Head: prof dr Thomas Vanwolleghem
We aim to study, improve and guide outcomes for patients with viral hepatitis by unraveling the pathophysiology and natural history of these infections. Through cutting-edge translational research, we analyze disease mechanisms at the cellular level using state-of-the-art techniques in well-characterized patient samples, while also leveraging patient registries and clinical trials to drive impactful discoveries.
We focus on virus-host interactions in Hepatitis B (HBV), Hepatitis Delta (HDV) and Hepatitis E (HEV) infections and their long-term complications by applying multi-parametric approaches using RNA sequencing, flowcytometry, in vitro cell cultures, multiplex/ELISPOT and microscopic imaging. Additionally, we assess the epidemiology, burden of disease and cascade of care by outreach screening activities in ethnic minorities both in Belgium as in Uganda.
Hepatitis B virus
Our specific interest lies in the kinetics and function of HBV-specific B cells throughout HBV’s natural history. We make use of recently developed fluorescently labelled HBV proteins to unequivocally identify and isolate B cells targeting either the hepatitis B surface or the core antigen in chronically infected patients.
In order to increase hepatitis B surface antigen loss rates in chronically infected patients, we are leading a multicenter prospective nucleos(t)ide analogue discontinuation clinical trial (COIN-B study: COntrolled Interruption of Nucleos(t)ide analogue treatment in chronic hepatitis B infections - NCT04779970). In this study host and viral markers to predict off-treatment responses will be investigated, in collaboration with international academic and industrial partners.
Answering the WHO call to eliminate viral hepatitis, our public health related activities focus on national serosurveys, screening and linkage to care campaigns and the prevention of mother to child transmission. Leveraging available national serumbanks we estimate HBV prevalence in Belgium. We have set-up  a large-scale HBsAg screening study in Uganda in collaboration with Lira University and assess the effectiveness of targeted interventions to reduce vertical transmission. Recognizing the burden of viral hepatitis in ethnic minorities, we coordinate viral hepatitis screening programs during citizenship classes for migrants in Flanders. This expertise will be furthered in a EU4H supported Hepatitis Outreach for Migrant Populations (HEP-HOP) project aimed at viral hepatitis screening, HBV vaccination and linkage to care in Spain and Latvia.
Hepatitis delta virus
Patients with an HBV-HDV coinfection have a worse prognosis compared to HBV mono-infections, yet long-term clinical outcome data are scarce. In collaboration with several viral hepatitis treatment centers, we have established a large Belgian HDV cohort with the aim of investigating the natural course, disease severity and prognosis of this devastating disease. In a representative national sample of 2000 HBsAg+ patients we are currently evaluating centralized HDV antibody and HDV RNA reflex testing, in order to prospectively estimate HDV’s prevalence and burden of disease in Belgium.
Hepatitis E virus
HEV is emerging as a foodborne infection in Europe. In collaboration with Sciensano and ILVO (Flanders Research Institute for Agriculture, Fisheries and Food), we are developing HEV quantification methods to detect infectious HEV particles in food matrices. Our research also explores food processing techniques to minimize zoonotic risks.
HEV infections show variable clinical presentations. In collaboration with Sciensano, we established a national patient cohort of HEV infections, in which we examine viral and host factors that determine clinical outcomes. Currently, we are studying HEV RNA in wastewater plants to estimate geographic and temporal changes in circulating HEV strains in Belgium.
Hepatitis B and D virus associated hepatocellular carcinoma (HCC)
So far none of the available non-invasive tests for early diagnosis of hepatocellular carcinoma (HCC) have shown adequate diagnostic accuracy and cost-effectiveness to deserve large-scale introduction in surveillance protocols. To address this, we are leveraging RNA sequencing data to identify high-accuracy biomarkers at the transcript level, aiming to improve early HCC prediction and surveillance protocols.
Key Publications
Furquim d'Almeida A, Ho E, Govaerts L, Michielsen P, Sersté T, Bourgeois S, Delwaide J, Moreno C, Orlent H, Van Vlierberghe H, de Galocsy C, Peeters M, Padalko E, Van Gucht S, Vanwolleghem T. Severe Liver-Related Outcomes in Patients With Hepatitis Delta: Results From a Multi-Ethnic Multicenter Long-Term Follow-Up Study. J Viral Hepat. 2025 Feb;32(2):1-15. doi: 10.1111/jvh.14060. PMID: 39846497; PMCID: PMC11756033.
Ho E, Vanderlinden A, Govaerts L, De Fooz B, Van Damme P, Michielsen P, Vanwolleghem T. Opportunistic screening using point-of-care testing leads to successful linkage to care of HBV-infected migrant populations in a low endemic country. J Virus Erad. 2024 Mar 27;10(1):100369. doi: 10.1016/j.jve.2024.100369. eCollection 2024 Mar. PMID: 38596321
Locus T, Lambrecht E, Lamoral S, Willems S, Van Gucht S, Vanwolleghem T, Peeters M. A Multifaceted Approach for Evaluating Hepatitis E Virus Infectivity In Vitro: Cell Culture and Innovative Molecular Methods for Integrity Assessment. Vet Sci. 2023 Nov 27;10(12):676. doi: 10.3390/vetsci10120676. PMID: 38133227
Locus T, Lambrecht E, Peeters M, Suin V, Verhaegen B, Van Hoorde K, Lamoral S, Vanwolleghem T, Van Gucht S. Hepatitis E virus in pork meat products and exposure assessment in Belgium. Int J Food Microbiol. 2023 Jul 16;397:110198. doi: 10.1016/j.ijfoodmicro.2023.110198. Epub 2023 Apr 5. PMID: 37086528
Peeters M, Schenk J, De Somer T, Roskams T, Locus T, Klamer S, Subissi L, Suin V, Delwaide J, Stärkel P, De Maeght S, Willems P, Colle I, Van Hoof M, Van Acker J, Van Steenkiste C, Moreno C, Janssens F, Reynders M, Steverlynck M, Verlinden W, Lasser L, de Galocsy C, Geerts A, Maus J, Gallant M, Van Outryve S, Marot A, Reynaert H, Decaestecker J, Bottieau E, Schreiber J, Mulkay JP, de Goeij S, Salame M, Dooremont D, Dastis SN, Boes J, Nijs J, Beyls J, Hens N, Nevens F, Van Gucht S, Vanwolleghem T; Belgian Association for the Study of the Liver. Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018. J Hepatol. 2023 Jan;78(1):67-77.
Furquim d'Almeida A, Ho E, Van Hees S, Vanwolleghem T. Clinical management of chronic hepatitis B: A concise overview. United European Gastroenterol J. 2022 Feb;10(1):115-123. doi: 10.1002/ueg2.12176. Epub 2021 Nov 30. PMID: 34846093
Vanwolleghem T, Adomati T, Van Hees S, Janssen HLA. Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV. JHEP Rep. 2021 Nov 19;4(2):100398.
Van Hees S, Cuypers B, Bourgeois S, Groothuismink ZMA, Meysman P, Van der Vlies P, de Knegt R, Vonghia L, Michielsen P, Francque S, Laukens K, Boonstra A, Vanwolleghem T. Sorted B cell transcriptomes point towards actively regulated B cell responses during ongoing chronic hepatitis B infections. Cell Immunol. 2021 Apr;362:104283.
Vanwolleghem T, Groothuismink ZMA, Kreefft K, Hung M, Novikov N, Boonstra A. Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV. J Hepatol. 2020 Jul;73(1):52-61.
Van Hees S, Muyindike W, Erem G, Ocama P, Seremba E, Paska A, Michielsen P, Okwir M, Vanwolleghem T. Challenges associated with the roll-out of HCC surveillance in sub-Saharan Africa - the case of Uganda. J Hepatol. 2020 Nov;73(5):1271-1273
Ho E, Michielsen P, Van Damme P, Ieven M, Veldhuijzen I, Vanwolleghem T. Point-of-Care Tests for Hepatitis B Are Associated with A Higher Linkage to Care and Lower Cost Compared to Venepuncture Sampling During Outreach Screenings in an Asian Migrant Population. Ann Glob Health. 2020 Jul 16;86(1):81.
Staff, Post docs, PhDs & Projects
Post docs:
Tom Adomati: HBV-specific B cells: study of their phenotype and function in relation to clinical outcomes in chronic HBV infections.
PhDs & Academic Researchers
Erwin Ho: HBV, HDV and HEV screening and seroprevalence studies. Natural history and disease severity of hepatitis delta infections in Belgium.
Arno Furquim d’Almeida: Nucleos(t)ide analogue cessation as an effective treatment strategy in chronic hepatitis B infections. Natural history and disease severity of hepatitis delta infections in Belgium. HBV seroprevalence in Belgium.
Marie Coessens: Prevalence of hepatitis B, C and delta virus in general and selected populations. Prevention of hepatitis B and C virus reactivation in patients undergoing chemotherapy and immunosuppression.
Axelle Vanderlinden: Establishment of a joint Belgian-Ugandan research team on Prevention of Mother to Child Transmission of HBV. Nucleos(t)ide analogue cessation as an effective treatment strategy in chronic hepatitis B infections. Outreach HBV and HCV screening initiatives conducted during civic integration classes targeting migrant populations in Flanders.
Fleur Ballet: Identification of variables that predict the outcome of nucleos(t)ide analogue cessation for chronic hepatitis B infections by statistical modelling and bio-informatic analyses.
Alumni:
Dr. Stijn Van Hees: Resident in Laboratory Medicine – University of Ghent
Dr. Nicolaas Van Renne: Postdoctoral researcher – Institut Jules Bordet
Dr. Tatjana Locus: Data analyst – Stichting Kankerregister