Frederik Nevens

Publications (121)613.83 Total impact

• Article: Heterozygous α1-antitrypsin Z allele mutation in presumed healthy donor livers used for transplantation.

  Philip Roelandt, Pieter Dobbels, Mina Komuta, Anniek Corveleyn, Marie-Paule Emonds, Tania Roskams, Raymond Aerts, Diethard Monbaliu, Louis Libbrecht, Wim Laleman, Chris Verslype, Werner Van Steenbergen, Schalk van der Merwe, Jacques Pirenne, Frederik Nevens, David Cassiman
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVES: The Z allele (Glu342Lys) in α1-antitrypsin (AAT) deficiency is a combined deficiency and dysfunctional allele. Carrying one Z allele induces a risk of a more aggressive evolution in patients with a chronic liver disease. As most of the carriers of Z allele do not have overt liver disease, it is likely that Z allele-containing livers have been used previously for liver transplantation. We analyzed the incidence, epidemiology, and clinical features of AAT accumulation in the hepatocytes after liver transplantation. METHODS: Follow-up biopsies of liver transplant recipients were analyzed with periodic acid Schiff staining until 2006 (n=486); from 2006 on (n=303), all biopsies were stained with a specific monoclonal antibody against mutated AATZ protein. Genotyping of both recipient and donor was performed in the case of positive staining. RESULTS: Of 789 liver transplantation patients, six patients (0.8%) showed mutated AATZ accumulation in the transplanted liver. Mutation analysis confirmed the presence of the Z allele in all donor organs including one transplanted organ with the SZ phenotype. There was a clear concordance between the isoelectrical focusing of the recipient AAT after transplantation and the genotype of the donor. CONCLUSION: Presumed healthy donor organs containing the Z allele were used for transplantation in 0.8% of cases in our series. As the presence of a Z allele is an independent risk factor of aggravation of chronic liver disease, AATZ accumulation in biopsies after liver transplantation should be actively looked for.
  European journal of gastroenterology & hepatology 05/2013; · 1.66 Impact Factor
• Article: Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinico-pathological characteristics and prognostic factors.

  Daan Dierickx, Thomas Tousseyn, Xavier Sagaert, Steffen Fieuws, Iwona Wlodarska, Julie Morscio, Lieselot Brepoels, Dirk Kuypers, Johan Vanhaecke, Frederik Nevens, Geert Verleden, Rita Van Damme-Lombaerts, Marleen Renard, Jacques Pirenne, Christiane De Wolf-Peeters, Gregor Verhoef
  [show abstract] [hide abstract]
  ABSTRACT: Abstract Hematopoietic stem cell and solid organ transplant recipients diagnosed with biopsy-confirmed posttransplant lymphoproliferative disorder (PTLD) at our institution from 1989 to 2010 were identified. Patient-, transplantation- and disease-related characteristics, prognostic factors and outcome were collected and analyzed. One hundred-forty biopsy-proven PTLD cases were included. Overall incidence in the transplant population was 2.12% with heart transplant recipients carrying the highest risk. Most PTLDs were monomorphic (83.6%) with diffuse large B cell lymphoma being the most frequent subtype. The majority of cases (70.7%) occurred > 1 year posttransplantation, whereas 66% were Epstein Barr virus positive. Following initial therapy overall response rate was 68.5%. Three-year relapse-free and overall survival were 59% and 49%, respectively. At last follow-up 44% of the patients were alive. Multivariable analysis identified several classical lymphoma-specific poor prognostic factors for the different outcome measures. The value of the International Prognostic Index was confirmed in our analysis.
  Leukemia & lymphoma 02/2013; · 2.40 Impact Factor
• Article: Histological features in western patients with idiopathic non-cirrhotic portal hypertension.

  Joanne Verheij, Jeoffrey N L Schouten, Mina Komuta, Frederik Nevens, Bettina E Hansen, Harry L A Janssen, Tania Roskams
  [show abstract] [hide abstract]
  ABSTRACT: AIMS: In the western world, idiopathic non-cirrhotic portal hypertension (INCPH) is a rare disease. This study aimed to investigate the histopathological features in western INCPH patients and to assess pathological differences between liver specimens of INCPH with and without HIV. METHODS AND RESULTS: Biopsies of 70 INCPH patients (of which 15 were HIV-infected) were compared to 23 patients with non-cirrhotic portal vein thrombosis (PVT), which served as a control group for non-cirrhotic portal hypertension. Phlebosclerosis, nodular regeneration (NR), sinusoidal dilatation, paraportal shunting vessels, perisinusoidal fibrosis and portal tract remnants were the most prevalent morphological features of INCPH. There were significant (P < 0.01) morphological differences between INCPH and PVT liver specimens with regard to portal tract remnants (46% versus 0%), phlebosclerosis (95% versus 65%), portal vein dilatation (34% versus 78%) and NR (56% versus 22%). The degree of NR correlated with the severity of phlebosclerosis (P < 0.01). NR was seen more frequently in the HIV-INCPH group, compared to the non-HIV-infected patients (P < 0.001). CONCLUSION: Portal tract remnants, phlebosclerosis and nodular regeneration are typical features of INCPH. Sinusoidal dilatation, paraportal shunting vessels and increased portal and parenchymal vessels might represent pressure-related morphological signs of portal hypertension. Finally, more nodular regeneration was observed in HIV-associated INCPH.
  Histopathology 02/2013; · 3.08 Impact Factor
• Article: SHOULD CHRONIC HEPATITIS B BE TREATED AS EARLY AS POSSIBLE?

  Frank Hulstaert, Christoph Schwierz, Frederik Nevens, Nancy Thiry, Mohamed Gamil, Isabelle Colle, Stefaan Van de Sande, Yves Horsmans
  [show abstract] [hide abstract]
  ABSTRACT: Objectives: We studied the cost-effectiveness of tenofovir and entecavir in e antigen positive (CHBe+) and negative (CHBe-) chronic hepatitis B. Methods: Using a multicenter survey including 544 patients we measured patient quality of life and attributable costs by clinical disease stage. Natural disease progression was studied in 278 patients in a single center. A Markov model was constructed to follow hypothetical cohorts of treated and untreated 40-year-old CHBe+ and CHBe- patients and 50-year-old patients with compensated cirrhosis. Results: We did not find an improvement in quality of life when viral load was reduced under treatment. Transition rates to liver cirrhosis were found to be age-dependent. Assuming equal effectiveness, tenofovir dominates the entecavir strategy because of its lower price in Belgium. The incremental cost-effectiveness ratio (ICER) of tenofovir after 20 years is more favorable for treating Caucasian cirrhotic patients (mean ICER €29,000/quality-adjusted life-year [QALY]) compared with treating non-cirrhotic patients (mean ICER €110,000 and 131,000/QALY for CHB e+ and e-, respectively). Within the non-cirrhotic patients the ICER decreases with increasing cohort starting age from 30 to 50 years. Conclusions: Results of long-term models for tenofovir or entecavir treatment of CHB need to be interpreted with caution as long-term trials with hard end points are lacking. Especially the effect on HCC remains highly uncertain. Based on cost-effectiveness considerations such antiviral treatment should be targeted at patients with cirrhosis or at risk of rapid progression to this disease stage.
  International Journal of Technology Assessment in Health Care 01/2013; · 1.37 Impact Factor
• Article: Long-term Exposure to Sorafenib of Liver Cancer Cells Induces Resistance with Epithelial-to-Mesenchymal Transition, Increased Invasion and Risk of Rebound Growth.

  Hannah van Malenstein, Jeroen Dekervel, Chris Verslype, Eric Van Cutsem, Petra Windmolders, Frederik Nevens, Jos van Pelt
  [show abstract] [hide abstract]
  ABSTRACT: Sorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed reduced adherent growth, became more invasive and lost liver-specific gene expression. Furthermore, following withdrawal of sorafenib, the resistant cells showed rebound growth, a phenomenon also found in patients. This cell model was further used to investigate strategies for restoration of sensitivity to sorafenib.
  Cancer letters 10/2012; · 4.86 Impact Factor
• Article: The accuracy of PET in the detection of Posttransplant Lymphoproliferative Disorder (PTLD).

  Daan Dierickx, Thomas Tousseyn, Annelies Requile, Raf Verscuren, Xavier Sagaert, Julie Morscio, Iwona Wlodarska, An Herreman, Dirk Kuypers, Johan Van Cleemput, Frederik Nevens, Lieven Dupont, Anne Uyttebroeck, Jacques Pirenne, Christiane De Wolf-Peeters, Gregor Verhoef, Lieselot Brepoels, Olivier Gheysens
  [show abstract] [hide abstract]
  ABSTRACT: Background. We investigated sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-fluorodeoxyglucose-positron emission tomography in 170 cases with suspected or biopsy-proven posttransplant lymphoproliferative disorder. Design and Methods. All solid organ and hematopoietic stem cell transplant recipients who underwent an 18F-fluorodeoxyglucose-positron emission tomography scan between 2003 and 2010 in our center for the indication posttransplant lymphoproliferative disorder, were retrospectively reviewed and results were compared with tissue biopsy, whenever possible. One hundred-seventy positron emission tomography-scans in hundred-fifty patients were eligible for evaluation. In 45 cases, the patient had a biopsy-confirmed posttransplant lymphoproliferative disorder before positron emission tomography scanning and positron emission tomography was performed for staging purposes. In the remaining 125 cases, positron emission tomography was performed to differentiate between posttransplant lymphoproliferative disorder and other diseases. 18F-fluorodeoxyglucose-uptake was quantitatively expressed by calculation of maximum and mean standardized uptake value in the most intense lesion, or, in the absence of attenuation corrected positron emission tomography scans by comparing uptake in target lesion to liver and mediastinal uptake. Results. We found an overall sensitivity of 89%, specificity of 89%, positive predictive value of 91% and negative predictive value of 87% for posttransplant lymphoproliferative disorder detection by 18F-fluorodeoxyglucose-positron emission tomography. In a subanalysis of the 125 scans performed for differentiating posttransplant lymphoproliferative disorder from other diseases, sensitivity, specificity, positive predictive value and negative predictive value were 90%, 89%, 85% and 93% respectively. 18F-fluorodeoxyglucose-uptake in posttransplant lymphoproliferative disorder was generally high with a median mean and maximum standardized uptake value of 9.0 [range 2.0-18.6] and 17.4 [range 2.6-26.4]. Posttransplant lymphoproliferative disorder often had an atypical presentation on positron emission tomography with high incidence of extranodal involvement. Conclusions. From these data, we can conclude that 18F-fluorodeoxyglucose-positron emission tomography is highly sensitive for detecting posttransplant lymphoproliferative disorder and has an excellent ability to differentiate posttransplant lymphoproliferative disorder from non-malignant diseases.
  Haematologica 10/2012; · 6.42 Impact Factor
• Article: Resource use and cost of hepatitis C-related care.

  Frederik Nevens, Isabelle Colle, Peter Michielsen, Geert Robaeys, Christophe Moreno, Karin Caekelbergh, Mark Lamotte, Veronique Wyffels
  [show abstract] [hide abstract]
  ABSTRACT: Chronic hepatitis because of the hepatitis C virus (CHC) is a major health problem that can lead to decompensated cirrhosis, hepatocellular carcinoma, and eventually death, all of which are associated with significant healthcare costs. To update the cost of care of CHC according to the different severity stages of the disease in a west European country (Belgium). Medical records of 157 patients, who were referred to the medical specialist at different stages of disease, were reviewed to identify the medical costs over a follow-up period of 3 years or 2 years in the case of liver transplantation (LT). Six disease stages were defined on the basis of histology (Metavir classification) and/or clinical data. In comparison with mild disease, the cost increased 1.6 times in the case of decompensated cirrhosis, 1.9 times in the case of hepatocellular carcinoma, and 3.4 in the case of LT. The costs for medication, hospitalization, and ambulatory care were, respectively, on the one hand, 81, 8, and 11% for mild disease and, on the other, 18, 79, and 3% for LT. In the case of a sustained viral response, the cost of follow-up within 3 years decreased by 45% for patients with mild and moderate disease. Antiviral treatment is the most important factor governing cost in mild and moderate disease, but once complications of CHC occur, hospitalization costs far exceed the cost of antiviral therapy. Already during the first 3 years of follow-up, sustained viral response decreased the cost significantly. Treatment of patients with CHC in an early stage has the potential to be cost-effective.
  European journal of gastroenterology & hepatology 07/2012; 24(10):1191-8. · 1.66 Impact Factor
• Source

  Available from: Philip Roelandt

  Article: HNF1B deficiency causes ciliary defects in human cholangiocytes.

  Philip Roelandt, Aline Antoniou, Louis Libbrecht, Werner Van Steenbergen, Wim Laleman, Chris Verslype, Schalk Van der Merwe, Frederik Nevens, Rita De Vos, Evelyne Fischer, Marco Pontoglio, Frédéric Lemaigre, David Cassiman
  [show abstract] [hide abstract]
  ABSTRACT: Heterozygous deletion or mutation in hepatocyte nuclear factor 1 homeobox B/transcription factor 2 (HNF1B/TCF2) causes renal cyst and diabetes syndrome (OMIM #137920). Mice with homozygous liver-specific deletion of Hnf1β revealed that a complete lack of this factor leads to ductopenia and bile duct dysplasia, in addition to mild hepatocyte defects. However, little is known about the hepatic consequences of deficient HNF1B function in humans. Three patients with heterozygous HNF1B deficiency were found to have normal bile duct formation on radiology and routine liver pathology. Electron microscopy revealed a paucity or absence of normal primary cilia. Therefore, heterozygous HNF1B deficiency is associated with ciliary anomalies in cholangiocytes, and this may cause cholestasis.
  Hepatology 06/2012; 56(3):1178-81. · 11.66 Impact Factor
• Article: Transcatheter arterial embolization for iatrogenic hemobilia is a safe and effective procedure: case series and review of the literature.

  Thomas Marynissen, Geert Maleux, Sam Heye, Johan Vaninbroukx, Wim Laleman, David Cassiman, Chris Verslype, Schalk Van der Merwe, Werner Van Steenbergen, Frederik Nevens
  [show abstract] [hide abstract]
  ABSTRACT: Hemobilia is an uncommon cause of gastrointestinal bleeding. The etiology is diverse, but most often, it is iatrogenic. The present study aims to reassess the clinical picture and the treatment of choice. We describe a case series from a single center of patients who presented with nontraumatic iatrogenic hemobilia. Over a period of 8 years, hemobilia occurred in 12 patients: following liver biopsy in six patients and after endoscopic biliary interventions in four patients, with a respective prevalence of 0.1 and 0.04%. The clinical presentation was characterized by an upper gastrointestinal bleeding (n=11) and/or biochemical signs of sudden biliary obstruction (n=9). The onset of the symptoms occurred after a median of 6 days (range: 1-23). Ultrasound and computed tomography scan missed the diagnosis in, respectively, 4/5 and 2/5 of patients. On arteriography, pseudoaneurysm (6/12) was the most common finding. Transcatheter arterial embolization controlled the bleeding in all cases (12/12) without major complications. The delay between the intervention and the clinical presentation and the fact that imaging studies may fail to diagnose hemobilia may mislead the physician. Transcatheter arterial embolization is the treatment of choice for hemobilia. It has proven to be effective and safe and it offers a long-term definitive cure.
  European journal of gastroenterology & hepatology 05/2012; 24(8):905-9. · 1.66 Impact Factor
• Article: Cholestasis-induced pruritus treated with ultraviolet B phototherapy: an observational case series study.

  Sofie Decock, Rik Roelandts, Werner Van Steenbergen, Wim Laleman, David Cassiman, Chris Verslype, Johan Fevery, Jos Van Pelt, Frederik Nevens
  [show abstract] [hide abstract]
  ABSTRACT: Pruritus is a disabling complication of cholestatic liver disorders. Its management remains challenging. Ultraviolet B (UVB) phototherapy has been successfully used to treat pruritus in other indications. This is an observational case series. The study population consists of 13 patients (10 females, mean age 52 years) with pruritus due to different cholestatic liver disorders: PBC (n=4), PSC (n=2), drug-induced (n=3) and persistent cholestasis after liver transplantation (LT) (n=4). Serum alkaline phosphatase levels were: 686 ± 363 μ/L and serum bile acids levels: 147 ± 15 μmol/L. In all patients, conventional medical treatment had failed to control pruritus. Perception of pruritus was recorded by the visual analogue scale (VAS). The mean follow-up was 3 years. Ten patients (77%) had more than 60% reduction in perceived pruritus of which 4 had more than an 80% reduction. Median [25-75% percentiles] VAS score before and after treatment decreased from 8.0 [8.0-10] to 2.0 [1.5-2.1] (p<0.001). The mean number of irradiations required to obtain this effect was 26 ± 17 (average duration of phototherapy: 8 weeks). No significant changes in cholestatic serum markers were observed. Four patients (30%) needed an additional phototherapy course because of recurrent pruritus and in all of them again a marked improvement of pruritus was observed. The therapy was well tolerated, except in two patients who developed, during retreatment, pronounced erythema in one case and paresthesia in the other case. UVB phototherapy appears to be a promising and well tolerated treatment also for cholestasis-associated pruritus.
  Journal of Hepatology 05/2012; 57(3):637-41. · 9.26 Impact Factor
• Source

  Available from: Philip Roelandt

  Article: Human pluripotent stem cell-derived hepatocytes support complete replication of hepatitis C virus.

  Philip Roelandt, Susan Obeid, Jan Paeshuyse, Jolien Vanhove, Alfons Van Lommel, Yaakov Nahmias, Frederik Nevens, Johan Neyts, Catherine M Verfaillie
  [show abstract] [hide abstract]
  ABSTRACT: Worldwide, about 180 million people are chronically infected with the hepatitis C virus (HCV). Current in vitro culture systems for HCV depend chiefly on human hepatoma cell lines. Although primary human hepatocytes support HCV infection in vitro, and immunodeficient mice repopulated with human hepatocytes support HCV infection in vivo, these models are limited because of shortage of human livers to isolate hepatocytes. Therefore, there is significant interest in the establishment from of a HCV culture system in human stem cell-derived hepatocyte-like cells. Human embryonic stem cell (hESC)-derived hepatocytes were infected with HCV in the presence or absence of direct acting antivirals. After inoculation, replication of HCV was analyzed extensively. We demonstrate that hESC-derived hepatocytes can be infected with the HCV JFH1 genotype 2a, resulting in the production of viral RNA in the stem cell progeny. Viral replication is inhibited by a non-nucleoside HCV polymerase-inhibitor (HCV-796), a cyclophilin binding molecule (Debio 025-Alisporivir) and the protease inhibitor VX-950 (Telaprevir). Stem cell-derived hepatocytes produced, for more than 10 days, the HCV core protein as well as virions that were capable of re-infecting hepatoma cells. Hepatocytes derived from hESC support the complete HCV replication cycle (including the production of infectious virus), and viral replication in these cells is efficiently inhibited by selective inhibitors of HCV replication.
  Journal of Hepatology 04/2012; 57(2):246-51. · 9.26 Impact Factor
• Article: Histology obtained by needle biopsy gives additional information on the prognosis of hepatocellular carcinoma.

  Hannah van Malenstein, Mina Komuta, Chris Verslype, Vincent Vandecaveye, Ben Van Calster, Baki Topal, Wim Laleman, David Cassiman, Werner Van Steenbergen, Raymond Aerts, Dirk Vanbeckevoort, Didier Bielen, Jacques Pirenne, Jos van Pelt, Tania Roskams, Frederik Nevens
  [show abstract] [hide abstract]
  ABSTRACT: Aim:  Hepatocellular carcinomas (HCC) have a strong biological heterogeneity. Current prognostic scores do not include histology. Information on the behavior of HCC based on histology has been characterized on retrospective data and large tissue specimens. We aimed to assess the additional value of needle biopsy and keratin 19 (K19) assessment in a prospective manner. Methods:  Between 2003 and 2008, all patients with a confirmed diagnosis of HCC by a percutaneous or laparoscopic needle biopsy at the time of diagnosis, and of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, were included. The exclusion criterion was a palliative setting. Biopsies were scored for microvascular invasion, differentiation, K19, epithelial cell adhesion molecule and α-fetoprotein staining. Clinical and radiological features were registered at time of biopsy. The added value of K19 was assessed using Cox proportional hazards regression. Results:  Of 74 patients screened, we included 58 patients. Based on the BCLC, 41% presented with early disease (BCLC A), 16% with intermediate disease (BCLC B) and 43% with advanced disease (BCLC C). In nine patients (16%), K19 staining was positive. Median follow up was 54 months (range 1-74) and 43 patients (72%) died. BCLC classification predicted the prognosis accurately, but histology offered additional prognostic information. In multivariate analysis, K19 was a strong predictor of overall survival (hazard ratio 4.57, 95% confidence interval 1.86-10.6), which improved predictive performance. No needle tract dissemination was observed. Conclusion:  Despite the possible problem of sampling error, needle biopsy offered additional prognostic information. This is especially the case for K19 staining.
  Hepatology Research 03/2012; 42(10):990-8. · 2.20 Impact Factor
• Article: Insulin resistance and response to telaprevir plus peginterferon α and ribavirin in treatment-naive patients infected with HCV genotype 1.

  Lawrence Serfaty, Xavier Forns, Tobias Goeser, Peter Ferenci, Frederik Nevens, Giampiero Carosi, Joost P Drenth, Isabelle Lonjon-Domanec, Ralph Demasi, Gaston Picchio, Maria Beumont, Patrick Marcellin
  [show abstract] [hide abstract]
  ABSTRACT: Insulin resistance is a predictor of poor response to peginterferon/ribavirin in patients infected with the chronic hepatitis C virus (HCV). There are no data on direct-acting antivirals. This exploratory analysis assessed the effect of metabolic factors and insulin resistance, measured by homoeostatic model assessment (HOMA), on virological response to telaprevir in Study C208. Overall, 161 HCV genotype 1-infected, treatment-naïve patients received 12 weeks of telaprevir plus peginterferon/ribavirin, then 12/36 weeks of peginterferon/ribavirin depending on on-treatment response criteria. The prognostic significance of several factors, including HOMA-insulin resistance (HOMA-IR), on virological response at weeks 4 and 12, end of treatment and 24 weeks after treatment was explored by multiple regression analysis. Baseline HOMA-IR data were available for 147 patients; baseline characteristics were consistent with the overall population. Baseline HOMA-IR <2, 2-4 and >4 was seen in 54%, 30% and 16% of patients, respectively. Neither response rates (any time point) nor week 4 viral load decline were significantly influenced by baseline HOMA-IR. In multivariate analyses, fibrosis stage and low-density lipoprotein cholesterol level were predictive of sustained virological response (OR 0.47 and 1.02, respectively). After the end of treatment, HOMA-IR was significantly lower in patients with sustained virological response than in those without (0.61 vs 1.34 for relapsers and 1.15 for non-responders; p<0.05). In this study, baseline HOMA-IR was not predictive of virological response to telaprevir in HCV genotype 1-infected, treatment-naïve patients, while sustained virological response was associated with improved HOMA-IR. These results suggest that metabolic factors and insulin resistance do not have a significant effect on telaprevir-based treatment efficacy.
  Gut 03/2012; 61(10):1473-80. · 10.11 Impact Factor
• Source

  Available from: Wim Laleman

  Article: A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System.

  Björn Meijers, Wim Laleman, Pieter Vermeersch, Frederik Nevens, Alexander Wilmer, Pieter Evenepoel
  [show abstract] [hide abstract]
  ABSTRACT: The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55±11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis. Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P<0.001) but remained within a safe range. We observed no major adverse events. Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure.
  Critical care (London, England) 02/2012; 16(1):R20. · 4.61 Impact Factor
• Article: Artificial liver support devices as treatment option for liver failure.

  Frederik Nevens, Wim Laleman
  [show abstract] [hide abstract]
  ABSTRACT: Non-biological artificial liver support (ALS) devices aim to remove albumin-bound and water-soluble toxins arising as a result of liver failure. They do not directly improve the liver synthetic capacity. The currently most used devices combine haemodialysis with albumin dialysis (MARS) or plasma separation and filtration (Prometheus). These devices have been used as a treatment for different types of liver failure: acute liver failure, acute-on-chronic liver failure and primary non- or poor-function after liver transplantation. Overall these devices are found to be safe. The following beneficial effects have been documented: improvement of jaundice, amelioration of haemodynamic instability, reduction of portal hypertension, lowering of intracranial pressure and improvement of hepatic encephalopathy. However, recently multicentre controlled trials failed to show a beneficial effect on transplant-free survival. Therefore the use of these devices at present seems only justified as a bridge to liver transplantation.
  Best practice & research. Clinical gastroenterology 02/2012; 26(1):17-26. · 2.48 Impact Factor
• Article: Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes.

  Mina Komuta, Olivier Govaere, Vincent Vandecaveye, Jun Akiba, Werner Van Steenbergen, Chris Verslype, Wim Laleman, Jacques Pirenne, Raymond Aerts, Hirohisa Yano, Frederik Nevens, Baki Topal, Tania Roskams
  [show abstract] [hide abstract]
  ABSTRACT: Cholangiocellular carcinoma (CC) originates from topographically heterogeneous cholangiocytes. The cylindrical mucin-producing cholangiocytes are located in large bile ducts and the cuboidal non-mucin-producing cholangiocytes are located in ductules containing bipotential hepatic progenitor cells (HPCs). We investigated the clinicopathological and molecular features of 85 resected CCs (14 hilar CCs [so-called Klatskin tumor], 71 intrahepatic CCs [ICCs] including 20 cholangiolocellular carcinomas [CLCs], which are thought to originate from HPCs]) and compared these with the different cholangiocyte phenotypes, including HPCs. Immunohistochemistry was performed with biliary/HPC and hepatocytic markers. Gene expression profiling was performed in different tumors and compared with nonneoplastic different cholangiocyte phenotypes obtained by laser microdissection. Invasion and cell proliferation assay were assessed using different types of CC cell lines: KMC-1, KMCH-1, and KMCH-2. Among 51 ICCs, 31 (60.8%) contained only mucin-producing CC features (muc-ICCs), whereas 39.2% displayed histological diversity: focal hepatocytic differentiation and ductular areas (mixed-ICCs). Clinicopathologically, muc-ICCs and hilar CCs showed a predominantly (peri-)hilar location, smaller tumor size, and more lymphatic and perineural invasion compared with mixed-ICCs and CLCs (predominantly peripheral location, larger tumor size, and less lymphatic and perineural invasion). Immunoreactivity was similar in muc-ICCs and hilar CCs and in mixed-ICCs and CLCs. S100P and MUC1 were significantly up-regulated in hilar CCs and muc-ICCs compared with mixed-ICCs and CLCs, whereas NCAM1 and ALB tended to be up-regulated in mixed-ICCs and CLCs compared with other tumors. KMC-1 showed significantly higher invasiveness than KMCH-1 and KMCH-2. Conclusion: Muc-ICCs had a clinicopathological, immunohistochemical, and molecular profile similar to that of hilar CCs (from mucin-producing cholangiocytes), whereas mixed-ICCs had a profile similar to that of CLCs (thought to be of HPC origin), possibly reflecting their respective cells of origin.
  Hepatology 01/2012; 55(6):1876-88. · 11.66 Impact Factor
• Article: High-frequency vagus nerve stimulation improves portal hypertension in cirrhotic rats.

  Ilse Bockx, Katrien Verdrengh, Ingrid Vander Elst, Jos van Pelt, Frederik Nevens, Wim Laleman, David Cassiman
  [show abstract] [hide abstract]
  ABSTRACT: The liver is innervated by the vagus nerve. Its efferent neurotransmitters acetylcholine (ACh) and vasoactive intestinal peptide (VIP) are both well-known vasodilators. A study was undertaken to determine whether electrical vagus nerve stimulation (STIM) influences portal vein pressure. The left vagus nerve upstream of the hepatic branch was stimulated at 5 Hz (ACh release) and 10 Hz (VIP release) in normal and cirrhotic rats. STIM at both frequencies decreased portal pressure in normal rats while, in cirrhotic rats, only 10 Hz STIM resulted in long-lasting reduction of portal pressure. Hepatic branch vagotomy prevented the STIM-induced decrease in pressure, proving that the effect is a direct hepatic effect. Deafferentation of the left vagus nerve by pretreatment with capsaicin did not change the effect of STIM, showing that the vagus efferents and not the afferents are responsible for the decrease in portal pressure. Injecting microspheres before and after STIM showed that STIM did not lead to redistribution of systemic blood flow but decreased portal pressure by lowering intrahepatic resistance. Using in situ liver perfusion to evaluate the intrahepatic effect of ACh and VIP, both neurotransmitters significantly decreased the perfusion pressure in normal rats. VIP also decreased portal pressure in cirrhotic rats, confirming the results of STIM. This VIP-induced decrease in pressure could be prevented by a VIP receptor 2 antagonist. L-NAME did not inhibit the VIP effect in cirrhotic rats, indicating that VIP does not act via nitric oxide. High-frequency electrical vagus stimulation improves portal hypertension in cirrhotic rats, most likely through release of VIP, binding to VIP receptor 2. As the technology is already in use for other applications, vagus nerve stimulation might be an important new strategy in the treatment of portal hypertension.
  Gut 12/2011; 61(4):604-12. · 10.11 Impact Factor
• Article: Prospective study comparing different indirect methods to measure portal pressure.

  Geert Maleux, Endry Willems, Steffen Fieuws, Sam Heye, Johan Vaninbroukx, Wim Laleman, David Cassiman, Chris Verslype, Frederik Nevens
  [show abstract] [hide abstract]
  ABSTRACT: To compare the accuracy of wedged hepatic venous pressure (WHVP) measurement with use of an end-hole catheter or an occlusion-balloon catheter versus direct portal pressure (PP) measurement in patients with cirrhosis with sinusoidal portal hypertension and to investigate the factors that affect the results of these indirect measurements. In a cohort of 174 patients with cirrhosis referred for transjugular intrahepatic portosystemic shunt creation, indirect PP was measured with an end-hole catheter and an occlusion-balloon catheter placed in the right hepatic vein. Direct PP was measured by a pigtail catheter in the main branch of the portal vein. PP was more accurately estimated by the occlusion-balloon technique: mean WHVP measurements were 25.5 mm Hg ± 7.9 and 30.6 mm Hg ± 13.9, respectively, for the occlusion-balloon and end-hole catheter techniques, and the direct PP measurement was 25.0 mm Hg ± 7.0. The median absolute differences between direct and the indirect methods were 6.0 mm Hg with the end-hole catheter and 2.0 mm Hg with the occlusion-balloon catheter (P < .0001, signed-rank test). Relative to direct PP measurements, the occlusion-balloon technique overestimated pressures in cases of higher Model for End-Stage Liver Disease (MELD) scores (Spearman ρ = -0.24; P = .0005). Compared with direct PP measurements, agreement was clearly higher for indirect WHVP measurement with occlusion-balloon catheters versus end-hole catheters. However, in patients with a high MELD score, there was an overestimation of PP with the occlusion-balloon method.
  Journal of vascular and interventional radiology: JVIR 11/2011; 22(11):1553-8. · 1.81 Impact Factor
• Source

  Available from: Samad Amini-Bavil-Olyaee

  Article: Molecular characterization of hepatitis B virus strains circulating in Belgian patients co-infected with HIV and HBV: overt and occult infection.

  Mahmoud Reza Pourkarim, Philippe Lemey, Samad Amini-Bavil-Olyaee, Lieselot Houspie, Jannick Verbeeck, Mustafizur Rahman, Piet Maes, Eric Vanwijngaerden, Frederik Nevens, Marc Van Ranst
  [show abstract] [hide abstract]
  ABSTRACT: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) have similar transmission routes, implying that patients infected with HIV are at particular risk for HBV infection. Patients who are co-infected with HIV and HBV progress more rapidly to end-stage liver disease and different HBV genotypes may have a distinct impact on disease progression. One hundred ninety-one anti-HBc-positive sera from Belgian patients co-infected with HIV and HBV were collected during 1998-2008. Full-length HBV genomes as well as large S or partial S genes were amplified and their molecular evolutionary history was analyzed. Clinically, 30 (65.8%) patients were categorized as "overt infection" and 16 (34.7%) cases were categorized as "occult infection." Five distinct HBV genotypes comprising A (69.6%), E (19.6%), followed by D, C, and G were detected. HBV genotype A was observed in all clinical groups and in patients with varying ethnical background. HBV genotype E could be detected in African patients who were mostly infected by heterosexual contacts. Several clinically important mutations at the HBs major hydrophilic region were detected in the new isolates but with no significant difference between occult and overt infection. The high prevalence of HBV genotype A in overt and occult cases, and in particular the detection of certain HBV subgenotypes in patients co-infected with HIV and HBV that carry diagnostic escape mutations, may provide useful information for national guidelines for prophylaxis and treatment.
  Journal of Medical Virology 11/2011; 83(11):1876-84. · 2.82 Impact Factor
• Article: Immune reactivity to β-tubulin isotype 5 and vesicular integral-membrane protein 36 in patients with autoimmune gastrointestinal disorders.

  Katrijn Op De Beéck, Karolien Van den Bergh, Séverine Vermeire, Sofie Decock, Rita Derua, Etienne Waelkens, Paul Rutgeerts, Frederik Nevens, Xavier Bossuyt
  Gut 11/2011; 60(11):1601-2. · 10.11 Impact Factor