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Mortality from liver cirrhosis and HCC in the DAA era:success in viral control is darkened by raise of metabolic disease

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 307-310页

作者： Antonio Saviano thomas f.baumert Inserm U1110 Institut de Recherche sur les Maladies Virales et HépatiquesUniversite de StrasbourgF-67000 StrasbourgFrance Pole Hépatodigestif Institut Hopitalo-UniversitaireHopitaux UniversitairesF-67000 StrasbourgFrance

Liver cirrhosis and primary liver cancers are leading causes of mortality worldwide with over than 1.7 million of deaths in 2010 representing about 3.4%of the overall deaths(1).Global liver cirrhosis deaths ceaselessly increased by 52.2%from 1980 to 2010(1).Similarly,primary liver cancers global deaths increased by 62.4%from 1990 to 2010(2).

关键词： cirrhosis liver mortality

fIB-4 score and hepatocellular carcinoma risk after hepatitis C virus cure:time to revise surveillance?

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Hepatobiliary Surgery and Nutrition 2020年第5期9卷 661-664页

作者： Antonio Saviano Simona Tripon thomas f.baumert Institut de Recherche sur les Maladies Virales et Hépatiques(IVH) Inserm U1110StrasbourgFrance Institut Hospitalo-Universitaire Pôle Hépato-digestifHôpitaux Universitaires de StrasbourgStrasbourgFrance University of Strasbourg StrasbourgFrance Institut Universitaire de france(IUf) ParisFrance

Hepatitis C virus(HCV)is a main cause and important risk factor for hepatocellular carcinoma(HCC)in Western countries(1).Direct antiviral agents(DAAs)for HCV are highly effective and well-tolerated antiviral drugs which allow HCV cure even in patients with advanced liver ***,whilst HCV cure improves liver function and decreases overall HCC risk,a significant HCC risk persists in particular in patients with advanced fibrosis including cirrhosis who have the highest risk of developing HCC(2-4).

关键词： drugs liver carcinoma

Pseudomonas exotoxin antisense RNA selectively kills hepatitis B virus infected cells

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World Journal of Gastroenterology 2008年第18期14卷 2810-2817页

作者： Peter Hafkemeyer Ulrich Brinkmann Elizabeth Brinkmann Ira Pastan Hubert E Blum thomas f baumert Department of Medicine Ⅱ University Hospital Freiburg Hugstetterstrasse 55 Freiburg D-79106 Germany Roche Diagnostics Nonnenwald 2 Penzberg D-82377 Germany National Cancer Institute National Institutes of Health Bethesda United States Inserm unit 748 Université Louis Pasteur 3 Rue Koeberle Strasbourg F-67000 France

AIM: To present an approach for selectively killing retrovirus-infected cells that combines the toxicity of Pseudomonas exotoxin (PE) and the presence of reverse transcriptase (RT) in infected cells. METHODS: PE antisense toxin RNA has palindromic stem loops at its 5' and 3' ends enabling self-primed generation of cDNA in the presence of RT. The RT activity expressed in retrovirus-infected cells converts "antisense-toxin-RNA" into a lethal toxin gene exclusively in these cells. RESULTS: Using cotransfection studies with PE-expressing RNAs and β-gal expressing reporter plasmids, we show that, in HepG2 and HepG2.2.15 hepatoma cells as well as in duck hepatitis B virus (DHBV) infected cells, HBV or DHBV-polymerase reverse transcribe a lethal cDNA copy of an antisense toxin RNA, which is composed of sequences complementary to a PE gene and eukaryotic transcription and translation signals. CONCLUSION: This finding may have important implications as a novel therapeutic strategy aimed at the elimination of HBV infection.

关键词： Gene therapy Pseudomonas exotoxin Retrovirus Reverse transcription

Hepatitis C treatment in patients with substance use disorder:the faster the better

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Hepatobiliary Surgery and Nutrition 2022年第1期11卷 129-131页

作者： Antonio Saviano Lucile Heroin Pierre Mayer thomas f.baumert Institut de Recherche sur les Maladies et Hépatiques(IVH) Inserm U1110StrasbourgFrance Institut Hospitalo-Universitaire Service d’hépato-gastroentérologieHôpitaux Universitaires de StrasbourgStrasbourgFrance University of Strasbourg StrasbourgFrance Institut Universitaire de france(IUf) ParisFrance

Hepatitis C virus(HCV)infection is a major cause of liver disease and hepatocellular carcinoma worldwide(1).HCV is a blood-borne infection and prevalence is particularly high in patients with a history of injective drug use or unsafe health care or sexual *** use disorder(SUD),and especially opioid misuse is a growing problem worldwide(2).This is particularly relevant in the United States(US)where opioid misuse has raised sharply in the last years(3,4),termed also opioid *** is associated with an increase incidence of HCV infections and reinfections and associated liver disease(2,4).Moreover,alcohol use disorder is frequent in patients with SUD(5),representing another major risk factor for chronic liver disease in this *** with SUD often experience poor access to health care resulting in higher mortality(5,6).finally,SUD is associated with psychiatric conditions and social problems such as housing instability,unemployment,and reduced access to medical care(7)which could result in a reduced access and compliance to HCV treatment.

关键词： patients mortality faster

Neutralizing antibodies in hepatitis C virus infection

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World Journal of Gastroenterology 2007年第36期13卷 4824-4830页

作者： Mirjam B Zeisel Samira fafi-Kremer Isabel fofana Heidi Barth franoise Stoll-Keller Michel Doffo■l thomas f baumert Inserm U748Strasbourg France Université Louis Pasteur Strasbourg France Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutesof Health Bethesda MD United States Universitaires de Strasbourg Strasbourg France Service d'Hépatogastro-entérologie Hpitaux Universitaires de Strasbourg

Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.

关键词： Hepatitis C virus Virus-host cell interaction Viral entry Neutralizing antibodies

Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81

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World Journal of Gastroenterology 2009年第2期15卷 240-244页

作者： Zhan-fei Tian Hong Shen Xi-Hua fu Yi-Chun Chen Hubert E Blum thomas f baumert Xi-Ping Zhao Department of Infectious Diseases 161 Hospital of PLA Wuhan 430030 Hubei Province China Department of Infectious Diseases Tongji Hospital Tongji Medical College Huazhong Science & Technology University Wuhan 430030 Hubei Province China Department of Medicine II University of Freiburg D-79106 Freiburg Germany Inserm U748 Universit6 Louis Pasteur Service d'Hepatogastroenterologie 3 Rue Koeberle F-67000 Strasbourg France

AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.

关键词： Hepatitis C virus E2 protein Tupaia CD81,Bind Enzyme-linked immunosorbent assay

Hepatitis B virus mutations potentially conferring adefovir/ tenofovir resistance in treatment-naive patients

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World Journal of Gastroenterology 2009年第6期15卷 753-755页

作者： Rebecca Pastor franois Habersetzer Samira fafi-Kremer Michel Doffoёl thomas f baumert Jean-Pierre Gut franoise Stoll-Keller Evelyne Schvoerer Laboratoire de Virologie CHRU de Strasbourg3 Rue Koeberlé67000 StrasbourgFrance Service d'Hépato-gastroentérologie Nouvel Hpital Civil1 Place de l'Hpital67091 StrasbourgFrance Inserm U 748 Strasbourg3 Rue Koeberlé67000 StrasbourgFrance Université Louis Pasteur Facultéde Médecine4 Rue Kirschleger67084 StrasbourgFrance

Anti-hepatitis B virus(HBV)therapy leads to the emer- gence of mutant viral strains during the treatment of chronic hepatitis B with nucleos(t)ides analogues. The existence of HBV variants with primary antiviral resistance may be important for treatment choice. We studied two patients with chronic HBV infection by sequencing the HBV polymerase *** had adefovir-and tenofovir-related mutations in the viral polymerase,although they had never been treated. These mutations were rtV214A/rtN238T in one patient and rtA194T in the ***,mutations in untreated patients deserve cautious *** data indicate that mutations that can theoretically confer adefovir or tenofovir resistance may emerge in treatmentnaive patients.

关键词： Hepatitis B virus Viral polymerase mutations Treatment-naive patients

Three Different functional Microdomains in the Hepatitis C Virus Hypervariable Region 1(HVR1 ) Mediate Entry and Immune evasion

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Three Different Functional Microdomains in the Hepatitis C V...

Virus-host Interactions during Hepatitis C Virus Entry-Implications for Pathogenesis and Novel Treatment Approaches

2012全国临床微生物与感染免疫学术研讨会

作者： Jean Dubuisson thomas f baumert Laure Aurelian 里尔大学巴斯德研究所感染与免疫中心斯特拉斯堡大学马里兰大学医学院药理与实验药物治疗研究室

High genetic heterogeneity is an important characteristic of Hepatitis C virus(HCV) that contributes to its ability to establish persistent *** hypervariable region 1(HVR1) that comprises the first 27 amino acid residues of the E2 envelope glycoprotein is the most variable region within the HCV *** plays a major role in both HCV cell entry and immune evasion,but the respective contribution of specific amino acid residues is still *** mutagenesis analyses of HCV pseudoparticles(HCVpp) and cell culture-derived HCV (HCVcc) using the H77 isolate indicate that five residues at positions 14,15 and 25-27 mediate binding of the

关键词： Hepatitis C Virus Hype rvariable Region 1 Virus entry Immune evasion

来源： cnki会议评论

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Virologica Sinica 2008年第2期23卷 124-131页

作者： Joachim Lupberger Mirjam B. Zeisel Anita Haberstroh Eva K. Schnober Sophie Krieger Eric Soulier Christine Thumann Cathy Royer Samira fafi-Kremer Catherine Schuster franoise Stoll-Keller Hubert E. Blum thomas f. baumert Inserm U748 Hpitaux Universitaires de Strasbourg Université Louis Pasteur 3 Rue Koeberle Department of Medicine II University of Freiburg

Hepatitis C virus (HCV) is a member of the flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between the virus and the target cell that is required for successful entry into the cell and initiation of infection. This step is an important determinant of tissue tropism and pathogenesis; it thus represents a major target for antiviral host cell responses, such as antibody-mediated virus neutralization. following the development of novel cell culture models for HCV infection our understanding of the HCV entry process and mechanisms of virus neutralization has been markedly advanced. In this review we summarize recent developments in the molecular biology of viral entry and its impact on pathogenesis of HCV infection, development of novel preventive and therapeutic antiviral strategies.

关键词： Hepatitis C virus Viral entry Entry inhibitor Neutralizing antibodies