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News

18 October 2018

ICCMg3

Conference by Dr RODRIGUEZ

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11 October 2018

XIIIth National Congress in Gastroenterology

Conference by Pr PAWLOTSKY and Pr HEZODE

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10 October 2018

Journée des Sciences de la Vie et de la Santé à Créteil

Thématique : « Maladies et agressions environnementales : pollutions, infections, alimentation, stress psycho-social, expositions professionnelles »

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8 October 2018

25th International Symposium on Hepatitis C Virus and Related Viruses

Find us at the congress

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3 October 2018

83e Journées de l'AFEF

Find us at the congress

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Story of a group

Prof Jean-Michel PAWLOTSKY

On May 1, 1990, I took my internship in Hepatology and Gastroenterology for a semester in the prestigious Department of Hepatology headed by Prof. Daniel Dhumeaux at the Henri Mondor University Hospital in Créteil (University of Paris-Est).This was the beginning of an inspiring translational career, fully dedicated to hepatology and virology.

The adventure started with myself alone, trying to run a home-made PCR for the detection of the RNA of the hepatitis C virus. Hopefully, many collaborators joined the group in the following years. Many of them still belong to it and contribute, at their level, to its production and reputation.

The first step was to put in place an organized, high-quality clinical research setting backed by a modern and innovative molecular virology laboratory. This led to the creation within our laboratory of the French National Reference Center for Viral Hepatitis B, C and D, under the auspices of the French Institute of Health Surveillance. In parallel, the basic research team was created and grew. It was labelled an "INSERM (French National Institute of Health) research team", within the Mondor Institute for Biomedical Research (IMRB, INSERM U955).

Our group provided a major contribution to the evolution of knowledge and to the management of patients with viral hepatitis B and C. This is our common pride. But the world is changing and science is happily bringing solutions to the most complex medical problems. The vast majority of chronic hepatitis C virus infections is now cured, while chronic hepatitis B virus infection is easily controlled by antiviral therapy. It is therefore time for our group to sail to new adventures, taking advantage of the expertise and technological capacity acquired.

We are now moving in 3 complementary directions. The development of novel approaches based on genomics and metagenomics using next-generation sequencing and original bio-analysis software pipelines for the diagnosis of infections. The development of new broad-spectrum antiviral approaches based on the inhibition of cyclophilins and the manipulation of cellular microRNAs, targeted in particular on respiratory viruses, which remain a major challenge for therapeutic developments.The understanding of the role of the hepatic inflammatory microenvironment on the progression of hepatocellular carcinoma and the identification of new therapeutic targets to limit it.

The future belongs to us ...


Last publication...

Frequent antiviral treatment failures in patients infected with hepatitis C virus genotype 4, subtype 4r.

Fourati S, Rodriguez C, Hézode C, Soulier A, Ruiz I, Poiteau L, Chevaliez S, Pawlotsky JM

19 august 2018

Abstract
Hepatitis C virus (HCV) genotype 4 is highly heterogeneous. HCV subtype 4r has been suggested to be less responsive to direct-acting antiviral (DAA) drug treatment than other genotype 4 subtypes. Among 537 DAA-treated patients who experienced a virological failure in France between 2015 and 2018, 121 (22.5%) were infected with genotype 4 and 27 of them (22.3%) with subtype 4r; subtype 4r was thus over-represented as compared to its prevalence in the French general population. Population sequencing of the NS3, NS5A and NS5B genes was performed in all subtype 4r patients at treatment failure and in 6 of them at baseline, while full-length HCV genome sequencing was performed in 2 baseline and 3 treatment failure samples by means of an original shotgun metagenomics method based on deep sequencing. At treatment failure, all subtype 4r patients harbored 2 to 3 dominant NS5A resistance-associated substitutions (RASs), including at least L28A/C/I/M/V and L30R. Among 13 patients exposed to sofosbuvir and an NS5A inhibitor (daclatasvir, ledipasvir or velpatasvir), 5 (38.5%) also harbored NS5B S282C/T RASs at treatment failure. An additional patient harbored S282C/T RASs at treatment failure by deep sequencing. The prevalence of S282C/T RASs at treatment failure was significantly higher in patients infected with genotype 4r than with other genotypes, including other subtypes of genotype 4.

CONCLUSION: The lower rates of SVR in patients infected with subtype 4r are related to the frequent preexistence at treatment baseline and subsequent selection by DAA treatment of both NS5A and NS5B S282 RASs. Our study suggests that these patients should be identified and receive a triple DAA combination regimen as first-line treatment. This article is protected by copyright. All rights reserved.

News

18 October 2018

ICCMg3

Conference by Dr RODRIGUEZ

Read more

11 October 2018

XIIIth National Congress in Gastroenterology

Conference by Pr PAWLOTSKY and Pr HEZODE

Read more

10 October 2018

Journée des Sciences de la Vie et de la Santé à Créteil

Thématique : « Maladies et agressions environnementales : pollutions, infections, alimentation, stress psycho-social, expositions professionnelles »

Read more

8 October 2018

25th International Symposium on Hepatitis C Virus and Related Viruses

Find us at the congress

Read more

3 October 2018

83e Journées de l'AFEF

Find us at the congress

Read more