PaThLiv – Pathobiologie et thérapie des maladies du foie

Menu
News
Contact
FR

Teams

HeLip Team

The “Hepatitis Viruses and Liver Pathogenesis” (HeLiP) team aims to understand the mechanisms of viral persistence and liver pathogenesis, in order to identify new biomarkers and therapeutic targets.
It is structured around two main axes:

  • Axis I. Pathogenesis of liver disease, decompensation and predisposition to hepatocellular carcinoma (HCC)
    Axis II. Eradication of hepatitis B and D: understanding viral persistence to identify innovative targets

 

Context

Hepatocellular Carcinoma (HCC) is the 5th most frequent cancer worldwide and ranks 3rd in terms of cancer mortality.

Globally, chronic HBV and HCV infections are the main cause of liver disease leading to HCC worldwide, while hepatitis Delta virus (HDV) co-infection with HBV significantly accelerates disease progression. Alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) are frequent and increasing causes of HCC especially in western countries. Chronic HBV infection is the first cause of HCC and a major public health problem, being the most prevalent chronic infectious disease worldwide with more than 296 million individuals concerned. Clinical resolution of HBV infection would require the control of persisting viral genomes and residual infected cells by the immune system, which is rarely achieved with standard-of-care therapy. Although the recent therapeutic revolution allowed the cure of most patients with chronic HCV infection, the observed residual risk of HCC development after the cure of the infection needs to be fully characterized. Possible mechanisms involved in HCV-induced HCC include HCV reprogramming of liver metabolism, chronic cellular stress and inflammation, and other modulations of cell signaling pathways, which may also be informative for MASLD and ALD. In addition, comorbidities such as MASLD and ALD, which have an increasing prevalence especially in developed countries, have been shown to increase the risk of liver disease complications, i.e. cirrhosis, HCC, and liver decompensation.

In this context, we capitalize on our expertise and the strong translational/clinical research program relying on numerous national and international patient cohorts and clinical trials to focus on two main axes:

  • Axe I. Pathogenesis of liver diseases, decompensation and predisposition to HCC

  • Axe II. Elimination of hepatitis B and Delta: understanding viral persistence to discover innovative targets

Axis I. Pathogenesis of liver diseases, decompensation and predisposition to HCC

Based on our expertise on molecular viral hepatitis pathology we are seeking for common denominators of the pathologies underlying chronic hepatitis B/C/D, ALD and MASLD. In all of these etiologies, altered metabolic fluxes, oxidative stress, inflammation and altered cell signaling have been shown to impact progression toward severe liver diseases. In end stage liver diseases (compensated advanced chronic liver diseases, acute decompensation of cirrhosis, with or without organ failure), disease progression, immune response dysfunction and multi-organ failure are in part driven by inflammation. The role of neuronal input in severe liver disease progression and specifically in HCC pathogenesis has started to be unveiled, thanks to our contribution6. Identification of common molecular targets, signaling pathways or inflammatory conditions, being prone or not to neural regulation should bring new approaches to answer current clinical issues as the development of robust individualized prognosis models and treatment options for liver fibrosis, liver failure and HCC.

Objectives :

We will investigate the role of metabolic, inflammatory and intrahepatic neural pathways in chronic liver diseases at different stages and aim to identify and/or characterize pathways that could serve as prognostic biomarkers or as novel therapeutic targets, through three specific aims :

  • Specific aim n°1 (HeLiP). Role of virally induced metabolic changes and oxidative stress in HCV- and HBV/HDVinduced liver disease
  • Specific aim n°2 (HeLiP). Neural contribution to liver metabolisms, fibrogenesis and carcinogenesis
  • Specific aim n°3 (HeLiP + EpiLiv). Role of inflammation in end stage liver disease (ESLD) and their contribution to cirrhosis complications and poor outcomes

Axis II. Elimination of hepatitis B and Delta: understanding viral persistence to discover innovative targets

Current treatments against CHB induce viral suppression but require life-long regimens in most patients, since they cannot eliminate cccDNA, the nuclear transcriptional template for viral replication. cccDNA is wrapped around nucleosomes to form a stable, chromatinized structure that is regulated by epigenetic mechanisms and is responsible for viral persistence and rebound after treatment withdrawal. Moreover, the ability of HBV to integrate into the host genome hampers the goal of a complete “sterilizing cure”. The residual viral replication, antigen production and persistence of nuclear viral genomes substantially contribute to the residual risk of HCC, also in virally suppressed patients under treatment. New therapeutic approaches are needed to overcome HBV persistence in the infected cells by eradicating or silencing viral cccDNA to allow a finite duration of therapy and, thus, to expand treatment to all HBV carriers. Re-educating the liver micro-environment will be also key to establish a sustained immune control of the infection. In this respect, a number of combinations of direct acting antivirals and immune modulators are under active clinical trial evaluation. The development of new combinatorial approaches requires the definition of new endpoints for the assessment of treatment efficacy and the development and validation of novel non-invasive biomarkers of the pool of intrahepatic cccDNA.

Fifteen million chronic HBV carriers are also co-infected with Hepatitis Delta virus (HDV), resulting in an accelerated progression to cirrhosis and HCC. The management of HBV/HDV co-infected patients is limited by the low response rate to interferon therapy. Therefore, efficient anti-HDV therapeutic interventions are urgently needed, since so far, only Bulevirtide, an entry inhibitor, has received a conditional approval from EMA, while few other inhibitors of HDV viral replication cycle are in phase II clinical trials.

Objectives :

  • Spectific aim n°1 (HeLiP). Generate new knowledge on cccDNA biology, in particular on the key steps leading to its formation and to its transcriptional regulation, in vitro and in vivo.
  • Spectific aim n°2 (HeLiP). Identify novel targets or approaches to degrade or functionally inactivate (“silence”) the cccDNA pool.
  • Spectific aim n°3 (HeLiP + EpiLiv). Characterize and evaluate non-invasive serum surrogate biomarkers for intrahepatic cccDNA amounts and transcriptional activity in vitro and in vivo in HBV mono-infected or HBV-HDV coinfected patients.
  • Spectific aim n°4 (HeLiP + EpiLiv). Evaluate novel therapeutic approaches in experimental models and in clinical trials.
  • Spectific aim n°5 (HeLiP). Evaluate the impact of both HBV and HDV genome variability in different region of world on liver disease outcome and response to therapy.
Team overview

The Hepatitis Viruses and Liver Pathogenesis (HeLiP) team aims to understand the mechanisms of viral persistence and liver pathogenesis in order to identify new biomarkers and therapeutic targets.

Principal investigators: B. Bartosch (DR), I. Chemin (DR), F. Lebossé (MCUPH), B. Grigorov (MCU), R. Parent (CR), C. Scholtes (MCUPH), B. Testoni (CR), F. Zoulim (PUPH)
Tenured ITAs: I. Bordes (Tech), E. Combe (IE), M. Michelet (IE), J. Molle (IE)
Other members: 7 post-docs, 5 PhD students, 5 contracted ITAs

Funding: Labex DevWeCan and HumanToCan (metabolic changes and neuronal regulation in HCC), ANRS (VDAC, HDV, netrin-4 & HCV), IRP HepDelta Mongolia (HDV), SNFGE (FARE 2021), HCL (Jeune Chercheur 2018), INCa PLBio (neuronal targeting in HCC), Inserm/INCa PCSI (characterization of an indole-ethanamine compound with anti-HCC activity), Cancéropôle CLARA (preclinical evaluation of netrin-1 targeting in chronic liver diseases), H2020 IP-cure-B (“immune profiling to guide host-directed interventions to cure HBV infections”), Beam Therapeutics (base edition), Blue Jay (neutralizing antibodies).

2025
  • Fernandes P, Wang Y, Doisne JM, Thaller A, Fiquet O, Dailleux R, Amblard F, Testoni B, Aronthippaitoon Y, Mouquet H, Sureau C, Reyné B, Tiezzi C, Soussan P, Levrero M, Zoulim F, Schinazi RF, Strick-Marchand H. Functional immune responses induced by a capsid assembly modulator in chronic hepatitis B virus-infected humanized mice. Cell Host Microbe. 2025 Dec 23:S1931-3128(25)00497-4. doi: 10.1016/j.chom.2025.12.001. Epub ahead of print. PMID: 41443190.

  • Begré L, Zoulim F, Boyd A. Hepatitis B virus functional cure in persons with HIV: what are the predictors and which novel markers are useful? Curr Opin HIV AIDS. 2025 Dec 18. doi: 10.1097/COH.0000000000001002. Epub ahead of print. PMID: 41417916.

  • Giraud G, Testoni B. Role of cccDNA in the Quest for HBV Cure- Implications for HIV-HBV Coinfection. Curr HIV/AIDS Rep. 2025 Dec 17;22(1):57. doi: 10.1007/s11904-025-00766-9. PMID: 41405783.

  • Zhang BH, Zhou Y, Horrigan S, Luckenbaugh L, Hu J, Zoulim F, Zhang YY. HBVZ10, an AAV8 vector-based new HBV therapy candidate for cccDNA elimination. Mol Ther Methods Clin Dev. 2025 Nov 19;33(4):101646. doi: 10.1016/j.omtm.2025.101646. PMID: 41404410; PMCID: PMC12704295.

  • Furquim d’Almeida A, Vanderlinden A, Bourgeois S, Mulkay JP, Sersté T, Struyve M, Deressa B, Sprengers D, de Vos M, Callens J, Shihao B, Reynaert H, Deltenre P, Janssens F, Negrin-Dastis S, Stärkel P, Orlent H, Van Roey G, Verhelst X, Moreno C, Delwaide J, Van Steenkiste C, Verlinden W, Colle I, Plissonnier ML, Mukadi BK, Testoni B, Zoulim F, Matheeussen V, Vanwolleghem T. Clinical Trial: Hepatitis B Virus Genotype and a Combination of End-of-Treatment Biomarkers Predict Severe Flares After Nucleos(t)ide Analogue Cessation. Aliment Pharmacol Ther. 2025 Nov 19. doi: 10.1111/apt.70465. Epub ahead of print. PMID: 41261561.

  • Stern C, Loustaud-Ratti V, Yurdaydin C, Brancaccio G, Jachs M, Reiberger T, Bardou-Jacquet E, Metivier S, Alric L, Colombain L, Meszaros M, Mathurin P, Yardeni D, Etzion O, Neumann-Haefelin C, Douglas M, Poulin S, Bazinet M, Metin RO, Vitale A, Gaeta GB, Schwarz M, Ben-Ali S, Bedoya JU, Testoni B, Zoulim F, Plissonnier ML, Levrero M, Paradis V, Francois S, de Freitas C, Kaysin F, Lecomte L, Morvan C, Schramko J, Bondezi K, Baril MÉ, Brichler S, Gerber A, Gordien E, Mackiewicz V, Dahari H, Svicher V, Chevaliez S, Vaillant A, Bourliere M. Safety and efficacy of REP 2139-Mg in patients with HDV-related advanced liver disease in an international compassionate access program. J Hepatol. 2025 Nov 6:S0168-8278(25)02612-1. doi: 10.1016/j.jhep.2025.10.029. Epub ahead of print. PMID: 41205755.

  • Dongelmans EJ, Patmore LA, Lim SG, Bourliere M, Jiang S, Ganne-Carrie N, Brouwer WP, Feld JJ, Huang Y, Carrion JA, Broquetas T, Hu Q, Fung S, Carrat F, Zoulim F, Hansen BE, Xie Q, Janssen HLA, Sonneveld MJ. HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER). Gut. 2025 Nov 5:gutjnl-2025-336251. doi: 10.1136/gutjnl-2025-336251. Epub ahead of print. PMID: 41198171.

  • Zhang B-H, Zhou Y, Horrigan S, Zoulim F, Hu J, Zhang Y-Y. Replication-driven HBV cccDNA loss in chimeric mice with humanized livers. J Virol. 2025 Nov 25;99(11):e0129525. doi: 10.1128/jvi.01295-25. Epub 2025 Nov 6. PMID: 41196060; PMCID: PMC12645921.

  • Cornberg M, Zoulim F, Gish R, Jacobson IM, Kushner T, Lampertico P, Rizzetto M, Yurdaydin C, Manns M. Best practices for screening, testing, diagnosing, and treating patients with hepatitis D (delta) virus based on global expert review and recent guidelines. Antivir Ther. 2025 Oct;30(4):13596535251349380. doi: 10.1177/13596535251349380. Epub 2025 Sep 29. PMID: 41024346.

  • European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2025 Aug;83(2):502-583. doi: 10.1016/j.jhep.2025.03.018. Epub 2025 May 10. PMID: 40348683.

  • Kennedy PT, Allweiss L, Bertoletti A, Cornberg M, Gehring AJ, Guidotti LG, Kerth HA, Lemoine M, Levrero M, Lim SG, Tavis JE, Testoni B, Tu T; International Coalition to Eliminate HBV. Scientific and medical evidence informing expansion of hepatitis B treatment guidelines. Lancet Gastroenterol Hepatol. 2025 Oct;10(10):941-951. doi: 10.1016/S2468-1253(25)00053-6. Epub 2025 Jul 23. PMID: 40714040.

  • Degasperi E, Sandmann L, Wedemeyer H, Lampertico P; Delta Cure 2024 Working Group. Hepatitis D Virus Infection: Pathophysiology, Epidemiology and Treatment. Report From the Third Delta Cure Meeting 2024. Liver Int. 2025 Jul;45(7):e70189. doi: 10.1111/liv.70189. PMID: 40540405.

  • Khomich OA, Giavalisco P, Parent R, Krasnov GS, Tessarz P, Meuleman P, Burm R, Zakirova NF, Molle J, Batbold E, Gottlieb E, Zoulim F, Ivanov AV, Bartosch B. IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures. Cell Death Dis. 2025 Jul 18;16(1):534. doi: 10.1038/s41419-025-07838-z. PMID: 40681530; PMCID: PMC12274286.

  • Lotto M, Ramier C, Carrat F, Périères L, Delaroque-Astagneau E, Nicol J, Marcellin F, Zoulim F, Di Beo V, Bertheau M, Pol S, Protopopescu C, Bourlière M, Carrieri P; ANRS/AFEF CO22 HEPATHER Study Group. Mortality risk in migrant and non-migrant individuals with chronic hepatitis B virus infection: a French hospital-based cohort study (ANRS CO22 HEPATHER). BMC Glob Public Health. 2025 Jul 1;3(1):58. doi: 10.1186/s44263-025-00173-7. PMID: 40598581; PMCID: PMC12220402.

  • Feld JJ, Gehring AJ, Zoulim F. Getting to HBV cure-Will new biomarkers help? Hepatology. 2025 Apr 1. doi: 10.1097/HEP.0000000000001334. Epub ahead of print. PMID: 40168396.

  • Roca Suarez AA, Jühling F, Moehlin J, Mailly L, Virzì A, Brignon N, Durand SC, Oudot MA, Schaeffer E, Martin R, Meiss-Heydmann L, Bach C, Boulahtouf Z, Girard L, Osswald E, Jamey C, Brumaru D, Dali-Youcef N, Mukherji A, Saez-Palma M, Testoni B, Zoulim F, Koneru B, Fujiwara N, Hoshida Y, Felli E, Pessaux P, Tremblay ML, Parent R, Schuster C, Baumert TF, Lupberger J. Protein tyrosine phosphatase delta is a STAT3-phosphatase and suppressor of metabolic liver disease. eGastroenterology. 2025 Jan 27;3(1):e100159. doi: 10.1136/egastro-2024-100159. PMID: 40124988; PMCID: PMC11927410.

  • Ramier C, Protopopescu C, Di Beo V, Parlati L, Marcellin F, Carrat F, Asselah T, Bourlière M, Carrieri P; ANRS/AFEF CO22 HEPATHER Study Group. Behaviour-Based Predictive Scores of Hepatocellular Carcinoma in People With Chronic Hepatitis B (ANRS CO22 HEPATHER). Liver Int. 2025 Apr;45(4):e70065. doi: 10.1111/liv.70065. PMID: 40087922; PMCID: PMC11909585.

  • Nahon P, Lusivika-Nzinga C, Merle P, Zoulim F, Decaens T, Ganne-Carrié N, Pageaux GP, Leroy V, Alric L, Bronowicki JP, Bourlière M, Gournay J, Tran A, Pol S, Mathurin P, Loustaud-Ratti V, Métivier S, De Ledinghen V, Abergel A, Thabut D, D’Alteroche L, Bouattour M, Asselah T, Ouzan D, Cales P, Chazouillères O, Gelu-Simeon M, Roulot D, Boursier J, Cagnot C, Tamazirt S, Pascale A, Nilusmas S, Lewin M, Ziol M, Carrat F, Duclos-Vallée JC; ANRS CO12 CirVir, CO22 Hepather, and LICAVIR groups. Value of non-invasive test dynamics in guiding HCC surveillance decisions after HCV cure in patients with cirrhosis. J Hepatol. 2025 Sep;83(3):701-711. doi: 10.1016/j.jhep.2025.02.008. Epub 2025 Feb 26. PMID: 40020929.

  • Delignette MC, Riff A, Antonini T, Soustre T, Bodinier M, Peronnet E, Venet F, Gossez M, Pantel S, Mabrut JY, Muller X, Mohkam K, Villeret F, Erard D, Dumortier J, Zoulim F, Heyer L, Guichon C, Blet A, Aubrun F, Monneret G, Lebossé F. Individual mHLA-DR trajectories in the ICU as predictors of early infections following liver transplantation: a prospective observational study. Crit Care. 2025 Feb 18;29(1):79. doi: 10.1186/s13054-025-05305-x. PMID: 39966934; PMCID: PMC11834174.

  • Block TM, Guo JT, Zoulim F, Rice CM, Thio CL, Schneider WM, Alter HJ, Jacobson IM, Gish RG, Block PD, Sulkowski M, Feld JJ, Cohen CA. New potent HBV replication inhibitors for the management of chronic hepatitis B are needed. Nat Rev Gastroenterol Hepatol. 2025 Mar;22(3):150-151. doi: 10.1038/s41575-025-01037-z. PMID: 39910374.

  • Barré T, Ramier C, Ory K, Saidi T, Sogni P, Zoulim F, Bureau-Stoltmann M, Protopopescu C, Marcellin F, Carrieri P; ANRS CO13 HEPAVIH Study Group. Liver Enzyme Elevation After Hepatitis C Virus Cure: Is There a Sex Effect? (ANRS CO13 HEPAVIH Cohort). J Viral Hepat. 2025 Mar;32(3):e70007. doi: 10.1111/jvh.70007. PMID: 39878781.

  • Barré T, Ramier C, Wittkop L, Sogni P, Zucman D, Tardieu R, Carrieri P, Marcellin F; ANRS CO13 HEPAVIH Study Group. Low CD4 Cell Count Is Associated With Post-Hepatitis C Virus Cure Mortality in People With HIV (ANRS CO13 HEPAVIH Cohort). Clin Infect Dis. 2025 Sep 16;81(2):e28-e30. doi: 10.1093/cid/ciaf016. PMID: 39812016.

  • Degasperi E, Anolli MP, Jachs M, Reiberger T, De Ledinghen V, Metivier S, D’Offizi G, di Maria F, Schramm C, Schmidt H, Zöllner C, Tacke F, Dietz-Fricke C, Wedemeyer H, Papatheodoridi M, Papatheodoridis G, Carey I, Agarwal K, Van Bömmel F, Brunetto MR, Cardoso M, Verucchi G, Ciancio A, Zoulim F, Aleman S, Semmo N, Mangia A, Hilleret MN, Merle U, Santantonio TA, Coppola N, Pellicelli A, Roche B, Causse X, D’Alteroche L, Dumortier J, Ganne N, Heluwaert F, Ollivier I, Roulot D, Viganò M, Loglio A, Federico A, Pileri F, Maracci M, Tonnini M, Arpurt JP, Barange K, Billaud E, Pol S, Gervais A, Minello A, Rosa I, Puoti M, Lampertico P. Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis. J Hepatol. 2025 Jun;82(6):1012-1022. doi: 10.1016/j.jhep.2024.12.044. Epub 2025 Jan 8. PMID: 39793613.

  • Barré T, Ramier C, Ory K, Sogni P, Aumaitre H, Saidi T, Carrieri P, Marcellin F; ANRS CO13 HEPAVIH Study Group. Transient CD4 cell recovery after hepatitis C virus cure in HIV/hepatitis C virus coinfected patients (ANRS CO13 HEPAVIH cohort). HIV Med. 2025 Mar;26(3):500-503. doi: 10.1111/hiv.13752. Epub 2024 Dec 11. PMID: 39663177.

  • Degasperi E, Scholtes C, Testoni B, Renteria SU, Anolli MP, Charre C, Facchetti F, Plissonnier ML, Sambarino D, Perbellini R, Monico S, Callegaro A, García-Pras E, Lens S, Cortese MF, Forns X, Pérez-Del-Pulgar S, Heil M, Levrero M, Zoulim F, Lampertico P. Differential HBV RNA and HBcrAg patterns in untreated patients with chronic hepatitis delta. J Hepatol. 2025 Jun;82(6):1004-1011. doi: 10.1016/j.jhep.2024.11.051. Epub 2024 Dec 9. PMID: 39662705.

  • Roulot D, Layese R, Brichler S, Ganne N, Asselah T, Zoulim F, Gordien E, Nahon P, Roudot-Thoraval F; DeltaVir and CirVir study groups. Hepatitis D Virus Infection Markedly Increases the Risk of Hepatocellular Carcinoma in Patients With Viral B Cirrhosis. Clin Gastroenterol Hepatol. 2025 Oct;23(11):1943-1953.e2. doi: 10.1016/j.cgh.2024.08.046. Epub 2024 Oct 24. PMID: 39461464.

  • Parent R, Lin RL, Ouillette L, Glass E, Burns H, Uhler MD, Case SL, Thibault O, Murphy GG. The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics. Biol Psychiatry Glob Open Sci. 2025 May 22;5(5):100537. doi: 10.1016/j.bpsgos.2025.100537. PMID: 40678692; PMCID: PMC12268564.

  • Elzinga SE, Guo K, Turfah A, Henn RE, Webber-Davis IF, Hayes JM, Pacut CM, Teener SJ, Carter AD, Rigan DM, Allouch AM, Jang DG, Parent R, Glass E, Murphy GG, Lentz SI, Chen KS, Zhao L, Hur J, Feldman EL. Metabolic stress and age drive inflammation and cognitive decline in mice and humans. Alzheimers Dement. 2025 Mar;21(3):e70060. doi: 10.1002/alz.70060. PMID: 40110679; PMCID: PMC11923576.

  • Meunier L, Delire B, De Martin E, Lebossé F, Anty R, Dumortier J, Houssel-Debry P, Delwaide J, Duclos-Vallee JC, Lutu A, Lemoinne S, Roux O, Péron JM, Saviano A, Abergel A, Prost A, Hountondji L, Thabut D, Dharancy S, Antonini T, Zahhaf A, Horsmans Y, Larrey D; REFHEPS group. Features and Outcomes of 280 Patients With Idiosyncratic Drug-induced Liver Injury: The REFHEPS Prospective Study. Clin Gastroenterol Hepatol. 2025 Nov 4:S1542-3565(25)00933-4. doi: 10.1016/j.cgh.2025.10.024. Epub ahead of print. PMID: 41197933.

  • Thévenot T, Elkrief L, Bureau C, Bardou-Jacquet E, Rosa I, Nguyen-Khac E, Oberti F, Pitta A, Mallet M, Lebossé F, Louvet A, Meunier L, Nahon P, Ollivier-Hourmand I, Anty R, Francoz C, Riachi G, Meunier A, Cervoni JP, Tio G, Muller A, Curé-Martin A, Ladeira R, Clairet AL, Hocquet D, Di Martino V, Weil D, Desmarets M. Effect of rifaximin in patients with severe cirrhosis and ascites: A randomized double-blind placebo-controlled trial. J Hepatol. 2025 Dec;83(6):1320-1327. doi: 10.1016/j.jhep.2025.06.019. Epub 2025 Jul 11. PMID: 40653111.
2024

  • Chapus F*, Giraud G*, Huchon P, Rodà M, Grand X, Charre C, Goldsmith C, Roca Suarez AA, Martinez MG, Fresquet J, Diederichs A, Locatelli M, Polvèche H, Scholtès C, Chemin I, Vargas HH, Rivoire M, Bourgeois CF, Zoulim F, Testoni Bc. Helicases DDX5 and DDX17 promote heterogeneity in HBV transcription termination in infected human hepatocytes. J Hepatol. 2024 May 21:S0168-8278(24)00351-9. doi: 10.1016/j.jhep.2024.05.016. Epub ahead of print. PMID: 38782119.

  • Asselah T, Chulanov V, Lampertico P, Wedemeyer H, Streinu-Cercel A, Pântea V, Lazar S, Placinta G, Gherlan GS, Bogomolov P, Stepanova T, Morozov V, Syutkin V, Sagalova O, Manuilov D, Mercier RC, Ye L, Da BL, Chee G, Lau AH, Osinusi A, Bourliere M, Ratziu V, Pol S, Hilleret MN, Zoulim Fc. Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D. N N Engl J Med. 2024 Jul 11;391(2):133-143. doi: 10.1056/NEJMoa2314134. Epub 2024 Jun 6. PMID: 38842520.

  • Degasperi E, Scholtes C, Testoni B, Renteria SU, Anolli MP, Charre C, Facchetti F, Plissonnier ML, Sambarino D, Perbellini R, Monico S, Callegaro A, García-Pras E, Lens S, Cortese MF, Forns X, Pérez-Del-Pulgar S, Heil M, Levrero M, Zoulim F, Lampertico P. Differential HBV RNA and HBcrAg patterns in untreated patients with chronic hepatitis delta. J Hepatol. 2024 Dec 9:S0168-8278(24)02759-4. doi: 10.1016/j.jhep.2024.11.051. Epub ahead of print. PMID: 39662705.

  • Molle J, Duponchel S, Rieusset J, Ovize M, Ivanov AV, Zoulim F, Bartosch Bc. Exploration of the Role of Cyclophilins in Established Hepatitis B and C
    Infections. Viruses. 2024 Dec 25;17(1):11. doi: 10.3390/v17010011. PMID: 39861799; PMCID: PMC11768883.

  • Yu X, Gong Q, Yu D, Chen Y, Jing Y, Zoulim F, Zhang X. Spatial transcriptomics reveals a low extent of transcriptionally active hepatitis B virus integration in patients with HBsAg loss. Gut. 2024 Apr 5;73(5):797-809. doi: 10.1136/gutjnl-2023-330577. PMID: 37968095; PMCID: PMC11041573.

  • Testoni B, Scholtès C, Plissonnier ML, Paturel A, Berby F, Facchetti F, Villeret F, Degasperi E, Scott B, Hamilton A, Heil M, Lampertico P, Levrero M, Zoulim F. Quantification of circulating HBV RNA expressed from intrahepatic cccDNA in untreated and NUC treated patients with chronic hepatitis B. Gut. 2024 Mar 7;73(4):659-667. doi: 10.1136/gutjnl-2023-330644. PMID: 37879886.

  • Grand X, Giraud G, Rifki A, Paturel A, Bousquet D, Roca Suarez AA, Bourgeois C, Levrero M, Zoulim F, Testoni BC.
Bolero: a dedicated workflow to decipher Hepatitis B virus transcriptome from long-reads sequencing method coupled to 5’RACE amplification of transcripts. bioRxiv 2024.09.17.613398; doi: https://doi.org/10.1101/2024.09.17.613398.

  • Zakirova NF, Khomich OA, Smirnova OA, Molle J, Duponchel S, Yanvarev DV, Valuev-Elliston VT, Monnier L, Grigorov B, Ivanova ON, Karpenko IL, Golikov MV, Bovet C, Rindlisbacher B, Khomutov AR, Kochetkov SN, Bartosch B, Ivanov AV. Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs the Urea Cycle. Cells. 2024 Jun 14;13(12):1036. doi: 10.3390/cells13121036. PMID: 38920664; PMCID: PMC11201506.

  • Paturel A, Casuscelli di Tocco F, Bousquet D, Plissonnier ML, Grand X, Tak H, Berby F, Scholtès C, Testoni B, Zoulim F, Levrero M. A molecular standard for circulating HBV RNA detection and quantification assays in patients with chronic hepatitis B. JHEP Rep. 2024 May 25;6(10):101124. doi: 10.1016/j.jhepr.2024.101124. PMID: 39328324; PMCID: PMC11424956.

  • Hernandez CA*, Verzeroli C*, Roca-Suarez AA*, Farca-Luna AJ, Tonon L, Esteban-Fabró R, Pinyol R, Plissonnier ML, Chicherova I, Dubois A, Bellaud P, Seffals M,Turlin B, Fautrel A, Ichim G, Rivoire M, Passot G, Macek-Jilkova Z, Decaens T,Viari A, Testoni B, Rebouissou S, Llovet JM, Zoulim F, Parent Rc. Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors. JHEP Rep. 2024 Nov 12;7(1):101245. doi: 10.1016/j.jhepr.2024.101245. PMID: 39717507; PMCID: PMC11663970.

  • Roca Suarez AA, Planel S, Grand X, Couturier C, Tran T, Porcheray F, Becker J, Reynier F, Delgado A, Cascales E, Peyrot L, Tamellini A, Saliou A, Elie C, Baum C, Vuong BQ, Testoni B, Roques P, Zoulim F, Hasan U, Chemin Ic. Interspecies comparison of the early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations. Front Cell Infect Microbiol. 2023 Sep 1;13:1248782. doi: 10.3389/fcimb.2023.1248782. eCollection 2023.PMID: 37727809.

  • Meyniel-Schicklin L, Amaudrut J, Mallinjoud P, Guillier F, Mangeot PE, Lines L, Aublin-Gex A, Scholtes C, Punginelli C, Joly S, Vasseur F, Manet E, Gruffat H, Henry T, Halitim F, Paparin JL, Machin P, Darteil R, Sampson D, Mikaelian I, Lane L, Navratil V, Golinelli-Cohen MP, Terzi F, André P, Lotteau V, Vonderscher J, Meldrum EC, de Chassey B. Viruses traverse the human proteome through peptide interfaces that can be biomimetically leveraged for drug discovery. Proc Natl Acad Sci U S A. 2024 Jan 30;121(5):e2308776121. doi: 10.1073/pnas.2308776121. Epub 2024 Jan 22. PMID: 38252831; PMCID: PMC10835127.

  • Smekalova EM, Martinez MG, Combe E, Kumar A, Dejene S, Leboeuf D, Chen CY, Dorkin JR, Shuang LS, Kieft S, Young L, Barrera LA, Packer MS, Ciaramella G, Testoni B, Gregoire F, Zoulim Fc. Cytosine base editing inhibits hepatitis B virus replication and reduces HBsAg expression in vitro and in vivo. Mol Ther Nucleic Acids. 2023 Dec 27;35(1):102112. doi: 10.1016/j.omtn.2023.102112. PMID: 38292874; PMCID: PMC10825689.

  • Giraud G, Rodà M, Huchon P, Michelet M, Maadadi S, Jutzi D, Montserret R, Ruepp MD, Parent R, Combet C, Zoulim F, Testoni Bc. G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes. Nucleic Acids Res. 2024 Mar 21;52(5):2290-2305. doi: 10.1093/nar/gkad1200. PMID: 38113270.

  • Roca Suarez AA, Plissonnier ML, Grand X, Michelet M, Giraud G, Saez-Palma M, Dubois A, Heintz S, Diederichs A, Van Renne N, Vanwolleghem T, Daffis S, Li L, Kolhatkar N, Hsu YC, Wallin JJ, Lau AH, Fletcher SP, Rivoire M, Levrero M, Testoni BC, Zoulim Fc. TLR8 agonist selgantolimod regulates Kupffer cell differentiation status and impairs HBV entry into hepatocytes via an IL-6-dependent mechanism. Gut. 2024 May 2:gutjnl-2023-331396. doi: 10.1136/gutjnl-2023-331396. Epub ahead of print. PMID: 38697771.

  • Chouik Y, Aubin A, Maynard-Muet M, Segrestin B, Milot L, Hervieu V, Zoulim F, Disse E, Levrero M, Caussy C. The grade of obesity affects the noninvasive diagnosis of advanced fibrosis in individuals with MASLD. Obesity (Silver Spring). 2024 Jun;32(6):1114-1124. doi: 10.1002/oby.24033. Epub 2024 May 3. PMID: 38699960.

  • Giraud G, El Achi K, Zoulim F, Testoni Bc. Co-Transcriptional Regulation of HBV Replication: RNA Quality Also Matters. Viruses. 2024 Apr 16;16(4):615. doi: 10.3390/v16040615. PMID: 38675956; PMCID: PMC11053573.

  • Tu T, Wettengel J, Xia Y, Testoni B, Littlejohn M, Le Bert N, Ebert G, Verrier ER, Tavis JE, Cohen C. Major open questions in the hepatitis B and D field – Proceedings of the inaugural International emerging hepatitis B and hepatitis D researchers workshop. Virology. 2024 Jul;595:110089. doi: 10.1016/j.virol.2024.110089. Epub 2024 Apr 16. PMID: 38640789; PMCID PMC11517827.

  • Cocca M*, Testoni B*c. New dimension in viral hepatitis research. eGastroenterology. 2024 Oct 2;2(3):e100136. doi: 10.1136/egastro-2024-100136. PMID: 39944365; PMCID: PMC11731076.

  • Pezy P, Rossignol G, Muller X, Delignette MC, Antonini T, Lebossé F, Mabrut JY, Mohkam K. Two-team Versus Single-team Liver Transplantation. Transplantation. 2024 Nov 1;108(11):e390-e392. doi: 10.1097/TP.0000000000004982. Epub 2024 Oct 22. PMID: 39466198.

  • Villeret F, Nahon P. Atezolizumab and bevacizumab with anticoagulant or antiplatelet therapy in hepatocellular carcinoma patients: Real-world data for clinical decision-making. Liver Int. 2024 Aug;44(8):1749-1750. doi: 10.1111/liv.15954. PMID: 39012158.

  • Zoulim F. Does siRNA-based therapy require pegylated interferon-alfa-2a to cure HBV infection? Lancet Gastroenterol Hepatol. 2024 Dec;9(12):1069-1071. doi: 10.1016/S2468-1253(24)00303-0. Epub 2024 Oct 8. PMID: 39389080.

  • Kumar A, Combe E, Mougené L, Zoulim F, Testoni Bc. Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics. Viruses. 2024 Oct 2;16(10):1565. doi: 10.3390/v16101565. PMID: 39459899; PMCID: PMC11512240.

  • Chouik Y, Corpechot C, Francoz C, De Martin E, Guillaud O, Abergel A, Altieri M, Barbier L, Besch C, Chazouillères O, Conti F, Dharancy S, Durand F, Duvoux C, Gugenheim J, Hardwigsen J, Hilleret MN, Houssel-Debry P, Kamar N, Minello A, Neau-Cransac M, Pageaux GP, Radenne S, Roux O, Saliba F, Samuel D, Vanlemmens C, Woehl-Jaegle ML, Leroy V, Duclos-Vallée JC, Dumortier J. Autoimmune hepatitis recurrence after liver transplantation: “Les jeux sont faits”. Liver Transpl. 2024 Apr 1;30(4):395-411. doi: 10.1097/LVT.0000000000000278. Epub 2023 Oct 4. PMID: 37788303.

  • Ceesay A, Drammeh S, Ndow G, Jallow AOA, Nyang H, Bittaye B, Mendy FS, Secka O, D’Alessandro U, Shimakawa Y, Vo-Quang E, Testoni B, Thursz M, Lemoine M, Chemin Ic. Real-Life Diagnostic Accuracy and Clinical Utility of Hepatitis B Virus (HBV) Nucleic Acid Testing Using the GeneXpert Point-of-Care Test System from Fresh Plasma and Dry Blood Spot Samples in The Gambia. Microorganisms. 2024 Nov 9;12(11):2273. doi: 10.3390/microorganisms12112273. PMID: 39597662; PMCID: PMC11596281.

  • Ndow G, Shimakawa Y, Leith D, Bah S, Bangura R, Mahmoud I, Bojang L, Ceesay A, Drammeh S, Bola-Lawal Q, Lambert G, Hardy P, Ingiliz P, Haddadin Y, Vo-Quang E, Chevaliez S, Cloherty G, Bittaye SO, Lo G, Toure-Kane C, Mendy M, Njie R, Chemin I, D’Alessandro U, Thursz M, Lemoine M. Clinical outcomes of untreated adults living with chronic hepatitis B in The Gambia: an analysis of data from the prospective PROLIFICA cohort study. Lancet Gastroenterol Hepatol. 2024 Dec;9(12):1133-1146. doi: 10.1016/S2468-1253(24)00226-7. PMID: 39521002.

  • Debsikréo N, Dehainsala M, Debsikréo O, Leye N, Lo G, Dia A, Flore MNB, Diaw NA, Diouf ND, Otchere ID, Toyé RM, Chemin I, Moussa AM, Toure-Kane NC, Lunel-Fabiani F. Prevalence and molecular characterization of hepatitis delta virus infection among hepatitis B virus surface antigen positive students and pregnant women in N’djamena, Chad. IJID Reg. 2024 Dec 28;14:100560. doi: 10.1016/j.ijregi.2024.100560. PMID: 39895833; PMCID: PMC11786080.

  • Parant F, Delignette MC, Charpiat B, Lacaille L, Lebosse F, Monneret G, Mohkam K, Mabrut JY, Aubrun F, Heyer L, Antonini Tc. Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method. Ther Drug Monit. 2024 Aug 1;46(4):446-455. doi: 10.1097/FTD.0000000000001201. Epub 2024 Apr 19. PMID: 38648663.

  • Roca Suarez AA, Plissonnier ML, Michelet M, Dubois A, Heintz S, Saez-Palma M, Delphin M, Bordes I, Molle J, Diederichs A, Rodà M, Combe E, Mougené L, Giraud G, Grand X, Rivoire M, Levrero M, Testoni B, Zoulim Fc. Protocol for isolating CD163<sup>+</sup> Kupffer cells from human liver resections. STAR Protoc. 2024 Dec 20;5(4):103359. doi: 10.1016/j.xpro.2024.103359. Epub 2024 Oct 4. PMID: 39368096; PMCID: PMC11491951.

  • Ndow G, Vo-Quang E, Shimakawa Y, Ceesay A, Tamba S, Njai HF, Bojang L, Hateley C, Takao Y, Opoku E, Warsop Z, Ingiliz P, D’Alessandro U, Chemin I, Mendy M, Thursz M, Njie R, Lemoine M. Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort study. Lancet Glob Health. 2023 Sep;11(9):e1383-e1392. doi: 10.1016/S2214-109X(23)00263-2.

  • Begré L, Boyd A, Plissonnier ML, Testoni B, Salazar-Vizcaya L, Suter-Riniker F, Scholtès C, Béguelin C, Rockstroh JK, Günthard HF, Calmy A, Cavassini M, Hirsch HH, Schmid P, Bernasconi E, Levrero M, Wandeler G, Zoulim F, Rauch A; Swiss HIV Cohort Study. Circulating HBV RNA and hepatitis B core-related antigen trajectories in persons with HIV/HBV coinfection and HBsAg loss on tenofovir therapy. J Infect Dis. 2024 Apr 16:jiae189. doi: 10.1093/infdis/jiae189. Epub ahead of print. PMID: 38626170.

Ludovic AILLOT

Postdoctoral Fellow

Postdoctoral fellow whose research aims to improve our understanding of the interactions between the host immune system and pathogens. I also conduct studies on innovative new compounds that stimulate the immune response in order to evaluate their antiviral potential.

Birke BARTOSCH

Senior Researcher

Her main research themes are virus-host interactions and, in particular, the role of viro-induced metabolic changes in chronic hepatitis pathologies. She has carried out a number of studies on the pathology of chronic hepatitis C. Research Director

Isabelle CHEMIN

Senior Researcher

For several years, she has focused on HBV variants and hepatocellular carcinoma, including prognostic and predictive markers for HCC development. She has contributed to the set-up and development of several collaborative studies, notably with South America, North Africa and West Africa.

Emmanuel COMBE

Research Engineer

Since 2020, as part of Dr. Barbara Testoni’s team, I am involved in several projects focusing on silencing the hepatitis B virus reservoir (cccDNA) using innovative genome-editing approaches, including CRISPR-Cas9 and cytosine and adenosine base editors, delivered to hepatocytes through clinically relevant strategies.

Marine DELEUME

PhD Student

As a biologist and pharmacist, I am pursuing a PhD on non-invasive and innovative biomarkers for the hepatitis B virus (HBcrAg, circulating RNAs and splicing variants, HBsAg isoforms). I am evaluating their diagnostic and prognostic value in HBV-HDV mono- and co-infections, in a cross-disciplinary research project with the Virology Department of the Hospices Civils de Lyon. This research aims to deepen our understanding of these biomarkers and advance the care of patients infected with or at risk of HBV viral reactivation.

Audrey DIEDERICHS

Research Engineer

I am a research engineer and work in Barbara Testoni’s team on various projects.

 – Testing different capsid assembly modulators (CAMs) and their impact on HBV replication.

 – Testing new therapeutic agents (i.e., ASOs) against HBV on primary cell models such as primary human hepatocytes (PHH) and precision-cut liver slices (PCLS) in order to better understand their mechanism of action.

Guillaume GIRAUD

Junior PI

My research focuses on bringing new molecular mechanisms insights controlling the metabolism of the Hepatitis B virus (HBV) RNAs. In particular, the different projects I lead aim first to identify the host factors regulating HBV RNA splicing and to determine the functional contribution of HBV spliced variants to the HBV-induced liver pathogenesis.    

Boyan GRIGOROV

Associate Professor

I am an Associate Professor in Biochemistry and Biotechnology at the Faculty of Pharmacy (Lyon 1 University), where I also coordinate the Master “Cancer” program. I am involved in international joint programs with USTH (Vietnam) and VIT (India), teaching Biomedical Biotechnology at the master’s level. My research focuses on virus–host interactions, and more specifically on the role of heparanase‑1 in viral infections. I lead a project assessing heparanase-1 inhibitors — particularly the heparan sulfate mimetic PI‑88 — as potential antivirals against HIV‑1, HBV and HDV. I also investigate the membrane cofactor protein CD46 and its potential involvement in chronic liver diseases.

Maud MICHELET

Research Engineer

I have been a tenured research engineer since 2010 in Professor Fabien Zoulim’s laboratory. I currently work in Dr. Barbara Testoni’s team on various projects:

– Testing different molecules (mainly Capsid Assembly Modulators – CAM) on HBV replication.

– Developing different cell culture models using human livers:

     – Primary Human Hepatocyte (PHH)

     – PCLS (Precision-cut liver slices)

In the laboratory, I am responsible, along with Dr. Marie Laure Plissonnier, for managing the retrieval and use of liver tissue samples (PHH and PCLS). We are also responsible for the Level 3 (L3) tissue culture lab on-site.

Jennifer MOLLE

Research Engineer

I am an engineer. I’m working with Birke Bartosch on the metabolic interactions of mitochondrial proteins with hepatitis viruses B, C, and D. I am responsible for the P2 laboratory and actively involved in risk prevention as a prevention officer, contributing to laboratory safety, compliance, and good experimental practices.

Léa MOUGENÉ

PhD Student

Currently a doctoral student under the supervision of Dr. Barbara Testoni, I am working on the evaluation of circulating HBV RNAs in extracellular vesicles. Ultimately, my research could lead to the discovery of new biomarkers useful for the diagnosis and monitoring of chronic hepatitis B.

Fanny LEBOSSÉ

MCU-PH

I am an associate professor of hepatology at Lyon 1 University and the Hospices Civils de Lyon. I have been working on immune dysfunctions associated with cirrhosis since 2015, and more generally on very advanced liver disease. My work focuses on the impact of immune dysfunction in cirrhosis on the prognosis of cirrhotic patients, particularly on the risk of infection. The aim is to understand the mechanisms that promote immune dysfunction in order to develop strategies to reduce the risk of infection. At the hospital, I treat patients with severe cirrhosis who are undergoing liver transplantation. In connection with these research topics, I coordinate and/or participate in three clinical studies:

– EmiC: Expression of circulating miRNA in acute decompensation of cirrhosis. Funding: HCL young investigators – IHU Lyon – SNFGE (FARE 2022 et 2025)

– I4 cirrhosis: Impact of CD4 response alterations in natural course of CIRRHOSIS. Funding: HCL young investigators – IHU Lyon – SNFGE (FARE 2022 et 2025)

– PREDITH: PREDIction of post liver Transplantation early infectious risk. Funding: IHU Myon – PHRCI AURA

Links towards my recent publications:

–https://pubmed.ncbi.nlm.nih.gov/39966934/

–https://pubmed.ncbi.nlm.nih.gov/37575179/

–https://pubmed.ncbi.nlm.nih.gov/37064910/

Romain PARENT

Senior Researcher

He is interested in liver pathologies from a neuronal point of view and in prognostic signatures of liver cancer risk. He has identified profound reconfigurations of the intrahepatic ANS that accompany progression to HCC, and the associated receptors and molecular pathogenic features. This work has led to the identification of neuronal or cholinergic processes as playing a role in HCC.

Octavie PARIS

Project Manager

As a European project manager, she has been working with Prof. Zoulim for several years to coordinate the H2020 IP-cure-B project, Immune profiling to guide host-directed interventions to cure HBV infections, leading this international consortium of 14 partner institutions.

She is also in charge of coordinating the ANRS HBV Cure Task Force and joined the team at the Lyon University Hospital Institute of Hepatology a year ago as project manager.

Andrea REVILLOT

Research Engineer

I am an engineer in Dr. Barbara Testoni’s team. I work under the supervision of Dr. Andres Roca on characterizing the anti-HBV and immunomodulatory effect of an activating antibody. To do this, I characterize immune populations, particularly γδ T cells, using spectral flow cytometry and test the effects of the antibody on HBV-infected hepatocytes.

Maureen RITTER

Postdoctoral Fellow

As a virology researcher currently pursuing postdoctoral studies, I am interested in the interactions between cellular and viral proteins from hepatotropic viruses. My research focuses on the formation of HBV cccDNA, a key process in establishing and maintaining infection.

Armando Andres ROCA SUAREZ

Junior PI

His research focuses on developing ex vivo models to evaluate novel host-targeting therapies against HBV and HDV infection. His broader interests include Kupffer cell biology and the use of single-cell transcriptomics to characterize the human liver microenvironment.

Coline SEURRE

PhD Student

As a doctoral student in virology, I am interested in molecules with antiviral potential and am writing my thesis under the supervision of Dr. Boyan Grigorov. My research focuses on the study of heparanase-1 in the viral cycles of HIV-1 and HBV, as well as the evaluation of heparanase inhibitors as potential antivirals against these infections.

Rucha THIGALE

PhD Student

I am a PhD student and my work involves studying the RNA splice variants of Hepatitis B Virus. I will be working on how the splice variants contribute to liver pathogenesis.

Barbara TESTONI

Senior Researcher

Her research focuses on the epigenetic mechanisms underlying the regulation of host and viral genes during HBV infection, with particular emphasis on the transcriptional regulation of the HBV minichromosome. She is also involved in translational studies aimed at understanding the relationships between HBV persistence and perturbations in intrahepatic innate immunity, and at characterizing new serum biomarkers for intrahepatic ccDNA activity.

Fabien ZOULIM

Senior Researcher

He focuses on chronic viral hepatitis, and in particular hepatitis B, which remains a major public health problem worldwide, with over 250 million chronic carriers. Chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma, the second most deadly cancer worldwide.

He has developed expertise in the field of hepatitis B to understand the mechanisms of viral persistence in experimental models, identify new antiviral targets and biomarkers predictive of response to antiviral treatments, and evaluate the efficacy of these new treatments in clinical trials.