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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(HbV) is a global public health problem 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 HbV-related liver disease. Antiviral therapy with nucleos/tide analogs(NA) targeting the HbV polymerase(P) can inhibit disease progression by long-term suppression of HbV replication. However, treatment may fail with first generation NA therapy due to the emergence of drugresistant mutants, as well as incomplete medication adherence. The HbV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HbV P can cause concomitant changes in the HbV surface gene(S) and vice versa. HbV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HbV variants and their clinical relevance may be important for monitoring chronic hepatitis b disease progression and treatment response. In this review, we will discuss HbV 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 Microbiology Immunologyand Infectious DiseasesCumming School of MedicineUniversity of CalgaryCalgary T2N 1N4ABCanada Department of Chemistry and biochemistry Alberta RNA Research and Training InstituteUniversity of LethbridgeLethbridge T1K3M4ABCanada

Chronic infection with viral hepatitis affects half a billion 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 contributing to complexity in diagnosis and *** infection with hepatitis b virus(HbV),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 by HbV,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 by viral *** integration to promote genome instability is a feature of HbV infection,and metabolic reprogramming leading to steatosis is driven by HCV *** current review aims to provide a brief overview of HbV,HCV and HDV molecular biology,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

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肠易激综合征患者的脊髓痛觉处理调节的变化

世界核心医学期刊文摘（胃肠病学分册） 2005年第3期1卷 39-40页

作者： coffin b. bouhassira D. SabatéJ.-M. 杨瑗 Service d'Hepato-Gastroenterologie Hpital Louis Mourier 178 rue des Renouillers 92701 Colombes Cedex France Dr.

background: Visceral hypersensitivity has been evidenced in patients with irritable bowel syndrome (IbS) but its mechanisms remain poorly elucidated. We investigated the spinal transmission of nociceptive signals in IbS patients by analysing the effects of rectal distensions on electromyographic recordings of the somatic nociceptive flexion (RIII) reflex, an objective index of spinal nociceptive processes. Methods: Fourteen IbS and 10 healthy volunteers were included in the study. Slow ramp (40 ml/min) and rapid phasic (900 ml/min, 10, 20, 30, and 40 mm Hg) rectal distensions were randomly performed while the RIII reflex evoked by electrical stimulation of the sural nerve at the ankle was continuously recorded from the ipsilateral biceps femoris. Results: In healthy volunteers, significant progressive inhibition of the RIII reflex was observed during slow ramp distension (61 (13)%of control values) while biphasic effects (facilitation and inhibition) were observed during rapid distensions. In contrast, in IbS patients, the RIII reflex was significantly facilitated during slow ramp distension (139 (15)%of control values) and inhibitions induced by rapid distensions were significantly reduced. Volumes of distension and rectal compliance were similar in both groups. Conclusions: Our results provide direct evidence that a hyperexcitability of spinal nociceptive processes is present in a large subgroup of IbS patients.

关键词：肠易激综合征脊髓痛躯体痛腓肠神经超敏反应电刺激对照值膨胀过程性抑制双相

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 brian Conway David Truong Philip Wong Lisa barrett Hin Hin Ko Sarah Haylock-Jacobs 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 Microbiology and Immunology Dalhousie UniversityHalifax b3h 4r2Canada Cumming School of Medicine University of CalgaryCalgary t2n 1n4Canada

bACKGROUND Hepatitis b virus(HbV)nucleos(t)ide analog(NA)therapy reduces liver disease but requires prolonged therapy to achieve hepatitis b surface antigen(HbsAg)*** is limited North American real-world data using non-invasive tools for fibrosis 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 fibrosis regression using liver stiffness measurement(LSM)(i.e.,FibroScan®).METHODS Retrospective,observational cohort study from the Canadian HbV *** collected included demographics,NA,HbV DNA,alanine aminotransferase(ALT),and *** were HbV 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 baseline,84%Asian,6%White,and 9%black).Percentage of 64(n=299)received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years,*** mean baseline 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 fibrosis regression between groups(i.e.,mean-4.2 kPa change in TDF and-1.6 kPa in LAM,Pble data on treatment showed that all had normal ALT,but more TDF patients were virologically suppressed(brosis regression rarely leads to HbsAg loss.

关键词： Nucleos(t)ide analog therapy Functional cure Hepatitis b virus surface antigen loss Fibrosis 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

Objectives-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 belonging to university teaching hospitals of the Parisian hospitals group(Assistance Publique-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 be *** mean time to relapse was to 3.9 ±3.1 ***-eight patients were on maintenance therapy at the end of the follow-up;37%exhibiting progressive lost of response to *** therapy was added to infliximab in 78%of cases but response to infliximab was not modified by 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 blot

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

作者： Robert 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 Roberts John C. Oertle III Dino Prato Envita Scottsdale USA

The controversial subject of chronic Lyme disease has occupied medical discourse for years while contributing to unprecedented patient suffering in the United States and abroad. 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 immunoblot followed by a confirmatory Western blot, yields accuracy rates as low as 29% for acute Lyme disease and 75% for chronic Lyme disease. While these practices have been a staple of microbiology for decades, these accuracy rates are unacceptable for diagnostic tests when better technology is available. PathoDNA, a Next-Generation DNA sequencing test for Lyme disease and other tick-borne pathogens, achieves accuracy rates of 98% for b. burgdorferi and 95% or greater for other common tick-borne pathogens with superior sensitivity and selectivity. PathoDNA is a Clinical Laboratory Improvement and Amendments (CLIA)-validated laboratory test that achieves these results utilizing Next Generational DNA Sequencing and a proprietary bioinformatics database. Thus, it allows for rapid results and specific identification of tick-borne illnesses. In this article, we will compare this promising technology against the existing standards for diagnosing and testing Lyme disease. We believe that PathoDNA can set a new standard for identifying borrelia and diagnosing Lyme disease along with other tick-borne infections.

关键词： Lyme Disease Ticks Tick-borne borrelia 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 bärbel Kahl-Nieke Michael Amling Thorsten Schinke Julian Petersen Till Koehne Department of Orthodontics University Medical Center Hamburg-EppendorfHamburgGermany Institute of Osteology and biomechanics University Medical Center Hamburg-EppendorfHamburgGermany

coffin–Lowry–Syndrome(CLS)is a X-linked mental retardation characterized by skeletal dysplasia and premature tooth *** and others have previously demonstrated that the ribosomal S6 kinase RSK2,mutated in CLS,is essential for bone and cementum formation;however,it remains to be established whether RSK2 plays also a role in mechanically induced bone 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 between the upper left molars and the *** untreated contralateral molars served as internal *** 12 days of OTM,the jaws were removed and examined by micro-computed tomography(μCT),decalcified histology,and *** analysis of the untreated teeth confirmed that the periodontal phenotype of Rsk2-deficient mice is characterized by alveolar bone 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 observed that OTM caused alveolar bone loss and root resorptions in WT and Rsk2-deficient ***,quantification of these orthodontic side effects revealed no differences between WT and Rsk2-deficient *** together,Rsk2 loss-of-function accelerates OTM in mice without causing more side effects.

关键词： impaired deficient movement