Joost P H Drenth

Radboud University Medical Centre (Radboudumc), Nymegen, Gelderland, Netherlands

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Publications (393)2789.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Immunosuppressive therapy may impact cancer risk in inflammatory bowel disease (IBD). Cancer specific data regarding risk and outcome are scarce and data for renal cell carcinoma (RCC) are lacking. We aimed(1) to identify risk factors for RCC development in IBD patients (2) to compare RCC characteristics, outcome and survival between IBD patients and the general population. Methods: A PALGA (Dutch Pathology Registry) search was performed to establish a case group consisting of all IBD patients with incident RCC in The Netherlands (1991-2013). Cases were compared with two separate control groups: (A) with a population-based IBD cohort for identification of risk factors (B) with a RCC cohort from the general population to compare RCC characteristics and outcomes. Results: 180 IBD patients with RCC were identified. Pancolitis (OR 1.8-2.5), penetrating Crohn's disease (OR 2.8), IBD related surgery (OR 3.7-4.5), male gender (OR 3.2-5.0) and older age at IBD onset (OR 1.0-1.1) were identified as independent risk factors for RCC development. IBD patients had a significantly lower age at RCC diagnosis (p < 0.001), lower N-stage (p = 0.025), lower M-stage (p = 0.020) and underwent more frequently surgical treatment for RCC (p < 0.001) compared to the general population. This translated into a better survival (p = 0.026; HR 0.7) independent of immunosuppression. Conclusions: IBD patients with a complex phenotype are at increased risk to develop RCC. They are diagnosed with RCC at a younger age and at an earlier disease stage compared to the general population. This translates into a better survival independent of immunosuppressive or anti-TNFα therapy.
    Oncotarget 10/2015; DOI:10.18632/oncotarget.5186 · 6.36 Impact Factor
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    ABSTRACT: Background: Isolated polycystic liver disease (ADPLD) is an autosomal dominant Mendelian disorder. Heterozygous PRKCSH (where PRKCSH is protein kinase C substrate 80K-H (80 kDa protein, heavy chain; MIM*177060) mutations are the most frequent cause. Routine molecular testing using Sanger sequencing identifies pathogenic variants in the PRKCSH (15%) and SEC63 (where SEC63 is Saccharomyces cerevisiae homolog 63 (MIM*608648); 6%) genes, but about approximately 80% of patients meeting the clinical ADPLD criteria carry no PRKCSH or SEC63 mutation. Cyst tissue often shows somatic deletions with loss of heterozygosity that was recently recognized as a general mechanism in ADPLD. We hypothesized that germline deletions in the PRKCSH gene may be responsible for hepatic cystogenesis in a significant number of mutation-negative ADPLD patients. Methods: In this study, we designed a multiplex ligation-dependent probe amplification (MLPA) assay to screen for deletions of PRKCSH exons. Genomic DNA from 60 patients with an ADPLD phenotype was included. Results: MLPA analysis detected no exon deletions in mutation-negative ADPLD patients. Conclusion: Large copy number variations on germline level are not present in patients with a clinical diagnosis of ADPLD. MLPA analysis of the PRKCSH gene should not be considered as a diagnostic method to explain hepatic cystogenesis.
    Journal of Clinical Laboratory Analysis 09/2015; DOI:10.1002/jcla.21875 · 1.04 Impact Factor
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    ABSTRACT: Background: Up to 33 per cent of patients with uncomplicated symptomatic cholecystolithiasis report persistent pain after cholecystectomy. The aim of this study was to determine characteristics associated with patient-reported absence of abdominal pain after cholecystectomy, improved abdominal symptoms, and patient-reported positive cholecystectomy results in a prospective cohort multicentre study. Methods: Patients aged 18 years or more with symptomatic cholecystolithiasis who had a cholecystectomy between June 2012 and June 2014 in one of three hospitals were included. Before surgery all patients were sent the Gastrointestinal Quality of Life Index (GIQLI) questionnaire and the McGill Pain Questionnaire (MPQ). At 12 weeks after surgery, patients were invited to complete the GIQLI and Patients' Experience of Surgery Questionnaire (PESQ). Logistic regression analyses were performed to determine associations. Results: Questionnaires were sent to 552 patients and returned by 342 before and after surgery. Postoperative absence of abdominal pain was reported by 60·5 per cent of patients. A high preoperative GIQLI score, episodic pain, and duration of pain of 1 year or less were associated with postoperative absence of pain. These factors showed no association with improved abdominal symptoms (reported by 91·5 per cent of patients) or a positive surgery result (reported by 92·4 per cent). Conclusion: Preoperative characteristics determine the odds for relief of abdominal pain after cholecystectomy. However, these factors were not associated with patient-reported improvement of abdominal symptoms or patient-reported positive cholecystectomy results, highlighting the variation of internal standards and expectations of patients before cholecystectomy.
    British Journal of Surgery 09/2015; 102(11):1402-9. DOI:10.1002/bjs.9887 · 5.54 Impact Factor
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    ABSTRACT: In autosomal dominant polycystic kidney disease (ADPKD), obtaining measured total kidney volume (mTKV) by magnetic resonance (MR) imaging and manual tracing is time consuming. Two alternative MR imaging methods have recently been proposed to estimate TKV (eTKVellipsoid and eTKVPANK), which require less time. Cross-sectional and longitudinal diagnostic test study. Patients with ADPKD with a wide range of kidney function and an approved T2-weighted MR image obtained at the University Medical Centers of Groningen, Leiden, Nijmegen, and Rotterdam, the Netherlands, in 2007 to 2014. Test set for assessing reproducibility, n=10; cohort for cross-sectional analyses, n=220; and cohort for longitudinal analyses, n=48. Average times for eTKVellipsoid and eTKVPANK were 5 and 15 minutes, respectively. Bias is defined as (mTKV - eTKV)/mTKV × 100%; precision, as one standard deviation of bias. mTKV using manual tracing to calculate the area within kidney boundaries times slice thickness. Average time for mTKV was 55 minutes. In the test set, intra- and intercoefficients of variation for mTKV, eTKVellipsoid, and eTKVPANK were 1.8% and 2.3%, 3.9% and 6.3%, and 3.0% and 3.4%, respectively. In cross-sectional analysis, baseline mTKV, eTKVellipsoid, and eTKVPANK were 1.96 (IQR, 1.28-2.82), 1.93 (IQR, 1.25-2.82), and 1.81 (IQR, 1.17-2.62) L, respectively. In cross-sectional analysis, bias was 0.02% ± 3.2%, 1.4% ± 9.2%, and 4.6% ± 7.6% for repeat mTKV, eTKVellipsoid, and eTKVPANK, respectively. In longitudinal analysis, no significant differences were observed between percentage change in mTKV (16.7% ± 17.1%) and percentage change in eTKVellipsoid (19.3% ± 16.1%) and eTKVPANK (17.8% ± 16.1%) over 3 years. Results for follow-up data should be interpreted with caution because of the limited number of patients. Both methods for eTKV perform relatively well compared to mTKV and can detect change in TKV over time. Because eTKVellipsoid requires less time than eTKVPANK, we suggest that this method may be preferable in clinical care. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 07/2015; DOI:10.1053/j.ajkd.2015.06.017 · 5.90 Impact Factor
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    ABSTRACT: Polycystic liver disease is associated with impaired health-related quality of life (HRQL). Somatostatin analogues reduce hepatomegaly in polycystic liver disease. To determine whether somatostatin analogues improve HRQL and to identify factors associated with change in HRQL in polycystic liver disease. We pooled data from two randomized, double-blind, placebo-controlled trials that evaluated HRQL using the Short-Form 36 (SF-36) in 96 polycystic liver disease patients treated 6-12 months with somatostatin analogues or placebo. The SF-36 contains a summarizing physical and mental component score and was administered at baseline and at the end of treatment. We used random effect models to delineate the effect of somatostatin analogues on HRQL. We determined the effect of demographics, height-adjusted liver volume, change in liver volume, somatostatin analogue-associated side effects with change in HRQL. In patients with autosomal dominant polycystic kidney disease, we estimated the effect of height-adjusted kidney volume and change in kidney volume in relation to HRQL. Physical component scores improved with somatostatin analogues, but remained unchanged with placebo (3.41 ± 1.29 vs. -0.71 ± 1.54, P = 0.044). Treatment had no impact on the mental component score. Large liver volume was independently associated with larger HRQL decline during follow up (-4.04 ± 2.02 points per logarithm liver volume, P = 0.049). In autosomal dominant polycystic kidney disease, patients with large liver and kidney volumes had larger decline in HRQL (5.36 ± 2.54 points per logarithm liver volume; P = 0.040 and -4.00 ± 1.88 per logarithm kidney volume; P = 0.039). Somatostatin analogues improve HRQL in symptomatic polycystic liver disease. Halting the progressive nature of polycystic liver disease is necessary to prevent further decline of HRQL in severe hepatomegaly. © 2015 John Wiley & Sons Ltd.
    Alimentary Pharmacology & Therapeutics 07/2015; 42(5). DOI:10.1111/apt.13301 · 5.73 Impact Factor
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    ABSTRACT: Background and study aims: The most frequently cited prevalence for serrated polyposis syndrome (SPS) is 1 in every 3000 people screened, but this value is debated. Additionally, changes in 2010 in the World Health Organization (WHO) diagnostic criteria for SPS might affect reported prevalence. An updated estimate of SPS prevalence is necessary to predict the number of cases in screening programs. Patients and methods: A systematic literature search was conducted in the PubMed, EMBASE, and Web of Science databases up to February 2014. Studies reporting the prevalence of SPS, as defined by WHO criteria, in screening populations were selected. Results: Six studies reported prevalence of SPS in screening populations, varying from 0 to 0.66 %. The highest prevalences (0.34 % and 0.66 %) were seen in studies from screening programs with patients pre-selected by fecal blood test. Primary colonoscopy-based screening programs, that have the lowest risk of bias, reported SPS prevalences ranging from 0 to 0.09 %. Across studies, 56 patients were diagnosed with SPS of whom 3 presented with synchronous colorectal cancer at index endoscopy. Conclusion: The true prevalence of SPS is unclear because of the risk of bias across studies, but is likely to be below 0.09 % as derived from primary colonoscopy screening programs. The prevalence in pre-selected screening populations after positive fecal testing is higher, with reported values of 0.34 % and 0.66 %. Large and high quality primary colonoscopy screening studies, reporting SPS prevalence in adequately described populations, are necessary for better estimation of the true prevalence of SPS in average-risk patients. © Georg Thieme Verlag KG Stuttgart · New York.
    Endoscopy 06/2015; DOI:10.1055/s-0034-1392411 · 5.05 Impact Factor
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    ABSTRACT: Background: HCV/HIV co-infected patients respond worse to dual therapy with ribavirin/peginterferon compared to HCV mono-infected patients. Several trials found that lower ribavirin plasma concentrations are associated with impaired virological response rates. The aim of this study was to determine ribavirin plasma concentrations in a cohort of HCV mono- and HCV/HIV co-infected patients. Our hypothesis is that HCV/HIV co-infected patients have lower ribavirin plasma concentrations, which may in part explain their inferior response to dual therapy. Methods: A retrospective cohort study was performed in chronic HCV mono- and HCV/HIV co-infected patients who received peginterferon and weight-based ribavirin. Plasma ribavirin concentrations were determined at week 4 and 12 by a validated high-performance liquid chromatography (HPLC) assay. Ribavirin concentrations were compared between mono- and co-infected patients. We calculated the proportion of patients with a subtherapeutic ribavirin plasma concentration, defined as < 2.0 mg/L. Results: A total of 61 HCV-infected patients were included of whom 21 (34%) were co-infected with HIV. Although there was no difference in the weight-based dose of RBV between mono- and co-infected patients, ribavirin exposure was significantly lower in HCV/HIV co-infected patients than in HCV mono-infected patients: the mean (±SD) ribavirin plasma concentrations were 1.82 ± 0.63 versus 2.25 ± 0.80 (p=0.04) at week 4, and 2.14 ± 0.65 versus 2.62 ± 0.81 (p=0.05) at week 12, respectively. The percentage of patients with subtherapeutic plasma concentrations of ribavirin in co-infected patients versus mono-infected patients was 62% versus 46% (p=0.240) at week 4, and 50% versus 16% (p=0.01) at week 12 of treatment, respectively. Conclusions: HIV/HCV co-infected patients yield significantly lower plasma concentrations of ribavirin than HCV mono-infected patients. This puts them at an increased risk of not achieving sustained virological response.
    Therapeutic drug monitoring 06/2015; DOI:10.1097/FTD.0000000000000226 · 2.38 Impact Factor
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    ABSTRACT: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive biliary cystogenesis. Current therapies show short-term and/or modest beneficial effects. Cystic cholangiocytes hyperproliferate as a consequence of diminished intracellular calcium levels ([Ca(2+)]i). Here, the therapeutic value of ursodeoxycholic acid (UDCA) was investigated. Effect of UDCA was examined in vitro and in polycystic (PCK) rats. Hepatic cystogenesis and fibrosis, and the bile acid (BA) content were evaluated in liver, bile, serum and kidneys by HPLC-MS/MS. Chronic treatment of PCK rats with UDCA inhibits hepatic cystogenesis and fibrosis, and improves their motor behaviour. As compared to wild-type animals, PCK rats show increased BA concentration ([BA]) in liver, similar hepatic Cyp7a1 mRNA levels, and diminished [BA] in bile. Likewise, [BA] is increased in cystic fluid of PLD patients compared to their matched serum levels. In PCK rats, UDCA decreases the intrahepatic accumulation of cytotoxic BA, normalizes their diminished [BA] in bile, increases the BA secretion in bile and diminishes the increased [BA] in kidneys. In vitro, UDCA inhibits the hyperproliferation of polycystic human cholangiocytes via a PI3K/AKT/MEK/ERK1/2-dependent mechanism without affecting apoptosis. Finally, the presence of glycodeoxycholic acid promotes the proliferation of polycystic human cholangiocytes, which is inhibited by both UDCA and tauro-UDCA. UDCA was able to halt the liver disease of a rat model of PLD through inhibiting cystic cholangiocyte hyperproliferation and decreasing the level of cytotoxic BA species in the liver, which suggests the use of UDCA as a potential therapeutic tool for PLD patients. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 06/2015; 62. DOI:10.1016/j.jhep.2015.05.023 · 11.34 Impact Factor
  • Joost P H Drenth · Sara Montagnese
    Journal of Hepatology 04/2015; 62(6). DOI:10.1016/j.jhep.2015.02.033 · 11.34 Impact Factor
  • Marten A Lantinga · Ruud G L de Sévaux · Joost P H Drenth
    Clinical nephrology 04/2015; 84(1). DOI:10.5414/CN108495 · 1.13 Impact Factor
  • Journal of Hepatology 04/2015; 62:S861. DOI:10.1016/S0168-8278(15)31523-3 · 11.34 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-1009. DOI:10.1016/S0016-5085(15)33445-4 · 16.72 Impact Factor
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    ABSTRACT: Background: As many as 33% of patients with symptomatic cholelithiasis report persisting abdominal pain after cholecystectomy, suggesting alternative causes of these symptoms. EGD may serve as a tool to identify additional symptomatic abdominal disorders beforehand to avoid unnecessary gallbladder surgery. There is controversy as to whether routine EGD before cholecystectomy is appropriate. Objective: To perform a systematic review and meta-analysis to assess the value of EGD before cholecystectomy. Design: A systematic literature search was conducted to identify studies that reported the proportion of patients who were referred for cholecystectomy, but in whom initial surgery could be avoided after treatment of abnormalities detected with EGD. Pooled estimates with 95% confidence intervals (CIs) were calculated by using random-effects models. Setting: Meta-analysis of 12 cohort studies. Patients: A total of 6317 patients with cholelithiasis underwent EGD. Results: The pooled estimate of abnormalities detected with EGD was 36.3% (95% CI, 28.0-45.0). In a total of 3.8% (95% CI, 1.4-7.6) of patients referred for cholecystectomy who underwent previous EGD, gallbladder surgery was avoided. Limitations: Lack of information regarding characteristics of patients referred for cholecystectomy, criteria for performing EGD, algorithms for the treatment of identified pathologies, and response criteria for the decision to avoid cholecystectomy in included studies. Conclusions: Our study indicates that, despite the high diagnostic yield of EGD, its value as a tool to prevent gallbladder surgery is limited. EGD should only be considered selectively in patients with cholelithiasis referred for cholecystectomy.
    Gastrointestinal Endoscopy 04/2015; 82(1). DOI:10.1016/j.gie.2015.01.024 · 5.37 Impact Factor
  • Journal of Hepatology 04/2015; 62:S254-S255. DOI:10.1016/S0168-8278(15)30141-0 · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S853. DOI:10.1016/S0168-8278(15)31505-1 · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S245-S246. DOI:10.1016/S0168-8278(15)30123-9 · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S848-S849. DOI:10.1016/S0168-8278(15)31496-3 · 11.34 Impact Factor
  • A M Peters van Ton · T J G Gevers · J P H Drenth
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    ABSTRACT: Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon-α can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and for articles and abstracts. The keywords '"Hepatitis E" or HEV' AND 'ribavirin or Rebetol or Copegus' OR 'pegylated interferon OR peginterferon' were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty-four studies matched our criteria, representing a total of 105 ribavirin-treated and 8 pegylated interferon-treated patients. The majority of patients had a solid organ transplant. Sixty-four per cent of ribavirin-treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon-treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E. © 2015 John Wiley & Sons Ltd.
    Journal of Viral Hepatitis 03/2015; DOI:10.1111/jvh.12403 · 3.91 Impact Factor
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    ABSTRACT: The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established AIH risk alleles. To study the immune modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch autoimmune hepatitis (AIH) type 1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five per cent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01 positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01 negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase (ALT) levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5), however HLA-DRB1*03:01 was independently associated with higher IgG levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01 positive patients were received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.
    Genes and Immunity 01/2015; DOI:10.1038/gene.2014.82 · 2.91 Impact Factor
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    ABSTRACT: Nephronophthisis-related ciliopathies (NPHP-RC) are recessive diseases characterized by renal dysplasia or degeneration. We here identify mutations of DCDC2 as causing a renal-hepatic ciliopathy. DCDC2 localizes to the ciliary axoneme and to mitotic spindle fibers in a cell-cycle-dependent manner. Knockdown of Dcdc2 in IMCD3 cells disrupts ciliogenesis, which is rescued by wild-type (WT) human DCDC2, but not by constructs that reflect human mutations. We show that DCDC2 interacts with DVL and DCDC2 overexpression inhibits β-catenin-dependent Wnt signaling in an effect additive to Wnt inhibitors. Mutations detected in human NPHP-RC lack these effects. A Wnt inhibitor likewise restores ciliogenesis in 3D IMCD3 cultures, emphasizing the importance of Wnt signaling for renal tubulogenesis. Knockdown of dcdc2 in zebrafish recapitulates NPHP-RC phenotypes, including renal cysts and hydrocephalus, which is rescued by a Wnt inhibitor and by WT, but not by mutant, DCDC2. We thus demonstrate a central role of Wnt signaling in the pathogenesis of NPHP-RC, suggesting an avenue for potential treatment of NPHP-RC. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 12/2014; 96(1). DOI:10.1016/j.ajhg.2014.12.002 · 10.93 Impact Factor

Publication Stats

7k Citations
2,789.93 Total Impact Points


  • 1997–2015
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 1992–2015
    • Radboud University Nijmegen
      • • Department of Gastroenterology and Hepatology
      • • Department of General Internal Medicine
      Nymegen, Gelderland, Netherlands
  • 2014
    • University Medical Center Utrecht
      • Department of Acute Medicine and Infectious Diseases
      Utrecht, Utrecht, Netherlands
  • 2013
    • Jeroen Bosch Ziekenhuis
      Hertogenbosch, North Brabant, Netherlands
  • 2011
    • University of Oxford
      Oxford, England, United Kingdom
  • 2007
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 2004
    • Slingeland Ziekenhuis
      Doetinchem, Gelderland, Netherlands
    • National Institute of Child Health and Human Development
      베서스다, Maryland, United States
  • 1996
    • MetroHealth Medical Center
      Cleveland, Ohio, United States
  • 1995
    • VU University Amsterdam
      • Department of Medicinal Chemistry
      Amsterdamo, North Holland, Netherlands
  • 1993–1994
    • Erasmus Universiteit Rotterdam
      • Department of Hematology
      Rotterdam, South Holland, Netherlands
  • 1990
    • Maastricht University
      Maestricht, Limburg, Netherlands