Head: prof dr Thomas Vanwolleghem
We aim to study, guide and improve outcomes of patients with viral hepatitis, by analysing pathophysiology and natural history, both at a cellular level with state of the art translational approaches in well-characterized patient samples, as well as in patient registries and clinical trials. We study virus-host interactions in HBV, HDV and 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. We examine the cascade of care and public health interventions in patients with chronic HBV, HDV and HEV, 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 during HBV’s natural history. We make use of recently developed fluorescently labelled HBV proteins to unequivally 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 coordinating 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.
Hepatitis delta virus
Patients with an HBV-HDV coinfection have a worse prognosis compared to HBV mono-infections, but 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.
Hepatitis E virus
Hepatitis E virus infections are emerging as a foodborne infection in Europe. In collaboration with Sciensano and ILVO, we aim to develop HEV quantification methods to detect infectious HEV particles in food matrices and investigate 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.
Hepatitis B and D virus associated hepatocellular carcinoma (HCC)
So far none of the available non-invasive tests for early diagnosis of HCC have shown adequate diagnostic accuracy and cost-effectiveness to deserve large-scale introduction in surveillance protocols. These limitations steer the importance to use RNA-Sequencing data for evaluating putative higher accuracy biomarkers at the transcript level that could help in early HCC prediction.
Key Publications
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.
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.
Stijn Van Hees HCC prediction study: Establishment of a predictive gene signature by identifying RNA transcripts that are associated with HCC incidence.
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: Project: 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.
Tatjana Locus: Development of methods for detection of infectious hepatitis E virus in pork meat products and optimization of processing practices to reduce infectivity.
Marie Coessens: Cost-effective screening strategies for viral hepatitis and non-alcoholic fatty liver disease in general and selective populations.
Axelle Vanderlinden: Establishment of a joint Belgian-Ugandan research team on Prevention of Mother to Child Transmission of HBV.
Co-Project: Nucleos(t)ide analogue cessation as an effective treatment strategy in chronic hepatitis B infections.