S H Yap

Universitair Ziekenhuis Leuven, Leuven, VLG, Belgium

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Publications (173)775.49 Total impact

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    ABSTRACT: Abstract Aplastic anemia is a rare complication of liver transplantation (<1%). However, an increasing number of cases of aplastic anemia have been recently reported when liver transplantation is performed for non-A, non-B, non-C fulminant hepatic failure. The aim of this study is to reevaluate the importance and the incidence of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure, and to propose preventive measures, diagnostic and management guidelines to try to reduce the incidence, morbidity and mortality associated with this complication. In this report a case of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure is described. In addition, the pertinent literature on aplastic anemia after liver transplantation, since the first description of that complication in 1987, is reviewed. A 20-year-old woman developed aplastic anemia 14 weeks after liver transplantation for fulminant non-A, non-B, non-C hepatitis. After failure of G-CSF treatment, she was treated with intensive immunosuppression (FK 506, ATG, high-dose steroids). She is well 1 year post-transplantation, with normal liver tests and with bone marrow recovery. Through a Medline literature search (1988–1999), we identified 30 additional cases of aplastic anemia following liver transplantation for non-A, non-B, non-C fulminant hepatic failure. Of all liver transplantations performed for that indication at five participating centers, the mean incidence of aplastic anemia was 23.2%. Mean age was 10 years (1.2–29) and the male/female ratio was 4.6. For treating aplastic anemia, different modalities were used: ATG (n=12), ALG (n=1), OKT 3 (n=1), G-CSF (n=6), a 6-HLA-compatible bone marrow transplantation (n=3), and none (n=12). The mortality rate remains high (39%), with infections and bleeding as the two most frequent causes of death. Based on this literature review, we conclude that aplastic anemia is a relatively common complication of liver transplantation for non-A, non-B, non-C fulminant hepatic failure in children and young adults. An unknown viral agent operating through immune-mediated mechanisms is probably responsible. The myelotoxic environment inherent to transplantation (e.g. azathioprine, trimethoprim) probably has a cumulative effect. Preventive measures (e.g. not using myelotoxic drugs) should be adopted in high-risk children and young adults transplanted for non-A, non-B, non-C fulminant hepatic failure. Early detection of bone marrow depression, a low threshold for performing a bone marrow biopsy, and prompt treatment are pivotal. Intensive standards supportive care with broad-spectrum antibiotics and anti-fungal agents os essencial during phasesof pancytopenia. Although spontaneous recovery has been described under maintenance immunosuppression, increased immunosuppression, in particular with ATG, may reverse the aplatic anemia and promote bone marrow recovery. In unresponsive patients, six-HLA-identical bone marrow transplanation has been successful.
    Full-text · Article · Mar 2005 · Transplant International
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    ABSTRACT: TT viruses are single-stranded DNA viruses, suggested to be involved in non A-E hepatitis. We studied the prevalence of TTV infection in acute or chronic hepatitis in Belgium in comparison with that in blood donors and in patients regularly receiving blood products. TTV-DNA was detected by PCR using the primer set of Takahashi et al (1998) or a nested-PCR specific for genotype-2, because it had been reported that this subtype might be more pathogenic (Tagger et al. 1999). TTV-DNA was present in 49% of 128 patients with chronic hepatitis C, in 54% of 54 with chronic hepatitis B and in 54% of 24 with acute liver failure. This prevalence is similar to the 47% in 127 patients with clotting disorders, or the 64% in 103 undergoing chronic haemodialysis, but lower than the 29.7% found in 340 healthy blood donors. Significant differences in clinical or biochemical characteristics between TTV- positive or TTV-negative patients could not be substantiated. The genotype-2 subgroup comprised 3.9%, but they also did not differ from non genotype-2 patients. The prevalence of TTV infection was higher in patients than in healthy blood donors. Its clinical significance remains questionable since clinical and biochemical characteristics were not different between TTV positive and TTV negative patients. The higher prevalence of TTV in patients might be related to parenteral transmission, but the relatively high prevalence in healthy blood donors points to an additional presumably faeco-oral infection. The presence of TTV in animals suggests that infection might also originate from food. Long term follow-up will have to define whether co-infection with TTV eventually alters the natural history of chronic hepatitis.
    No preview · Article · Apr 2004 · Acta gastro-enterologica Belgica
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    ABSTRACT: Auto-immune pancreatitis is a distinct entity of chronic pancreatitis, with clearly different features from those seen in chronic alcoholic or chronic hereditary pancreatitis. Abdominal pain is usually absent. Patients often present with jaundice caused by a distal bile duct obstruction. Radiological features are often compatible with pancreatic carcinoma. In most patients, the correct diagnosis is only made at histological examination of a pancreatic resection specimen obtained after a Whipple resection. However, early diagnosis of this condition is imperative since this form of pancreatitis can be treated with corticosteroids. In our experience, autoantibodies are usually absent.
    No preview · Article · May 2002
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    ABSTRACT: We investigated the degree of tumor cell killing after radiotherapy regimens commonly used in clinical practice in comparison with an accelerated schedule. Mtln3 mammary adenocarcinoma tumor cells were inoculated subcutaneously in the hind leg of syngeneic Fischer 344 rats. Tumors were irradiated with 5 x 5 Gy in 5 days, 10 x 3 Gy over 10 days, or 5 x (2 x 3) Gy in 5 days. After excision of the irradiated tumors, the dye exclusion, a tetrazolium-based colorimetric and the clonogenic assays were used to determine tumor cell viability and surviving fractions. Estimated potential doubling time values indicate a rapid proliferation capacity, comparable with potential doubling time values in human rectal cancer. The dye exclusion and clonogenic assays revealed a significantly higher degree of cell killing after the hypofractionated and the accelerated regimens of, respectively, 5 x 5 Gy and 5 x (2 x 3) Gy over 5 days compared with 10 x 3 Gy over 10 days. A shorter treatment time offered the best therapeutic efficacy. The schedule involving two daily fractions of 3 Gy over 5 days should be less toxic than 5 x 5 Gy and may therefore provide a therapeutic advantage.
    No preview · Article · May 2002 · Annals of Surgical Oncology
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    ABSTRACT: A novel DNA virus, TT virus (TTV), has been proposed as a possible etiologic agent for non A-E hepatitis. The aim of the present study was to determine the prevalence of TTV infection using PCR in healthy blood donors and in patients with clotting disorders who have been investigated previously for GBV-C/HGV and HCV infection in Belgium. In this study, PCR using primers proposed by Takahashi et al. [(1998) Hepatology Research 12:233-239] proved far more sensitive than those used by Okamoto et al. [(1998) Journal of Medical Virology 56:128-132]. The sequence of the PCR products showed 87% identity to the published sequence. TTV was present in 29.7% of healthy blood donors, a figure intermediate between the low rate of infection observed in Scotland and the high rates in the Far East. TTV was detected in 46.5% of 127 patients studied with clotting disorders as compared to 79.5% for HCV and 11.8% for GBV-C/HGV infection. However, there was no impact on the level of serum transaminases. Treatment with interferon for HCV infection co-infected with TTV suppressed temporarily serum TTV DNA. Therefore, it was concluded that TTV DNA is detected frequently in serum of healthy blood donors in Belgium and more often in patients with clotting disorders. TTV does not cause liver disease or contribute to the severity of liver disease.
    No preview · Article · Apr 2002 · Journal of Medical Virology
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    ABSTRACT: Aplastic anemia is a rare complication of liver transplantation (<1%). However, an increasing number of cases of aplastic anemia have been recently reported when liver transplantation is performed for non-A, non-B, non-C fulminant hepatic failure. The aim of this study is to reevaluate the importance and the incidence of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure, and to propose preventive measures, diagnostic and management guidelines to try to reduce the incidence, morbidity and mortality associated with this complication. In this report a case of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure is described. In addition, the pertinent literature on aplastic anemia after liver transplantation, since the first description of that complication in 1987, is reviewed. A 20-year-old woman developed aplastic anemia 14 weeks after liver transplantation for fulminant non-A, non-B, non-C hepatitis. After failure of G-CSF treatment, she was treated with intensive immunosuppression (FK 506, ATG, high-dose steroids). She is well 1 year post-transplantation, with normal liver tests and with bone marrow recovery. Through a Medline literature search (1988-1999), we identified 30 additional cases of aplastic anemia following liver transplantation for non-A, non-B, non-C fulminant hepatic failure. Of all liver transplantations performed for that indication at five participating centers, the mean incidence of aplastic anemia was 23.2%. Mean age was 10 years (1.2-29) and the male/female ratio was 4.6. For treating aplastic anemia, different modalities were used: ATG ( n=12), ALG ( n=1), OKT 3 ( n=1), G-CSF ( n=6), a 6-HLA-compatible bone marrow transplantation ( n=3), and none ( n=12). The mortality rate remains high (39%), with infections and bleeding as the two most frequent causes of death. Based on this literature review, we conclude that aplastic anemia is a relatively common complication of liver transplantation for non-A, non-B, non-C fulminant hepatic failure in children and young adults. An unknown viral agent operating through immune-mediated mechanisms is probably responsible. The myelotoxic environment inherent to transplantation (e.g. azathioprine, trimethoprim) probably has a cumulative effect. Preventive measures (e.g. not using myelotoxic drugs) should be adopted in high-risk children and young adults transplanted for non-A, non-B, non-C fulminant hepatic failure. Early detection of bone marrow depression, a low threshold for performing a bone marrow biopsy, and prompt treatment are pivotal. Intensive standard supportive care with broad-spectrum antibiotics and anti-fungal agents is essential during phases of pancytopenia. Although spontaneous recovery has been described under maintenance immunosuppression, increased immunosuppression, in particular with ATG, may reverse the aplastic anemia and promote bone marrow recovery. In unresponsive patients, six-HLA-identical bone marrow transplantation has been successful.
    No preview · Article · Mar 2002 · Transplant International
  • Lan Lin · Johan Fevery · Sing Hiem Yap
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    ABSTRACT: Hepatitis C virus (HCV) is reported to be lymphotropic under certain circumstances. In order to evaluate viral replication in peripheral blood mononuclear cells (PBMCs), a novel strand-specific RT-PCR was developed for the determination of HCV negative-strand RNA. The detection limit of this strand-specific RT-PCR was 100 copies of HCV negative-strand RNA in the presence of 1 microg liver RNA and 10(7)-10(8) copies of positive-strand RNA. False positive PCR signals occurred only when HCV positive-strand RNA exceeded 10(9) copies. With this RT-PCR, the replicative-intermediates could be detected specifically in eight of ten liver tissues, but not in any samples of serum or plasma (0/65) of patients with chronic hepatitis C. When examining the PBMCs of 46 hepatitis C patients, including 12 patients who had undergone orthotopic liver transplantation, HCV negative-strand RNA was detected in only one patient (1/46). In addition, HCV replicative intermediates were not detected in PBMCs of patients using immunosuppressive agents. It is concluded that the replication of HCV in PBMCs is very unusual.
    No preview · Article · Mar 2002 · Journal of Virological Methods
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    ABSTRACT: Studies on the in vitro hepatitis C virus (HCV) infection are hampered by the lack of an appropriate system to culture permissive cells to be continuously infected with HCV. Trypsinization required for cell passage can lead to possible temporary loss of permissiveness for infection, whereas refreshment of the medium can result in loss of infectious particles necessary for perpetuation of the infection; it is therefore very difficult to maintain a continuous HCV infection in cell cultures. A new infection method was designed and evaluated in order to prevent these unfavourable circumstances. A cell line derived from the human hepatoblastoma cell line Hep G2 was grown in the extracapillary space of a haemodialysis cartridge, in the presence of a HCV-positive inoculum, while the culture medium was recirculated through the intracapillary space, supplying the cells with nutrients and oxygen. HCV RNA could continuously be detected in the cells up to 77 days of culture. Sequence analysis of the HCV hypervariable region 1 (HVR1) revealed that 56% and 75%, respectively, of the clones obtained from the cells at day 20 and 40 after start of the infection were different from the clones obtained from the original inoculum and that certain nucleotide positions in this region were more susceptible to mutations, leading to an alteration in amino acid sequence. As none of these sequences were present in the clones from the inoculum, it is suggested that new HCV quasispecies have emerged as a result of viral replication in the hepatocytes in vitro. This system seems a valuable tool for the in vitro evaluation of antiviral drugs.
    No preview · Article · Apr 2001 · Journal of Viral Hepatitis
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    ABSTRACT: Six 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (the present cholesterol-lowering drugs known as statins), lovastatin (L), simvastatin (S), pravastatin (P), fluvastatin (F), atorvastatin (A) and cerivastatin (C) are shown to be potent inhibitors of cholesterol synthesis in human hepatocytes, the target tissue for these drugs in man. All six inhibited in the nM range (IC(50) values: 0.2-8.0 nM). As daily used cholesterol-lowering drugs they are likely coadministered with other drugs. While several cytochrome P450 (CYP) enzymes are involved in drug metabolism in the liver and thus play an important role in drug-drug interaction it was investigated which of these enzymes are influenced by the active forms of the six statins. These enzyme activities were studied in human liver microsomal preparations, and in simian and human hepatocytes in primary culture. The following CYP reactions were used: nifedipine aromatization (CYP3A4), testosterone 6beta-hydroxylation (CYP3A4), tolbutamide methylhydroxylation (CYP2C9), S-mephenytoin 4-hydroxylation (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), aniline 4-hydroxylation (CYP2E1), coumarin 7-hydroxylation (CYP2A6) and 7-ethoxyresorufin O-dealkylation (CYP1A1/2). In the human liver microsomes the statins (concentrations up to 400 microM) did not influence the CYP1A1/2 activity and hardly the CYP2A6 and CYP2E1 activities. Except P, the other five statins were stronger inhibitors of the CYP2C19 activity with IC(50) values around 200 microM and the same holds for the effect of A, C and F on the CYP2D6 activity. L and S were weaker inhibitors of the latter enzyme activity, whereas P did not influence both activities. About the same was observed for the statin effect on CYP2C9 activity, except that F was a strong inhibitor of this activity (IC(50) value: 4 microM). Using the assay of testosterone 6beta-hydroxylation the CYP3A4 activity was decreased by L, S and F with IC(50) values of about 200 microM and a little more by C and A (IC(50) around 100 microM). P had hardly an effect on this activity. To a somewhat less extent the same trend was seen when CYP3A4 activity was measured using nifedipine as substrate. The inhibitory effects observed in microsomes were verified in suspension culture of freshly isolated hepatocytes from Cynomolgus monkey (as a readily available model) and of human hepatocytes. In general the same trends were seen as in the human microsomes, except that in some cases the inhibition of the CYP activity was less, possibly by the induction of the particular CYP enzyme by incubation of the cells with a particular statin. F remained a strong inhibitor of CYP2C9 activity in human and monkey hepatocytes. A induced the CYP2C9 in monkey hepatocytes but was an inhibitor of the CYP2C9 in human hepatocytes. A, S, L and C were moderate inhibitors in both cellular systems of CYP3A4. P was not affecting any of the CYP activities in the three systems studied. It is concluded that different CYP enzymes interact with different statins and therefore differences in between these drugs are to be expected when drug-drug interaction is considered.
    No preview · Article · Jan 2001 · Biopharmaceutics & Drug Disposition

  • No preview · Article · Dec 2000 · Transplantation
  • G Basha · M Ghirardi · K Geboes · S H Yap · F Penninckx
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    ABSTRACT: Exfoliated or soiled free malignant cells have serious consequences in patients undergoing gastrointestinal cancer surgery. The present study evaluates the toxicity and efficacy of cytotoxic agents in the prevention of cell seeding and tumor growth in the peritoneal cavity in an experimental model. Mtln3 adenocarcinoma cell viability was tested in vitro using the trypan blue exclusion test after incubation with povidone-iodine or chlorhexidine. In vivo, Fischer rats were inoculated with 10(5) or 10(6) cells followed by peritoneal lavage with physiological saline, chlorhexidine 0.02 percent, povidone-iodine low molecular weight 1 percent or povidone-iodine high molecular weight 1 and 2 percent in different quantities and incubation times. Chlorhexidine 0.02 percent and povidone-iodine low molecular weight 1 percent or high molecular weight 2 percent, killed over 98 percent of 10(5) or 10(6) tumor cells in vitro. Povidone-iodine low molecular weight 1 percent and high molecular weight 2 percent were toxic and lethal when 5 ml were applied in the peritoneal cavity three times for five minutes. Chlorhexidine 0.02 percent applied after inoculation of 10(5) or 10(6) cells, reduced the tumor development only to 70 and 80 percent. Application of 5 ml povidone-iodine 1 percent low molecular weight or high molecular weight, three times for one and five minutes, after inoculation of 10(6) cells did not change the tumor take. However, inhibition of Mtln3 cells to form metastases was observed. When povidone-iodine low molecular weight 1 percent was used three times for one minute after 10(5) tumor cells were "soiled", no toxicity was observed and the tumor take was reduced to 30 percent (P < 0.05). Povidone-iodine toxicity proved to be a major issue in vivo. However, povidone-iodine low molecular weight 1 percent was safe when used for short periods and very effective when a limited number of tumor cells was inoculated. The use of cytotoxic agents to prevent recurrent disease caused by tumor cell seeding in patients seems to make sense only when the "inoculum size" of exfoliated or soiled cancer cells is limited.
    No preview · Article · Dec 2000 · Diseases of the Colon & Rectum
  • [Show abstract] [Hide abstract]
    ABSTRACT: Six 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (the present cholesterol-lowering drugs known as statins), lovastatin (L), simvastatin (S), pravastatin (P), fluvastatin (F), atorvastatin (A) and cerivastatin (C) are shown to be potent inhibitors of cholesterol synthesis in human hepatocytes, the target tissue for these drugs in man. All six inhibited in the nM range (IC50 values: 0.2–8.0 nM). As daily used cholesterol-lowering drugs they are likely coadministered with other drugs. While several cytochrome P450 (CYP) enzymes are involved in drug metabolism in the liver and thus play an important role in drug–drug interaction it was investigated which of these enzymes are influenced by the active forms of the six statins. These enzyme activities were studied in human liver microsomal preparations, and in simian and human hepatocytes in primary culture. The following CYP reactions were used: nifedipine aromatization (CYP3A4), testosterone 6β-hydroxylation (CYP3A4), tolbutamide methylhydroxylation (CYP2C9), S-mephenytoin 4-hydroxylation (CYP2C19), bufuralol 1′-hydroxylation (CYP2D6), aniline 4-hydroxylation (CYP2E1), coumarin 7-hydroxylation (CYP2A6) and 7-ethoxyresorufin O-dealkylation (CYP1A1/2). In the human liver microsomes the statins (concentrations up to 400 µM) did not influence the CYP1A1/2 activity and hardly the CYP2A6 and CYP2E1 activities. Except P, the other five statins were stronger inhibitors of the CYP2C19 activity with IC50 values around 200 µM and the same holds for the effect of A, C and F on the CYP2D6 activity. L and S were weaker inhibitors of the latter enzyme activity, whereas P did not influence both activities. About the same was observed for the statin effect on CYP2C9 activity, except that F was a strong inhibitor of this activity (IC50 value: 4 µM). Using the assay of testosterone 6β-hydroxylation the CYP3A4 activity was decreased by L, S and F with IC50 values of about 200 µM and a little more by C and A (IC50 around 100 µM). P had hardly an effect on this activity. To a somewhat less extent the same trend was seen when CYP3A4 activity was measured using nifedipine as substrate. The inhibitory effects observed in microsomes were verified in suspension culture of freshly isolated hepatocytes from Cynomolgus monkey (as a readily available model) and of human hepatocytes. In general the same trends were seen as in the human microsomes, except that in some cases the inhibition of the CYP activity was less, possibly by the induction of the particular CYP enzyme by incubation of the cells with a particular statin. F remained a strong inhibitor of CYP2C9 activity in human and monkey hepatocytes. A induced the CYP2C9 in monkey hepatocytes but was an inhibitor of the CYP2C9 in human hepatocytes. A, S, L and C were moderate inhibitors in both cellular systems of CYP3A4. P was not affecting any of the CYP activities in the three systems studied. It is concluded that different CYP enzymes interact with different statins and therefore differences in between these drugs are to be expected when drug–drug interaction is considered. Copyright © 2000 John Wiley & Sons, Ltd.
    No preview · Article · Dec 2000 · Biopharmaceutics & Drug Disposition
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    ABSTRACT: PURPOSE: Exfoliated or soiled free malignant cells have serious consequences in patients undergoing gastrointestinal cancer surgery. The present study evaluates the toxicity and efficacy of cytotoxic agents in the prevention of cell seeding and tumor growth in the peritoneal cavity in an experimental model. METHODS: Mtln3 adenocarcinoma cell viability was testedin vitro using the trypan blue exclusion test after incubation with povidone-iodine or chlorhexidine.In vivo, Fischer rats were inoculated with 105 or 106 cells followed by peritoneal lavage with physiological saline, chlorhexidine 0.02 percent, providone-iodine low molecular weight 1 percent or povidone-iodine high molecular weight 1 and 2 percent in different quantities and incubation times. RESULTS: Chlorhexidine 0.02 percent and povidone-iodine low molecular weight 1 percent or high molecular weight 2 percent, killed over 98 percent of 105 or 106 tumor cellsin vitro. Povidone-iodine low molecular weight 1 percent and high molecular weight 2 percent were toxic and lethal when 5 ml were applied in the peritoneal cavity three times for five minutes. Chlorhexidine 0.02 percent applied after inoculation of 105 or 106 cells, reduced the tumor development only to 70 and 80 percent. Application of 5 ml povidone-iodine 1 percent low molecular weightor high molecular weight, three times for one and five minutes, after inoculation of 106 cells did not change the tumor take. However, inhibition of Mtln3 cells to form metastases was observed. When povidone-iodine low molecular weight 1 percent was used three times for one minute after 105 tumor cells were soiled, no toxicity was observed and the tumor take was reduced to 30 percent (P<0.05). CONCLUSIONS: Povidone-iodine toxicity proved to be a major issuein vivo. However, povidone-iodine low molecular weight 1 percent was safe when used for short periods and very effective when a limited number of tumor cells was inoculated. The use of cytotoxic agents to prevent recurrent disease caused by tumor cell seeding in patients seems to make sense only when the inoculum size of exfoliated or soiled cancer cells is limited.
    No preview · Article · Nov 2000 · Diseases of the Colon & Rectum
  • Inge Fourneau · J Pirenne · T Roskams · S H Yap
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    ABSTRACT: A reproducible and potentially reversible model of acute liver failure in the pig is feasible based on transient ischemia of the liver. To determine the shortest period of liver ischemia sufficient to cause 100% mortality, ischemia of the liver was induced for different lengths of time, starting with 6 hours. If the pig survived, ischemia time was prolonged for 2 hours in the next animal. In the first group, the common bile duct was not tightened. In the second group, the common bile duct was tightened. The Laboratory for Hepatopathophysiology, Catholic University, Leuven, Belgium. Female stress-negative Belgian Landrace pigs weighing 18 to 22 kg. During preparatory surgery, all ligaments around the liver and connective tissue around the liver hilum were transected and an end-to-side portacaval shunt was made. Vessel loops were placed around the branches of the hepatic artery and bile duct. Three days later, in fully awake pigs, the loops were tightened. Mortality. Development of acute liver failure was determined based on neurologic, biochemical, and pathological variables. When occluded for 10 hours, all pigs in group 2 (n = 5) [corrected] died between 12 and 17 hours after the induction of ischemia. All pigs developed typical acute liver failure. Tissue specimens showed 90% necrosis of the liver parenchyma. A highly reproducible and potentially reversible model of acute liver failure in the large animal has been established.
    No preview · Article · Nov 2000 · Archives of Surgery
  • I. Fourneau · H. De Jonge · J. Pirenne · S.H. Yap

    No preview · Article · Aug 2000
  • C Verslype · S H Yap

    No preview · Article · Apr 2000 · Acta gastro-enterologica Belgica
  • S De Meyer · S H Yap

    No preview · Article · Apr 2000 · Acta gastro-enterologica Belgica
  • C Clarysse · J Fevery · S H Yap

    No preview · Article · Apr 2000 · Acta gastro-enterologica Belgica
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    ABSTRACT: Previously, we have determined that human annexin V (hAV), a Ca2+-dependent phospholipid-binding protein, and not rat AV, binds specifically to small hepatitis B surface antigen (SHBsAg), and that transfection of a rat hepatoma cell line with a construct containing the hAV gene led to hAV expression and conferred susceptibility to hepatitis B virus (HBV) infection. In this work, we have examined the effect of administration of hAV on in vitro binding of SHBsAg to human and to rat hepatocytes and on in vitro HBV infection. The results showed that hAV could bind to human as well as to rat hepatocytes. Because of this property, excess hAV was unable to prevent HBV infection in primary cultures of human hepatocytes. On the other hand, it enabled rat hepatocytes to specifically bind SHBsAg and conferred susceptibility to HBV infection. After infection of primary cultures of rat hepatocytes in the presence of hAV, HBV mRNA, covalently closed circular (ccc) DNA, replicative intermediates, hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and secreted HBV DNA were detected. After infection in the absence of hAV, no markers of HBV replication were detected. Hence, from the present study we conclude that hAV is involved in facilitating HBV entry, leading to successful HBV infection in primary cultures of rat hepatocytes, while it is not effective in preventing HBV infection in primary cultures of human hepatocytes.
    No preview · Article · Apr 2000 · Journal of Viral Hepatitis
  • B Topal · F Penninckx · S H Yap

    No preview · Article · Mar 2000 · Acta chirurgica Belgica

Publication Stats

3k Citations
775.49 Total Impact Points

Institutions

  • 1990-2005
    • Universitair Ziekenhuis Leuven
      • Department of Hepatology
      Leuven, VLG, Belgium
  • 2001
    • TNO
      Delft, South Holland, Netherlands
  • 2000
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1990-2000
    • University of Leuven
      Louvain, Flanders, Belgium
  • 1998
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 1979-1997
    • Radboud University Nijmegen
      • • Department of Gastroenterology and Hepatology
      • • Department of Surgery
      Nymegen, Gelderland, Netherlands
  • 1995
    • Cliniques Universitaires Saint-Luc
      Bruxelles, Brussels Capital, Belgium
  • 1993-1994
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
  • 1991
    • VU University Amsterdam
      • Department of Medicinal Chemistry
      Amsterdamo, North Holland, Netherlands
  • 1981-1991
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands