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Physiopathology and treatment of viral hepatitis

Team Asselah

Department Hepato-Gastroenterology Department

 

Team leader

 

Line-up

Team leader

 

Presentation

The Team Project

Hepatitis B virus (HBV) infection remains a major global health concern as over 257 million individuals are estimated to be carriers of hepatitis B ‘surface’ antigen (HBsAg), the hallmark of chronic HBV infection (CHB). CHB has potential adverse outcomes, including cirrhosis, hepatic decompensation, and hepatocellular carcinoma.

The Hepatology team from Hospital Beaujon is a worldwide leader in clinical trials and has been successful in drug development for chronic hepatitis C, for which the team has been involved as a coordinator/principal investigator in several clinical trials. In particular the team coordinated major international clinical trials on HCV Genotype 4 infection.

The team project is currently working on HBV physiopathology and for strategies to achieve HBV cure. The team is involved as a coordinator/principal investigator in several clinical trials on drugs in development to fight against HBV infection. The team fields of research include also chronic liver diseases, translational medicine and treatment of HBV and HCV infections with new direct-acting antivirals.

The development of antibodies against HBsAg is a hallmark of the resolution of acute infection and is a therapeutic goal for the functional recovery of CHB. CHB causes exhaustion of virus-specific T cells, but its impact on humoral immunity has been poorly studied. The identification of T and B cell response mechanisms will provide a better understanding of their role in seroconversion of HBsAg.

Thanks to the expertise of Dr Abdellah Mansouri, the team has also a project on mitochondrial involvement in the pathophysiology of viral hepatitis. Mitochondria play important role in cellular antiviral defense because they serve as the platform for innate immune signaling and for inflammasome formation. The mitochondrial unfolded protein response (UPRmt, a recently discovered protein quality control pathway that resolves the mitochondrial stress by retrograde signaling to the nucleus) is characterized by transcriptional activation of innate immune and proinflammatory genes. Mitophagy and UPRmt may thus act as a negative modulator of mitochondrial antiviral protein (MAVS)-mediated innate immune signaling and may unravel how HBV or HCV usurp mitochondrial dysfunction to cripple the interferon synthesis, interferon responsive genes expression and cellular antiviral response. One of the objectives of the Team is thus to demonstrate viral involvement in mitochondrial dynamics (biogenesis, fission, fusion, mitophagy), function/dysfunction, oxidative stress and UPRmt. These studies may highlight the novel role of mitochondrial stresses in antiviral signaling and in the responses to the treatments. 

 

 

Landmark publications

  • Publication date : 07 October 2020 More

    COVID-19: discovery, diagnostics and drug development Journal of Hepatology

    Autors : Asselah Tarik David Durantel Eric Pasmant George Lau Raymond F. Schinazi

  • Publication date : 01 August 2020 More

    Hepatitis B surface antigen seroclearance: Immune mechanisms, clinical impact, importance for drug development J Hepatol .

    Autors : Tout Issam Alex Loureiro Dimitri Mansouri Abdellah Vassili Soumelis Boyer Nathalie Asselah Tarik

  • Publication date : 01 November 2019 More

    Targets and future direct-acting antiviral approaches to achieve hepatitis B virus cure Lancet Gastroenterol Hepatol

    Autors : Asselah Tarik Loureiro Dimitri Boyer Nathalie Mansouri Abdellah

  • Publication date : 01 January 2019 More

    Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus genotype 5 or 6 infection (ENDURANCE-5,6): an open-label, multicentre, phase 3b trial Lancet Gastroenterol Hepatol

    Autors : Asselah Tarik Samuel S Lee Betty B Yao Tuan Nguyen Florence Wong Adam Mahomed Seng Gee Lim Armand Abergel Joe Sasadeusz Edward Gane Neddie Zadeikis Gretja Schnell Zhenzhen Zhang Ariel Porcalla Federico J Mensa Kinh Nguyen

  • Publication date : 01 September 2018 More

    Mitochondrial Dysfunction and Signaling in Chronic Liver Diseases Gastroenterology .

    Autors : Mansouri Abdellah Charles-Henry Gattolliat Asselah Tarik

  • Publication date : 01 April 2018 More

    Eliminating hepatitis C within low-income countries – The need to cure genotypes 4, 5, 6 J Hepatol

    Autors : Asselah Tarik Tarek Hassanein Imam Waked Mansouri Abdellah Geoffrey Dusheiko Edward Gane

  • Publication date : 01 March 2018 More

    Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis Clin Gastroenterol Hepatol

    Autors : Asselah Tarik Kris V Kowdley Neddie Zadeikis Stanley Wang Tarek Hassanein Yves Horsmans Massimo Colombo Filipe Calinas Humberto Aguilar Victor de Ledinghen Parvez S Mantry Christophe Hezode Rui Tato Marinho Kosh Agarwal Frederik Nevens Magdy Elkhashab Jens Kort Ran Liu Teresa I Ng Preethi Krishnan Chih-Wei Lin Federico J Mensa

  • Publication date : 01 February 2018 More

    Treatment of hepatitis C virus infection with direct-acting antiviral agents: 100% cure? Liver Int .

    Autors : Asselah Tarik Marcellin Patrick Raymond F Schinazi

  • Publication date : 01 February 2018 More

    Towards HBV curative therapies Liver Int.

    Autors : Raymond F. Schinazi Maryam Ehteshami Leda Bassit Asselah Tarik

  • Publication date : 12 October 2016 More

    MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C Scientific Reports

    Autors : Kevin Appourchaux Dokmak Safi Matthieu Resche-Rigon Treton Xavier Martine Lapalus Charles-Henry Gattolliat Emmanuelle Porchet Michelle Martinot-Peignoux Boyer Nathalie Michel Vidaud Bedossa Pierre Marcellin Patrick Ivan Bièche Emilie Estrabaud Asselah Tarik

  • Publication date : 26 March 2014 More

    Reduction of MicroRNA 122 Expression in IFNL3 CT/TT Carriers and during Progression of Fibrosis in Patients with Chronic Hepatitis C J Virol, 2014 Jun;88(11):6394-402. doi: 10.1128/JVI.00016-14

    Autors : Estrabaud E Lapalus M Broët P Appourchaux K Muynck SD Lada O Martinot-Peignoux M Bièche I Valla Dominique Bedossa Pierre Marcellin Patrick Vidaud M Asselah Tarik

 
 

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Latest Publications

  • Publication date : 30 December 2020 More

    Mast Cell Chymase and Kidney Disease International Journal of Molecular Sciences

    Autors : Vibhushan Shamila Bratti Manuela Juan Eduardo Montero-Hernández Alaa El Ghoneimi Benhamou Marc Charles Nicolas Daugas Eric Blank Ulrich

  • Publication date : 21 December 2020 More

    Liver stiffness by transient elastography to detect porto-sinusoidal vascular liver disease with portal hypertension Hepatology

    Autors : Elkrief Laure Marie Lazareth Sylvie Chevret Paradis Valérie Marta Magaz Lorraine Blaise Laura Rubbia-Brandt Moga Lucile Durand François Audrey Payancé Plessier Aurélie Cendrine Chaffaut Valla Dominique Marion Malphettes Alba Diaz Jean-Charles Nault Pierre Nahon Etienne Audureau Vlad Ratziu Castera Laurent Juan-Carlos Garcia Pagan Nathalie Ganne-Carrie Rautou Pierre-Emmanuel ANRS CO12 CirVir group

  • Publication date : 19 November 2020 More

    Iron chelation rescues hemolytic anemia and skin photosensitivity in congenital erythropoietic porphyria Blood

    Autors : Jean-Marc Blouin Cécile Ged Magalie Lalanne Isabelle Lamrissi-Garcia Fanny Morice-Picard Pierre Costet Daher Raed François Moreau-Gaudry Aurélie Bedel Puy Hervé Gouya Laurent Emmanuel Richard