J Fevery

Universitair Ziekenhuis Leuven, Louvain, Flanders, Belgium

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Publications (307)1370.97 Total impact

  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
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    S Decock, C Verslype, J Fevery
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    ABSTRACT: Worldwide approximately 200 million people are chronically infected with hepatitis C virus (HCV). Chronic HCV infection represents the leading cause of liver cirrhosis and the main indication for liver transplantation in the western world. In addition, chronic HCV infection is associated with numerous clinical manifestations, including type 2 diabetes. An obvious and frequently suggested explanation for the connection between HCV infection and type 2 diabetes is that cirrhosis by itself causes insulin resistance. However, the prevalence of type 2 diabetes in HCV cirrhosis is higher than in HBV cirrhosis (23.6% vs 9.4%). This suggests that HCV infection by itself can lead to insulin resistance and predispose to the onset of type 2 diabetes. First, HCV core protein induces hepatic steatosis by inhibition of microsomal triglyceride transfer protein and hepatic steatosis causes insulin resistance. Secondly, HCV core protein inhibits, through elevation of TNF-alfa and other factors, the insulin-signalling pathways causing insulin resistance. Moreover, recent data strongly suggest that insulin resistance is an important predictor of poor response to antiviral therapy in chronic hepatitis patients treated with peginterferon plus ribavirin.
    Acta clinica Belgica 03/2007; 62(2):111-9. · 0.59 Impact Factor
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    ABSTRACT: This study reports the findings of an electron microscopic search for so-called non-A, non-B nuclear particles in liver biopsies from patients with mainly chronic or prolonged liver disease and from chimpanzees. In patients without hepatitis B virus or acute hepatitis A virus serological markers, non-A, non-B-like nuclear particles were seen in hepatocytes in 28 of 31 cases of presumed non-A, non-B hepatitis, but also in 11 of 12 cases of liver disease not usually attributed to hepatitis viruses. They were also seen in 22 of 24 patients with HBsAg, in 3 of 3 patients with anti-HBc and no HBsAg, in 1 of 2 patients with hepatitis A, in a case of cytomegalovirus hepatitis, and in 16 of 19 patients whose serology was not available or inconclusive. The particles were present in 1 of 8 untreated HBsAg-negative chimpanzees and in 2 of 2 HBsAg-positive chimpanzees. They appeared in 4 of 4 chimpanzees developing non-A, non-B hepatitis following exposure to various inocula. Three patterns of particle aggregates were distinguished, all of which had been shown by others in non-A, non-B hepatitis. Dense aggregates were predominant, while others have shown intermediate aggregates more often; reasons for this difference could be technical. No pattern was specific for any condition. Either non-A, non-B-like nuclear particles, although associated with non-A, non-B hepatitis, are not specific for this condition, or non-A, non-B hepatitis viruses are extremely more common than is currently appreciated.
    Hepatology 01/2007; 3(4):532-44. · 12.00 Impact Factor
  • Tijdschrift voor Geneeskunde 01/2007; 63(23):1190-1197.
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    BOURS S, FEVERY J
    Tijdschrift Voor Geneeskunde. 01/2007; 63(7):277-288.
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    ABSTRACT: A method was developed to extract quantitatively the bilirubins from bile, urine, serum, stool, and preparations from liver with a chloroform-ethanol mixture at pH 1.8 in the presence of ascorbic acid and NaCl. Extracted pigment was submitted to thin-layer chromatography, and the separated bilirubins were either immediately eluted and determined spectrophotometrically or individually converted to ethyl anthranilate azo derivatives for thin-layer chromatographic analysis of each isolated pigment band. Bilirubins in duodenal bile of eight healthy adults comprised 1.5 +/- 1.3% unconjugated bilirubin-IX alpha, 69 +/- 6% bilirubin diglucuronide, and 16 +/- 4% bilirubin monoglucuronides. Mixed diconjugates containing one glucuronosyl moiety and either one xylosyl or one glucosyl group amounted to 10 +/- 3%. Most samples (6 of 8) contained trace amounts (0.6 +/- 0.6%) of unconjugated bilirubin-IX beta, in agreement with nearly exclusive cleavage of heme at the alpha-meso position. The composition of the bilirubins in bile was normal in 6 patients with cholesterol gallstones, 4 with chronic hepatitis, and 3 with hemolysis. In duodenal bile of individuals with Gilbert's syndrome (n = 10), the concentration of bilirubin conjugates was comparable to that in healthy adults, but the proportion of bilirubin diglucuronides (52 +/- 8%) was decreased. The concentration of unconjugated bilirubin-IX alpha showed a fair positive correlation with that of bilirubin monoglucuronide and was increased in half of the patients with Gilbert's syndrome.
    Hepatology 01/2007; 3(2):177-83. · 12.00 Impact Factor
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    Tijdschrift Voor Geneeskunde. 01/2007; 63(12):549-555.
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    ABSTRACT: Cytokeratin (CK) 7 and CK19 expression, present in hepatic progenitor cells (HPCs) and in cholangiocytes but not in normal hepatocytes, has been reported in some hepatocellular carcinomas (HCCs); however, the incidence and relevance of this expression in HCC in Caucasians is not known. Therefore, our aim was to study the occurrence and clinicopathological characteristics of HCC expressing CK7 and/or CK19 in 109 Caucasian patients. The expression of hepatocellular differentiation markers (Hepar, canalicular polyclonal carcinoembryonic antigen), biliary/progenitor cell markers (CK7, CK19), alpha-fetoprotein (AFP), p53 and beta-catenin in HCC was semiquantitatively assessed by immunohistochemistry. Of 109 HCCs, 78 were CK7-/CK19- (72%), 13 CK7+/CK19- (12%), seven CK7-/CK19+ (6%), 11 CK7+/CK19+ (10%). CK19 expression was significantly associated with elevated serum AFP (400 ng/ml) (P = 0.023), tumour AFP expression (P < 0.0001), presence in serum of anti-hepatitis B core (P = 0.016), less fibrosis in non-neoplastic parenchyma (P = 0.009) and less nuclear beta-catenin expression (P = 0.021). CK7 expression was significantly associated with elevated serum bilirubin (> 2 mg/dl) (P = 0.0005) and less nuclear beta-catenin expression (P = 0.003). HCC expressing CK19 had a higher rate of recurrence (P = 0.009, hazard ratio 12.5, n = 31) after liver transplantation compared with CK19- tumours. In our series, 28% of HCCs contained cells expressing CK7 and/or CK19. They potentially derive from HPCs. The higher recurrence rate of CK19+ HCC after transplantation suggests a worse prognosis for these HCCs compared with CK19- HCC.
    Histopathology 08/2006; 49(2):138-51. · 2.86 Impact Factor
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    ABSTRACT: Cirrhotic animal models are vital to investigate complications of chronic liver disease. We chronologically characterized the effect of thioacetamide, administrated orally and adapted weekly to weight changes, focusing on the optimal moment to obtain all typical features of portal hypertension and cirrhosis. Male Wistar rats, 200-250 g, were intoxicated for 6, 12 or 18 weeks (n = 8 per group), respectively, and compared with age-matched controls (n = 4 per group). An in-situ perfusion model was used to evaluate intrahepatic resistance and endothelial function. Splanchnic blood flow and portosystemic shunting were assessed by a perivascular flow probe. Rats intoxicated for 6 or 12 weeks had no mortality and histologically showed hepatitis and advanced fibrosis, respectively. At 18 weeks, mortality was 16% (on a total of 56 animals) and only at that moment all animals showed homogenous macronodular cirrhosis with signs of high-grade hepatocellular dysplasia. Portal hypertension was present at 12 weeks (11 +/- 0.4 vs. 5.9 +/- 0.4 mmHg, P < 0.001), but was not associated with the hyperdynamic state until 18 weeks (12.1 +/- 0.8 vs. 5.6 +/- 0.5 mmHg, P < 0.001). At this latter time-point, we also observed increased intrahepatic resistance associated with endothelial dysfunction, hyperresponsiveness to vasoconstrictors, splanchnic hyperaemia and portosystemic shunting. These alterations were associated with increased systemic levels of nitrate/nitrite and thromboxane A(2). Thioacetamide, adapted to weekly weight changes, leads to a homogenous, reproducible model of cirrhosis in the rat in 18 weeks, which is associated with all the typical characteristics of portal hypertension, including endothelial dysfunction.
    European Journal of Clinical Investigation 05/2006; 36(4):242-9. · 3.37 Impact Factor
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    ABSTRACT: Liver failure, whether acute or acute-on-chronic, remains an important cause of morbidity and mortality. The lack of liver detoxification, metabolic and regulatory functions of the liver leads to life-threatening complications, such as renal failure, altered immune response, hepatic coma and systemic haemodynamic dysfunction, eventually culminating in multiorgan failure. Current medical therapy involves the management of the precipitating event and treatment of complications until the liver eventually recovers, leaving us with no other treatment options than transplantation if these attempts fail. However, the shortage in cadaveric organs and other transplant-related problems, have prompted the need for alternative methods to provide liver support. As liver failure is often potentially reversible, considerable effort has been invested in the development of liver support systems. Currently, most of the experience is available for non-biological support systems. They represent the focus of this review, which aims to define the goals of liver support, to describe the design of the different existing devices and to analyse the available data to determine their current status in the management of patients with liver failure.
    Alimentary Pharmacology & Therapeutics 03/2006; 23(3):351-63. · 4.55 Impact Factor
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    ABSTRACT: Until 1998, intestinal transplantation (SBT) had not been performed in our region of Flanders, Belgium. Potential SBT activity was not known and selection criteria had not been validated. A multidisciplinary SBT program was launched in 1998. We analyzed requests for SBT and outcomes in these patients whether with or without SBT. Listing for SBT was only considered for patients with irreversible short bowel syndrome who had developed life-threatening complications of total parenteral nutrition, but whose general condition was still thought compatible with surgery and immunosuppression. During the study period 1998 to 2004, one third of the requests for SBT (10/31) were deemed suitable. SBT in this group was lifesaving (100% survival) when performed in time. Mortality in this group without SBT was high (67%). Two thirds of the patients (21/31) did not fulfill the SBT inclusion criteria, either because they were "too moribund" to tolerate transplantation or because they were "too well". This preliminary study emphasized the importance of (1) early referral of potential SBT candidates, (2) adherence to strict criteria for listing patients for SBT, and (3) referral of intestinal donors to procurement organizations.
    Transplantation Proceedings 01/2006; 38(6):1671-2. · 0.95 Impact Factor
  • European Journal of Gastroenterology & Hepatology 01/2006; 18(1). · 1.92 Impact Factor
  • European Journal of Gastroenterology & Hepatology 01/2006; 18(1). · 1.92 Impact Factor
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    ABSTRACT: A male patient with portal hypertension, portal vein thrombosis, spontaneous splenorenal shunt formation, and encephalopathy, thought to have post-hepatitis B cirrhosis, is described. His condition deteriorated and necessitated liver transplantation. In the explant liver, nodular regenerative hyperplasia with pronounced vascular lesions both in portal venules and in arterioles was found instead of classical cirrhosis. Two years post-transplant he developed bilateral ischaemic femur head necrosis. The three disorders (portal vein thrombosis, nodular regenerative hyperplasia, and ischaemic hip necrosis) seemed to be due to a common vasculopathy induced by hyperhomocyteinaemia. Genetic studies showed that he carried a mutation in the gene encoding for formation of methylenetetrahydrofolate reductase. Treatment with folic acid combined with pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) normalised his serum homocysteine levels.
    Gut 08/2005; 54(7):1021-3. · 10.73 Impact Factor
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    ABSTRACT: To study features in older patients with autoimmune hepatitis, as this was considered mainly a disease of young females. Analysis of 28 patients diagnosed at age > or =65 years compared with 84 younger patients. The incidence was similar at all age decades. The ratio M:F was 1:3 (> or =65 years) vs. 1:2 (<65 years). Presenting symptoms were not different when compared with younger patients and consisted of general malaise and fatigue (36%), jaundice +/- other symptoms (50%), or ascites (11%). Antinuclear antibodies (ANA) > or = 1/80 were positive in 93%, smooth muscle antibodies (SMA) > 1/40 in 50%, anti-liver kidney microsomes (anti-LKM) proved always negative. Histology showed acute necrotizing hepatitis in 19%, severe interphase hepatitis in 15%, chronic hepatitis with plasmo-lymphocytic infiltrate in 30%, cirrhosis in 29% (with active inflammation in one-third); biopsy was refused in 11%. The elderly responded very well to low doses of methylprednisolone (< or =8 mg) and azathioprine (1 mg/kg). This schedule obviates side-effects such as infections seen with higher dosages. Autoimmune hepatitis has to be also looked for in the elderly with acute and chronic hepatitis. The steroid therapy should be individualized but kept at a low dose.
    Alimentary Pharmacology & Therapeutics 04/2005; 21(6):695-9. · 4.55 Impact Factor
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    ABSTRACT: Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.
    Transplantation Proceedings 04/2005; 37(2):1180-1. · 0.95 Impact Factor
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    ABSTRACT: Complete venous thrombosis of the splanchnic system remains a major challenge in liver transplantation surgery. Some of these patients have been treated successfully by multivisceral transplantation. Cavoportal transposition is another alternative to treat these patients. We reviewed our single-center experience with this technique. Five patients with operatively confirmed complete splanchnic thrombosis were transplanted with the cava portal transposition technique. All survived the procedure; 60% survived long term. This technique is a useful salvage procedure in moribund patients with diffuse portal thrombosis who would otherwise rapidly succumb.
    Transplantation Proceedings 04/2005; 37(2):1112-4. · 0.95 Impact Factor
  • Tijdschrift voor Geneeskunde 01/2005; 61(9):691-699.
  • Tijdschrift voor Geneeskunde 01/2005; 61(17):1177-1185.
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    ABSTRACT: Liver fatty acid-binding protein (L-FABP) is a small protein (15 kD) involved in the intracellular transport of long-chain fatty acids in the liver. The L-FABP is regarded as a sensitive marker for liver cell damage. In a pig model for liver transplantation (LTx) from non-heart-beating donors (NHBD), we evaluated plasma changes of L-FABP early after reperfusion of grafts exposed to increasing periods of warm ischemia (WI). Porcine livers were procured after 0, 15, 30, 45, and 60 minutes' WI. After 4 hours' cold ischemia (CI), LTx was performed. Primary graft nonfunction (PNF) and day 4 survival were recorded. Plasma samples were collected prior to and 15, 60, and 180 minutes after graft reperfusion for determination of L-FABP and aspartate transaminase (AST). Early after reperfusion, levels of L-FABP correlated well with the duration of WI. The PNF developed in 100% of animals after 60 minutes of WI, 50% after 30, and 45 minutes' WI, and was absent after no WI and 15 minutes of WI. Day 4 survival was 100% in 0 minutes' WI, 83% in 15 minutes' WI, 50% in 30 and 45 minutes' WI, and 0% in 60 minutes of WI. Plasma levels of L-FABP correlated well with WI and concomitant hepatocellular damage in LTx from NHBD. Monitoring of posttransplant L-FABP plasma levels is a valuable new tool to quantify early the extent of parenchymal cell damage of NHBD livers and to predict their viability and function.
    Transplantation Proceedings 01/2005; 37(1):413-6. · 0.95 Impact Factor

Publication Stats

4k Citations
1,370.97 Total Impact Points

Institutions

  • 1984–2007
    • Universitair Ziekenhuis Leuven
      • • Department of Hepatology
      • • Department of Abdominal Surgery
      • • Department of Gastroenterology
      • • Department of Radiology
      • • Department of Pathology
      Louvain, Flanders, Belgium
    • Leuven University College
      Louvain, Flanders, Belgium
  • 1972–2007
    • University of Leuven
      • • Academic Centre of General Practice
      • • Department of Reproduction, Development and Regeneration
      • • Rega Institute for Medical Research
      • • Department of Clinical and Experimental Medicine
      • • Department of Human Genetics
      Louvain, Flanders, Belgium
  • 2003
    • University of Pretoria
      Πρετόρια/Πόλη του Ακρωτηρίου, Gauteng, South Africa
  • 2000
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 1991–2000
    • Charles University in Prague
      • 1st Faculty of Medicine
      Praha, Praha, Czech Republic
  • 1998
    • Evangelismos Hospital
      Athínai, Attica, Greece
    • Erasmus Universiteit Rotterdam
      • Department of Gastroenterology and Hepatology
      Rotterdam, South Holland, Netherlands
  • 1990
    • Universität Heidelberg
      • University Hospital of Internal Medicine
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1983–1990
    • University of Padova
      Padua, Veneto, Italy
  • 1980
    • Catholic University of Louvain
      Walloon Region, Belgium