10 results on '"Blokzijl H"'
Search Results
2. Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals.
- Author
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Tilborg, M., Lieveld, F. I., Smolders, E. J., Erpecum, K. J., Kanter, C. T. M. M., Maan, R., Valk, M., Arends, J. E., Dofferhoff, A. S. M., Blokzijl, H., Bijmolen, M., Drenth, J. P. H., Knegt, R. J., and Burger, D. M.
- Subjects
RIBAVIRIN ,CHRONIC hepatitis C ,ANTIVIRAL agents ,HEPATITIS C virus ,SOFOSBUVIR ,PATIENTS ,THERAPEUTICS - Abstract
Background In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. Aim To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). Methods Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. Results A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL). Conclusion In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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3. High plasma levels of betaine, a trimethylamine N-Oxide-related metabolite, are associated with the severity of cirrhosis.
- Author
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van den Berg EH, Flores-Guerrero JL, Garcia E, Connelly MA, de Meijer VE, Bakker SJL, Blokzijl H, and Dullaart RPF
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- Humans, Biomarkers, Cohort Studies, Liver Cirrhosis, Severity of Illness Index, Betaine metabolism, End Stage Liver Disease
- Abstract
Background and Aims: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity., Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score., Results: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively)., Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2023
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4. Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population.
- Author
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Damba T, Bourgonje AR, Abdulle AE, Pasch A, Sydor S, van den Berg EH, Gansevoort RT, Bakker SJL, Blokzijl H, Dullaart RPF, van Goor H, and Moshage H
- Subjects
- Cohort Studies, Humans, Liver Function Tests, Oxidative Stress, Risk Factors, Non-alcoholic Fatty Liver Disease
- Abstract
Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, inflammation and an imbalanced redox homeostasis. We hypothesized that systemic free thiol levels, as a proxy of systemic oxidative stress, are associated with NAFLD., Methods: Protein-adjusted serum free thiol concentrations were determined in participants from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort study (n = 5562). Suspected NAFLD was defined by the Fatty Liver Index (FLI ≥ 60) and Hepatic Steatosis Index (HSI > 36)., Results: Protein-adjusted serum free thiols were significantly reduced in subjects with FLI ≥ 60 (n = 1651). In multivariable logistic regression analyses, protein-adjusted serum free thiols were associated with NAFLD (FLI ≥ 60) (OR per doubling of concentration: 0.78 [95% CI 0.64-0.96], P = .016) even when adjusted for potential confounding factors, including systolic blood pressure, diabetes, current smoking, use of alcohol and total cholesterol (OR 0.80 [95% CI 0.65-0.99], P = .04). This association lost its significance (OR 0.94 [95% CI 0.73-1.21], P = .65) after additional adjustment for high-sensitive C-reactive protein. Stratified analyses showed significantly differential associations of protein-adjusted serum free thiol concentrations with suspected NAFLD for gender (P < .02), hypertension (P < .001) and hypercholesterolemia (P < .003). Longitudinally, protein-adjusted serum free thiols were significantly associated with the risk of all-cause mortality in subjects with NAFLD (FLI ≥ 60) (HR 0.27 [95% CI 0.17-0.45], P < .001)., Conclusion: Protein-adjusted serum free thiol levels are reduced and significantly associated with all-cause mortality in subjects with suspected NAFLD. Quantification of free thiols may be a promising, minimally invasive strategy to improve detection of NAFLD and associated risk of all-cause mortality in the general population., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2020
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5. Author response to Letter to the Editor: "Statins and non-alcoholic fatty liver disease".
- Author
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van den Berg EH, de Meijer VE, and Blokzijl H
- Subjects
- Humans, Risk Factors, Cardiovascular Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Non-alcoholic Fatty Liver Disease
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- 2019
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6. Prescription of statins in suspected non-alcoholic fatty liver disease and high cardiovascular risk, a population-based study.
- Author
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van den Berg EH, Wolters AAB, Dullaart RPF, Moshage H, Zurakowski D, de Meijer VE, and Blokzijl H
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- Adult, Cohort Studies, Cross-Sectional Studies, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Liver Function Tests, Logistic Models, Male, Middle Aged, Netherlands epidemiology, Non-alcoholic Fatty Liver Disease complications, Prevalence, Risk Factors, Severity of Illness Index, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Non-alcoholic Fatty Liver Disease drug therapy
- Abstract
Background & Aims: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing, with concomitant high incidence of lipoprotein abnormalities. Cardiovascular disease (CVD) is the main cause of death in subjects with NAFLD and management of dyslipidaemia is pivotal for prevention. We aimed to determine cardiovascular risk and indication for statin therapy in subjects with NAFLD., Methods: A cross-sectional analysis of the population-based Lifelines Cohort Study of 34 240 adult individuals. Subjects with reported use of lipid-lowering drugs were excluded. Suspected NAFLD was defined as Fatty Liver Index (FLI) ≥60 and advanced hepatic fibrosis as NAFLD fibrosis score (NFS) >0.676. Cardiovascular risk and indication for statin therapy were defined according to the European Society of Cardiology and European Atherosclerosis Society Guideline for the Management of Dyslipidaemias., Results: FLI ≥ 60 was present in 7067 (20.6%) participants and coincided with increased prevalence of type 2 diabetes mellitus, metabolic syndrome, CVD and impaired renal function (all P < 0.001). 10-year predicted cardiovascular risk was significantly increased in subjects with elevated FLI and NFS (both P < 0.001). Indication for statin use was significantly increased in subjects with FLI ≥ 60 (31.0% vs 15.6%, P < 0.001) and NFS > 0.676 (73.2% vs 30.6%, P < 0.001). In multivariable analyses, FLI ≥ 60 (OR 1.26, 95%CI: 1.13-1.41, P < 0.001) and NFS > 0.676 (OR 5.03, 95%CI: 2.76-9.17, P < 0.001) were independent predictors for indication regarding statin therapy., Conclusions: Because of increased cardiovascular risk, substantial proportions of subjects with suspected NAFLD and/or fibrosis have an indication for lipid-lowering treatment and could benefit from statin therapy., (© 2019 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2019
- Full Text
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7. Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals.
- Author
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van Tilborg M, Lieveld FI, Smolders EJ, van Erpecum KJ, de Kanter CTMM, Maan R, van der Valk M, Arends JE, Dofferhoff ASM, Blokzijl H, Bijmolen M, Drenth JPH, de Knegt RJ, and Burger DM
- Subjects
- Adult, Antiviral Agents pharmacokinetics, Drug Therapy, Combination, Female, Genotype, Hepacivirus genetics, Hepatitis C, Chronic virology, Humans, Liver Cirrhosis blood, Liver Cirrhosis drug therapy, Liver Cirrhosis virology, Male, Middle Aged, Prospective Studies, Ribavirin pharmacokinetics, Sofosbuvir therapeutic use, Sustained Virologic Response, Antiviral Agents blood, Antiviral Agents therapeutic use, Hepatitis C, Chronic blood, Hepatitis C, Chronic drug therapy, Ribavirin blood, Ribavirin therapeutic use
- Abstract
Background: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients., Aim: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR)., Methods: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses., Results: A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL)., Conclusion: In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR., (© 2017 John Wiley & Sons Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
8. Infusion of DDAVP does not improve primary hemostasis in patients with cirrhosis.
- Author
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Arshad F, Stoof SC, Leebeek FW, Ruitenbeek K, Adelmeijer J, Blokzijl H, van den Berg AP, Porte RJ, Kruip MJ, and Lisman T
- Subjects
- ADAM Proteins blood, ADAMTS13 Protein, Adult, Biomarkers blood, Factor VIII metabolism, Female, Hemophilia A blood, Hemophilia A diagnosis, Humans, Infusions, Intravenous, Liver Cirrhosis blood, Liver Cirrhosis diagnosis, Male, Middle Aged, Netherlands, Time Factors, Treatment Outcome, von Willebrand Factor metabolism, Deamino Arginine Vasopressin administration & dosage, Hemophilia A drug therapy, Hemostasis drug effects, Hemostatics administration & dosage, Liver Cirrhosis drug therapy
- Abstract
Background & Aims: Cirrhosis frequently affects multiple components of hemostasis. Reversal of the coagulopathy of these patients is frequently required in case of bleeding episodes, or as prophylaxis before invasive procedures. Although 1-deamino-8-D-arginine vasopressin (DDAVP) is widely used as a pro-hemostatic agent in patients with cirrhosis, it is unclear whether DDAVP truly enhances hemostasis in these patients. Here we investigated the hemostatic effects of a single bolus of DDAVP in patients with cirrhosis., Methods: Ten patients with cirrhosis (child B or C) and ten patients with mild haemophilia A received an intravenous single bolus of 0.3 microgram/kg DDAVP. Plasma was collected prior to and at 1, 3, 6, and 24 h after DDAVP administration. Levels of Von Willebrand factor (VWF), VWF propeptide, factor VIII (FVIII), and ADAMTS13 were measured in all plasma samples, whereas VWF multimers and functional VWF-dependent platelet adhesion were determined in the samples pre- and 1 h after DDAVP administration., Results: Following DDAVP administration, VWF, FVIII, and VWF propeptide levels increased in patients with haemophilia, while patients with cirrhosis only showed an increase in VWF propeptide and FVIII levels. High molecular weight VWF multimers and VWF-dependent platelet adhesion increased in patients with haemophilia one hour after DDAVP administration, but did not change in the patients with cirrhosis. Levels of ADAMTS13 were unaffected in both patient groups after DDAVP., Conclusion: The lack of relevant effects of DDAVP on laboratory indices of primary hemostasis in patients with cirrhosis is in line with previous clinical study results in these patients., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
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9. Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis.
- Author
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Potze W, Arshad F, Adelmeijer J, Blokzijl H, van den Berg AP, Porte RJ, and Lisman T
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- Anticoagulants pharmacology, Antithrombins blood, Antithrombins pharmacology, Benzimidazoles blood, Benzimidazoles pharmacology, Benzimidazoles therapeutic use, Blood Coagulation drug effects, Dabigatran, Diagnostic Tests, Routine, Factor Xa Inhibitors, False Negative Reactions, Female, Fondaparinux, Heparin blood, Heparin pharmacology, Heparin therapeutic use, Heparin, Low-Molecular-Weight blood, Heparin, Low-Molecular-Weight pharmacology, Heparin, Low-Molecular-Weight therapeutic use, Humans, Liver Cirrhosis complications, Liver Cirrhosis drug therapy, Male, Middle Aged, Morpholines blood, Morpholines pharmacology, Morpholines therapeutic use, Polysaccharides blood, Polysaccharides pharmacology, Polysaccharides therapeutic use, Prothrombin antagonists & inhibitors, Rivaroxaban, Sensitivity and Specificity, Thiophenes blood, Thiophenes pharmacology, Thiophenes therapeutic use, Thrombophilia blood, Thrombophilia etiology, beta-Alanine analogs & derivatives, beta-Alanine blood, beta-Alanine pharmacology, beta-Alanine therapeutic use, Anticoagulants blood, Blood Coagulation Tests, Drug Monitoring methods, Liver Cirrhosis blood
- Abstract
There is increasing recognition that thrombotic complications may occur in patients with cirrhosis, and literature on antithrombotic treatment in these patients is rapidly emerging. Due to extensive haemostatic changes in patients with cirrhosis, careful monitoring of anticoagulant therapy may be required. Recent data suggest that plasma levels of low molecular weight heparin (LMWH) are substantially underestimated by the anti-activated factor X (anti-Xa) assay in patients with cirrhosis. We studied the in vitro recovery of antithrombin (AT)-dependent and -independent anticoagulant drugs in plasma from 26 patients with cirrhosis and 30 healthy controls and found substantially reduced anti-Xa levels when AT-dependent anticoagulant drugs were added to the plasma of patients with cirrhosis. LMWH (0·2 U/ml) had the poorest recovery in plasma from patients with cirrhosis (0·13 ± 0·06 U/ml, compared to 0·23 ± 0·03 U/ml in controls, P < 0·0001), followed by unfractionated heparin and fondaparinux. In contrast, the recovery of rivaroxaban and dabigatran was identical between patients and controls. These data suggest that the anti-Xa assay cannot be used to monitor AT-dependent anticoagulant drugs in patients with cirrhosis, as it substantially underestimates drug levels. The direct factor Xa and IIa inhibitors, however, may be monitored through the respective anti-Xa and anti-IIa assays in patients with cirrhosis., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
- Full Text
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10. Decreased tissue factor pathway inhibitor (TFPI)-dependent anticoagulant capacity in patients with cirrhosis who have decreased protein S but normal TFPI plasma levels.
- Author
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Potze W, Arshad F, Adelmeijer J, Blokzijl H, van den Berg AP, Meijers JC, Porte RJ, and Lisman T
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- Case-Control Studies, Female, Humans, Lipoproteins deficiency, Lipoproteins genetics, Liver Cirrhosis genetics, Male, Middle Aged, Lipoproteins blood, Liver Cirrhosis blood, Protein S metabolism, Protein S Deficiency blood, Thrombin metabolism
- Abstract
Protein S acts as a cofactor for tissue factor pathway inhibitor (TFPI) in the down regulation of thrombin generation, and acquired and congenital protein S deficiencies are associated with a concomitant TFPI deficiency. In contrast, in patients with liver diseases, decreased protein S, but normal or increased levels of TFPI have been reported. We compared TFPI and protein S plasma levels between 26 patients with cirrhosis and 20 healthy controls and found that TFPI levels were comparable between patients (111 ± 38%) and controls (108 ± 27%), despite reduced protein S levels (74 ± 23% in patients vs. 98 ± 10% in controls). Subsequently, we quantified the activity of the TFPI-protein S system by measuring thrombin generation in the absence and presence of neutralizing antibodies to protein S or TFPI. Ratios of peak thrombin generation in the absence and presence of these antibodies were calculated. Both the protein S and the TFPI ratios were increased in patients with cirrhosis compared to controls. Protein S ratios were (0·62 [0·08-0·93] in patients vs. 0·32 [0·20-0·54] in controls; TFPI ratios were 0·50 [0·05-0·90] in patients vs. 0·18 [0·11-0·49] in controls). Thus, although the acquired protein S deficiency in patients with cirrhosis is not associated with decreased TFPI levels, the TFPI/protein S anticoagulant system is functionally impaired., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
- Full Text
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