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Review of Clinically Relevant Drug Interactions with Next Generation Hepatitis C Direct-acting Antiviral Agents

Journal of Clinical and Translational Hepatology 2020年第3期8卷 322-335页

作者： Jenny Hong Robert C.Wright Nilu Partovi eric m.yoshida Trana Hussaini Pharmaceutical Sciences Vancouver General HospitalVancouverBCCanada Faculty of Pharmaceutical Sciences University of British ColumbiaVancouverBCCanada Liver Transplant Program Vancouver General HospitalVancouverBCCanada Division of Gastroenterology Faculty of MedicineUniversity of British ColumbiaVancouverBCCanada

In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(maviret®),and elbasvir/grazoprevir(Zepatier®).We searched mEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,2020.The search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference proceedings.All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted.Numerous clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed drugs.NS3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase inhibitor.The majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do occur.As expected,many drug interactions exist between newer generation DAAs and commonly prescribed medications.While the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting drugs.In select cases,severe and unpredictable drug interactions can occur.Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.

关键词： Hepatitis C Drug interactions Pharmacokinetics Direct-acting antiviral agents

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Chronic pancreatitis:a sequela of acute fatty liver of pregnancy

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Hepatobiliary & Pancreatic Diseases International 2008年第1期7卷 101-104页

作者： Wichian Apiratpracha eric m.yoshida Scudamore H.Charles Alan A.Weiss michael F.Byrne Division of Gastroenterology Department of medicine University of British ColumbiaVancouverBCCanada Division of Surgery Department of MedicineUniversity of British ColumbiaVancouverBCCanada

BACKGROUND: Chronic pancreatitis following acute fatty liver of pregnancy is rarely reported.mETHODS: We treated a 34-year-old woman who developed acute fatty liver of pregnancy (AFLP) after delivery by caesarean section at 32 weeks of gestation. AFLP was complicated by acute pancreatitis and multiple organ failure. The management of the disease was primarily supportive. She recovered from acute fulminant liver failure and multi-organ failure, apart from the development of symptomatic chronic pancreatitis thereafter. RESULTS: Investigations failed to identify any other causes of chronic pancreatitis. The patient responded very well to pancreatic enzyme supplement for the treatment of steatorrhoea.CONCLUSION: To our knowledge, this is the first report of chronic pancreatitis as a consequence of multi-organ dysfunction caused by AFLP.

关键词： pancreatitis, chronic fatty liver acute pregnancy multiorgan dysfunction syndrome

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Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review

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Journal of Clinical and Translational Hepatology 2016年第3期4卷 192-205页

作者： Jillian Reardon Trana Hussaini majid Alsahafi Vladimir marquez Azalgara Siegfried R.Erb Nilufar Partovi eric m.yoshida Faculty of Pharmaceutical Sciences The University of British Columbia Vancouver British Columbia Canada Division of Gastroenterology The University of British Columbia Diamond Health Vancouver British Columbia Canada Pharmaceutical Sciences Clinical Service Unit Vancouver General Hospital Vancouver British Columbia Canada Division of Gastroenterology The University of British Columbia Diamond Health Vancouver British Columbia Canada Faculty of Pharmaceutical Sciences The University of British Columbia Vancouver British Columbia Canada Pharmaceutical Sciences Clinical Service Unit Vancouver General Hospital Vancouver British Columbia Canada

Aims:To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions.methods:Searches were conducted on the databases of medline (1948-march 31,2015),Embase (1980-march 31,2015) and the Cochrane Central Register of Controlled Trials,and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications.Combinations of the following search terms were used:ursodeoxycholic acid,ursodiol,bile acids and/or salts,non alcoholic fatty liver,non alcoholic steatohepatitis,fatty liver,alcoholic hepatitis,alcohol,liver disease,autoimmune,autoimmune hepatitis,liver transplant,liver graft,transplant rejection,graft rejection,ischemic reperfusion injury,reperfusion injury,hepatitis B,hepatitis C,viral hepatitis,chronic hepatitis,acute hepatitis,transaminases,alanine transaminase,liver enzymes,aspartate aminotransferase,gamma-glutamyl transferase,gammaglutamyl transpeptidase,bilirubin,alkaline phosphatase.No search limits were applied.Additionally,references of the included studies were reviewed to identify additional articles.Results:The literature search yielded articles meeting inclusion criteria for the following indications:non-alcoholic fatty liver disease (n =5);alcoholic liver disease (n =2);autoimmune hepatitis (n =6),liver transplant (n =2) and viral hepatitis (n =9).Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease,autoimmune hepatitis and hepatitis B and C infections.In contrast,liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation.The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease.In the prospective trials reviewed,adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often,diarrhea) and did not occur at increased frequency as compa

关键词： Non-alcoholic fatty liver disease Alcoholic liver disease Autoimmune hepatitis Liver transplantation Viral hepatitis

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Occult Hepatitis B Reactivation after Liver Transplant: The Role of a Novel mutation in the Surface Antigen

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 136-138页

作者： Harjot K.Bedi Daljeet Chahal Christopher F.Lowe Gordon Ritchie Trana Hussaini Vladimir marquez eric m.yoshida Department of medicine University of British ColumbiaVancouverBCCanada Division of Gastroenterology University of British ColumbiaVancouverBCCanada Department of Pathology&Laboratory medicine University of British ColumbiaVancouverBCCanada Faculty of Pharmaceutical Sciences University of British ColumbiaVancouverBCCanada

Occult hepatitis B infection is characterized by loss of hepa-titis B surface antigen(HBsAg)and persistence of low levels of hepatitis B virus(HBV)replication that may or may not be detectable in plasma/serum.We present a case of HBV reactivation in a male patient who underwent orthotopic liver transplant for hepatocellular carcinoma secondary to active hepatitis C(HCV)infection.Pre-transplant,he was HBsAg-negative and hepatitis B core antibody-positive,with an undetectable HBV viral load that was incidentally found to be positive at a very low HBV viral load on the day of transplant.Post-transplant,his HBsAg remained undetect-able,with an undetectable HBV viral load,until eradication of his HCV infection with direct acting antiviral agents.Af-ter eradication of HCV,there was reactivation of HBV,with a high viral load and emergence of serum HBsAg.A deep sequencing genetic analysis of his HBV both pre-and post-transplant revealed the presence of a mutation in the"a"determinant of the HBV surface antigen.The role of HBV genotype'a'determinant mutation in HBV reactivation post-transplant is unknown and needs further examination.Our experience suggests a possible role for antiviral prophylaxis in these patients or monitoring of HBV viral loads post-transplant.

关键词： Antigen infection activation

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What Has the COVID-19 Pandemic Taught Us so Far?Addressing the Problem from a Hepatologist's Perspective

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Journal of Clinical and Translational Hepatology 2020年第2期8卷 109-112页

作者： Nahum méndez-Sánchez Alejandro Valencia-Rodríguez Xingshun Qi eric myoshida manuel Romero-Gómez Jacob George mohammed Eslam Ludovico Abenavoli Weifen Xie Rolf Teschke Andres FCarrion Andrew PKeaveny Department of Internal medicine II Division of Gastroenterology and HepatologyKlinikum HanauHanauAcademic Teaching Hospital of the Medical FacultyGoethe University Frankfurt/MainFrankfurt/MainGermany The Fifth medical Center General Hospital of PLABeijingChina Department of Gastroenterology General Hospital of Northern Theater Command(Formerly General Hospital of Shenyang Military Area)ShenyangChina Division of Gastroenterology University of British ColumbiaVancouverBCCanada UCm Digestive Diseases and CIBERehd Institute of Biomedicine of Seville(IBiS)SeLiver GroupVirgen del Rocío University HospitalUniversity of SevilleSevilleSpain Storr Liver Centre Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyNSWAustralia Department of Health Sciences University Magna Graecia of CatanzaroItaly Department of Gastroenterology Changzheng Hospital of the Second Military Medical UniversityShanghaiChina Department of Internal medicine II Division of Gastroenterology and HepatologyKlinikum HanauAcademic Teaching Hospital of the Medical FacultyGoethe University Frankfurt/MainHanauGermany Division of Gastroenterology and Hepatology University of MiamiMiller School of MedicineMiamiFLUSA Department of Transplantation Mayo ClinicJacksonvilleFloridaUSA

As of today, march 30, 2020, when this Editorial is being written, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19) has been confirmed in more than 745,000 cases worldwide and has claimed the lives of more than 35,000 people.1 In addition to the morbidity and mortality associated with COVID-19, this betacoronavirus has placed several of the world's major economies in strife, mainly in Western Europe and North America, paralyzing travel and regular social interactions, making COVID-19 undoubtedly one of the most important pandemics in human history.

关键词： doubt travel COV

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Efficacy and safety of semaglutide in non-alcoholic fatty liver disease

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世界胃肠病学杂志:英文版 2023年第37期29卷 5327-5338页

作者： Kai Zhu Rohan Kakkar Daljeet Chahal eric m.yoshida Trana Hussaini Internal medicine University of British ColumbiaVancouver V5Z 1M9BCCanada Department of Gastroenterology University of British ColumbiaVancouver V5Z 1M9BCCanada BC Liver Transplant Program Vancouver General HospitalVancouver V5Z 1M9BCCanada Pharmaceutical Sciences University of British ColumbiaVancouver V5Z 1M9BCCanada

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease.The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower healthrelated quality of life.To date,there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis(NASH).Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD.AIm To investigate the efficacy and safety of semaglutide in patients with NAFLD.mETHODS mEDLINE,CENTRAL,and EmBASE were searched from inception to may 1,2023,to identify eligible randomized controlled trials(RCTs).meta-analysis was performed using random effects model expressing continuous outcomes as mean differences(mD)or standardized mDs(SmD),and dichotomous outcomes as odds ratios(OR)with 95%confidence intervals(CI).Statistical heterogeneity was assessed using the Cochran’s Q test and I2 statistic.RESULTS Three RCTs involving 458 patients were included.Semaglutide increased the likelihood of NASH resolution(OR:3.18,95%CI:1.70,5.95;Pmprovement in steatosis(OR:2.83,95%CI:1.19,6.71;P=0.03),lobular inflammation(OR:1.81,95%CI:1.11,2.96;P=0.02),and hepatocellular ballooning(OR:2.92,95%CI:1.83,4.65;Pmaglutide reduced liver stiffness(SmD:-0.48,95%CI:-0.86,-0.11;P=0.01)and steatosis(mD:-4.96%,95%CI:-9.92,0.01;P=0.05).It also reduced alanine aminotransferase(mD:-14.06 U/L,95%CI:-22.06,-6.07;Pminotransferase(mD:-11.44 U/L,95%CI:-17.23,-5.65;Pmaglutide led to improved cardiometabolic outcomes,including decreased HgA1c(mD:-0.77%,95%CI:-1.18,-0.37;PmD:-6.53 kg,95%CI:-11.21,-1.85;P=0.006),but increased the occurrence of GIrelated side effects(OR:3.72,95%CI:1.68,8.23;P=0.001).Overall risk of serious adverse events was similar compared to placebo(OR:1.40,95%CI:0.75,2.62;Pmaglutide is effective in the treatme

关键词： Non-alcoholic fatty liver disease Fatty liver metabolic-associated fatty liver Semaglutide

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Deciphering the enigmatic spikelet traits:Resolving trade-offs for enhancing rice yield

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molecular Plant 2024年第5期17卷 694-695页

作者： Hideki yoshida makoto matsuoka Institute of Fermentation Sciences Fukushima UniversityFukushima 960-1248Japan

Increasing the yield is one of the most important goals of crop improvement.Since the beginning of rice cultivation thousands of years ago,many efforts have been made to increase rice yield.One of the successes in this history was the Green Revolution.This tremendous improvement in the 1960s was achieved by increasing rice and wheat production through the development and widespread adoption of semi-dwarf varieties with the extensive use of fertilizers(Hedden,2003).Dwarfism in crops lowers the center of gravity of the plant body,reducing the risk of lodging and enabling farmers to use more fertilizer to increase yields.Semi-dwarf mutations in both rice and wheat created during the Green Revolution are related to the plant growth hormone gibberellin(GA).Although other mechanisms cause dwarf mutants,only GA-related semi-dwarf mutants were selected during the Green Revolution(Wang et al.,2021).While GA-related abnormalities only make plants shorter,most cases caused by other mechanisms involve not only dwarfism but also other morphological abnormalities.

关键词： dwarf crops traits

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Association of Congenital Heart Defects (CHD) with Factors Related to maternal Health and Pregnancy in Newborns in Puerto Rico

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Congenital Heart Disease 2024年第1期19卷 19-31页

作者： Yamixa Delgado Caliani Gaytan Naydi Perez eric miranda Bryan Colón morales mónica Santos Biochemistry&Pharmacology Department San Juan Bautista School of MedicineCaguas00726Puerto Rico Hispanic Alliance for Clinical and Translational Research University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico Department of Internal medicine University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico

Background:Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States,there is a compelling need to investigate the intricate interplay among body mass index(BmI),pregesta-tional,and gestational maternal diabetes,and their potential impact on the occurrence of congenital heart defects(CHD)during neonatal development.methods:Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico,we conducted a focused analysis on neonates diagnosed with CHD between 2016 and 2020.Our assessment encompassed a range of variables,including maternal age,gestational age,BmI,pregestational diabetes,gestational diabetes,hypertension,history of abortion,and presence of preeclampsia.Results:A cohort of 673 patients was included in our study.The average maternal age was 26 years,within a range of 22 to 32 years.The mean gestational age measured 39 weeks,with a median span of 38 to 39 weeks.Of the 673 patients,274(41%)mothers gave birth to neonates diagnosed with CHD.Within this group,22 cases were linked to pre-gestational diabetes,while 202 were not;20 instances were associated with gestational diabetes,compared to 200 without;and 148 cases exhibited an overweight or obese BmI,whereas 126 displayed a normal BmI.Conclusion:We identiﬁed a statistically signiﬁcant correlation between pre-gestational diabetes mellitus and the occurrence of CHD.However,our analysis did not show a statistically signiﬁcant association between maternal BmI and the likelihood of CHD.These results may aid in developing effective strategies to prevent and manage CHD in neonates.

关键词： Congenital heart defects(CHD) obesisty maternal health diabetes body mass index(BmI)

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Autoimmune liver disease and the Canadian First Nations Aboriginal Communities of British Columbia's Pacific Northwest

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World Journal of Gastroenterology 2006年第23期12卷 3625-3627页

作者： eric m.yoshida mark Riley Laura T Arbour Department of medicine University of British ColumbiaVancouverBCCanada Department of Pediatrics University of British Columbia Vancouver BC Canada Department of medical Genetics the University of British Columbia. Vancouver BC Canada

Primary biliary cirrhosis (PBC) is a well-known but uncommon chronic liver disease that is presumed to be of autoimmune etiology. Recently, investigations in British Columbia (BC), a province of Canada situated along the Pacific North-West of North America, have suggested that PBC is not a rare disease amongst BC's Aboriginal (i.e. First Nations) communities. Geographically, BC is adjacent to South East Alaska, an American state that has also reported an increased prevalence of PBC amongst its Aboriginal communities. In this article, the medical evidence supporting a hypothesis of increased risk of PBC amongst BC's First Nations communities is reviewed. Evidence suggesting that autoimmune hepatitis is also more likely amongst BC's First Nations communities is also presented.

关键词：自体免疫肝疾病土著社会加拿大哥伦比亚英国

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Untangling the biotic stress in the late maastrichtian Deccan-benchmark interval of Bidart(France)

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Journal of Palaeogeography 2024年第2期13卷 181-198页

作者： Subham Patra Gerta Keller eric Font Thierry Adatte Jahnavi Punekar Indian Institute of Technology Bombay PowaiMumbai 400076India Princeton University PrincetonNJ 08544USA Departamento de Ciencias da Terra Faculdade de Ciencias e TecnologiaUniversidade de Coimbra3000-272 CoimbraPortugal Institute of Earth Sciences University of Lausanne1015 LausanneSwitzerland

The late maastrichtian witnessed substantial surges in Deccan volcanism,prompting the hypothesis that these voluminous pulses may have instigated repeated episodes of ocean acidification during this period.The Cretaceous-Palaeogene(K/Pg)boundary at Bidart(France)is preceded by a~0.5 m thick interval with geochemical and taphonomic vestiges of an ocean acidification event linked with Deccan volcanism.New planktic foraminifera census and morphometric data now confirm biotic stress conditions related to acidification in the Deccan benchmark interval.The absolute abundance data of larger(>150μm)heavily calcified planktic morphogroups show fluctuating populations throughout zone CF1(spanning the final~225 ky),lowest peaks within the Deccan benchmark,and a demographic collapse(>90%)at the K/Pg boundary.The analyzed species are generally reduced in size,with thinner test walls in this~0.5 m interval,indicating the likelihood of calcification stress as a contributor to the overall biotic stress.At the K/Pg boundary,maximum biotic stress is recorded in all the tested faunal proxies.A preliminary graphic correlation of zone CF1 at Bidart with the auxiliary GSSP at Elles(Tunisia)constrains the Deccan benchmark interval of high biotic stress to the final~58ky of the late maastrichtian,culminating in the K/Pg mass extinction.The volcanogenic Hg peaks coincident with faunal and taphonomic evidence of ocean acidification strengthen the Deccan-related ocean acidification hypothesis.

关键词： Deccan volcanism K/Pg mass extinction Biotic stress Calcification stress

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