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Biomedical subjects

T Poynard

Publications and source records attributed to T Poynard.

At least 127 records · Page 7Linked to original sources
PubMed1997

Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. METAVIR and CLINIVIR Cooperative Study Groups.

The aim of this study was to identify clinical and biological factors associated with histological lesions in patients with chronic hepatitis C and to construct a simple diagnostic index. A database consisting of 500 patients with untreated biopsy-proven chronic non-A non-B hepatitis was used. Liver biopsies were reviewed, blind, by a panel of pathologists. Patients were classified according to the presence of necroinflammatory lesions (histological activity) and fibrosis. The diagnostic value of nine clinical and 10 biological factors was assessed using logistic regression analysis, sensitivity, specificity and predictive values, and a score was constructed combining the most significant factors identified. The validation used an independent population of 120 patients. Serum platelet concentration and age were the two main factors significantly and independently correlated with the presence of fibrosis and/or histological activity. A simple score referred to as AP, combining age and platelet count, varied from 0-10. For the presence of significant histological disease (moderate to severe necroinflammatory lesions and/or septal fibrosis to cirrhosis), an AP score of 6 or more had a specificity of 0.93 and a sensitivity of 0.52%. In the validation population, the area under the curve was 0.690 +/- 0.085, not significantly different from that of the first population, 0.763 +/- 0.043. Hence, a simple score combining age and platelet count enabled the accurate prediction of the presence of activity and fibrosis in patients infected with the hepatitis C virus. When this score reached 6, liver biopsy could be avoided owing to its high predictive value. However, the negative predictive value was not high enough to prevent a liver biopsy in patients with a lower score.

Adult↗
PubMed1997

Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in patients with cirrhosis: a meta-analysis.

A meta-analysis of 12 selected randomized trials was performed to assess the efficacy of beta-blockers in the prevention of rebleeding and the effect on long-term survival in patients with cirrhosis. Five end points were assessed: rebleeding, variceal rebleeding, death, death from bleeding, and adverse events. Analyses were performed according to the intention-to-treat method. For each end point, heterogeneity and treatment efficacy were assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to treatment duration, cause of initial bleeding, use of placebo, type of beta-blocker, type of publication, certainty of randomization, severity of cirrhosis, interval between index bleed and randomization, and methodological quality. Beta-blockers significantly increased the mean percentage of patients free of rebleeding (21% mean improvement rate, CI 95%: 10%-32%, P < .001, relative risk 1.42), the mean percentage of patients free of variceal rebleeding (20% mean improvement rate, CI 95%: 11%-28%, P < .001), the mean survival rate (5.4% mean improvement rate, CI 95%: 0%-11%, P = .05, relative risk 1.27), the mean percentage of patients free of bleeding death (7.4%, CI 95%: 2%-13%, P < .01, relative risk 1.50). Five patients would need to be treated with beta-blockers to prevent one rebleeding episode, 14 treated to prevent one death, and 13 treated to prevent one death from bleeding. There was no significant heterogeneity among studies by both methods of analysis. In patients with esophageal varices, beta-blockers significantly increase the mean percentage of patients free of rebleeding and the mean survival rate at 2 years.

Adrenergic beta-Antagonists↗
PubMed1997

In situ detection of lipid peroxidation by-products in chronic liver diseases.

Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. The deleterious consequences of this mechanism are related in part to the formation of reactive aldehydic products that bind to intra- or extracellular molecules to form adducts. Specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, allowed us to investigate in situ, with an immunohistochemical procedure, the occurrence of lipid peroxidation in a panel of different chronic liver diseases. Intracellular HNE and MDA adducts were detected respectively in 24 of 39 cases (62%) and in 12 of 34 cases investigated (35%). They were localized mainly in the cytoplasm of hepatocytes, with the strongest staining observed in hemochromatosis, Wilson's disease, and in areas of acute alcoholic hepatitis in cases of alcoholic liver diseases. A peculiar pattern of immunostaining was observed in primary biliary cirrhosis where biliary cells of destroyed but also intact bile ducts strongly expressed HNE adducts. The liver extracellular matrix also displayed MDA adducts (30 of 34 cases, 88%) and HNE adducts (23 of 39 cases, 59%). While HNE adducts were specifically localized on large bundles of collagen fibers, MDA adducts were detected in a thin reticular network and in sinusoidal cells around portal tracts or fibrous septa. In conclusion, lipid peroxidation by-products are detectable in chronic liver diseases. Immunohistochemical results suggest that this mechanism is implicated very early in the pathogenesis of some of these diseases.

Adolescent↗
PubMed1997

In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features.

AIMS: To assess the occurrence of lipid peroxidation in chronic hepatitis C and to evaluate its relation to pathological features and liver iron concentrations. METHODS: Liver biopsy samples of 43 patients with untreated chronic hepatitis C were studied by immunohistochemistry using specific antibodies directed against two major aldehyde metabolites of lipid peroxidation, malondialdehyde (MDA), and 4-hydroxynonenal (HNE). RESULTS: MDA and HNE adducts (aldehydes covalently linked to another molecule) were detected in the liver samples in 77% and 30% of cases, respectively. MDA adducts were detected both in the extracellular matrix and sinusoidal cells localised in areas of periportal and lobular necrosis. HNE adducts appeared in the cytoplasm of only a few hepatocytes. Comparison of the semiquantitative assessment of adducts (MDA and HNE indexes) with the grading and the staging of chronic hepatitis showed that the MDA index was correlated with fibrosis score (p < 0.001) and the grade of activity (p < 0.01). There was also a tendency to correlation with liver iron concentration (p = 0.09). No correlation was observed between the HNE index and pathological features or liver iron concentration. CONCLUSION: Lipid peroxidation products are detectable in the liver of chronic hepatitis C patients. The presence of MDA adducts in areas of active fibrogenesis and the correlation between the MDA index and fibrosis score suggest a role for lipid peroxidation in liver fibrosis.

Adult↗
PubMed1997

[Influence of anemia on hemodynamic changes in patients with cirrhosis].

OBJECTIVE: The aim of this retrospective study was to evaluate the systemic and splanchnic hemodynamic changes induced by anemia in patients with cirrhosis. METHOD: 148 patients (Child-Pugh A: 46 patients, Child-Pugh B: 64 patients and Child-Pugh C: 38 patients) were included in the study. Anemia was defined by a blood hemoglobin level < 12 g/dL. A systemic and splanchnic hemodynamic study was performed in all patients. RESULTS: A significant elevation of the hepatic venous pressure gradient was observed in Child-Pugh A patients with anemia but not in Child-Pugh B and C patients. In the 2 latter groups, cardiac index was significantly increased and systemic vascular resistance decreased in patients with anemia. CONCLUSION: Anemia may worsen the hemodynamic changes associated with cirrhosis.

Adult↗
PubMed1997

[Recurrent lower digestive hemorrhage in young adults: a surgical indication].

The cause of low digestive bleeding remains unknown despite numerous investigations in less than 15% of cases. The case of a 22-year-old young female who presented 3 episodes of low digestive bleeding during a 25 months period, without any cause identified despite numerous investigations, is presented. Laparoscopy performed to establish a diagnosis showed a large Meckel's diverticulum which was removed. In adults, Meckel's diverticulum causes uncommonly symptoms and are revealed by an episode of digestive bleeding in less than 10% of cases. After several episodes of low digestive bleeding, a surgical procedure can be proposed, by coelioscopy better than laparotomy, to look for Meckel's diverticulum. This observation shows that this attitude, recommended in children, can be proposed also in young adults.

Adult↗
PubMed1997

[Evaluation by a randomized trial of the usefulness of endoscopy after treatment of a flare-up of non-severe esophagitis].

OBJECTIVES: The clinical usefulness of esophageal endoscopy at the end of a treatment of non-severe esophagitis due to gastro-esophageal reflux is unknown. The aim of this randomized trial was to compare two strategies for the management of non-severe esophagitis, one with endoscopy at the end of the initial treatment including a retreatment of persistent ulcerations (group 1) and one without final endoscopy (group 2). PATIENTS AND METHODS: Eligible patients had heartburn and endoscopically proved esophagitis, non-confluent or confluent erosions and must have been relieved of their heartburn after a 4 to 6 week treatment with H2 blockers or by proton pump inhibitor. When the ulcerations were healed in group 1 and immediately at the end of the initial treatment in group 2, a self-care treatment by sodium alginate was prescribed. A total of 369 patients were randomized, 178 in group 1, 191 in group 2. RESULTS: At 6 months, there was no difference in the percentage of patients with clinical and endoscopical success, 52% and 55% in group 1 versus 47% and 60% in group 2 respectively. In group 1, 29 patients (16%) needed another treatment than alginate versus 31 patients in group 2 (16%, NS). Among patients with endoscopy at 6 months, the percentage of patients with confluent erosions was 4% (5/140) and with non-confluent erosion 26% (37/140) in group 1 versus 6% (9/158) and 22% (34/158) in group 2 respectively (NS). The percentage of patients with at least one sick day related to reflux was 12% in group 1 versus 5% in group 2 (P = 0.03). There was no difference in pharmacy costs (331,40 vs 264,3 Francs). CONCLUSION: Endoscopic verification is not necessary in patients with non-severe esophagitis who have been clinically improved by an initial treatment by H2 blockers or proton pump inhibitor, even among patients with confluent esophageal erosions.

Adult↗
PubMed1997

Anticardiolipin, anti-beta2-glycoprotein I, and antinucleosome antibodies in hepatitis C virus infection and mixed cryoglobulinemia. Multivirc Group.

OBJECTIVE: To investigate anticardiolipin antibodies (aCL), anti-beta2-glycoprotein I (anti-beta2GPI), and antinucleosome antibodies in patients with hepatitis C virus (HCV) with or without mixed cryoglobulinemia. aCL can appear in infectious diseases, but are not then associated with thrombotic events. Antibodies directed to beta2GPI, a co-factor of aCL, have been said to be associated with the presence of "autoimmune" aCL. About 50% of cases of essential mixed cryoglobulinemia are associated with HCV infection. High prevalence of autoantibodies directed to nuclear antigens has been found in HCV infection but the prevalence of antibody to nucleosome has not yet been reported. METHODS: Group 1: 29 patients with chronic HCV infection and mixed cryoglobulinemia. Group 2: 17 patients with chronic HCV infection but without mixed cryoglobulinemia. To analyze the possible effect of mixed cryoglobulinemia itself on aCL production, we also studied 22 patients with essential mixed cryoglobulinemia and no HCV infection (Group 3). In addition, 96 healthy blood donors were used as a control group (Group 4). Mixed cryoglobulinemia was detected by immunofixation. Anti-HCV antibodies were detected by 3rd generation tests, aCL, anti-beta2GPI, and antinucleosorne antibodies were detected by ELISA. In patients with mixed cryoglobulinemia, we also looked for aCL separately in cryoprecipitate and in serum after extraction of mixed cryoglobulins to investigate a possible "capture" of aCL in the cryoprecipitate. RESULTS: IgG aCL were more frequently found in patients with HCV than in controls [9/46 (20%) vs 2/96 (2%); p < 0.001]. The prevalence of aCL was similar in patients with HCV with or without mixed cryoglobulinemia (6/29 vs 3/17; p = NS). No patient with positive aCL had anti-beta2GPI, antinucleosome antibodies, thrombotic events, or thrombocytopenia. IgG aCL were more frequent in patients with mixed cryoglobulinemia, whatever their status for HCV infection, than in subjects without mixed cryoglobulinemia [8/51 (16%) vs 5/113 (4%); p < 0.02]. The prevalence of aCL was similar in patients with type II or type III mixed cryoglobulinemia. When we looked for aCL separately in serum and in cryoprecipitate, we did not find aCL in cryoprecipitate. In patients with HCV, the prevalence of aCL was not different whether patients were treated or not with interferon alpha. CONCLUSION: IgG aCL are frequently found in patients with HCV regardless of status for mixed cryoglobulinemia. These aCL have the characteristics of infection related aCL: low titer, absence of thrombotic events, and absence of anti-beta2GPI. The high proportion of aCL in patients with mixed cryoglobulinemia compared to those without, and the absence of antinucleosome antibodies, suggest that these aCL may be secondary to endothelial damage induced by mixed cryoglobulinemia or HCV itself, rather than to nonspecific polyclonal lymphocyte activation.

Antibodies, Anticardiolipin↗
PubMed1997

Acute hepatitis during hypersensitivity syndrome due to midecamycin.

We report here the first case of symptomatic acute hepatic injury due to midecamycin in a 58-year-old man. The clinical picture was compatible with a hypersensitivity syndrome with cutaneous, renal and hepatic involvement. Liver eosinophil polynuclear infiltrate, hypereosinophilia and acute interstitial nephritis were consistent with the hypothesis of an immunoallergic mechanism.

Acute Disease↗
PubMed1996

Effects of lamivudine on replication of hepatitis B virus in HIV-infected men.

BACKGROUND: Therapy for hepatitis B virus (HBV) infection is still unsatisfactory, particularly in patients who are co-infected with the human immunodeficiency virus (HIV). Lamivudine, a retroviral inhibitor, has been shown to have activity against HBV replication in vitro, in animal models, and in studies of immunocompetent persons. OBJECTIVE: To assess the efficacy of lamivudine in inhibiting HBV replication during a 12-month period in patients with both HBV and HIV infection. DESIGN: Prospective, open study. SETTING: University hospital. PATIENTS: 40 consecutive patients (39 men and 1 woman) infected with both HIV and HBV. All had progressive HIV disease; were refractory to or unable to tolerate therapies other than lamivudine; and received lamlvudine, 600 mg/d or 600 mg/d followed by 300 mg/d, as therapy for HIV disease. MEASUREMENTS: Serum concentrations of HBV DNA were assessed every 2 months by using molecular hybridization. Polymerase chain reaction (PCR) for HBV DNA was done at baseline and was done at months 2, 6, and 12 only if the HBV DNA concentration was less than 5 pg/mL. RESULTS: Two groups were retrospectively identified at baseline: patients with high HBV replication (serum HBV DNA concentrations > 5 pg/mL) (n = 30) and patients with low HBV replication (serum HBV DNA concentrations < 5 pg/mL) (n = 10). After 12 months of treatment, 26 of 27 patients (96.3% [95% Cl, 81% to 99.9%]) who had had high HBV replication at baseline had serum HBV DNA concentrations less than 5 pg/mL. However, PCR could still detect HBV DNA in serum in 11.5% (Cl, 2% to 30%) of these patients. Among patients who had had low HBV replication at baseline, the results of PCR for serum HBV DNA became negative in the 6 patients who had had a positive result on PCR at baseline. No serious adverse events occurred during treatment. CONCLUSION: Although this study was not a randomized, blinded trial, it suggests that lamivudine is active against.

AIDS-Related Opportunistic Infections↗
PubMed1996

Quantification of apolipoprotein A-I and B messenger RNA in heavy drinkers according to liver disease.

It has previously been shown that, in heavy drinkers, serum apolipoprotein A-I (ApoA-I) levels are closely related to the degree of liver injury: they are at a maximum in patients with steatosis, begin to decrease in patients with fibrosis, and reach a minimum in patients with severe cirrhosis. In contrast with serum ApoA-I variations, serum apolipoprotein B (ApoB) levels are stable. The assessment of messenger RNA (mRNA) levels of ApoA-I and ApoB using a quantitative competitive polymerase chain reaction (PCR) method was performed in 18 alcoholic patients: 8 with normal livers or steatosis (group I), 6 with fibrosis or nonsevere cirrhosis (group II), and 4 with severe cirrhosis (group III). For ApoA-I, group I had higher serum levels (208.4 +/- 37.6 mg/dL mean +/- SE) and mRNA levels (0.51 +/- 0.12) than group II (serum 116 +/- 19 mg/dL, P < .01, mRNA 0.40 +/- 0.11, P < .09) or group III (serum 56.5 +/- 28.6 mg/dL, P < .01, mRNA 0.27 +/- .02, P = .008). For ApoB, the three groups had similar serum ApoB levels: 129.9 +/- 37.7, 121 +/- 51, 120.7 +/- 57.4 mg/dL. Group I presented higher levels of ApoB mRNA than those of group III (0.68 +/- 0.21 vs. 0.41 +/- 0.18, P < .06). There was a significant correlation between serum and mRNA levels of ApoA-I (r = .65, P = .003) but no correlation between serum and mRNA levels of ApoB (r = .19, NS). We suggest that (1) steatosis is associated with increased ApoA-I mRNA; (2) fibrosis is associated with decreased serum ApoA-I, probably caused by a posttranscriptional mechanism; (3) severe alcohol-induced cirrhosis is associated with a nonspecific decrease in ApoA-I and ApoB mRNA; and (4) in contrast to ApoA-I mRNA, the ApoB mRNA level makes a slight contribution to the ApoB serum concentration.

Adult↗
PubMed1996

An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.

Histological activity reflects the global assessment of basic necroinflammatory lesions and is a criterion of major importance in chronic hepatitis C. The aim of this study was to propose and test the accuracy of a simple algorithm that generates a single activity score based on basic pathological features. A panel of 10 pathologists reviewed 363 chronic hepatitis C liver biopsies and graded the activity of hepatitis according to their own experience (reference activity). Then, a consensual algorithm on the grading of activity was established by the 10 experts in a panel discussion. Finally, stepwise discriminant analysis was performed to define which basic features had been intuitively used in the reference activity (statistical activity). To test the accuracy of the algorithm, concordance between the activity defined by the algorithm and the reference activity was assessed. It was compared with concordance between the activity defined by the statistical model and the reference activity. The algorithm proposed by the panel for the grading of activity included piecemeal necrosis and lobular necrosis. Concordance between reference activity and activity defined by the algorithm was substantial (305 cases, 84%, kappa = .75). Discriminant analysis showed that piecemeal necrosis, lobular necrosis, and portal inflammation were independently used to grade the activity. Concordance between reference activity and activity defined by the statistical model was substantial (300 cases, 83%, kappa = .73), virtually identical to the concordance between reference activity and activity defined by algorithm. This study proposes a simple algorithm for the grading of activity in chronic hepatitis. Its accuracy is as high as that obtained using a statistical approach.

Algorithms↗
PubMed1996

Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C: effects of dose and duration.

The aims of this study were to evaluate the benefits of higher doses or of longer duration in comparison with a standard interferon regimen (3 MU three times per week for 6 months) in chronic hepatitis C, and to assess the efficacy of interferon in acute hepatitis C. Meta-analysis made use of the Peto et al. and the Der Simonian and Laird methods, with heterogeneity and sensitivity analyses. In chronic hepatitis, a total of 17 trials versus controls and of 16 trials comparing different interferon regimens were included. Standard regimen, 3 MU three times per week for 6 months, was associated with an increase of the complete alanine transaminase (ALT) response rate and sustained (ALT) response rate by 45% (95% confidence interval: 35% to 55%; P < .001) and 21% (13% to 28%; P < .001), respectively, with the natural course being less than 2% of spontaneous responses. There was a significant dose effect (6 vs. 3 MU three times per week) upon the sustained response rate at 12 months, with a mean 17% increase (7% to 28%; P < .001), but not at 6 months. There was a significant duration effect (12 vs. 6 months) upon the sustained response rate both at the dose of 3 MU with a mean of 16% (9% to 23%; P < .001), and at the dose of 6 MU three times per week with a mean of 20% (7% to 33%; P = .003). In acute hepatitis C, 3 months of interferon treatment showed significant efficacy versus controls (4 trials), upon the complete ALT response (69% vs. 29%; P < .001), the sustained response rate during the 12 months following treatment (53% vs. 32%; P = .02), and hepatitis C virus (HCV)-RNA clearance (41% vs. 4%; P < .001). The best efficacy/risk ratio was in favor of 3 MU three times per week for at least 12 months in patients with chronic hepatitis C who had never been treated with interferon. Patients with acute hepatitis should be treated with at least 3 MU three times per week for 3 months.

Acute Disease↗
PubMed1996

Treatment of chronic hepatitis C by interferon for longer duration than six months.

The efficacy of various regimens using interferon-alpha (IFN-alpha) in the treatment of hepatitis C virus (HCV) infection was analyzed in a meta-analysis of 33 randomized clinical trials (RCTs). The results of the meta-analysis showed increased complete and sustained ALT response rates in patients receiving IFN 3 MU three times a week for six months compared with patients receiving placebo or no treatment. The dose effect (6 MU three times a week versus 3 MU three times a week) on complete ALT response rate at the end of treatment was significant, with a mean 10% improvement at both six and 12 months. There also was a significant dose effect on sustained response for 12 months treatment, with a mean 17% improvement. There was a significant treatment duration effect on sustained response rate at 3 MU three times a week and 6 MU three times a week, with a mean improvement of 16% (> or = 12 months vs six months) with 3 MU three times a week. Due to adverse events, we conclude that the best efficacy-risk ratio favors IFN treatment with 3 MU three times a week for at least 12 months. The results of our RCT comparing three IFN regimens showed that patients receiving 3 MU three times a week for up to 18 months exhibited significant improvements in histological activity score, normalization of serum ALT concentrations, and sustained response compared with patients receiving a lower dose or shorter duration of treatment with IFN. Together, these results support the conduct of another RCT to evaluate the hypothesis that long-term, continuous IFN treatment may significantly reduce the incidence of cirrhosis in patients with HCV infection.

Chronic Disease↗
PubMed1996

Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. French Group of Clinicians and a Group of Biologists.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunts reduce portal pressure and can control ascites in patients with cirrhosis. We carried out a controlled study to evaluate this procedure for the management of refractory ascites in patients with cirrhosis and to clarify its mechanism of action. METHODS: Twenty-five patients with refractory ascites were included in the trial; 13 were randomly assigned to shunts and 12 to paracentesis. Four patients in each group were Child-Pugh class C and the others were class B. Follow-up ranged from 9 to 34 months. Hemodynamic values, liver and renal tests and neurohumoral factors were measured before and at 4 months after inclusion. RESULTS: Shunts were successfully placed in 10 out of 13 patients. At 4 months, ascites had improved in all class B patients in the shunt group and in none of the patients in the paracentesis group (p < 0.05); ascites did not improve in any of the class C patients in either of the groups. At 2 years, the overall survival rate was 29 +/- 13% (mean +/- SE) in the shunt group and 56 +/- 17% in the paracentesis group (p < 0.05). In class B patients, there was no significant difference in mortality. At 4 months, portal pressure was significantly lower than before the shunt, while plasma levels of atrial natriuretic peptide were significantly higher and plasma levels of renin and norepinephrine significantly lower. CONCLUSIONS: In this trial, intrahepatic shunts were effective on refractory ascites in patients with cirrhosis. However, the overall survival rate was lower in shunted patients than in those treated with paracentesis. The efficacy of intrahepatic shunts on ascites was only observed in class B patients. Survival did not improve in class B patients, and decreased in class C patients compared to paracentesis. The efficacy of shunts on ascites might be due to neurohumoral factors which control natriuresis and depend on hepatic sinusoidal pressure.

Ascites↗