷 275-279页

作者： Ines Bilic Curcic Maja Cigrovski Berkovic Lucija Kuna Hrvoje Roguljic robert smolic Silvija Canecki Varzic Lucija Virovic Jukic Martina smolic Department of Pharmacology Faculty of MedicineJ.J.Strossmayer University of OsijekOsijekCroatia Department of Diabetes Endocrinology and Metabolism DisordersOsijek University Hospital CentreFaculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department for Endocrinology Diabetes and Metabolism University Hospital Center"Sestre Milosrdnice"ZagrebCroatia Department of Pharmacology and Biochemistry Faculty of Dental Medicine and HealthJ.J.Strossmayer University of OsijekOsijekCroatia Department for Cardiovascular Disease Osijek University HospitalOsijekCroatia Department of Gastroenterology and Hepatology Osijek University Hospital CentreFaculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology Faculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Internal Medicine Faculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Gastroenterology and Hepatology Sisters of Mercy University HospitalUniversity of Zagreb School of MedicineZagrebCroatia Department of Pharmacology J.J.Stross-mayer University of Osijek Faculty of Medicine OsijekJ.Huttlera 4Osijek 31000Croatia

In recent years,evidence supporting the theory of obesity paradox has increased,showing that obese/overweight people with prevalent chronic diseases experience lower mortality compared with patients of normal *** far,evidence is most comprehensive in cardiovascular and chronic renal diseases;however,published studies are prone to many biases,enabling us to reach a definite *** data in chronic liver disease is scarce and *** is traditionally associated with nonalcoholic fatty liver disease and steatosis in viral hepatitis and as such one would not expect the obesity paradox to be a real possibility in liver ***,there seem to be new data indicating the opposite-the obesity paradox exists in severe and end-stage liver cirrhosis,which could be attributed to a better lean mass in patients with higher body mass index,meaning that sarcopenia,as one of the most important prognostic factors of survival,is less likely to be ***,the problem of various methodological problems addressing the association between body weight and mortality,which is present both in liver disease and other chronic diseases,are preventing us from attaining an unanimous ***,we should be aware that the obesity paradox might be true,especially in severe and end-stage *** suggests focusing our efforts toward preserving or building up fat-free mass and decreasing infiammatory activity responsible for catabolism and sarcopenia,and implying that the underlaying cause should be treated.

关键词： Obesity paradox Chronic liver disease NAFLD NASH Cirrhosis

Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1228-1238页

作者： Kristina Bojanic Mirta Sudaric Bogojevic Sonja Vukadin Renata Sikora Gordana Ivanac Nikola Raguz Lucic Martina smolic Ashraf ATabll George YWu robert smolic Faculty of Dental Medicine and Health Osijek Josip Juraj Strossmayer University of OsijekOsijekCroatia Faculty of Medicine Osijek Josip Juraj Strossmayer University of OsijekOsijekCroatia Health Center Osijek-Baranja County OsijekCroatia Department of Biology Josip Juraj Strossmayer University of OsijekOsijekCroatia University Hospital Dubrava ZagrebCroatia School of Medicine University of ZagrebZagrebCroatia Microbial Biotechnology Department Biotechnology Research InstituteNational Research CenterGizaEgypt Egypt Center for Research and Regenerative Medicine(ECRRM) CairoEgypt University of Connecticut Health Center FarmingtonCTUSA

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C ***,with the introduction and validation of noninvasive tests(NITs)to evaluate advanced fibrosis,and the direct-acting antiviral agents for treatment of chronic hepatitis C virus(HCV),the role of NITs have become even more *** is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological *** aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.

关键词： Hepatitis C virus Fibrosis Noninvasive serum fibrosis markers Transient elastography Shear wave elastography Magnetic resonance elastography Steatohepatitis

Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options:An Update

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Journal of Clinical and Translational Hepatology 2021年第6期9卷 960-971页

作者： Kristina Duspara Kristina Bojanic Josipa Ivanusic Pejic Lucija Kuna Tea Omanovic Kolaric Vjera Nincevic robert smolic Aleksandar Vcev Marija Glasnovic Ines Bilic Curcic Martina smolic Department of Pharmacology and Biochemistry Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pharmacology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Radiology Health Center OsijekOsijekCroatia Department of Medi-cine Division of Gastroenterology/HepatologyUniversity Hospital OsijekOsijekCroatia Department of Pathophysiology Physiology and ImmunologyFaculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Family Medicine and History of MedicineFaculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Division of EndocrinologyUniversity Hospital OsijekOsijekCroatia

morbidity and mortality for healthcare systems *** imparts an enormous economic burden to societies,making continuous research and informational updates about its pathogenesis and treatment *** review′s focus is on the current knowledge about the Wnt signaling path-way,serving as an important pathway in liver fibrosis development and activation of hepatic stellate cells(HSCs).Two types of Wnt pathways are distinguished,namely the ß-catenin-dependent canonical and non-canonical Ca^(2+) or planar cell polarity(PCP)-dependent *** dynamic balance of physiologically healthy liver and hepatocytes is disturbed by repeated liver *** of theß-catenin Wnt pathway prevents the regeneration of hepatocytes by the replacement of extracellular matrix(ECM),leading to the appearance of scar tissue and the formation of regenerated nodular hepatocytes,lacking the original function of healthy ***,liver function is reduced due to the severely advanced *** inhibition ofß-catenin inhibits inflammatory processes(since chemokines and pro-inflammatory cytokines are produced during Wnt activation),reduces growth of activated HSCs and reduces collagen synthesis and angiogenesis,thereby reducing the progression of liver fibrosis in *** the canonical Wnt pathway is usually inactive in a physiologically healthy liver,it shows activity during cell regeneration or renewal and in certain pathophysiological conditions,such as liver diseases and *** blocking of some of the basic components of the Wnt path-way is a therapeutic *** include the frizzled transmembrane receptor(Fz)receptors using the secreted frizzled-related protein family(sFRP),Fz-coreceptors low-density LRP 5/6 through dickkopf-related protein 1(DKK1)or niclosamide,glycogen kinase-3 beta(GSK-3β)using SB-216763,cyclic-AMP response element-binding protein(CBP)using PRI-724 and ICG-001,the lymphoid enhancer binding factor(LEF)/T cell-spec

关键词： Liver fibrosis Wnt signaling pathway Hepatic stellate cell Therapeutic solutions

Update on the Development of Anti-Viral Agents Against Hepatitis C

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Journal of Clinical and Translational Hepatology 2013年第1期1卷 9-21页

作者： Kristin L. MacArthur robert smolic Martina V. smolic Catherine H. Wu George Y. Wu Department of Medicine Beth Israel Deaconess Medical Center Boston MA02215 Faculty of Medicine Osijek Croatia University of Connecticut Health Center Farmington CT USA Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV. Direct data from agents in phase Ⅲ/Ⅳ clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly important public health concern, and it is important for physicians to stay up to date on the rapidly growing novel therapeutic options.

关键词： HCV Protease Polymerase Triple therapy Drug.