Research Thomas Vanwolleghem

Abstract

Hepatitis B virus (HBV) causes 1.3 million deaths per year worldwide, with South Africa's burden intensified by the risks of HIV co-infection. The burden of vaccine-preventable HBV in South Africa has not been accurately determined, complicating the tracking of progress against the goals of elimination of Agenda 2030. We will adopt a modeling framework to estimate the burden of HBV disease more accurately and assess the (cost-)effectiveness of prevention strategies while accounting for HBV and HIV co-infection. The latter increases, for example, mother-to-child transmission during pregnancy. We will share our data-driven insights through close science-policy engagement to inform maternal and neonatal health interventions. Concurrently, we will raise educational standards in disease modeling, leading to a global cadre of emerging researchers. Our focus on bridging the gap for vulnerable populations, preventing mother-to-child transmission, will leverage policy action to integrate HBV services for equitable healthcare.

Researcher(s)

• Promoter: Willem Lander
• Co-promoter: Vanwolleghem Thomas

Research team(s)

• Primary and interdisciplinary care Antwerp (ELIZA)

Project type(s)

• Research Project

Abstract

Chronic Hepatitis B Virus infections affect 3.6% of the worldwide population and result in liver-related death in over 700000 people annually. Current standard of care, consisting of nucleos(t)ide analogues (NA), efficiently suppress viral replication, prevent liver disease, but do not cure the infection, defined as Hepatitis B surface antigen (HBsAg) loss. Lifelong NA treatment is therefore often required. However, in some patients with long term viral suppression, treatment withdrawal may lead to persistent off-treatment viral control and an upto 40% chance of HBsAg loss after 5 years. Obviously, identifying upfront which patients will benefit from a treatment cessation is of utmost importance. We are currently coordinating the COIN-B study, a multicentric national study in which 90 patients stop their antiviral treatment, and 50 continue. The design of this study allows for the evaluation of baseline host factors, such as ethnicity, on off-treatment outcomes, but not the effects of viral flares or retreatment. To this end, we will combine the data of the COIN-B study with several international prospective NA withdrawal studies with intensive monitoring schedules and retreatment criteria. We will apply and refine advanced statistical modelling to evaluate rare events, such as off-treatment HBsAg loss. This will enable a full picture of the different viral and host factors associated with viral control or functional cure (HBsAg loss) after NA withdrawal. This will further establish the optimal monitoring interval, retreatment indications and role of flares. Apart from statistical modelling, we will apply bio-informatics approaches to investigate gene signatures in blood of COIN-B patients. The goal of this substudy is to find a genetic biomarker able to select patients upfront for a NA treatment cessation. In addition, this will learn how the blood transcriptome is modulated during off-treatment responses and yield insight in the pathogenesis of flares and viral control. The combination of both approaches will ultimately lead to the optimal predictive model of clinical parameters and gene signatures that will guide future treatment decisions in the vast number of NA-treated patients.

Researcher(s)

• Promoter: Vanwolleghem Thomas
• Co-promoter: Hens Niel
• Fellow: Ballet Fleur

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Chronic Hepatitis B Virus infections affect 3.6% of the worldwide population and result in liver related death in over 700000 people annually. Current standard of care, consisting of nucleos(t)ide analogues (NA), efficiently suppress viral replication, prevent liver disease, but do not cure the infection, defined as Hepatitis B surface antigen (HBsAg) loss. Lifelong NA treatment is therefore often required. However, in some patients with long term viral suppression, treatment withdrawal may lead to persistent off-treatment viral control and an upto 40% chance of HBsAg loss after 5 years. Obviously, identifying upfront which patients will benefit from a treatment cessation is of utmost importance. We recently found in a multicenter international study that off-treatment HBsAg loss differs between ethnicities. In the current proposal we aim to prospectively investigate the contribution of ethnicity, host and viral markers to off-treatment viral outcomes. In addition, we will establish the incremental cost effectiveness of treatment withdrawal using real-life health related quality of life questionnaires and queried costs. P: chronic hepatitis B infection, virally suppressed with NA for at least 12 months (HBeAg seroconversion) or 36 months (HBeAg- infection at treatment start), liver fibrosis upto F2 I: antiviral treatment withdrawal C: ethnic background (Caucasian versus non-Caucasian) O: Primary endpoint: viral control (HBV DNA< 2000 IU/mL) at 72 weeks. Secondary endpoint: HBsAg loss

Researcher(s)

• Promoter: Vanwolleghem Thomas

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Chronic Hepatitis B Virus infections affect 3.6% of the worldwide population and result in liver related death in over 700000 people annually. Current standard of care, consisting of nucleos(t)ide analogues (NA), efficiently suppress viral replication, prevent liver disease, but do not cure the infection, defined as Hepatitis B surface antigen (HBsAg) loss. Lifelong NA treatment is therefore often required. However, in some patients with long term viral suppression, treatment withdrawal may lead to persistent off-treatment viral control and an upto 40% chance of HBsAg loss after 5 years. Obviously, identifying upfront which patients will benefit from a treatment cessation is of utmost importance. We recently found in a multicenter international study that off-treatment HBsAg loss differs between ethnicities. In the current proposal we aim to prospectively investigate the contribution of ethnicity, host and viral markers to off-treatment viral outcomes. In addition, we will establish the incremental cost effectiveness of treatment withdrawal using real-life health related quality of life questionnaires and queried costs. P: chronic hepatitis B infection, virally suppressed with NA for at least 12 months (HBeAg seroconversion) or 36 months (HBeAg- infection at treatment start), liver fibrosis upto F2 I: antiviral treatment withdrawal C: ethnic background (Caucasian versus non-Caucasian) O: Primary endpoint: viral control (HBV DNA< 2000 IU/mL) at 72 weeks. Secondary endpoint: HBsAg loss

Researcher(s)

• Promoter: Vanwolleghem Thomas
• Co-promoter: Beutels Philippe

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Hepatitis B Virus (HBV) infections affect 3.6% of the worldwidepopulation, putting them at risk for liver cirrhosis and cancer. Antiviralmedicines efficiently suppress HBV replication, but do not cure theinfection. Novel antiviral drugs will require in-depth insight in HBV'simmunopathogenesis and disease outcomes. In this regard, B cellshave been highly neglected. Thanks to the development offluorescently labelled Hepatitis B surface (HBsAg) and core antigen(HBcAg) baits, we and others very recently unraveled part of thevirus-B cell interaction in blood of cross-sectional adult HBV cohorts:In contrast to HBsAg-specific B cells, humoral immune responsesagainst HBcAg remain vigorous in untreated patients and associatewith HBV's natural history. Building on this expertise, in the currentproposal we will examine the effect of recent HBV exposure, B celldepletion, antiviral treatment initiation and controlled treatmentinterruption in longitudinal cohorts. In addition we will sample liver,bone marrow and blood to fully survey HBV's humoural immunity.Combined, these approaches should define the heterogeneity,compartmentalization and association of HBV-specific B cellresponses with disease outcomes. Finally, after optimizing andvalidating HBV-specific B cell receptor sequencing in sorted cells, themost promising identified clinical association will be examined forBCR signatures, which may ultimately lead to a clinical applicabletest.

Researcher(s)

• Promoter: Vanwolleghem Thomas
• Fellow: Vanwolleghem Thomas

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Mother-to-child transmission (MTCT) is a major route for hepatitis B virus (HBV) infection in Uganda. The risk of developing chronic hepatitis, subsequent liver fibrosis and/or hepatocellular carcinoma is higher in MTCT compared to horizontal transmission acquired later in life. Interruption of early transmission is essential to break the cycle of ongoing HBV infection. As there is no funding by GAVI for birth-dose hepatitis B vaccines in Uganda, focus on administration of antiviral treatment from the late second or early third trimester of pregnancy to reduce maternal HBV viral load is key to prevent MTCT. Although being the cornerstone in the management of HBV, HBV DNA quantification in Uganda is hampered by the limited availability of q-PCR machines. In this project, we will set-up a unit for HBV screening and viral load testing by q-PCR in Lira, North-Eastern Uganda, to reduce the burden of HBV caused by MTCT. We also strive to increase awareness and reduce the social stigma on HBV among pregnant women and health care workers.

Researcher(s)

• Promoter: Vanwolleghem Thomas

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Hepatitis E (HEV) infections are emerging in Europe, especially HEV genotype 3. Pigs and wild boars are identified as the main source of HEV in Western countries and foodborne transmission seems a significant infection route. Detection methods for HEV in foods are not well standardized. Furthermore a paucity of permissive in vitro and in vivo HEV models, precludes exhaustive infectivity studies. In a recent Scientific Opinion concerning the public health risks associated with HEV as a food-borne pathogen published by the EFSA BIOHAZ Panel, the need for infectivity assays for quantitative risk assessment and for efficient control measures is emphasized. In this project, a first work package will deal with the prioritization of food products based on their risk for HEV in a Belgian context. This will be performed in collaboration with the Belgian meat industry. A second work package of the project will establish alternative molecular methods to detect infectious particles of HEV in high risk food products. For this purpose, molecular methods will be developed that assess the integrity of the RNA genome and capsid of HEV detected in food. These will be evaluated for their potency to estimate infectivity by comparison with an appropriate in vitro cell culture infectivity system for HEV that will be optimized. In a third work package, the effect of meat processing practices on HEV infectivity will be tested. The purpose of this WP is to define food preparatory conditions that will eliminate HEV infectivity.

Researcher(s)

• Promoter: Francque Sven
• Promoter: Vanwolleghem Thomas

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

We aim to kick-start a Belgian-Ugandan collaboration using the requested grant as seed money. An on-site kick-off meeting will be planned. Output of the research grant will include a systematic review article on HCC screening in resource limited settings and a joint grant application for the South Initiative of VLIR-UOS. In addition, the grant will allow to start storage of clinical samples and will thus substantially increase the chance of successful translational research grant applications. In the long-term this grant will allow the strengthening of both the research and operational capacity of several Ugandan Universities and the broadening of an existing research line for the Belgian applicant.

Researcher(s)

• Promoter: Vanwolleghem Thomas

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project