12 results on '"Verwer, Bart J."'
Search Results
2. Drug withdrawal in patients with autoimmune hepatitis in long-term histological remission: A prospective observational study
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van den Brand, Floris F., Snijders, Romée J.A.L.M., de Boer, Ynto S., Verwer, Bart J., van Nieuwkerk, Carin M.J., Bloemena, Elisabeth, Kuiken, Sjoerd D., Drenth, Joost P.H., and Bouma, Gerd
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- 2021
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3. Role of age in presentation, response to therapy and outcome of autoimmune hepatitis
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Baven-Pronk, Martine A. M. C., Biewenga, Maaike, van Silfhout, Joanne J., van den Berg, Aad P., van Buuren, Henk R., Verwer, Bart J., van Nieuwkerk, Carin M. J., Bouma, Gerd, and van Hoek, Bart
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- 2018
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4. NAFLD is related to Post‐prandial Triglyceride‐enrichment of HDL Particles in Association with Endothelial and HDL Dysfunction.
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Verwer, Bart J., Scheffer, Peter G., Vermue, Rick P., Pouwels, Petra J., Diamant, Michaela, and Tushuizen, Maarten E.
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ENDOTHELIUM diseases , *TYPE 2 diabetes , *FATTY liver , *METABOLIC syndrome , *CARDIOVASCULAR diseases - Abstract
NAFLD is closely related with the metabolic syndrome (MetS) and increased risk of cardiovascular disease. Liver fat associates with post‐prandial hypertriglyceridemia, potentially contributing to triglyceride‐enrichment of high‐density lipoproteins (HDL‐TG), and subsequent HDL dysfunction. We assessed liver fat by MR spectroscopy, and its association with HDL physiochemical properties, and endothelial function, measured as flow‐mediated dilation (FMD), before and following three consecutive meals, in 36 men with type 2 diabetes mellitus (T2DM), with the MetS, and controls. Plasma triglycerides increased significantly following the meals (P <.001). Fasting HDL‐TG was highest in T2DM, relative to MetS and controls (P =.002), and increased post‐prandially in all groups (P <.001). HDL function was negatively associated with HDL‐TG following three meals (r = −.32, P<.05). Liver fat associated with HDL‐TG after three meals (r =.65, P <.001). HDL‐TG was independently associated with FMD following three consecutive meals (r = −.477, P =.003). We conclude liver fat is associated with post‐prandial HDL‐TG enrichment which was closely related with endothelial and HDL dysfunction. [ABSTRACT FROM AUTHOR]
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- 2020
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5. Plasma Cathepsin D Activity Rather Than Levels Correlates With Metabolic Parameters of Type 2 Diabetes in Male Individuals.
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Ding, Lingling, Houben, Tom, Oligschlaeger, Yvonne, Bitorina, Albert V., Verwer, Bart J., Tushuizen, Maarten E., and Shiri-Sverdlov, Ronit
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TYPE 2 diabetes ,CATHEPSIN D ,PEOPLE with diabetes ,FREE fatty acids ,GLYCOSYLATED hemoglobin - Abstract
Objective: Type 2 diabetes mellitus is a metabolic disorder characterized by insulin resistance. Previous studies in patients demonstrated that plasma levels of cathepsin D (CTSD), which is optimally active in the acidic environment of lysosomes, correlate with insulin resistance. As plasma pH is slightly reduced in type 2 diabetic patients and we have previously shown that plasma CTSD activity is causally linked to insulin levels in vivo , it is likely that the activity of CTSD in plasma will be increased in type 2 diabetes compared to healthy individuals. However, so far the interaction between CTSD activity and levels to postprandial metabolic derangements in type 2 diabetes is not known. Methods: Eighteen type 2 diabetes and 16 age-matched healthy males were given 2 consecutive standardized mixed meals, after which blood samples were collected. Plasma metabolic parameters as well as CTSD levels and activity were measured, and changes in plasma pH was assessed. Results: In line with the elevation of plasma free fatty acids (FFA) levels in male type 2 diabetics patients, plasma pH in type 2 diabetic individuals was decreased compared to male healthy individuals. While plasma CTSD levels were similar, plasma CTSD activity was increased in male type 2 diabetic compared to male healthy individuals. Besides, plasma CTSD activity rather than levels significantly correlated with indicators of type 2 diabetes (HbA1c, HOMA-IR and glucose). Furthermore, FFA was also independently associated with plasma CTSD activity (standardized β = 0.493, p = 0.007). Conclusions: Despite similar plasma CTSD levels, type 2 diabetic male individuals showed increased plasma CTSD activity compared to healthy males, which was independently linked to plasma FFA levels. Our data therefore point toward plasma CTSD as a metabolic regulator in male type 2 diabetes. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands.
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van den Brand, Floris F., van Nieuwkerk, Carin M. J., de Boer, Ynto S., de Boer, Nanne K. H., Mulder, Chris J. J., Bouma, Gerd, van den Hazel, Sven J., Inderson, Akin, Tushuizen, Maarten E., Verwer, Bart J., Bloemena, Elisabeth, Bakker, Christine M., Vrolijk, Jan M., Drenth, Joost P. H., Tan, Adriaan C. I. T. L., ter Borg, Frank, and ter Borg, Martijn J.
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CHRONIC active hepatitis ,AZATHIOPRINE ,IMMUNOGLOBULIN G ,AMINOTRANSFERASES - Abstract
Summary: Background: Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid‐sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to these regimens. Aim: To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes. Methods: Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first‐line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G. Results: No serious adverse events occurred in patients treated with TG during a median follow‐up of 18 months (range 1‐194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty‐eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non‐response (n = 2). TG was effective in all AIH patients as first‐line maintenance treatment. Conclusion: In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy. [ABSTRACT FROM AUTHOR]
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- 2018
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7. Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands.
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van Gerven, Nicole M.F., Verwer, Bart J., Witte, Birgit I., van Erpecum, Karel J., van Buuren, Henk R., Maijers, Ingrid, Visscher, Arjan P., Verschuren, Edwin C., van Hoek, Bart, Coenraad, Minneke J., Beuers, Ulrich H.W., de Man, Robert A., Drenth, Joost P.H., den Ouden, Jannie W., Verdonk, Robert C., Koek, Ger H., Brouwer, Johannes T., Guichelaar, Maureen M.J., Vrolijk, Jan Maarten, and Mulder, Chris J.J.
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EPIDEMIOLOGY , *CHRONIC active hepatitis , *AUTOIMMUNE diseases , *CIRRHOSIS of the liver , *DISEASE prevalence , *TRANSPLANTATION of organs, tissues, etc. - Abstract
Background and aims. Epidemiological data on autoimmune hepatitis (AIH) are scarce. In this study, we determined the clinical and epidemiological characteristics of AIH patients in the Netherlands (16.7 million inhabitants). Methods. Clinical characteristics were collected from 1313 AIH patients (78% females) from 31 centers, including all eight academic centers in the Netherlands. Additional data on ethnicity, family history and symptoms were obtained by the use of a questionnaire. Results. The prevalence of AIH was 18.3 (95% confidential interval [CI]: 17.3-19.4) per 100,000 with an annual incidence of 1.1 (95% CI: 0.5-2) in adults. An incidence peak was found in middle-aged women. At diagnosis, 56% of patients had fibrosis and 12% cirrhosis in liver biopsy. Overall, 1% of patients developed HCC and 3% of patients underwent liver transplantation. Overlap with primary biliary cirrhosis and primary sclerosing cholangitis was found in 9% and 6%, respectively. The clinical course did not differ between Caucasian and non-Caucasian patients. Other autoimmune diseases were found in 26% of patients. Half of the patients reported persistent AIH-related symptoms despite treatment with a median treatment period of 8 years (range 1-44 years). Familial occurrence was reported in three cases. Conclusion. This is the largest epidemiological study of AIH in a geographically defined region and demonstrates that the prevalence of AIH in the Netherlands is uncommon. Although familial occurrence of AIH is extremely rare, our twin data may point towards a genetic predisposition. The high percentage of patients with cirrhosis or fibrosis at diagnosis urges the need of more awareness for AIH. [ABSTRACT FROM AUTHOR]
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- 2014
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8. Genome-Wide Association Study Identifies Variants Associated With Autoimmune Hepatitis Type 1.
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de Boer, Ynto S., van Gerven, Nicole M. F., Zwiers, Antonie, Verwer, Bart J., van Hoek, Bart, van Erpecum, Karel J., Beuers, Ulrich, van Buuren, Henk R., Drenth, Joost P. H., den Ouden, Jannie W., Verdonk, Robert C., Koek, Ger H., Brouwer, Johannes T., Guichelaar, Maureen M. J., Vrolijk, Jan M., Kraal, Georg, Mulder, Chris J. J., van Nieuwkerk, Carin M. J., Fischer, Janett, and Berg, Thomas
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Background & Aims Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. Methods We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. Results We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 x 10
-78 ). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 x 10-49 ) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 x 10-18 ) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 x 10-8 ) and CARD10 (rs6000782, 22q13.1; P = 3.0 x 10-6 ). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. Conclusions In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. [ABSTRACT FROM AUTHOR]- Published
- 2014
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9. Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission
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van Gerven, Nicole M.F., Verwer, Bart J., Witte, Birgit I., van Hoek, Bart, Coenraad, Minneke J., van Erpecum, Karel J., Beuers, Ulrich, van Buuren, Henk R., de Man, Rob A., Drenth, Joost P.H., den Ouden, Jannie W., Verdonk, Robert C., Koek, Ger H., Brouwer, Johannes T., Guichelaar, Maureen M.J., Mulder, Chris J.J., van Nieuwkerk, Karin M.J., and Bouma, Gerd
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DRUG withdrawal symptoms , *IMMUNOSUPPRESSIVE agents , *CHRONIC active hepatitis , *ADRENOCORTICAL hormones , *AZATHIOPRINE - Abstract
Background & Aims: Current treatment strategies in autoimmune hepatitis (AIH) include long-term treatment with corticosteroids and/or azathioprine. Here we determined the risk of relapse after drug withdrawal in patients in long-term remission and factors associated with such a relapse. Methods: A total of 131 patients (out of a cohort including 844 patients) from 7 academic and 14 regional centres in the Netherlands were identified in whom treatment was tapered after at least 2years of clinical and biochemical remission. Relapse was defined as alanine-aminotransferase levels (ALT) three times above the upper limit of normal and loss of remission as a rising ALT necessitating the reinstitution of drug treatment. Results: During follow-up, 61 (47%) patients relapsed and 56 (42%) had a loss of remission. In these 117 patients, 60 patients had fully discontinued medication whereas 57 patients were still on a withdrawal scheme. One year after drug withdrawal, 59% of the patients required retreatment, increasing to 73% and 81% after 2 and 3years, respectively. Previous combination therapy of corticosteroids and azathioprine, a concomitant autoimmune disease and younger age at time of drug withdrawal were associated with an increased risk of relapse. Subsequent attempts for discontinuation after initial failure in 32 patients inevitably resulted in a new relapse. Conclusions: This retrospective analysis indicates that loss of remission or relapse occurs in virtually all patients with AIH in long-term remission when immunosuppressive therapy is discontinued. These findings indicate a reluctant attitude towards discontinuation of immunosuppressive treatment in AIH patients. [ABSTRACT FROM AUTHOR]
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- 2013
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10. Risk Assessment of Posthepatectomy Liver Failure Using Hepatobiliary Scintigraphy and CT Volumetry.
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Dinant, Sander, de Graaf, Wilmar, Verwer, Bart J., Bennink, Roelof J., van Lienden, Krijn P., Gouma, Dirk J., van Vliet, Arlène K., and van Gulik, Thomas M.
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- 2007
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11. Epidemiology of Autoimmune Hepatitis in the Netherlands: A Nationwide Study.
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van Gerven, Nicole M., Verwer, Bart J., van Hoek, Bart, Brouwer, Johannes T., Visscher, Arjan P., Pronk, Martine, Coenraad, Minneke J., van Buuren, Henk R., De Man, Robert A., Van Erpecum, Karel J., Drenth, Joost P., Beuers, Ulrich, de Zwart, Brenda, den Ouden, Jannie, Koek, Ger H., van Nieuwkerk, Karin, and Bouma, Gerd
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- 2011
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12. Maintenance Treatment is Necessary Even When Auto Immune Hepatitis is in Remission.
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van Gerven, Nicole M., Verwer, Bart J., Mulder, Chris J., Guichelaar, Maureen, van Hoek, Bart, Pronk, Martine, Coenraad, Minneke J., van Buuren, Henk R., De Man, Robert A., Van Erpecum, Karel J., Drenth, Joost P., Beuers, Ulrich, den Ouden, Jannie, Koek, Ger H., Brouwer, Johannes T., van Nieuwkerk, Karin, and Bouma, Gerd
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- 2011
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