Joost P H Drenth

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

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Publications (333)2025.6 Total impact

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    ABSTRACT: Abstract Background and aims. Epidemiological data on autoimmune hepatitis (AIH) are scarce. Here, 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.
    Scandinavian journal of gastroenterology. 08/2014;
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    ABSTRACT: 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. 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 MHC region. We associated AIH with a variant in the MHC region, at rs2187668 (P=1.5x10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3x10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P=2.8x10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P=7.7x10(-8)) and CARD10 (rs6000782, 22q13.1; P=3.0x10(-6)). Furthermore, strong inflation of association signal was found with single-nucleotide polymorphisms (SNPs) associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with SNPs associated with other genetic traits. In a genome-wide association study, we associated AIH type-1with variants in the MHC 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.
    Gastroenterology 08/2014; 147(2):443-452. · 12.82 Impact Factor
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    ABSTRACT: To date, inter-genotypic recombinant hepatitis C viruses (HCV) and their treatment outcomes have not been well characterized. This study characterized 12 novel HCV recombinant strains and their response to sofosbuvir in combination with ribavirin (SOF/RBV) treatment. Across the phase II/III studies of sofosbuvir, HCV samples were genotyped using both the Siemens VERSANT® HCV Genotype INNO-LiPA 2.0 assay and NS5B sequencing. Among these patient samples, genotype assignment discordance between the two methods was found in 0.5% of all cases (12/2363) of which all were identified as genotype 2 by INNO-LiPA (12/487=2.5%). HCV full genome sequences were obtained for these 12 samples by a sequence-independent amplification method coupled with next-generation sequencing. HCV full genome sequencing revealed that these viruses were recombinant HCV strains with the 5’ part corresponding to genotype 2 and the 3’ part corresponding to genotype 1. The recombination breakpoint between genotype 2 and genotype 1 was consistently located within 80 amino acids of the NS2/NS3 junction. Interestingly, one of the recombinant viruses had a 34 amino acid duplication at the location of the recombination breakpoint. Eleven of these 12 patients were treated with a regimen for genotype 2 HCV infection, but responded like they had genotype 1 infection; one patient had received placebo. Conclusion: Twelve new HCV inter-genotypic recombinant genotype 2/1 viruses have been characterized. The antiviral response to a 12-16 week course of SOF/RBV treatment in these patients was more similar to responses among genotype 1 patients than genotype 2 patients, consistent with their genotype 1 NS5B gene. (Hepatology 2014;)
    Hepatology 08/2014; · 12.00 Impact Factor
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    ABSTRACT: Up to 41 % of patients report pain after cholecystectomy and in most studies follow-up for these symptoms did not exceed 5 years. The episodic nature of abdominal pain associated with symptomatic cholelithiasis warrants long-term follow-up studies. We assessed which patient and surgical factors were associated with absence of pain and patient-reported success of surgery after ≥5 years of follow-up.
    Surgical endoscopy. 06/2014;
  • Marten A Lantinga, Joost P H Drenth, Tom J G Gevers
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    ABSTRACT: Cyst infection is a severe complication of renal and hepatic cystic disease that frequently leads to hospitalization. In most cases the diagnosis of cyst infection is made empirically as a cyst aspirate is frequently unavailable. This study aims to evaluate diagnostic criteria, microbiological findings and imaging modalities needed to diagnose cyst infection. In order to do so, we evaluated reports that characterize cyst infection cases published in the English language between 1948 and January 2014. We identified 70 articles documenting a total of 215 cyst infection cases (renal n = 119; hepatic n = 96). Six studies, including 74 cases of renal and 61 cases of hepatic cyst infection, used diagnostic criteria. The criteria that led to a definite cyst infection diagnosis were consistent, whereas criteria for a 'probable diagnosis' varied considerably. Cyst infection cases commonly have abdominal pain, fever and elevated serum inflammatory markers. Urine and blood cultures frequently remained negative, even in definite cases. The diagnostic properties of (18)fluorodeoxyglucose positron-emission computed tomography ((18)F-FDG PET/CT) are probably best to diagnose cyst infection. Cyst aspirate indicating infection is currently the gold standard in diagnosing cyst infection. If not available, a combination of clinical and biochemical parameters is necessary to make a well-considered diagnosis, preferably including (18)F-FDG PET/CT.
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    Wybrich R Cnossen, Joost P Drenth
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    ABSTRACT: Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg complexes (VMC). In these patients embryonic remnants develop into small hepatic cysts and usually remain silent during life. Symptomatic PLD occurs mainly in the context of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have massively enlarged livers which cause a spectrum of clinical features and complications. Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ. Renal failure due to polycystic kidneys and non-renal extra-hepatic features are common in ADPKD in contrast to VMC and PCLD. In general, liver function remains prolonged preserved in PLD. Ultrasonography is the first instrument to assess liver phenotype. Indeed, PCLD and ADPKD diagnostic criteria rely on detection of hepatorenal cystogenesis, and secondly a positive family history compatible with an autosomal dominant inheritance pattern. Ambiguous imaging or screening may be assisted by genetic counseling and molecular diagnostics. Screening mutations of the genes causing PCLD (PRKCSH and SEC63) or ADPKD (PKD1 and PKD2) confirm the clinical diagnosis. Genetic studies showed that accumulation of somatic hits in cyst epithelium determine the rate-limiting step for cyst formation. Management of adult PLD is based on liver phenotype, severity of clinical features and quality of life. Conservative treatment is recommended for the majority of PLD patients. The primary aim is to halt cyst growth to allow abdominal decompression and ameliorate symptoms. Invasive procedures are required in a selective patient group with advanced PCLD, ADPKD or liver failure. Pharmacological therapy by somatostatin analogues lead to beneficial outcome of PLD in terms of symptom relief and liver volume reduction.
    Orphanet Journal of Rare Diseases 05/2014; 9(1):69. · 4.32 Impact Factor
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    ABSTRACT: Chronic hepatitis C is a global health problem. To prevent or reduce complications, the hepatitis C virus (HCV) infection needs to be eradicated. There have been several developments in treating these patients since the discovery of the virus. As of 1 January 2014, the drugs that are approved for treatment of chronic HCV infection are peginterferon-α, ribavirin, boceprevir, telaprevir, simeprevir and sofosbuvir. In this review we provide an overview of the clinical pharmacokinetic characteristics of these agents by describing their absorption, distribution, metabolism and excretion. In the pharmacodynamic part we summarize what is known about the relationships between the pharmacokinetics of each drug and efficacy or toxicity. We briefly discuss the pharmacokinetics and pharmacodynamics of chronic hepatitis C treatment in special patient populations, such as patients with liver cirrhosis, renal insufficiency or HCV/HIV coinfection, and children. With this knowledge, physicians, pharmacists, nurse practitioners, etc. should be educated to safely and effectively treat HCV-infected patients.
    Clinical Pharmacokinetics 04/2014; · 5.49 Impact Factor
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    ABSTRACT: Polycystic livers are seen in the rare inherited disorder isolated polycystic liver disease (PCLD) and are recognized as the most common extrarenal manifestation in autosomal dominant polycystic kidney disease. Hepatic cystogenesis is characterized by progressive proliferation of cholangiocytes, ultimately causing hepatomegaly. Genetically, polycystic liver disease is a heterogeneous disorder with incomplete penetrance and caused by mutations in PRKCSH, SEC63, PKD1, or PKD2. Genome-wide SNP typing and Sanger sequencing revealed no pathogenic variants in hitherto genes in an extended PCLD family. We performed whole-exome sequencing of DNA samples from two members. A heterozygous variant c.3562C > T located at a highly conserved amino acid position (p.R1188W) in the low density lipoprotein receptor-related protein 5 (LRP5) gene segregated with the disease (logarithm of odds score, 4.62) but was not observed in more than 1,000 unaffected individuals. Screening of LRP5 in a PCLD cohort identified three additional mutations in three unrelated families with polycystic livers (p.V454M, p.R1529S, and p.D1551N), again all undetected in controls. All variants were predicted to be damaging with profound structural effects on LRP5 protein domains. Liver cyst tissue and normal hepatic tissue samples from patients and controls showed abundant LRP5 expression by immunohistochemistry. Functional activity analyses indicated that mutant LRP5 led to reduced wingless signal activation. In conclusion, we demonstrate that germ-line LRP5 missense mutations are associated with hepatic cystogenesis. The findings presented in this study link the pathophysiology of PCLD to deregulation of the canonical wingless signaling pathway.
    Proceedings of the National Academy of Sciences 03/2014; · 9.74 Impact Factor
  • Edgar S Wills, Ronald Roepman, Joost P H Drenth
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    ABSTRACT: Polycystic livers are found in autosomal dominant polycystic kidney disease (ADPKD), caused by polycystic kidney disease (PKD)1 and PKD2 mutations in virtually all cases, and in isolated polycystic liver disease (PCLD), where 20% of cases are caused by mutations in Protein kinase C substrate 80K-H (PRKCSH) or SEC63. Loss of heterozygosity in single hepatoblasts leads to underlying cystogenic ductal plate malformations. Crucially, actual components driving this development remain elusive. Recent advances have unraveled the roles of transforming growth factor (TGF)-β, Notch and Wnt signaling, transcriptional regulators such as hepatocyte nuclear factor (HNF)6 and HNF1β, as well as cilium function in hepatobiliary organogenesis. In polycystic liver disease, mutation or defective co-translational processing of key elements required for primary cilium formation have been implicated. This review recapitulates liver patterning factors in hepatobiliary development and extracts molecular players in hepatic cystogenesis.
    Trends in Molecular Medicine 02/2014; · 9.57 Impact Factor
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    ABSTRACT: Gallstone disease is one of the most common problems in the gastroenterology and is associated with significant morbidity. It may present as stones in the gallbladder (cholecystolithiasis) or in the common bile duct (choledocholithiasis). At the end of the 1980s laparoscopy was introduced and first laparoscopic cholecystectomy was performed in 1985. The laparoscopic technique for removing the gallbladder is the current treatment of choice, although indications for open surgery exist. To perform laparoscopic cholecystectomy as safe as possible multiple safety measures were developed. The gold standard for diagnosing and removing common bile duct stones is Endoscopic Retrograde Cholangiopancreatography (ERCP). The surgical treatment option for choledocholithiasis is laparoscopic cholecystectomy with common bile duct exploration. If experience is not available, than ERCP followed by elective cholecystectomy is by far the best therapeutic modality. The present review will discuss the use, benefits and drawbacks of laparoscopy in patients with cholecystolithiasis and choledocholithiasis.
    Best practice & research. Clinical gastroenterology 02/2014; 28(1):195-209. · 2.48 Impact Factor
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    ABSTRACT: Background Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon. Methods We isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis who had distinct clinical phenotypes. We then performed proteome-wide analysis and validated these observations in five large cohorts of patients with systemic sclerosis. Next, we compared the results with those in patients with systemic lupus erythematosus, ankylosing spondylitis, and hepatic fibrosis. We correlated plasma levels of CXCL4 protein with features of systemic sclerosis and studied the direct effects of CXCL4 in vitro and in vivo. Results Proteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in systemic sclerosis, both in circulation and in skin. The mean (±SD) level of CXCL4 in patients with systemic sclerosis was 25,624±2652 pg per milliliter, which was significantly higher than the level in controls (92.5±77.9 pg per milliliter) and than the level in patients with systemic lupus erythematosus (1346±1011 pg per milliliter), ankylosing spondylitis (1368±1162 pg per milliliter), or liver fibrosis (1668±1263 pg per milliliter). CXCL4 levels correlated with skin and lung fibrosis and with pulmonary arterial hypertension. Among chemokines, only CXCL4 predicted the risk and progression of systemic sclerosis. In vitro, CXCL4 down-regulated expression of transcription factor FLI1, induced markers of endothelial-cell activation, and potentiated responses of toll-like receptors. In vivo, CXCL4 induced the influx of inflammatory cells and skin transcriptome changes, as in systemic sclerosis. Conclusions Levels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension. (Funded by the Dutch Arthritis Association and others.).
    New England Journal of Medicine 12/2013; · 51.66 Impact Factor
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    ABSTRACT: Polycystic liver disease (PLD) follows a progressive course ultimately leading to severe hepatomegaly and mechanical complaints in a subset of patients. It is still unknown to what extent this compromises health-related quality of life (HRQL). To determine HRQL in PLD patients and investigate its association with concurrent abdominal symptoms and liver volume. Pooled data of 92 severe PLD patients from two randomized clinical trials were used for our cross-sectional analysis. HRQL was assessed using the generic short-form health survey (SF-36) resulting in eight scale scores and the summarizing physical (PCS) and mental component score (MCS). Subsequently, these were compared to the general population. Abdominal symptoms were measured with a standardized, 7-point scale questionnaire in 54 patients. We dichotomized symptoms for absence or presence and compared them with the component scores. Finally, a possible correlation between liver volume and HRQL was explored. Demographics showed severe polycystic livers (mean 4906±2315 ml). PCS was significantly lower compared to the general population (p < 0.001), in contrast to a similar MCS (p = 0.82). PLD patients had statistically significant (p < 0.05) diminished physical functioning, role physical, general health, vitality and social functioning scores. Upper- and lower abdominal pain and dyspnea were significantly associated with a reduced PCS (p < 0.01). No correlation was found between liver volume and HRQL. PLD patients had significantly lower HRQL in the physical dimension compared to the general population. Abdominal pain and dyspnea had a significant impact on this physical dimension of HRQL. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 12/2013; · 3.87 Impact Factor
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    ABSTRACT: Although restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) substantially reduces the risk of colorectal cancer in patients with inflammatory bowel disease (IBD), subsequent pouch neoplasia can develop. There are few data on the incidence of and risk factors for neoplasia, so there is no consensus on the need for pouch surveillance. We aimed to determine the cumulative incidence of pouch neoplasia in patients with IBD and identify risk factors for developing pouch neoplasia. We searched the Dutch Pathology Registry (PALGA) to identify all patients with IBD and IPAA in The Netherlands from January 1991 through May 2012. We calculated the cumulative pouch neoplasia incidence and performed a case-control study to identify risk factors. Demographic and clinical variables were analyzed with univariable and multivariable Cox regression analyses. We identified 1200 IBD patients with IPAA; 25 (1.83%) developed pouch neoplasia, including 16 adenocarcinomas. Respective cumulative incidences at 5, 10, 15, and 20 y were 1.0%, 2.0%, 3.7%, and 6.9% for pouch neoplasia and 0.6%, 1.4%, 2.1%, and 3.3% for pouch carcinoma. A history of colorectal neoplasia was the only risk factor associated with pouch neoplasia. Hazard ratios were 3.76 (95% confidence interval, 1.39-10.19) for prior dysplasia and 24.69 (95% confidence interval, 9.61-63.42) for prior carcinoma. The incidence of pouch neoplasia in patients with IBD without a history of colorectal neoplasia is relatively low. Prior dysplasia or carcinoma of the colon is associated with an approximate 4- and 25-fold increase in risk, respectively, for developing pouch neoplasia.
    Gastroenterology 09/2013; · 12.82 Impact Factor
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    ABSTRACT: In this new Dutch guideline for hepatitis C virus infection we provide recommendations for the management of hepatitis C infection. Until 2012 the standard for treatment consisted of pegylated interferon alpha (peg-IFNa) and ribavirin. The advent of first-generation direct antiviral agents such as boceprevir and telaprevir has changed the concept of treatment of adult chronic hepatitis C genotype 1 infected patients. There are three benefits of boceprevir and telaprevir. They increase the likelihood of cure in 1) naive genotype 1 patients and 2) in patients who did not respond to earlier treatment with peg-IFNa and ribavirin, while 3) allowing shortening of treatment duration from 48 weeks to 24 or 28 weeks, which is possible in 40-60% of non-cirrhotic naive (boceprevir and telaprevir) and relapsing patients (telaprevir). The use of boceprevir and telaprevir is associated with multiple side effects and awareness of these side effects is needed to guide the patient through the treatment process. This guideline, formulated on behalf of The Netherlands Association of Hepato-gastroenterologists, The Netherlands Association of Internal Medicine, and The Dutch Association for the Study of Liver Disease, serves as a manual for physicians for the management and treatment of acute and chronic hepatitis C virus monoinfection in adults.
    The Netherlands Journal of Medicine 09/2013; 71(7):377-85. · 2.38 Impact Factor
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    ABSTRACT: Correlations between ribavirin (RBV) concentrations and sustained virological response (SVR) to hepatitis C virus treatment have been demonstrated previously. As steady state is reached after several weeks of RBV treatment, dose modifications based on steady-state levels can only be applied relatively late in treatment, possibly too late to influence SVR rates. The authors aimed to determine whether measurement of early concentrations is useful to predict optimal steady-state RBV concentrations. In 61 treatment-naive genotype 1/4 patients RBV concentrations were determined in samples collected after 1, 2, 4, 8, 12, and 24 weeks of therapy. RBV concentrations were compared between responders and nonresponders; Receiver Operating Characteristic analyses were conducted to find optimal cut-off values to predict week 8 concentrations from earlier measurements. Median week 8 RBV concentrations were significantly higher in patients with SVR compared with those without: 3.4 (interquartile range 2.4-3.9) versus 2.6 (interquartile range 2.0-3.5) mg/L (P < 0.05). RBV concentration at week 8 was an independent predictor of SVR [adjusted odds ratio 2.3 (95% confidence interval: 1.1-4.9; P = 0.03)]. The optimal cut-off value of week 8 RBV concentration to predict SVR was 2.20 mg/L [sensitivity 87%, specificity 40%, positive predictive value 64%, negative predictive value 71%]. Optimal cut-off values at weeks 1, 2, or 4 to predict an RBV concentration ≥2.20 mg/L at week 8 were 0.92, 1.29, and 1.67 mg/L, respectively, with positive predictive values and negative predictive values ranging from 88% to 91% and 71% to 86%, respectively. RBV concentrations in the earliest stages of antiviral therapy predict therapeutic steady-state concentrations, allowing timely dose adjustments with potential implications for treatment outcome.
    Therapeutic drug monitoring 07/2013; · 2.43 Impact Factor
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    ABSTRACT: Long-acting lanreotide (LAN) 120 mg every 4 weeks reduces liver volume (LV) in patients with polycystic liver diseases (PCLD). Animal studies demonstrated that the inhibition of hepatic and renal cystogenesis is dose dependent. To investigate the safety and efficacy of two different LAN doses in PCLD patients. The 6-month results of the LOCKCYST I trial, its extension study and the LOCKCYST II trial were pooled. LV at baseline and month 6 was measured by CT-scan and blindly re-analysed by two independent radiologists. The study population [132 treatment periods, age 49 years (IQR: 45-55), 114 women] consisted of three groups. Each received treatment every 4 weeks during 6 months: placebo (n = 26); LAN 90 mg (n = 55) or LAN 120 mg (n = 51). The inter-observer variability and agreement in the calculation of LV were excellent. Severe side effects occurred with placebo, LAN 90 mg and LAN 120 mg in respectively 0%, 7% and 16%. Change in LV's after 6 months in these three groups were respectively: increase of +36 mL [(-45)-(+138)]; decrease of -82 mL [(-285)-(+92)] and decrease of -123 mL [(-312)-(+4)] (Kruskal-Wallis One Way anova on Ranks; P = 0.002). Based on ROC analysis, a reduction of ≥120 mL in LV has a positive predictive value of 64% for improving symptoms (ROC analysis AUC: 0.729; sensitivity 73%, specificity 69%, P < 0.0001). Both LAN 90 mg and LAN 120 mg reduce liver volume. LAN 90 mg has less side effects. This suggests that in case of intolerance to LAN 120 mg, a dose reduction to LAN 90 mg is meaningful.
    Alimentary Pharmacology & Therapeutics 06/2013; · 4.55 Impact Factor
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    ABSTRACT: Extensive population-based studies are much needed to accurately establish the epidemiology and disease course in patients with primary sclerosing cholangitis (PSC). We aimed to obtain population-based prevalence and incidence figures, insight in disease course with regard to survival, liver transplantation and occurrence of malignancies, as well as risk factors thereof. Four independent hospital databases were searched in 44 hospitals in a large geographically defined area of the Netherlands, comprising 50% of the population. In addition, all PSC patients in the three Dutch liver transplant centers and all inflammatory bowel disease (IBD) patients in the adherence area of a large district hospital were identified. All medical records were reviewed on site verifying diagnosis. Five hundred and ninety PSC patients were identified, resulting in an incidence of 0.5 and a point prevalence of 6.0 per 100,000. Median follow up was 92 months. Estimated median survival from diagnosis until liver transplantation or PSC-related death in the entire cohort was 21.3 years, as opposed to 13.2 years in the combined transplant centers cohort (n=422)(P<0.0001). Colorectal carcinoma (CRC) risk was 10-fold increased as compared to ulcerative colitis controls and developed at a much younger age (39 yrs[range 26-64]) compared to IBD controls (59 yrs[range 34-73])(P=0.019). Colonoscopic surveillance was associated with significantly better outcome. Conclusion: This study exemplifies that for relatively rare diseases it is paramount to collect observational data from large population-based cohorts, because incidence and prevalence rates of PSC are markedly lower and survival much longer than previously reported. The selection bias-free population-based cohort showed a significantly longer survival compared to the tertiary referral cohort. CRC can develop at an early age, warranting surveillance from time of PSC diagnosis. (HEPATOLOGY 2013.).
    Hepatology 06/2013; · 12.00 Impact Factor
  • H M A D'Agnolo, J P H Drenth
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    ABSTRACT: Toxic hepatitis is a rare but serious complication of high-dose prednisolone treatment. We report a case of high-dose prednisolone-induced acute hepatitis in a 48-year-old woman suffering from multiple sclerosis that recurred after repeated administration. Timely recognition is paramount to avoid this complication. This report includes a brief review of the literature on methylprednisolone- induced hepatitis.
    The Netherlands Journal of Medicine 05/2013; 71(4):199-202. · 2.38 Impact Factor
  • Joost P H Drenth
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    ABSTRACT: The landscape of therapy for hepatitis C virus (HCV) infection is changing rapidly. Until recently, the standard of care for HCV infection was a combination of peginterferon and ribavirin. Our increased understanding of the basic biology of HCV led to the identification of specific proteins involved in the replication of the virus. These proteins can be targeted by protease and polymerase inhibitors. Two years ago, the advent of protease inhibitors, such as telaprevir and boceprevir, profoundly affected the field.(1),(2) These agents improved the likelihood of cure but came with a number of inherent limitations. Protease inhibitors do not have . . .
    New England Journal of Medicine 04/2013; · 51.66 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Polycystic liver disease (PLD) is associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PCLD). The resulting hepatomegaly compromises quality of life. Somatostatin analogues reduce PLD volume by ∼5% when given for 6-12 months. A pilot trial in 16 ADPKD patients demonstrated that sirolimus, a mTOR inhibitor, reduced PLD volume by 26%. The aim of this study was to assess the PLD volume reducing effect of everolimus and octreotide relative to octreotide monotherapy. METHODS: We designed a randomized controlled trial that compared 48 weeks of everolimus 2,5 mg daily combined with octreotide 40 mg intramuscularly every 4 weeks to octreotide monotherapy. We included PCLD and ADPKD patients. Exclusion criteria were MDRD-GFR <60 ml/min/1.73m2 and liver volume <2500 mL. Primary outcome was change in liver volume measured with CT-volumetry. RESULTS: We randomized 44 PLD patients (29 PCLD, 15 ADPKD, 89% female) to treatment with octreotide (n=23) or octreotide-everolimus (n=21). Liver volume decreased by 3.5% (p<0.01) in the monotherapy arm, compared to 3.8% with combination therapy (p<0.01). The difference between treatment arms was not significant (p=0.73). CONCLUSIONS: Adding everolimus to octreotide in PLD does not increase the liver volume reducing effect of octreotide.
    Journal of Hepatology 03/2013; · 9.86 Impact Factor

Publication Stats

5k Citations
2,025.60 Total Impact Points


  • 1996–2014
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
    • Catharina Hospital
      Eindhoven, North Brabant, Netherlands
    • MetroHealth Medical Center
      Cleveland, Ohio, United States
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 2013
    • Jeroen Bosch Ziekenhuis
      Hertogenbosch, North Brabant, Netherlands
  • 2007–2013
    • VU University Medical Center
      • • Department of Gastroenterology and Hepatology
      • • Department of Medical Microbiology and Infection Control
      Amsterdam, North Holland, Netherlands
  • 1992–2013
    • Radboud University Nijmegen
      • • Department of Gastroenterology and Hepatology
      • • Department of Human Genetics
      • • Department of General Internal Medicine
      • • Department of Endocrinology
      Nijmegen, Provincie Gelderland, Netherlands
  • 2012
    • University of Leipzig
      • Klinik und Poliklinik für Gastroenterologie und Rheumatologie
      Leipzig, Saxony, Germany
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 2011
    • University of Oxford
      Oxford, England, United Kingdom
  • 2010–2011
    • Yale University
      • Department of Neurology
      New Haven, CT, United States
  • 2007–2009
    • Charité Universitätsmedizin Berlin
      • Medical Department, Division of Hepatology and Gastroenterology
      Berlin, Land Berlin, Germany
  • 2008
    • Université de Montréal
      • Center for Mathematical Research
      Montréal, Quebec, Canada
  • 2006
    • Can Tho University of Medicine and Pharmacy
      Kan Tho, Cần Thơ, Vietnam
  • 2005
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 2004–2005
    • National Institutes of Health
      • Cell Biology and Metabolism Program
      Bethesda, MD, United States
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 2001
    • Institut de Génétique Moléculaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 1995–2001
    • VU University Amsterdam
      • Faculty of Medicine/VU University Medical Center
      Amsterdam, North Holland, Netherlands
  • 1999
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • Sheba Medical Center
      • Department of Pathology
      Gan, Tel Aviv, Israel
  • 1992–1994
    • Erasmus Universiteit Rotterdam
      • Department of Hematology
      Rotterdam, South Holland, Netherlands