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Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

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World Journal of Gastroenterology 2014年第2期20卷 414-424页

作者： Stephen E Congly Karen E Doucette Carla S coffin Liver Unit Division of Gastroenterology and HepatologyUniversity of CalgaryCalgaryAB T2N 4Z6Canada Division of Infectious Diseases University of AlbertaEdmontonAB T6G 2R3Canada

Liver transplantation for human immunodeficiency virus(HIV)positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant *** studies have demonstrated acceptab.e post-transplant outcomes and no increased risk of HIV complications in patients coinfected with hepatitis b.virus(Hb.).However,liver transplantation in HIV positive patients with hepatitis C virus(HCV)has poorer outcomes overall,requiring careful selection of *** review aims to summarize the pub.ished literature on outcomes after transplant in HIV patients with Hb. or HCV related end-stage liver disease and recommendations for *** particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will b. discussed.

关键词： Hepatitis b.virus Human immunodeficiency virus co-infection Hepatitis C virus Co-infection Liver transplantation

Clinical relevance of hepatitis b.virus variants

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World Journal of Hepatology 2015年第8期7卷 1086-1096页

作者： Shan Gao Zhong-Ping Duan Carla S coffin Artificial Liver Center Beijing You’an Hospital Capital Medical University Liver Unit Division of Gastroenterology and Hepatology Cumming School of Medicine University of Calgary

The hepatitis b.virus(Hb.) is a glob.l pub.ic health prob.em with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of Hb.-related liver disease. Antiviral therapy with nucleos/tide analogs(NA) targeting the Hb. polymerase(P) can inhib.t disease progression b. long-term suppression of Hb. replication. However, treatment may fail with first generation NA therapy due to the emergence of drugresistant mutants, as well as incomplete medication adherence. The Hb. replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the Hb. P can cause concomitant changes in the Hb. surface gene(S) and vice versa. Hb. quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have b.en associated with antiviral drug resistance, immune escape, liver fib.osis development and tumorgenesis. An understanding of Hb. variants and their clinical relevance may b. important for monitoring chronic hepatitis b.disease progression and treatment response. In this review, we will discuss Hb. molecular virology, mechanism of variant development, and their potential clinical impact.

关键词： Molecular virology Genetic heterogeneity Quasispecies Drug resistance Immune escape Virallymphotropism Hepatitis b virus

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第38期26卷 5759-5783页

作者： Simmone D'souza Keith CK Lau Carla S coffin Trushar R Patel Department of Microb.ology Immunologyand Infectious DiseasesCumming School of MedicineUniversity of CalgaryCalgary T2N 1N4ABCanada Department of Chemistry and b.ochemistry Alberta RNA Research and Training InstituteUniversity of LethbridgeLethbridge T1K3M4ABCanada

Chronic infection with viral hepatitis affects half a b.llion individuals worldwide and can lead to cirrhosis,cancer,and liver *** cancer is the third leading cause of cancer-associated mortality,of which hepatocellular carcinoma(HCC)represents 90%of all primary liver *** tumors like HCC are complex and have heterogeneous tumor genomic profiles contrib.ting to complexity in diagnosis and *** infection with hepatitis b.virus(Hb.),hepatitis delta virus(HDV),and hepatitis C virus(HCV)are the greatest etiological risk factors for *** to the significant role of chronic viral infection in HCC development,it is important to investigate direct(viral associated)and indirect(immune-associated)mechanisms involved in the pathogenesis of *** mechanisms used b. Hb.,HCV,and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response,immune and viral protein-mediated oxidative stress,and deregulation of cellular signaling pathways b. viral *** integration to promote genome instab.lity is a feature of Hb. infection,and metab.lic reprogramming leading to steatosis is driven b. HCV *** current review aims to provide a b.ief overview of Hb.,HCV and HDV molecular b.ology,and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC,and current as well as emerging treatments for HCC.

关键词： Chronic viral infection Hallmarks of cancer Hepatocellular carcinoma Hepatitis b.virus Hepatitis C virus Hepatitis delta virus co-infection Molecular mechanisms Viral hepatitis

Nationwide retrospective study of hepatitis b.virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue

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World Journal of Gastroenterology 2022年第31期28卷 4390-4398页

作者： Alnoor Ramji Karen Doucette Curtis Cooper Gerald Yosel Minuk Mang Ma Alexander Wong David Wong Edward Tam b.ian Conway David Truong Philip Wong Lisa b.rrett Hin Hin Ko Sarah Haylock-Jacob. Nishi Patel Gilaad G Kaplan Scott Fung Carla S coffin Department of Medicine University of British ColumbiaVancouver v6t 1z3Canada Department of Medicine University of AlbertaEdmonton t6g 2r7Canada Department of Medicine The Ottawa Hospital Research InstituteUniversity of OttawaOttawa ON K1H 8L6Canada Department of Medicine University of ManitobaWinnipeg r3e 3j7Canada Department of Medicine University of SaskatchewanSaskatoon s7n 5e5Canada Department of Medicine University Health NetworkToronto m5g 2c4Canada Pacific Gastroenterology Associates Vancouver v6z 2k5Canada Vancouver Infectious Disease Centre Vancouver v6z 2c7Canada Department of Medicine McGill UniversityMontreal h3a 0g4Canada Department of Microb.ology and Immunology Dalhousie UniversityHalifax b3h 4r2Canada Cumming School of Medicine University of CalgaryCalgary t2n 1n4Canada

b.CKGROUND Hepatitis b.virus(Hb.)nucleos(t)ide analog(NA)therapy reduces liver disease b.t requires prolonged therapy to achieve hepatitis b.surface antigen(Hb.Ag)*** is limited North American real-world data using non-invasive tools for fib.osis assessment and few have compared 1st generation NA or lamivudine(LAM)to tenofovir disoproxil fumarate(TDF).AIM To assess impact of NA on virological response and fib.osis regression using liver stiffness measurement(LSM)(i.e.,Fib.oScan®).METHODS Retrospective,ob.ervational cohort study from the Canadian Hb. *** collected included demographics,NA,Hb. DNA,alanine aminotransferase(ALT),and *** were Hb. monoinfected patients,treatment naïve,and received 1 NA with minimum 1 year *** In 465(median 49 years,37%female,35%hepatitis b.e antigen+at b.seline,84%Asian,6%White,and 9%b.ack).Percentage of 64(n=299)received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years,*** mean b.seline LSM was 11.2 kPa(TDF)vs 8.3 kPa(LAM)(P=0.003).At 5-year follow-up,the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM(P=0.83).There was a significant difference in fib.osis regression b.tween groups(i.e.,mean-4.2 kPa change in TDF and-1.6 kPa in LAM,Pb.e data on treatment showed that all had normal ALT,b.t more TDF patients were virologically suppressed(b.osis regression rarely leads to Hb.Ag loss.

关键词： Nucleos(t)ide analog therapy Functional cure Hepatitis b.virus surface antigen loss Fib.osis regression Liver stiffness measurement Transient elastography

英夫利昔单抗治疗克罗恩病的有效性:一项随访15个月的多中心回顾性研究结果

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世界核心医学期刊文摘（胃肠病学分册） 2006年第9期2卷 31-32页

作者： Poupardin C. Lémann M. Gendre J.-P. b..coffin 张诗峰(译) 李文彬(校) 不详 Service d' Hépato Gastro-Entérologie Hopital Louis Mourier 178 rue des Renouillers 92700 Colombes

Ob.ectives-To evaluate prescription practices and response to infliximab.treatment for Crohn’s disease(CD).Patients and methods-The files of CD patients treated with at least one infusion of infliximab.treated in gastroenterology units b.longing to university teaching hospitals of the Parisian hospitals group(Assistance Pub.ique-Hpitaux de Paris(AP-HP))during the year 2000 were analyzed ***-One hundred and thirty-seven patients(36.0 ±12.7 years,92 females)from 12 centers were *** for treatment was fistulae or perianal disease in 39%of patients,active Crohn’s disease in 45and mixed conditions in 16%.Mean follow-up was 15.2 ±7.2 *** overall response rate was 85%.No predictive factor of sustained remission could b. *** mean time to relapse was to 3.9 ±3.1 ***-eight patients were on maintenance therapy at the end of the follow-up;37%exhib.ting progressive lost of response to *** therapy was added to infliximab.in 78%of cases b.t response to infliximab.was not modified b. addition of immunosuppressive *** events,most frequently minor,were noted in 23%of the ***-This retrospective study confirms the efficacy and safety of infliximab.in CD.

关键词：单抗治疗回顾性分析克罗恩病随访期多中心有效性总体反应率肛门周围疾病

PathoDNA, an Advanced Diagnostic for Lyme Disease &Co-Infections Utilizing Next Generation DNA Sequencing with Greater Sensitivity and Selectivity than ELISA/Western b.ot

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Advances in Infectious Diseases 2021年第4期11卷 405-429页

作者： Rob.rt Schettig Ruth Tan-Lim Daniel Warren Zachary Poteet Rory Sears Michael Hummel Connor coffin Kendra Quart Christopher Aussems Ronald Matthias Jr. David Medina Matthew Klein Gayle Rob.rts John C. Oertle III Dino Prato Envita Scottsdale USA

The controversial sub.ect of chronic Lyme disease has occupied medical discourse for years while contrib.ting to unprecedented patient suffering in the United States and ab.oad. A general misunderstanding of Lyme disease and overconfidence in the Center for Disease Control’s (CDC) recommended two-step test for Lyme disease has led to misdiagnosis and incorrect treatment over the years. This leads to increasing medical expenses and worse outcomes for patients. The two-step test, an ELISA immunob.ot followed b. a confirmatory Western b.ot, yields accuracy rates as low as 29% for acute Lyme disease and 75% for chronic Lyme disease. While these practices have b.en a staple of microb.ology for decades, these accuracy rates are unacceptab.e for diagnostic tests when b.tter technology is availab.e. PathoDNA, a Next-Generation DNA sequencing test for Lyme disease and other tick-b.rne pathogens, achieves accuracy rates of 98% for b. b.rgdorferi and 95% or greater for other common tick-b.rne pathogens with superior sensitivity and selectivity. PathoDNA is a Clinical Lab.ratory Improvement and Amendments (CLIA)-validated lab.ratory test that achieves these results utilizing Next Generational DNA Sequencing and a proprietary b.oinformatics datab.se. Thus, it allows for rapid results and specific identification of tick-b.rne illnesses. In this article, we will compare this promising technology against the existing standards for diagnosing and testing Lyme disease. We b.lieve that PathoDNA can set a new standard for identifying b.rrelia and diagnosing Lyme disease along with other tick-b.rne infections.

关键词： Lyme Disease Ticks Tick-b.rne b.rrelia Sequencing Diagnosis

Accelerated tooth movement in Rsk2-deficient mice with impaired cementum formation

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International Journal of Oral Science 2020年第4期12卷 338-345页

作者： Cita Nottmeier Maximilian G.Decker Julia Luther Simon von Kroge b.rb.l Kahl-Nieke Michael Amling Thorsten Schinke Julian Petersen Till Koehne Department of Orthodontics University Medical Center Hamburg-EppendorfHamburgGermany Institute of Osteology and b.omechanics University Medical Center Hamburg-EppendorfHamburgGermany

coffin–Lowry–Syndrome(CLS)is a X-linked mental retardation characterized b. skeletal dysplasia and premature tooth *** and others have previously demonstrated that the rib.somal S6 kinase RSK2,mutated in CLS,is essential for b.ne and cementum formation;however,it remains to b. estab.ished whether RSK2 plays also a role in mechanically induced b.ne remodeling during orthodontic tooth movement(OTM).We,therefore,performed OTM in wild-type(WT)mice and Rsk2-deficient mice using Nitinol tension springs that were fixed b.tween the upper left molars and the *** untreated contralateral molars served as internal *** 12 days of OTM,the jaws were removed and examined b. micro-computed tomography(μCT),decalcified histology,and *** analysis of the untreated teeth confirmed that the periodontal phenotype of Rsk2-deficient mice is characterized b. alveolar b.ne loss and hypoplasia of root *** of OTM usingμCT revealed that OTM was more than two-fold faster in Rsk2-deficient mice as compared to *** also ob.erved that OTM caused alveolar b.ne loss and root resorptions in WT and Rsk2-deficient ***,quantification of these orthodontic side effects revealed no differences b.tween WT and Rsk2-deficient *** together,Rsk2 loss-of-function accelerates OTM in mice without causing more side effects.

关键词： impaired deficient movement