Publications by authors named "Robert J De Knegt"

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming increasingly prevalent in the general population. This study aimed at describing the cardiometabolic burden of the MASLD population and to identify patients at the highest risk of all-cause mortality and liver fibrosis.

Methods: We analysed individuals with MASLD enrolled in the National Health and Nutrition Survey (NHANES) III study (N = 3,628) and in the NHANES 2017-2020 study (n = 2,618).

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Article Synopsis
  • Metabolic dysfunction-associated fatty liver disease (MAFLD) is a rising cause of chronic liver disease globally, prompting the need for dietary intervention strategies.
  • A panel of 55 international experts conducted a study to reach a consensus on dietary modifications for preventing MAFLD, covering various aspects from epidemiology to management.
  • Recommended strategies include following a balanced diet, increasing whole grains and plant-based foods, and reducing red meat and processed foods, along with advocating for physical activity and possibly maintaining Mediterranean or DASH diets.
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Background And Aims: Systematic reviews and medical guidelines are widely used in clinical practice. However, these are often not up-to-date and focussed on the average patient. We therefore aimed to evaluate a guideline add-on, TherapySelector (TS), which is based on monthly updated data of all available high-quality studies, classified in specific patient profiles.

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Background: Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into the activation status of B cells, we investigated gene profiles of B cells in the blood and liver of patients with chronic HBV.

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Studies have traditionally focused on the role of T cells in chronic hepatitis B (CHB), but recent evidence supports a role for B cells. The enrichment of so-called atypical memory (AtM) B cells, which show reduced signaling and impaired differentiation, is believed to be a characteristic feature of CHB, potentially contributing to the observed dysfunctional anti-HBsAg B-cell responses. Our study, involving 62 CHB patients across clinical phases, identified AtM B cells expressing IFNLR1 and interferon-stimulated genes.

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Article Synopsis
  • New research shows some people with chronic hepatitis B might be able to stop taking their medicine safely.
  • A 68-year-old man stopped his medicine and ended up with serious liver problems and had to get a liver transplant.
  • Even though some people can stop their medicine, it's important to follow guidelines carefully, because stopping it can lead to dangerous situations.
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Background And Aims: Historical paired liver biopsy studies are likely to underestimate current progression of disease in patients with chronic hepatitis C virus (HCV) infection. We aimed to assess liver disease progression according to the non-invasive Fibrosis-4 (FIB-4) index in patients with chronic HCV and early disease.

Methods And Results: Patients diagnosed with chronic HCV and FIB-4 <3.

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  • There is a growing need for noninvasive tests to help primary care physicians identify patients at high risk for liver disease, leading to the development of the MAF-5 score.
  • The MAF-5 score was created from a study of 21,797 individuals with metabolic dysfunction and is based on factors such as waist circumference, body mass index, diabetes, and specific blood tests.
  • MAF-5 demonstrated higher diagnostic accuracy compared to existing scores, particularly in predicting fibrosis and assessing liver stiffness, making it a promising tool for clinical use.
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Background & Aims: HBsAg secretion may impact immune responses to chronic HBV infection. Thus, therapeutic approaches to suppress HBsAg production are being investigated. Our study aims to examine the immunomodulatory effects of high and low levels of circulating HBsAg and thereby improve our understanding of anti-HBV immunity.

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We studied whether 48 weeks of PEG-IFN alfa-2a add-on increases HBsAg-decline and clearance in HBeAg-negative patients on long-term nucleo(s)tide analogue (NA) therapy. In this investigator-initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg-negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG-IFN alfa-2a add-on (180 μg per week) or continued NA-monotherapy with subsequent follow-up to Week 72.

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Early detection of liver transplantation (LT) vascular complications enables timely management. Our aim was to assess if routine Doppler ultrasound (rDUS) improves the detection of hepatic artery thrombosis (HAT), portal vein thrombosis (PVT) and hepatic venous outflow obstruction (HVOO). We retrospectively analysed timing and outcomes, number needed to diagnose one complication (NND) and positive predictive value (PPV) of rDUS on post-operative day (POD) 0,1 and 7 in 708 adult patients who underwent primary LT between 2010-2022.

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Background & Aim(s): Current guidelines suggest that nucleos(t)ide analogues (NA) can be discontinued before HBsAg loss in a selected group of chronic hepatitis B (CHB) patients. We aimed to study the safety and off-treatment response after NA cessation.

Methods: This is a prospective, multicentre, cohort study in which eligible patients discontinued NA therapy.

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Background And Aims: The path to hepatitis C virus (HCV) elimination is complicated by individuals who become lost to follow-up (LTFU) during care, particularly before receiving effective HCV treatment. We aimed to determine factors contributing to LTFU and whether LTFU is associated with mortality.

Methods: In this secondary analysis, we constructed a database including individuals with HCV who were either LTFU (data from the nationwide HCV retrieval project, CELINE) or treated with directly acting antivirals (DAA) (data from Statistics Netherlands) between 2012 and 2019.

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Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60-80 years who had an MI ≤10 years prior to study enrolment.

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Background And Purpose: Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults.

Methods: In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania.

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Article Synopsis
  • Liver cirrhosis is a significant global health issue that often goes undiagnosed until severe complications arise, highlighting the need for tools to identify at-risk individuals earlier.
  • Researchers developed the LiverRisk score, utilizing demographic and lab data from a large international cohort to categorize individuals into different risk groups for future liver-related issues.
  • The LiverRisk score demonstrated superior predictive accuracy for liver stiffness and related outcomes compared to existing serum biomarkers, effectively aiding in the identification of those at heightened risk for liver disease complications.
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Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH.

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Objectives: Spleen stiffness measurement (SSM) provides a non-invasive surrogate marker for clinical significant portal hypertension (CSPH). Results obtained in highly selected populations were promising but require validation across the spectrum of liver disease. We aimed to investigate the clinical applicability of SSM in a real-world setting.

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Article Synopsis
  • - MAFLD (metabolic dysfunction-associated fatty liver disease) is a common condition affecting about 25-30% of people worldwide and is linked to increased cardiovascular disease (CVD) risk, often underestimated by cardiologists.
  • - An international panel of 52 experts conducted a Delphi survey to create consensus statements on the connection between MAFLD and CVD, covering topics like epidemiology, mechanisms, screening, and management.
  • - The panel highlighted the significance of recognizing the cardiovascular risks associated with MAFLD, aiming to raise awareness and identify future research directions.
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Background And Aims: HBV infection is restricted to the liver, where it drives exhaustion of virus-specific T and B cells and pathogenesis through dysregulation of intrahepatic immunity. Our understanding of liver-specific events related to viral control and liver damage has relied almost solely on animal models, and we lack useable peripheral biomarkers to quantify intrahepatic immune activation beyond cytokine measurement. Our objective was to overcome the practical obstacles of liver sampling using fine-needle aspiration and develop an optimized workflow to comprehensively compare the blood and liver compartments within patients with chronic hepatitis B using single-cell RNA sequencing.

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