Papers by Jeroen Aerssens
Proceedings of the National Academy of Sciences of the United States of America, 2002
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Journal of Hepatology, Jun 1, 2023
Alimentary Pharmacology & Therapeutics, 2015
SummaryBackgroundFibrosis progression in hepatitis C virus (HCV)‐infected patients varies greatly... more SummaryBackgroundFibrosis progression in hepatitis C virus (HCV)‐infected patients varies greatly between individuals. Chemokines recruit immune cells to the infected liver and may thus play a role in the fibrosis process.AimTo investigate plasma levels of a diverse chemokine panel in relation to liver fibrosis.MethodsAfrican‐American and Caucasian HCV genotype 1 infected patients were treated with peginterferon (pegIFN) and ribavirin (RBV) for 48 weeks (VIRAHEP‐C cohort). Plasma levels of 13 cytokines were studied at baseline (n = 386). Subsequently, GROα levels were assessed in a sub cohort (n = 99) at baseline, and at 4 and 12 weeks after start of pegIFN/RBV treatment.ResultsIncreased severity of fibrosis (Ishak fibrosis score 0–2 vs. 3–6) was associated with increased plasma IP‐10 (CXCL10) and IL‐8 (CXCL8) levels, and decreased plasma levels of the chemokine growth‐related oncogene (GRO, CXCL1‐3). Plasma GRO levels were also positively correlated with platelet counts, and were h...
Journal of Hepatology, 2012
Journal of Hepatology, Aug 1, 2020
Background and aims: Sodium glucose transporter-2 inhibitors (SGLT2) are now widely approved trea... more Background and aims: Sodium glucose transporter-2 inhibitors (SGLT2) are now widely approved treatment against diabetes, whereas the effect on hepatic outcome of nonalcoholic fatty liver disease (NAFLD) remains uncertain. We aimed to evaluate the SGLT2 effect on pathogenesis of NAFLD including pathological findings. Method: Multicenter randomized controlled trial was conducted and diabetic patients with NAFLD were included. Liver biopsy was performed before randomization and 2nd liver biopsy was performed after the treatment for 72 weeks with ipragliflozin (50 mg/day, n = 21; IPR) or active control treatment, except SGLT2, pioglitazone, and/or glucagon-like peptide-1 analogs (n = 25; CTR). All liver biopsies were evaluated by two pathologists who were blind to group assignment and clinical parameters. Nonalcoholic steatohepatitis (NASH) was diagnosed using Matteoni's classification. Results: There were no significant differences in basal bodyweight, hemoglobin A1c, frequency of concomitant diseases, or pathological NAFLD findings between the groups. Hepatic fibrosis was observed in 17 patients (81%) of IPR and 18 patients (72%) of CTR. After the treatment, IPR showed more significant decrease in body weight, BMI, visceral fat area evaluated by CT scan and hemoglobin A1c comparing with CTR. Liver fibrosis improved in 70.6% (12/17) of patients with liver fibrosis in the IPR group and 22.2% (4/18) of those in the CTR group (p < 0.01). Improvement in hepatocyte ballooning was greater in IPR than CTR (52.4% vs. 24%, p < 0.05). There was no significant difference between the groups in steatosis. NASH resolution was obtained in 66.7% of NASH patients of IPR and 27.3% of those of CTR. There was no patient with development to NASH from non-NASH in IPR whereas 33.3% of non-NASH patients developed to NASH in CTR. Conclusion: Long term ipragliflozin treatment ameliorates hepatic fibrosis of NAFLD. Ipragliflozin brings NASH resolution and prevent aggravation of non-NASH, as well as improve glycemic control and obesity. SGLT2 inhibitor could be a therapeutic choice of diabetic patients with NAFLD.
Twin Research and Human Genetics, 2007
KULeuven. ...
Background: Maintenance of high muscular fitness is positively related to bone health, functional... more Background: Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque-length relationship for knee flexors and extensors. Methods: In total, 283 informative male siblings (17-36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis. Results: The strongest evidence for linkage was found for the torque-length relationship of the knee flexors at 14q24.3 (LOD = 4.09; p,10 25). Suggestive evidence for linkage was found at 14q32.2 (LOD = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD = 2.57; p = 0.01) for isometric knee torque at 30u flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD = 2.33, 2.69 and 2.21; p,10 24 for all) for the torque-length relationship of the knee extensors and at 18p11.31 (LOD = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque. Conclusions: We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes. 1080 c Ciliary neurotrophic factor (CNTF), 1270 c Ciliary neurotrophic factor receptor (CNTFR), 1271 c Collagen type 1 alpha-1 (COL1A1), 403651 c Deiodinase iodothyronine type I (DIO1), 1733 c Myostatin (GDF8), 2660 c Hypoxia-inducible factor 1 alpha subunit (HIF1A), 3091 c Insulin-like growth factor 1 (IGF1), 3479 c Insulin-like growth factor 2 (IGF2), 3481 c Myosin light chain kinase (MYLK), 4638 c Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1), 2908 c Retinoblastoma (RB1), 5925 c Tumour necrosis factor (TNF), 7124 c Vitamin D receptor (VDR), 7421
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2016
Background & Aims-Sustained virological response (SVR) following peginterferon (pegIFN) and ribav... more Background & Aims-Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV) infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response. Methods-African-American and Caucasian HCV genotype 1 infected patients (n=401) were treated with pegIFN/RBV for 48 weeks (ViraHep-C cohort). Pretreatment plasma levels of MIG (CXCL9), I-TAC (CXCL11) and the type III interferon IL29 were investigated by Luminex and DPP4 activity by using a luciferase assay. Results-Patients achieving SVR had higher baseline MIG plasma levels and lower DPP4 activity than non-SVR patients. MIG was higher in Caucasians, IL28B CC (rs1297860) genotype carriers and patients with higher ALT levels. MIG correlated with IP-10 in SVR patients, but not in non-SVRs. A high DPP4 activity correlated with higher IP-10 levels, while DPP4 activity was not associated with MIG or I-TAC levels. Conclusions-The associations of MIG with SVR status and IL28B genotype imply that higher MIG plasma levels could reflect a beneficial immunological state for response to pegIFN/RBV treatment. The correlation between MIG and IP-10 observed only in SVR patients may contribute to a better treatment response whereas this MIG/IP-10 balance might be disrupted in non-SVR patients due to increased DPP4 cleavage of IP-10 into a dysfunctional form.
See "Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irrit... more See "Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome" by Camilleri M,
Book of abstracts, 2008
KULeuven. ...
Neurogastroenterology and Motility, 2004
Nature Communications, 2021
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in ... more Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017–2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalen...
The Journal of Infectious Diseases, 2020
Targeted metagenomics using strand-specific libraries with target enrichment is a sensitive, gene... more Targeted metagenomics using strand-specific libraries with target enrichment is a sensitive, generalized approach to pathogen sequencing and transcriptome profiling. Using this method, we recovered 13 (76%) complete human respiratory syncytial virus (RSV) genomes from 17 clinical respiratory samples, reconstructed the phylogeny of the infecting viruses, and detected differential gene expression between 2 RSV subgroups, specifically, a lower expression of the P gene and a higher expression of the M2 gene in RSV-A than in RSV-B. This methodology can help to relate viral genetics to clinical phenotype and facilitate ongoing population-level RSV surveillance and vaccine development. Clinical Trials Registration. NCT03627572 and NCT03756766.
The Journal of Infectious Diseases, 2021
BackgroundRespiratory syncytial virus (RSV) infections occur in human populations around the glob... more BackgroundRespiratory syncytial virus (RSV) infections occur in human populations around the globe, causing disease of variable severity, disproportionately affecting infants and older adults (>65 years of age). Immune responses can be protective but also contribute to disease. Experimental studies in animals enable detailed investigation of immune responses, provide insights into clinical questions, and accelerate the development of passive and active vaccination. We aimed to review the role of antibody and T-cell responses in relation to RSV disease severity in animals.MethodsSystematic review and meta-analysis of animal studies examining the association between T-cell responses/phenotype or antibody titers and severity of RSV disease. The PubMed, Zoological Record, and Embase databases were screened from January 1980 to May 2018 to identify animal studies of RSV infection that assessed serum antibody titer or T lymphocytes with disease severity as an outcome. Sixty-three studi...
The Journal of Infectious Diseases, 2020
Respiratory syncytial virus (RSV) is the leading viral pathogen associated with acute lower respi... more Respiratory syncytial virus (RSV) is the leading viral pathogen associated with acute lower respiratory tract infection and hospitalization in children < 5 years of age worldwide. While there are known clinical risk factors for severe RSV infection, the majority of those hospitalized are previously healthy infants. There is consequently an unmet need to identify biomarkers that predict host response, disease severity, and sequelae. The primary objective is to identify biomarkers of severe RSV acute respiratory tract infection (ARTI) in infants. Secondary objectives include establishing biomarkers associated with respiratory sequelae following RSV infection and characterizing the viral load, RSV whole-genome sequencing, host immune response, and transcriptomic, proteomic, metabolomic and epigenetic signatures associated with RSV disease severity. Six hundred thirty infants will be recruited across 3 European countries: the Netherlands, Spain, and the United Kingdom. Participants w...
British Journal of Clinical Pharmacology, 2020
The ability to benefit from knowledge of human genomic data in medicine has been anticipated sinc... more The ability to benefit from knowledge of human genomic data in medicine has been anticipated since the sequencing of the human genome. That promise has experienced some degree of realization, particularly in oncology where biomarker-specific clinical trials and patient treatment specific to the genetics of their tumours now occur. With whole genome sequencing and related technologies becoming more affordable, and the generation and management of vast amounts of data and information, more capable, new opportunities to benefit from these developments lie ahead. Already emerging are many studies describing the association of genomic variation with molecular underpinnings of disease, association with patient response to drugs and informing the nomination of new drug targets. These developments are accompanied by some ethical, legal and regulatory challenges, which we discuss in this article.
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Papers by Jeroen Aerssens