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Biomedical subjects

Johan Fevery

Publications and source records attributed to Johan Fevery.

32 records · Page 2Linked to original sources
PubMed2003

Low NO bioavailability in CCl4 cirrhotic rat livers might result from low NO synthesis combined with decreased superoxide dismutase activity allowing superoxide-mediated NO breakdown: A comparison of two portal hypertensive rat models with healthy controls.

BACKGROUND: In cirrhotic livers, the balance of vasoactive substances is in favour of vasoconstrictors with relatively insufficient nitric oxide. Endothelial dysfunction has been documented in cirrhotic rat livers leading to a lower activity of endothelial nitric oxide synthase but this might not be sufficient to explain the low nitric oxide presence. We compared the amount of all nitric oxide synthase isoforms and other factors that influence nitric oxide bioavailability in livers of two portal hypertensive rat models: prehepatic portal hypertension and carbon tetrachloride induced cirrhosis, in comparison with healthy controls. RESULTS: Endothelial nitric oxide synthase was the solely detected isoform by Western blotting in all livers. In cirrhotic livers, the amount of endothelial nitric oxide synthase protein was lower than in healthy controls, although an overlap existed. Levels of caveolin-1 messenger RNA were within the normal range but endothelin-1 messenger RNA levels were significantly higher in cirrhotic livers (p < 0.05). A markedly lower superoxide dismutase activity was observed in cirrhotic livers as compared to healthy controls (p < 0.05). CONCLUSIONS: In contrast to prehepatic portal hypertension, cirrhotic livers had decreased endothelial nitric oxide synthase protein and enhanced endothelin-1 messenger RNA amount. We hypothesise that a vasodilator/vasoconstrictor imbalance may be further aggravated by the reduced activity of superoxide dismutase. Decreased activity allows enhanced superoxide action, which may lead to breakdown of nitric oxide in liver sinusoids.

Journal Article↗
PubMed2003

Hepatic immunohistochemical staining with a monoclonal antibody against HCV-E2 to evaluate antiviral therapy and reinfection of liver grafts in hepatitis C viral infection.

BACKGROUND/AIMS: A simple and reproducible hepatic immunohistochemical staining (IHS) for hepatitis C virus (HCV) is not available. We aimed to validate hepatic IHS with monoclonal antibody (Mab) IG222, directed against the HCV-envelope 2 (E2) protein. METHODS: A three-step indirect immunoperoxidase method was used for frozen sections and a two-step indirect EnVision technique was used for paraffin-embedded sections. RESULTS: Naturally or in vitro HCV infected primary human hepatocytes were immunoreactive to HCV-E2. In the patient study (n=253), IHS had a sensitivity of 96% and a specificity of 91%. Six patients who showed positivity in the liver with Mab IG222, but remained anti-HCV and HCV-RNA negative, had hepatitis C-like changes in their liver biopsy. In one patient HCV-RNA could be detected in the liver biopsy. We confirmed early graft reinfection in patients transplanted for HCV-related disease (34 patients with serial biopsies). Treatment for acute cellular rejection with steroids was associated with an increase in staining intensity. In nine patients with clearance of HCV-RNA during antiviral therapy, seven achieved negativation of immunoreactivity and two a marked reduction. CONCLUSIONS: The IHS with Mab IG222 is an accurate tool for diagnosis and clinical management of chronic hepatitis C.

Animals↗
PubMed2003

Identification of HepG2 variant cell lines by short tandem repeat (STR) analysis.

In the past years, in our laboratory, several cell lines have been generated starting from a human liver (H7). Some of them have been used successfully in studies of the infection with and propagation of Hepatitis B and Hepatitis C viruses. Recently, several lines of evidence indicated that the origin of these cell lines was uncertain. Therefore, we now have determined the genetic characteristics of these cell lines in comparison to HepG2 cells received from ATCC and to HepG2 isolates grown at other laboratories. Quadruplex fluorescent short tandem repeat (STR) typing and karyotyping were performed. In addition, some biochemical characteristics of selected clones were studied. Genetically, all H7-derived cell lines were identical to HepG2 cells. However, some liver-specific functions varied between the different sub-cloned lines. The H7-derived cell lines that were generated proved to be sub-cloned lines of HepG2. The problem of cross-contamination during cloning of cell lines appears to be not uncommon. We found that two out of six HepG2 isolates obtained from other laboratories were not derived from the same individual as the original HepG2 cells. Therefore, STR typing should be applied as a rapid and sensitive technique to determine and monitor the origin of cell lines and to safeguard against contamination.

Albumins↗
PubMed2003

Steroid-free immunosuppression during and after liver transplantation--a 3-yr follow-up report.

BACKGROUND/AIMS: Steroids are traditionally used in liver transplantation as a part of a triple or quadruple immunosuppressive regimen. Steroids act non-specifically and cause multiple side-effects. Most liver transplantation centers reduce the dosage of steroids and eventually withdraw them after various time intervals. A few steroid-free trials have been recently conducted after liver transplantation but long-term data are not yet available. In addition, in these trials steroids were usually given during surgery. We report the long-term (median = 40 months) follow-up data of a prospective pilot study designed to determine whether liver transplantation could be performed with no steroids at all (neither during nor after surgery). METHODS: Twenty-one consecutive liver transplantations in 20 adult patients between August 1998 and July 1999 were prospectively included in an ab initio steroid-free immunosuppressive protocol. Mean age was 54 yr (40-67 yr). Tacrolimus (through levels, 8-10 ng/mL) and azathioprine (1-2 mg/kg) were started after liver transplantation. Patients were not given steroids during or after liver transplantation except in the event of rejection or in case of tacrolimus or azathioprine toxicity requiring significant dose reduction and/or withdrawal. RESULTS: There has been no case of primary graft dysfunction or non-function. Eleven of 21 liver transplantations (52%) received no steroids throughout the whole study. Rejection developed in five of 21 liver transplantations (23.5%). These rejections responded to standard i.v. steroids (plus ATG in one patient), followed by an oral steroid taper stopped 3 months after rejection. Steroids were transiently given in six liver transplantations for non-immune reasons: two with tacrolimus-induced neurotoxicity, three cases where azathioprine was discontinued, and one for an allergic reaction; four of these six patients are off steroids at last follow-up. The 3-yr graft and patient survival is 95 and 100%, respectively. CONCLUSIONS: Steroids are not necessary in more than 50% of liver transplantations. Steroids were transiently needed to treat acute rejection in 23.5% liver transplantations and for toxicity of calcineurin inhibitors or azathioprine or other reason in 28%. Of the patients who received steroids, the majority (70%) was eventually taken off steroids. This prospective single-center pilot study shows that liver transplantation without steroids is feasible and yields no penalty in terms of acute and chronic rejection, immune graft loss, graft function, patient and graft survival.

Azathioprine↗
PubMed2003

Detoxifying capacity and kinetics of the molecular adsorbent recycling system. Contribution of the different inbuilt filters.

The molecular adsorbent recycling system (MARS) represents a cell-free, extracorporeal, liver assistance method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the short- and long-term removal capacity and selectivity of the different inbuilt dialysers and adsorption columns (uncoated charcoal, anion exchanger resin). Levels of endogenous toxins and parameters of hepatic synthesis and necrosis were therefore monitored before, during and after the MARS treatment phase in 10 patients. Moreover, blood and dialysate clearances of urea, creatinine, bilirubin and bile acids were determined during a single treatment. The significant increasing time course of total bilirubin blood levels before the start of the treatment could be stopped and reversed in a significant decreasing time course. The removal rates of urea nitrogen, bilirubin and bile acids during a single treatment amounted to 55.5 +/- 4.0, 28.3 +/- 3.9, and 55.4 +/- 4.0% (mean +/- SEM), respectively. The efficacy of removal of albumin-bound toxins sharply declined early after initiation of the treatment to become negligible after 6 h. In conclusion, both albumin-bound and water-soluble toxins are adequately removed by the MARS. Our data suggest that the rate and efficacy of removal of albumin-bound toxins are related to both the strength of the albumin binding and the saturation of the adsorption columns.

Adult↗
PubMed2002

Aplastic anemia after transplantation for non-A, non-B, non-C fulminant hepatic failure: case report and review of the literature.

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.

Adult↗
PubMed2002

A novel strand-specific RT-PCR for detection of hepatitis C virus negative-strand RNA (replicative intermediate): evidence of absence or very low level of HCV replication in peripheral blood mononuclear cells.

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.

Hepacivirus↗
PubMed2002

Ultrastructural visualization of hepatitis C virus components in human and primate liver biopsies.

BACKGROUND/AIMS: Molecular and structural studies of hepatitis C virus (HCV) replication and infection have been performed on cultured cells and on serum of infected patients. No conclusive studies were conducted yet on human liver biopsies. This paper describes the ultrastructural findings of hepatitis C virus components in liver biopsies. METHODS: Liver specimens from acutely and chronically HCV-infected chimpanzees (five each) and 29 chronic hepatitis C patients were studied. Diagnosis of HCV infection was based on clinical, serological, light microscopic and immunohistochemical data and on HCV RNA polymerase chain reaction. RESULTS: In HCV-infected chimpanzees, tubular aggregates were observed in the cytoplasm of a significant number of hepatocytes and proven by immuno-electron microscopy to contain HCV-E2 viral envelope material. Identical tubular aggregates were seen in hepatocytes of chronic HCV-infected patients, although in smaller quantity and less frequently. A few single enveloped virus-like particles of 50-60 nm in diameter were seen for the first time in the hyaloplasm of hepatocytes of HCV-infected chimpanzees and patients. CONCLUSIONS: For the first time, HCV envelope material was ultrastructurally identified in hepatocytes of HCV-infected chimpanzees and patients. Virus-like particles, although strongly suggestive for HCV, failed final confirmation at least by routinely used methods.

Animals↗
PubMed2002

The Molecular Adsorbent Recirculating System in patients with severe liver failure: clinical results at the K.U. Leuven.

BACKGROUND: The Molecular Adsorbent Recirculating System (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in the first 13 patients with severe liver failure treated at our institution. METHODS: Patients with acute or acute on chronic liver failure of various aetiologies were treated with varying numbers of MARS sessions of six hours duration. RESULTS: Mean APACHE II score was 18. In general, patients with multiple organ failure faired poorly even with MARS treatment. Five patients (38%) survived the hospitalisation. Eight patients (62%) fulfilled criteria for UNOS type I or 2 A status. Two of these patients survived. Five patients had a UNOS 2B status and three survived. In proportion, patients with severe itch, patients with primary non-function and those where MARS was used as a bridge to transplantation seemed to profit most from the treatment. The median reduction in bilirubin concentrations after the treatment period was -28.2%. In survivors, the median reduction was -37.7% and in patients who died was -15.9%. The median encephalopathy score improved from 1.7 to 0.5. CONCLUSION: The molecular adsorbent recycling system (MARS) might be lifesaving in patients with severe liver failure of different aetiologies.

Adult↗
PubMed2002

Improvement of autoimmune hepatitis during pregnancy followed by flare-up after delivery.

OBJECTIVES: Pregnancy in autoimmune hepatitis has been a rare event, but it has become more frequent with improved therapy. The present study aimed to analyze the consequences for mother and child in patients with autoimmune hepatitis. METHODS: Fourteen pregnancies have been followed in five patients with autoimmune chronic hepatitis (AIH) and in one with autoimmune sclerosing cholangitis (overlap AIH-PSC). RESULTS: Features of AIH improved markedly from the second trimester of pregnancy onward, allowing a decrease in immunosuppressive therapy. After delivery (or stillbirth in one patient), the activity of the autoimmune disease flared up rapidly in 12 of 14 events. CONCLUSIONS: Pregnancy induces a state of immune tolerance with improvement of the liver tests in AIH. This could result from a transition of TH1 to TH2 predominance during pregnancy. A flare-up often occurs after delivery. Preemptive increase of the immunosuppressive therapy is therefore advocated consecutive to delivery. Azathioprine use seems to be safe during pregnancy.

Adolescent↗
PubMed2002

TTV infection and its relation to serum transaminases in apparently healthy blood donors and in patients with clotting disorders who have been investigated previously for hepatitis C virus and GBV-C/HGV infection in Belgium.

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.

Adolescent↗
PubMedDate not supplied

Primary human hepatocytes are protected against prolonged and repeated exposure to ethanol by silibinin-dihemisuccinate.

AIMS AND METHODS: We investigated the effect of silibinin-C-2',3'-dihydrogensuccinate (SDH) on primary human hepatocytes when exposed to ethanol for 14 days. At regular intervals, the medium was refreshed and liver enzymes and secreted protein in the medium were determined. RESULTS: The ethanol-induced release of lactate dehydrogenase (at 34 mM ethanol) was completely blocked by 20 microM SDH. SDH itself stimulated fibrinogen release and had no toxic effect. CONCLUSIONS: We can conclude that SDH has a beneficial effect on human hepatocytes when exposed to ethanol in vitro.

Adolescent↗
PubMedDate not supplied

TT virus infection in acute and chronic liver diseases and in patients regularly receiving blood products in Belgium.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Acute Disease↗