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Current trends in access to treatment for hepatitis B in immigrants vs non-immigrants

Gastroenterology Report 2020年第5期8卷 362-366,I0002页

作者： Mireia Miquel Albert Pardo Montse Forné Gemma Martínez-Alpin AdriàRodríguez-Castellano Meritxell Casas MercèRosinach MercèRoget Blai Dalmau Rocío Temiño joan carlos quer Jordi Sanchez-Delgado Jordi Ortiz Mercedes Vergara Liver Unit Gastroenterology DepartmentParc TaulíUniversity HospitalInstitut d’Investigacio i InnovacióParc TaulíI3PTAutonomous University of BarcelonaSabadellSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadridSpain Gastroenterology Department University Hospital Joan XXIIITarragonaSpain Liver Unit Gastroenterology DepartmentUniversity Hospital Mútua TerrassaBarcelonaSpain Liver Unit Gastroenterology DepartmentConsorci Sanitari de TerrassaTerrassaSpainó

Background:Universal vaccination for hepatitis B virus(HBV)and migratory movements have changed the demographic characteristics of this disease in Spain and in ***,we evaluated the characteristics of the disease and the possible differences according to origin(immigrants vs non-immigrants)and access to ***:This is a multicenter cross-sectional study(June 2014 to May 2015)in which outpatients with a positive HBsAg were seen and followed in four Hepatology *** and clinical data and indication and access to treatment were collected in two different regions of Catalonia(Spain)where there are no barriers to treatment due to a comprehensive coverage under the National Health ***:A total of 951 patients were evaluated(48.1%men).Of these,46.6%were immigrants(58.7%of them were born in Africa)and were significantly younger compared to *** proportions of patients with alcohol consumption,being overweight,and other indicators of metabolic co-morbidities were significantly higher in *** the 937 patients receiving HBeAg examination,91.7%were *** HBeAg-positive infection was significantly higher in immigrants(3.9%vs 0.6%,P=0.001)and chronic HBeAg-negative hepatitis was higher non-immigrants(31.7%vs 21.4%,P<0.001).Not only was the proportion of patients who met treatment criteria significantly higher among nonimmigrants(38.4%vs 29.2%,P=0.003),but also the proportion of those with indication of effectively receiving therapy at the time of data collection(83.2%vs 57.8%,P<0.001).Conclusions:The immigrant population with HBV is younger and has a lower prevalence of metabolic co-morbidities and a higher frequency of chronic HBeAg *** having access to care and an indication for treatment,some do not get adequately treated due to several factors including local adaptation that precludes access to treatment.

关键词： hepatitis B prevalence immigration access to treatment

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Olfactory receptors in neural regeneration in the central nervous system

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Neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： Rafael Franco Claudia Garrigós Toni Capó joan Serrano-Marín Rafael Rivas-Santisteban Jaume Lillo Molecular Neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network Center for Biomedical Research in Neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

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Role of aldehyde dehydrogenase 2 in ischemia reperfusion injury:An update

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World Journal of Gastroenterology 2018年第27期24卷 2984-2994页

作者： Arnau Panisello-Roselló Alexandre Lopez Emma Folch-Puy Teresa Carbonell Anabela Rolo carlos Palmeira René Adam Marc Net joan Roselló-Catafau Department of Experimental Pathology Institute of Biomedical Research of Barcelona(IIBB)-CSICBarcelona 08036Spain Centre Hepatobiliare AP-HP Hopital Paul BrousseVillejuif 75008France Department of Physiology Faculty of BiologyUniversitat de BarcelonaBarcelona 08036Spain Center for Neuroscience and Cell Biology University of CoimbraCoimbra 3004-517Portugal Institute Georges Lopez Lissieu 69380France

Aldehyde dehydrogenase 2(ALDH2) is best known for its critical detoxifying role in liver alcohol metabolism. However, ALDH2 dysfunction is also involved in a wide range of human pathophysiological situations and is associated with complications such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases and aging. A growing body of research has shown that ALDH2 provides important protection against oxidative stress and the subsequent loading of toxic aldehydes such as 4-hydroxy-2-nonenal and adducts that occur in human diseases, including ischemia reperfusion injury(IRI). There is increasing evidence of its role in IRI pathophysiology in organs such as heart, brain, small intestine and kidney; however, surprisingly few studies have been carried out in the liver, where ALDH2 is found in abundance. This study reviews the role of ALDH2 in modulating the pathways involved in the pathophysiology of IRI associated with oxidative stress, autophagy and apoptosis. Special emphasis is placed on the role of ALDH2 in different organs, on therapeutic "preconditioning" strategies, and on the use of ALDH2 agonists such as Alda-1, which may become a useful therapeutic tool for preventing the deleterious effects of IRI in organ transplantation.

关键词： Aldehyde dehydrogenase 2 4-hydroxy-2-nonenal autophagy Apoptosis Ischemia reperfusion injury Preconditioning

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Sirtuin 1 in rat orthotopic liver transplantation:An I GL-1 preservation solution approach

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World Journal of Gastroenterology 2015年第6期21卷 1765-1774页

作者： Eirini Pantazi Mohamed Amine Zaouali Mohamed Bejaoui Emma Folch-Puy Hassen Ben Abdennebi Ana Teresa Varela Anabela Pinto Rolo carlos Marques Palmeira joan Roselló-Catafau Experimental Hepatic Ischemia Reperfusion Unit Institute of Biomedical Research of Barcelona Faculty of Pharmacy Molecular Biology and Anthropology Applied to Development and Health Department of Life Sciences and Center for Neuroscience and Cell Biology University of Coimbra Department of Biology University of Aveiro

AIM:To investigate the possible involvement of Sirtuin1(SIRT1)in rat orthotopic liver transplantation(OLT),when Institute Georges Lopez 1(IGL-1)preservation solution is enriched with trimetazidine(TMZ).METHODS:Male Sprague-Dawley rats were used as donors and *** were stored in IGL-1 preservation solution for 8h at 4℃,and then underwent OLT according to Kamada’s cuff technique without *** another group,livers were stored in IGL-1 preservation solution supplemented with TMZ,at10-6 mol/L,for 8 h at 4℃and then underwent *** were sacrificed 24 h after reperfusion,and liver and plasma samples were *** injury(transaminase levels),mitochondrial damage(glutamate dehydrogenase activity)oxidative stress(malondialdehyde levels),and nicotinamide adenine dinucleotide(NAD+),the cofactor necessary for SIRT1 activity,were determined by biochemical ***1 and its substrates(acFox O1,ac-p53),the precursor of NAD+,nicotinamide phosphoribosyltransferase(NAMPT),as well as the phosphorylation of adenosine monophosphate activated protein kinase(AMPK),p-m TOR,p-p70S6K(direct substrate of m TOR),autophagy parameters(beclin-1,LC3B)and MAP kinases(p-p38 and p-ERK)were determined by Western ***:Liver grafts preserved in IGL-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preservedin IGL-1 solution *** addition,livers preserved in IGL-1+TMZ presented reduced levels of oxidative *** was consistent with enhanced SIRT1 protein expression and elevated SIRT1 activity,as indicated by decreased acetylation of p53 and Fox *** elevated SIRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD+/NADH ***-regulation of SIRT1 was consistent with activation of AMPK and inhibition of phosphorylation of m TOR and its direct substrate(p-p70S6K).As a consequence,autophagy mediators(beclin-1 and LC3B)were ***,MAP kinases w

关键词： Sirtuin 1 Ischemia-reperfusion injury Liver transp

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Relevance of proteolysis and proteasome activation in fatty liver graft preservation: An Institut Georges Lopez-1 vs University of Wisconsin appraisal

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World Journal of Gastroenterology 2017年第23期23卷 4211-4221页

作者： Mohamed Amine Zaouali Arnau Panisello-Roselló Alexandre Lopez carlos Castro Benítez Emma Folch-Puy Agustín García-Gil Teresa Carbonell RenéAdam joan Roselló-Catafau Experimental Hepatic Ischemia-Reperfusion Unit Institut d’Investigacions Biomèdiques de BarcelonaSpanish National Research Council Research Unit of Biology and molecular anthropology applied to development and Health(UR12ES11) Faculty of PharmacyUniversity of Monastir Tunisia and Institute of Biotechnology of Monastir University of Monastir Centre Hépatobiliaire AP-PHHopital Paul Brousse Hospital Clínico de Zaragoza Facultat Biologia Universitat de Barcelona

To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) *** liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to “ex vivo” normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity and 20S and 19S proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3).RESULTSProfiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury (AST/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 *** comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a hig

关键词： Liver proteolysis Proteasome activation Fatty liver preservation Institut Georges Lopez-1 University of Wisconsin High mobility group box 1 Cold ischemia reperfusion injury

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Polyethylene glycols: An effective strategy for limiting liver ischemia reperfusion injury

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World Journal of Gastroenterology 2016年第28期22卷 6501-6508页

作者： Gianfranco Pasut Arnau Panisello Emma Folch-Puy Alexandre Lopez carlos Castro-Benítez Maria Calvo Teresa Carbonell Agustín García-Gil RenéAdam joan Roselló-Catafau Department of Pharmaceutical and Pharmacological University of Padova and Veneto Institute of Oncology IRCCS 35128 Padova Italy Experimental Pathology Department Institute of Biomedical Research of Barcelona 08036 Barcelona Spain Centre Hepatobiliaire AP-HP Hopital Paul Brousse Inserm U935 Universite Paris-Sud Villejuif 75008 Paris France Unitat de Microscopia Optic Avancada CCiTUB Centre Cientifics i Tecnologics Faculty of Medicine University of Barcelona 08036 Barcelona Spain Physiology Department Faculty of Biology Universitat de Barcelona 08036 Barcelona Spain Hospital Clinico de Zaragoza 50009 Zaragoza Spain

Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.

关键词： Ischemia reperfusion injury Polyethylene glycol Liver preconditioning Liver transplantation UW solution IGL-1 solution SCOT solution PEG rinse solution Machine perfusion

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Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2021年第4期20卷 323-329页

作者： Adriano-Valerio Schettini Laura Llado JulieK Heimbach JoseGonzalez Costello Marie Tranäng Olivier Van Caenegem Richard C Daly Peter Van den Bergh carlos Casasnovas joan Fabregat John J Poterucha Maxime Foguenne Bo Göran Ericzon Jan Lerut Institute for Experimental and Clinical Research(IREC) Catholic University of Louvain(UCL)Avenue Hippocrate 55Brussels 1200Belgium Liver Transplant Unit Department of SurgeryHospital Universitari de BellvitgeCalle de la Feixa LlargaBarcelona 08907Spain Division of Transplantation Surgery William J.von Liebig Transplant CenterMayo Clinic2001st St SWRochesterMN 55905USA Advanced Heart Failure and Transplant Unit Cardiology DepartmentHospital Universitari de BellvitgeCalle de la Feixa LlargaBarcelona 08907Spain Familial Amyloidotic Polyneuropathy World Transplant Registry(FAPWTR) Division of Transplantation SurgeryKarolinska Universitetssjukhuset HuddingeF82Karolinska InstitutetStockholm 14186Sweden Cardiothoracic Intensive Care Unit Department of Cardiovascular DiseasesUniversity Hospitals Saint-Luc-UCLAvenue Hippocrate 10Brussels 1200Belgium Cardiovascular Surgery Department Mayo Clinic2001st St SWRochesterMN 55905USA Neuromuscular Reference Centre University Hospital Saint-Luc-UCLAvenue Hippocrate 10Brussels 1200Belgium Neuromuscular Unit Neurology DepartmentHospital Universitari de BellvitgeCalle de la Feixa LlargaBarcelona 08907Spain Division of Gastroenterology and Hepatology Mayo Clinic2001st St SWRochester MN 08907USA Division of Transplantation Surgery CLINTECKarolinska Universitetssjukhuset HuddingeF82Karolinska InstitutetStockholm 14186Sweden

Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.

关键词： Hereditary transthyretin amyloidosis Heart transplantation Liver transplantation Non-Val30Met mutation Val122del mutation Domino liver transplantation

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Acute esophageal variceal bleeding:Current strategies and new perspectives

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World Journal of Hepatology 2010年第7期2卷 261-274页

作者： Salvador Augustin Antonio González joan Genescà Liver Unit Department of Internal MedicineHospital Universitari Vall d’HebronInstitut de RecercaUniversitat Autònoma de Barc elona

Management of acute variceal bleeding has greatly improved over recent years. Available data indicates that general management of the bleeding cirrhotic patient by an experienced multidisciplinary team plays a major role in the f inal outcome of this complication. It is currently recommended to combine pharmacological and endoscopic therapies for the initial treatment of the acute bleeding. Vasoactive drugs (preferable somatostatin or terlipressin) should be started as soon as a variceal bleeding is suspected (ideally during transfer to hospital) and maintained afterwards for 2-5 d. After stabilizing the patient with cautious fluid and blood support, an emergency diagnostic endoscopy should be done and, as soon as a skilled endoscopist is available, an endoscopic variceal treatment (ligation as f irst choice, sclerotherapy if endoscopic variceal ligation not feasible) should be performed. Antibiotic prophylaxis must be regarded as an integral part of the treatment of acute variceal bleeding and should be started at admission and maintained for at least 7 d. In case of failure to control the acute bleeding, rescue therapies should be immediately started. Shunt therapies (especially tran sjugular intrahepatic portosystemic shunt) are very effective at controlling treatment failures after an acute variceal bleeding. Therapeutic developments and increasing knowledge in the prognosis of this complication may allow optimization of the management strategy by adapting the different treatments to the expected risk of complications for each patient in the near future. Theoretically, this approach would allow the initiation of early aggressive treatments in high-risk patients and spare low-risk individuals unnecessary proce dures. Current research efforts will hopefully clarify this hypothesis and help to further improve the outcomes of the severe complication of cirrhosis.

关键词： Portal hypertension Variceal bleeding Complic ations of cirrhosis

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Usefulness of Impella support in different clinical settings in cardiogenic shock

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Journal of Geriatric Cardiology 2022年第2期19卷 115-124页

作者： María Isabel Barrionuevo-Sánchez Albert Ariza-Solé Daniel Ortiz-Berbel JoséGonzález-Costello joan Antoni Gómez-Hospital Victòria Lorente Oriol Alegre Isaac Llaó Josécarlos Sánchez-Salado Josep Gómez-Lara Arnau Blasco-Lucas Josep Comin-Colet Cardiology Department Intensive Cardiac Care UnitBellvitge University HospitalL’Hospitalet de LlobregatBarcelonaSpain Cardiac Surgery Department Heart Disease InstituteBellvitge University HospitalL’Hospitalet de LlobregatBarcelonaSpain

BACKGROUND The Impella pump has emerged as a promising tool in patients with cardiogenic shock(CS).Despite its attractive properties,there are scarce data on the specific clinical setting and the potential role of Impella devices in CS patients from routine clinical *** This is an observational,retrospective,single center,cohort *** consecutive patients with diagnosis of CS and undergoing support with Impella 2.5?,Impella CP?or Impella 5.0?from April 2015 to December 2020 were *** characteristics,management and outcomes were assessed according to CS severity,age and cause of *** outcome measured was in-hospital *** A total of 50 patients were included(median age:59.3±10 years).The most common cause of CS was acute coronary syndrome(ACS)(68%),followed by decompensation of previous cardiomyopathy(22%).A total of 13 patients(26%)had profound *** patients(54%)improved pulmonary congestion at 48 h after Impella support.A total of 19 patients(38%)presented significant ***-hospital mortality was 42%.Among patients with profound CS(n=13),five patients were previously supported with venoarterial extracorporeal membrane oxygenation.A total of eight patients(61.5%)died during the admission,and no patient achieved ventricular *** patients(≥67 years,n=10)had more comorbidities and the highest mortality(70%).Among patients with ACS(n=34),35.3%of patients had profound CS;and in most cases(52.9%),Impella support was performed as a bridge to *** contrast,only one patient from the decompensated cardiomyopathy group(n=11)presented with profound *** 90.9%of these cases,Impella support was used as a bridge to cardiac *** were no cases of *** In this cohort of real-life CS patients,Impella devices were used in different settings,with different clinical profiles and *** a significant rate of complications,mortality was acceptable and lower than those observed

关键词： Impella clinical routine

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Quasispecies dynamics in main core epitopes of hepatitis B virus by ultra-deep-pyrosequencing

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World Journal of Gastroenterology 2012年第42期18卷 6096-6105页

作者： Maria Homs Maria Buti David Tabernero Josep quer Alex Sanchez Noelia Corral Rafael Esteban Francisco Rodriguez-Frias Network Medical Research Center Hepatic and Digestive Diseases(CIBERehd)Institute of Health Carlos Ⅲ08036 BarcelonaSpain Department of Biochemistry Vall d'Hebron HospitalAutonomous University of Barcelona08035 BarcelonaSpain Department of Hepatology Vall d' Hebron HospitalAutonomous University of Barcelona08035 BarcelonaSpain Statistics and Bioinformatics Unit Research InstituteVall d'Hebron Hospital08035 BarcelonaSpain

AIM:To investigate the variability of the main immunodominant motifs of hepatitis B virus(HBV) core gene by ultra-deep-pyrosequencing(UDPS).METHODS:Four samples(2 genotype A and 2 genotype D) from 4 treatment-na ve patients were assessed for baseline *** additional samples from one patient(patient 4,genotype D) were selected for analysis:one sample corresponded to a 36-mo treatment-free period from baseline and the other to the time of viral breakthrough after 18 mo of lamivudine *** HBV region analyzed covered amino acids 40 to 95 of the core gene,and included the two main epitopic regions,Th50-69 and *** was carried out in the Genome Sequencer FLX system(454 Life Sciences,Roche).After computer filtering of UDPS data based on a Poisson statistical model,122 813 sequences were *** most conserved position detected by UDPS was analyzed by site-directed mutagenesis and evaluated in cell ***:Positions with highest variability rates were mainly located in the main core epitopes,confirming their role as immune-stimulating *** addition,the distribution of variability showed a relationship with HBV *** 1(genotype A) presented the lowest variability rates and patient 2(genotype A) had 3 codons with variability higher than 1%.Patient 3 and 4(both genotype D) presented 5 and 8 codons with variability higher than 1%,*** median baseline frequencies showed that genotype A samples had higher variability in epitopic positions than in the other positions analyzed,approaching significance(P = 0.07,sample 1 and P = 0.05,sample 2).In contrast,there were no significant differences in variability between the epitopic and other positions in genotype D ***,patient 1 presented a completely mutated motif from amino acid 64 to 67(E 64 LMT 67),which is commonly recognized by T helper ***,the variability observed in all 4 patients was particularly associated with the E 64 LMT 67 mo

关键词： Hepatitis B virus Ultra-deep-pyrosequencing Epitopes Quasispecies Linkage analysis

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