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Biomedical subjects

R Poupon

Publications and source records attributed to R Poupon.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Hemorrhagic ascites disclosing massive Fasciola hepatica infection].

Multi-organ infection with Fasciola hepatica is uncommon. We report a case of severe infection with Fasciola hepatica as a cause of liver and peritoneum injuries with hemorrhagic ascites as well as pulmonary, pericardial, splenic and portal system injuries in a 37-year old man who was a native of Green Cape. The patient was in poor general health, had a major inflammatory syndrome, and polyclonal hypergammaglobulinemia (90 g/L). The diagnosis was confirmed by positive distomatosis serology and the presence of eggs of Fasciola hepatica in the histological samples of the liver and peritoneum. After treatment with praziquantel then triclabendazole, the global outcome was favorable.

Adult↗
PubMed1996

Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis.

Between 10% and 42% of patients with primary biliary cirrhosis (PBC) have been reported to have autoantibodies directed against a restricted epitope of gp210, a glycoprotein of the nuclear pore membrane. The prevalence and specificity of these antibodies was studied in a French series of 285 patients with PBC and 497 control individuals affected with other liver or autoimmune diseases. Sera were analyzed by an enzyme-linked immunosorbent assay (ELISA) that used a synthetic polypeptide containing the predominant autoepitope of gp210, in parallel to immunoblotting of gp210 protein and immunofluorescence microscopy. Autoantibodies to the gp210 epitope detected by ELISA were 25.5% sensitive and 99.5% specific for the diagnosis of PBC. These results were in agreement with a 99.4% specificity with immunoblotting analysis and a 96.6% specificity with immunofluorescence. In a subset of PBC patients without detectable antimitochondrial autoantibodies (AMA), gp210 autoantibodies were found in 7 of 15 patients (47%). Therefore, gp210 autoantibodies are highly specific for PBC and may be of particular utility in assessing patients without AMA or with other atypical presentations.

Amino Acid Sequence↗
PubMed1996

A randomized trial comparing colchicine and ursodeoxycholic acid combination to ursodeoxycholic acid in primary biliary cirrhosis. UDCA-PBC Study Group.

The efficacy of colchicine combined with ursodeoxycholic acid (UDCA) and UDCA alone in the treatment of patients with nonadvanced primary biliary cirrhosis (PBC) was evaluated in a 2-year controlled study. Seventy-four patients with PBC who had been treated previously with UDCA (at least 8 months) but still had abnormal liver test results, especially elevated alkaline phosphatase activity, were randomized to be administered colchicine (1 mg/d, 5 days per week) (n = 37) or a placebo (n = 37). In addition, the patients were treated with UDCA (13-15 mg x kg(-1) x day(-1)). The patients underwent clinical examination and liver tests every 6 months and upper endoscopy and liver biopsy at entry and at 2 years. Procollagen type III aminoterminal peptide (PIIINP), hyaluronic acid, and sulfobromophthalein (BSP) elimination kinetics were determined at entry and after 2 years. After 2 years of treatment, relative to UDCA, colchicine combined with UDCA did not significantly improve symptoms, laboratory findings (serum bilirubin level, alkaline phosphatase and alanine transaminase [ALT] activities, immunoglobulin [Ig] M level), serum markers of fibrosis, or histological features, except lobular inflammation. Colchicine did tend to slightly reduce the progression of esophageal varices; however, the difference was not significant. BSP elimination kinetics (45-minute retention percentage) was significantly improved when treated with colchicine. During the 2-year study, the only clinical complications were variceal bleeding in one patient administered colchicine and two administered the placebo. Two patients died from nonliver causes. One severe adverse effect (peripheral neuromyopathy) was observed in a colchicine-treated patient. In conclusion, this study suggests that colchicine appears to provide a slight advantage relative to UDCA alone in patients with nonadvanced PBC.

Adult↗
PubMed1996

Ileal absorption of bile acids in patients with chronic cholestasis: SeHCAT test results and effect of ursodeoxycholic acid (UDCA).

The effect of cholestasis on ileal bile acid absorption is controversial in animal models (up- or down-regulation) and unknown in humans. We therefore studied values of the selena homotaurocholic acid (SeHCAT) test before and after long-term administration (>3 months, 13-15 mg/kg/day) of ursodeoxycholic acid (UDCA) in 27 patients with chronic cholestatic liver diseases (24 women, 3 men; mean age, 50 years; 24 primary biliary cirrhosis, 2 secondary biliary cirrhosis, 2 others). The control group consisted of 14 healthy volunteers. Seven-day SeHCAT percentage retention was identical in the 12 untreated cholestatic patients (serum bilirubin, 75+/-42 micromol/L, alkaline phosphatase, 4.2+/-1.0 N; mean+/-SEM) and in the control group (43.6+/-2.9 and 43.8+/-4.2%, respectively). In the 22 patients treated by UDCA for 38+/-8 months, SeHCAT percentage retention was 20.3+/-3.0%. In the seven patients with the SeHCAT test done before and after UDCA treatment (16+/-5 months), SeHCAT percentage retention decreased significantly under UDCA therapy (42.0+/-4.4 vs 19.4+/-4.1%; P < 0.02). We conclude that, in patients with chronic cholestasis (1) SeHCAT percentage retention is not altered-taken together with the known defect of biliary excretion, this lack of increase in SeHCAT percentage retention argues against up-regulation of bile acid ileal transport; and (2) UDCA treatment induces a decrease in the SeHCAT percentage retention-this effect may be related primarily to a decreased bile acid ileal absorption.

Alkaline Phosphatase↗
PubMed1996

Immunosuppressive effects of endotoxins and bile acids in vivo in the rat.

Cell-mediated immunity is impaired during cholestasis. The aim of this study was to evaluate in vivo the effects on this immune defect of high serum levels of endotoxin and bile acids. Heterotopic cardiac allotransplantations were performed in the DA/Lewis rat combination. Cholestasis, induced by ligation/section of the common bile duct, was responsible for a significant delay in the rejection time (16 +/- 0.5 vs. 7.1 +/- 0.4 days in controls, P < 0.01). Elimination of Gram-negative intestinal bacteria from cholestatic rats by a vancocin/colimycin/tobramycin (VCT) mixture induced a significant reduction in endotoxin levels and a reduction in rejection times (9.5 +/- 1.0 days, P < 0.01) that remained, however, significantly longer than those of controls (P < 0.05). Oral administration of chenodeoxycholic acid in non-cholestatic rats significantly enhanced the serum concentration of total bile acids (60.6 +/- 15.3 mumol L(-1) vs. 17.4 +/- 1.9 mol L(-1) in controls, P < 0.01) and postponed allograft rejection (10.7 +/- 0.6 days, P < 0.01 vs. controls). These data suggest that increased endotoxin level and serum bile acid concentration may play a role in the immunosuppressive effect of cholestasis.

Animals↗
PubMed1996

Interferon alfa therapy in patients with chronic hepatitis C and persistently normal aminotransferase activity.

BACKGROUND & AIMS: Chronic hepatitis C virus carriers may have repeatedly normal aminotransferase activity despite detectable viremia and histological hepatitis. The aim of this study was to determine the effect of interferon in this population. METHODS: Three million units of interferon alfa was administered 3 times weekly for 6 months in 10 patients with chronic hepatitis C virus infection, repeatedly normal alanine aminotransferase activity, and chronic hepatitis on liver biopsy. Serum hepatitis C virus RNA was detected by polymerase chain reaction and quantified by branched DNA before, at the end, and 1 year after treatment. A liver biopsy was performed 1 year after treatment withdrawal. RESULTS: At treatment withdrawal, hepatitis C virus RNA levels had significantly decreased, but RNA was still detectable by polymerase chain reaction in 8 of 10 patients. During the 1-year follow-up period, 6 of 9 patients had elevated aminotransferase activity on at least one occasion. One year after treatment withdrawal, RNA levels had returned to pretreatment values and no significant histological improvement was observed in the 7 patients who underwent liver biopsy. CONCLUSIONS: In patients with chronic hepatitis C and repeatedly normal aminotransferase activity, standard interferon therapy does not lead to sustained virological or histological responses despite a transient effect on hepatitis C virus replication.

Adult↗
PubMed1996

Antineutrophil cytoplasmic autoantibodies in autoimmune liver and inflammatory bowel diseases.

Perinuclear antineutrophil cytoplasmic autoantibodies have been described in inflammatory bowel diseases and in primary sclerosing cholangitis. Because the data concerning their occurrence are conflicting, we have used indirect immunofluorescence on ethanol-fixed neutrophils to test the sera from a large population of 382 patients with various liver and digestive diseases: in particular, from 27 patients with primary sclerosing cholangitis, 105 patients with autoimmune chronic active hepatitis, 30 patients with primary biliary cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative colitis and 15% in Crohn's disease. They would not be helpful in the differential diagnosis between these two inflammatory bowel diseases. Within the group of autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies were detected in 44% of sera from patients with primary sclerosing cholangitis and in 36% of sera from patients with type I autoimmune active hepatitis, but not in primary biliary cirrhosis. When primary sclerosing cholangitis was associated with an inflammatory bowel disease, the prevalence of these autoantibodies was 60%. They were 88% specific for primary sclerosing cholangitis and 86% specific for type I autoimmune active hepatitis. Despite their moderate sensitivity and specificity in primary sclerosing cholangitis, they remain the only serologic marker of this autoimmune liver disease. Moreover, they turned out to be a more sensitive marker for inflammatory bowel disease with associated primary sclerosing cholangitis.

Adolescent↗
PubMed1996

Antimitochondrial antibodies in patients with chronic hepatitis C.

Although autoantibodies have been found in the serum of patients with chronic hepatitis C virus (HCV) there has been no convincing evidence of the presence of antimitochondrial antibodies, until now. Sera from 460 untreated patients with chronic hepatitis C were tested for antimitochondrial antibodies, using an indirect immunofluorescence technique; and if they tested positive for the antibodies (titer more than 1:50), they also were treated by Western blot analysis. Seven (1.5%) sera were positive. None of the patients had biological or histological evidence of primary biliary cirrhosis. Antimitochondrial antibodies recognized one of the oxo-dehydrogenase multienzyme complexe's epitopes by Western blot assay in three patients only. All seven patients were then treated by interferon alpha for six months. None showed exacerbation of liver disease during treatment. HCV-RNA disappeared from the serum in one patient who became negative for anti-M2 antibodies. The four patients who did not respond to interferon-alpha therapy, and the two who relapsed after treatment withdrawal, had sustained positive antimitochondrial antibodies. These data suggest that: 1) antimitochondrial antibodies present in patients with chronic hepatitis C do not always recognize the same epitopes as in primary biliary cirrhosis; 2) these antibodies may disappear after eradication of HCV, suggesting that the production of antimitochondrial antibodies is linked to the presence of the virus and 3) the clinical and biological course of chronic hepatitis C, and the response to interferon-alpha therapy, does not seem to be different in patients who are positive for antimitochondrial antibodies.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1996

Serum levels of endothelial injury markers creatine kinase-BB and soluble thrombomodulin during human liver transplantation.

Endothelial damage within the sinusoids of the liver probably plays a key role in primary liver dysfunction following transplantation. The aim of this work was to study the serum levels of two potential markers of endothelial damage, creatine kinase-BB and soluble thrombomodulin, during human graft revascularization. Thirteen human liver grafts were preserved in UW solution (mean time: 13.8 h). Creatine kinase-BB and transaminase activities and soluble thrombomodulin levels were measured: 1) in effluent and 2) in serum samples sequentially collected before revascularization, then during the first 120 min of revascularization and first post-operative week. No correlation was observed between serum values (peak) and effluent values. In serum, pre-operative creatine kinase-BB activities were correlated with soluble thrombomodulin levels (p = 0.01). Both increased significantly during the first minutes of the revascularization, then decreased markedly. In contrast, AST activity was maximal at day 1. This detectable and early release of creatine kinase-BB and soluble thrombomodulin in blood is in keeping with the early occurence of endothelial damage. Together with previous data, these findings suggest that serum determination of these two markers may be a useful tool in the assessment of endothelial injury in liver transplantation.

Alanine Transaminase↗
PubMed1996

Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis.

Diagnostic accuracy of two serum markers of liver fibrosis, hyaluronan (HA) and amino-terminal peptide of type III procollagen (P-III-P), was studied in a cohort of 326 untreated patients with chronic viral hepatitis C. Both P-III-P (RIA-gnost P-III-P, Behring Diagnostic) and HA (HA-test, Pharmacia) serum concentrations correlated with the histological grades of liver fibrosis (P < 0.001). Receiver-operating characteristic (ROC) curves showed that serum HA had greater diagnostic performance than P-III-P, both for discriminating patients with extensive liver fibrosis from those with no or mild fibrosis (area under the ROC curves: 0.864 vs 0.691, P <0.001) or for discriminating patients with cirrhosis from those without cirrhosis (area under the ROC curves: 0.924 vs 0.734, P <0.001). At cutoff values of 0.8 kU/L for serum P-III-P and 85 micrograms/L for serum HA, sensitivities were 70.0% and 64.5%, and specificities were 63.4% and 91.2%, respectively, for discriminating patients with extensive liver fibrosis from those with no or mild fibrosis. At the cutoff values of 1.0 kU/L for serum P-III-P and 110 micrograms/L for serum HA, sensitivities were 60.0% and 79.2%, and specificities were 74.0% and 89.4%, respectively, for discriminating patients with liver cirrhosis from those without cirrhosis. We conclude that, because the diagnostic accuracy of serum HA is greater than that of serum P-III-P as a marker of liver fibrosis, serum HA should be preferred when monitoring liver fibrosis in patients with chronic viral hepatitis C.

Adult↗
PubMed1995

Effect of cholestasis and bile acids on interferon-induced 2',5'-adenylate synthetase and NK cell activities.

BACKGROUND/AIMS: The mechanisms involved in resistance to interferon alfa in patients with chronic hepatitis C are unclear. Both cirrhosis and cholestasis have been shown to be predictive of resistance. The aim of this study was to evaluate the influence of cholestasis and bile acids on 2',5'-oligoadenylate synthetase and natural killer activities, which are both involved in the antiviral activity of interferon. METHODS: 2',5'-Oligoadenylate synthetase activity was evaluated in spleen, liver, and isolated hepatocytes from bile duct-ligated rats, and the effect of bile acids in vitro on interferon-induced 2',5'-oligoadenylate synthetase and natural killer activities was examined in fresh mononuclear cells from healthy subjects. RESULTS: Cholestasis had a time-dependent inhibitory effect on 2',5'-oligoadenylate synthetase activity in liver, spleen, and isolated hepatocytes from cholestatic rats (-70%, 86%, and 70% relative to baseline, respectively). In vitro, endogenous bile acids had a concentration-dependent inhibitory effect on interferon-induced 2',5'-oligoadenylate synthetase and natural killer activities, which was related to their structure. This inhibitory effect correlated with the surface activity index. CONCLUSIONS: Cholestasis and bile acids diminish the biological activity of interferon and natural killer activity. The results suggest a decrease in the antiviral defenses in cholestatic conditions.

2',5'-Oligoadenylate Synthetase↗
PubMed1995

Ursodeoxycholic acid therapy of chronic cholestatic conditions in adults and children.

Cholestasis can be defined as the manifestation of defective bile acid transport from the liver to the intestine. Most chronic cholestatic conditions can progress towards cirrhosis. At this stage, liver transplantation is the treatment of choice. Most of the drugs so far evaluated show some degree of efficacy but have major side effects. Given that ursodeoxycholic acid (UDCA) has no apparent toxicity in humans, it was postulated that long-term treatment with this drug might displace endogenous bile acids and thus reverse their suspected toxicity. We demonstrated that long-term UDCA therapy slows the progression of primary biliary cirrhosis and reduces the need for liver transplantation. In this review, we give the rationale for the use of UDCA in cholestasis and discuss its possible mechanisms of action. We also give an overview of current data on UDCA therapy of chronic cholestatic disorders in adults and children.

Adult↗
PubMed1995

Serum hyaluronan as a marker of liver fibrosis in chronic viral hepatitis C: effect of alpha-interferon therapy.

BACKGROUND/AIMS: It has been suggested that increases in serum hyaluronan levels might be a marker of fibrosis in chronic viral hepatitis C. Patients receiving alpha-interferon therapy are an excellent model to determine the relationship between serum hyaluronan and liver fibrosis, since results suggest that alpha-interferon could reduce liver fibrosis. METHODS: We studied the relationship between serum hyaluronan and histopathological indices of liver fibrosis, inflammation and necrosis, before and after alpha-interferon therapy (3 MU, three times weekly for 6 months), and the effect of treatment on serum hyaluronan and on histological liver fibrosis, in 52 patients. Hyaluronan levels were measured using a radiometric assay and the liver histopathological indices were scored according to the Knodell system. RESULTS: The serum hyaluronan level correlated with the extent of liver fibrosis both before and after alpha-interferon therapy (p < 0.0001), but not with the histopathological indices of liver inflammation or necrosis. Parallel changes in serum hyaluronan and liver fibrosis occurred: serum hyaluronan levels fell significantly in patients in whom fibrosis improved (p < 0.01, n = 11), increased significantly in patients in whom fibrosis worsened (p < 0.05, n = 10), and did not change significantly in patients in whom fibrosis was unmodified (n = 31). Furthermore, fibrosis improved only when the antiviral effect of alpha-interferon was reflected by persistent normalization of serum alanine aminotransferase, although there was no correlation between serum hyaluronan levels and alanine aminotransferase activities. CONCLUSION: Serum hyaluronan thus appears to be a non-invasive index of liver fibrosis.

Adult↗