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T Poynard

Publications and source records attributed to T Poynard.

At least 145 records · Page 8Linked to original sources
PubMed1996

Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone.

BACKGROUND & AIMS: Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis. However, independent factors associated with a favorable outcome and long-term survival are unknown. The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis. METHODS: Of 183 patients studied, 61 had been randomized in a previous trial; 32 of them were treated with prednisolone (group I) and 29 were not treated (group II); 61 were treated from the end of this randomized trial (group III); and 61 were simulated (group IV). RESULTS: At 1 year, survival in group I (69%; confidence interval [CI], 57%-81%) and group III (71%; CI, 55%-87%) was better than in the nontreated groups (group II, 41%; CI, 23%-59%; P = 0.01) (group IV, 50%; CI, 37%-63%; P = 0.05). At 2 years, survival was not significantly different. Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival (76%; CI, 64%-88%) than the others (53%; CI, 35%-71%; P = 0.05). Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival (77%; CI, 65%-89%) than the others (40%; CI, 14%-66%; P = 0.003). In the 93 treated patients, liver polymorphonuclear infiltrate (P < 0.03) and polymorphonuclear count (P < 0.001) were independently correlated with 1-year survival. CONCLUSIONS: Prednisolone reduced mortality by at least 1 year. Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors.

Female↗
PubMed1996

Binding of apolipoprotein A-I and acetaldehyde-modified apolipoprotein A-I to liver extracellular matrix.

Apolipoprotein A-I (Apo A-I), a protein produced mainly by hepatocytes, is decreased in the sera of alcoholic patients with liver fibrosis and cirrhosis. To explain this decrease, we investigated possible interactions between liver extracellular matrix (ECM) and Apo A-I. Using a solid-phase binding assay, we evaluated the binding of Apo A-I to the different liver matrix components. Apo A-I bound significantly to fibronectin (FN) (optical density [OD] = 1.11 +/- .26, P = .01) and collagen (C) I (OD = 0.91 +/- 0.22, P = .02) in comparison with bovine serum albumin (BSA) (OD = 0.26 +/- 0.16). Binding of Apo A-I to fibronectin was concentration dependent and saturable. Apo A-I bound also to ECM in vivo because Apo A-I was detected by immunofluorescence on fibrous septa in liver biopsy specimens of alcoholic patients. Because a negative correlation between Apo A-I and liver fibrosis is amplified in alcoholic patients, we investigated whether the in vitro formation of Apo A-I/acetaldehyde complex (adducts) increased the binding of Apo A-I to the ECM. We showed that the amount of Apo A-I that bound to FN was significantly higher with acetaldehyde-modified Apo A-I (OD = 2.18 +/- 0.19, P = .01) than with native Apo A-I. This increase was probably related to the formation and binding of Apo A-I dimers, because immunoblot of in vitro acetaldehyde-modified Apo A-I showed the formation of dimeric Apo A-I. In conclusion, FN binds both native and acetaldehyde-modified Apo A-I. Because FN is deposited early and in excess during liver fibrosis, a storage mechanism of Apo A-I on newly deposited fibronectin would explain, in part, the decrease observed in alcoholic patients with liver fibrosis.

Acetaldehyde↗
PubMed1996

Marked increase in serum CA 19-9 level in patients with alcoholic cirrhosis: report of four cases.

We report four cases of marked increase in serum carbohydrate antigen (CA 19-9) levels in patients with severe alcoholic cirrhosis without any evidence of gastric or pancreatic carcinoma. Brief reports were obtained from two hepatology units of four cirrhotic patients, three of them with alcoholic hepatitis. In the four cases, improvement of liver function and disappearance of jaundice were associated with a decrease to normal serum CA 19-9 levels. These observations show that a marked increase in serum CA 19-9 level in patients with severe hepatic dysfunction is not diagnostic of pancreatic or gastric carcinoma.

Alcoholism↗
PubMed1996

Histological features predictive of liver fibrosis in chronic hepatitis C infection.

AIMS: To assess which pathological features are associated with a sensitive marker of liver fibrogenesis and thus of the potential development of fibrosis in hepatitis C. METHODS: The degree of liver fibrogenesis was evaluated by quantification of type I collagen mRNA and transforming growth factor (TGF) beta 1 mRNA (a major profibrogenic cytokine) in liver biopsy specimens from 28 patients with chronic hepatitis C and five controls, using a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Results of mRNA quantification were correlated with histological lesions scored semiquantitatively in the same specimens. RESULTS: Type I collagen mRNA was more strongly expressed in patients than in controls and correlated with the degree of fibrosis, but not with any of the necro-inflammatory lesions (portal inflammation, piecemeal necrosis, and lobular necrosis). TGF beta 1 mRNA concentration was higher in patients than in controls and correlated with histological grade of activity and lobular necrosis. This result was confirmed by in situ hybridisation experiments which showed that TGF beta 1 mRNA was mainly expressed in areas of focal lobular necrosis in chronic hepatitis C. CONCLUSION: This study shows that fibrosis, rather than necro-inflammatory lesions or activity scores, is associated with fibrogenesis and thus with potential aggravation of the fibrous deposit in chronic hepatitis C. Lobular necrosis is an important predictor of prognosis in chronic hepatitis C, as shown by its strong association with TGF beta 1 mRNA expression.

Adult↗
PubMed1996

Gene transfer in hepatocarcinoma cell lines: in vitro optimization of a virus-free system.

Many approaches exist for hepatic gene delivery, including viral vectors and non-viral vectors. In this study, we tested a panel of liposomes to transfer pAGO, a plasmid containing one copy of herpes simplex virus (HSVtk) gene, and pYED11, a plasmid containing two copies of the HSVtk gene, into a murine hepatocarcinoma cell line (Hepa 1-6) and a human hepatocarcinoma cell line (Hep-G2). The efficiency of gene delivery and expression was characterized by beta-galactosidase staining, flow cytometric analysis and quantitative lacZ activity. Different combinations of liposomes and DNA and the ratio of the concentration of liposome to DNA were tested. The efficient transfer was shown with DOTAP followed by transfectam and lipofectamine. Under these conditions, we tested the cytotoxicity of ganciclovir (GCV) exposure on Hepa 1-6 and Hep-G2 transfected separately with liposome-pAGO and liposome-pYED11 complexes. This study demonstrates the in vitro efficacy of each liposome tested to transduce the HSVtk gene into hepatocarcinoma cell lines. The transfer of two copies of the HSVtk gene rendered cells 1.5 times more sensitive to GCV than cells transduced by pAGO as compared to controls. This was achieved most efficiently by the DOTAP-pYED11 complex. Thus, pYED11 may be considered as an alternative to pAGO as a gene transfer vector.

Animals↗
PubMed1996

Role of liver extracellular matrix in transcriptional and post-transcriptional regulation of apolipoprotein A-I by hepatocytes.

Apolipoprotein A-I, a protein produced mainly by hepatocytes, is of major importance in prevention of atherosclerosis. Its serum level varies according to the degree of liver fibrosis and the mechanism of this regulation is unknown. The aim of this study was to investigate the role of extracellular matrix in the regulation of apolipoprotein A-I by the liver. Primary mouse hepatocytes were cultured on different extracellular matrix components. The apolipoprotein A-I mRNA level was quantified in these different culture conditions by a sensitive quantitative RT-PCR procedure and compared according to the extracellular matrix component used as substrate. A significant decrease in the apolipoprotein A-I mRNA level was observed when cells were plated on fibronectin by comparison with cells cultured on all other components. Potential binding of apolipoprotein A-I to the different matrix components was also studied in vitro. We demonstrated that apolipoprotein A-I significantly bound to fibronectin in a concentration-dependent, saturable and specific manner. Thus, fibronectin, a major liver extracellular matrix component, can interact with apolipoprotein A-I both by downregulating its mRNA level in liver cells and by binding this molecule after its secretion in the extracellular space. Since fibronectin is the first matrix component to be produced in excess and deposited in liver fibrosis, it could be involved in the decrease in serum apolipoprotein A-I in alcoholic patients with liver fibrosis and cirrhosis.

Animals↗
PubMed1996

[Prevalence of serum anti-hepatitis C virus antibodies and risk factors of contamination in the personnel of a hospital in the Paris region. A prospective survey].

OBJECTIVES: The aim of this prospective study was to estimate the prevalence of subjects with serum anti-HCV antibodies in a University Hospital in the Paris area, and to identify the risk factors associated with contamination. METHODS: Over an 18 month period, each person working in the hospital was systematically requested to fill out an anonymous questionnaire including 23 questions and to undergo a blood test for an anti-HCV assay during their annual medical visit. RESULTS: 557 (33%) of 1693 employees accepted to fill out the questionnaire and the anti-HCV assay. Serum anti-HCV antibodies were present in 9 subjects, which represents a prevalence of 1.6%, and serum RNA was positive by PCR, m 7. The prevalence was significantly higher in subjects working in clinical units (3.0%) compared to subjects working in non-clinical units (0.7%: P = 0.04) and in subjects with a history of acute hepatitis (5.5% vs 0.9%; P = 0.002%) Anti-HCV-positive subjects had more history of manipulating blood products than HCV-negative subjects (17.0 vs 8.8 years of exposure; P = 0.01), other human samples (17.0 vs 7.6 years; P = 0.01), and of having at risk contacts (16.7 vs 6.2 years; P = 0.0004). CONCLUSION: These results suggest the importance of systematic anti-HCV screening among health care workers particularly those in contact with patients.

Adult↗
PubMed1995

A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group.

BACKGROUND: We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis. METHODS: Consecutive patients who met the inclusion criteria were enrolled in the study. The diagnosis of chronic non-A, non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value (greater than 1.5 times the normal value) for at least one year. All patients were treated for six months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then randomly assigned to the same treatment for an additional 12 months (group 1), a regimen of 1 million units three times a week for 12 months (group 2), or no further treatment (group 3). Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again. Follow-up continued for two years after the discontinuation of treatment. Histologic improvement was defined as a decrease of at least one grade in the score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3, severe) between the first liver biopsy and a biopsy performed at 18 months. RESULTS: Of the 329 patients initially treated, 303 were randomized: 103 to group 1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1 percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis, 46 of the patients in group 1 (44.7 percent) had normal serum alanine aminotransferase values at 18 months, as compared with 27 of the patients in group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P = 0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent) continued to have normal serum alanine aminotransferase values (measured every six months), as compared with 10 of the patients in group 2 (9.9 percent, P = 0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients with repeated liver biopsies at 18 months, more patients in group 1 had improved histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P = 0.02) or group 3 (38.6 percent, P < 0.001). CONCLUSIONS: Among patients with chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment.

Alanine Transaminase↗
PubMed1995

Weak immunogenicity of the preS2 sequence and lack of circumventing effect on the unresponsiveness to the hepatitis B virus vaccine.

The preS2 sequence is known to circumvent immunological unresponsiveness to the S protein and to induce a 'carrier' effect on the anti-S antibody production, in mice. In humans, an anti-S response was found in 100% and 97% of healthy subjects vaccinated with the S and S + preS2 preparations, respectively, whereas less than 50% of drinkers responded whatever the vaccine used. Anti-preS2 were found in 44% of healthy recipients of the S + preS2 vaccine, whereas there were no anti-preS2 responders in drinkers. Anti-preS2 remained undetectable in 32% of the blood donors hyperimmunized with the S + preS2 vaccine, whereas anti-S antibody boosted in all cases. In humans, in contrast to mice, immunogenicity of the preS2 sequence appears weak and the preS sequence does not circumvent the anti-S unresponsiveness.

Adult↗
PubMed1995

Prevalence of cholelithiasis according to alcoholic liver disease: a possible role of apolipoproteins AI and AII.

Moderate alcohol intakes decreases the risk of gallstones; in contrast, the prevalence of gallstones is increased in patients with alcoholic cirrhosis. The aims of this prospective study were to assess the prevalence of cholelithiasis among drinkers according to the histological severity of liver disease, and to estimate the importance of serum apolipoproteins AI and apolipoprotein AII as risk factors for gallstones. Among the 320 drinkers included, 53 patients had cholelithiasis. The prevalence increased (p < 0.0001) from 5% in patients with normal liver (1 of 22) and 6% in patients with steatosis only (3 of 47) to 13% in patients with fibrosis (7 of 54), reaching 27% among patients with biopsy-proven cirrhosis (28 of 103). Among patients with clinically obvious cirrhosis on whom biopsy was not performed mainly because of the severity of liver disease, the prevalence of cholelithiasis reached a maximum of 46% (6 of 13). Among drinkers with nonsevere liver disease, patients with cholelithiasis were older (59 +/- 9 years, mean +/- SD vs. 45 +/- 11, p = 0.003) with lower apolipoprotein AI (118 +/- 37 vs. 163 +/- 45 mg/dl; p = 0.002) and apolipoprotein AII (30 +/- 12 vs. 53 +/- 20 mg/dl; p = 0.0002) in comparison with patients without cholelithiasis. These differences persisted after considering by multiple logistic regression analysis, sex, and ideal body weight. Alcohol consumption during the last 5 years was lower in patients with cholelithiasis (83 g/day) in comparison with patients without cholelithiasis (142 g/day; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 1 receptors in normal, cirrhotic, and neoplastic human livers.

Transforming growth factor-Beta 1 (TGF-beta 1) is an important mediator of control of liver cell proliferation and replication. The aim of the current study was to compare TGF-beta 1 gene expression, protein synthesis, and cell membrane receptors in normal liver, cirrhotic nodules, and neoplastic human livers. Five surgical resections for metastasis in an otherwise normal liver and 25 resections for hepatocellular carcinoma with cirrhosis were included in this study. Messenger RNA (mRNA) and TGF-beta 1 protein were detected on serial tissue sections of normal, cirrhotic, and tumoral livers using in situ hybridization and immunohistochemistry. TGF-beta 1 type II receptors were detected on tissue sections using immunohistochemistry. In normal livers, TGF-beta 1 mRNA and protein were not significantly expressed. In cirrhotic nodules, a few sinusoidal cells and mesenchymal cells of fibrous septa displayed TGF-beta 1 mRNA. By immunohistochemistry, protein was detected in the extracellular matrix along the fibrous septa. Hepatocytes from normal and cirrhotic livers did not express TGF-beta 1. In contrast, the cytoplasm of hepatocytes in neoplastic nodules showed intense staining for TGF-beta 1 mRNA and protein. Although TGF-beta 1 receptor II was expressed on the plasma membrane of normal liver cells, tumoral hepatocytes no longer displayed membrane labeling but rather diffuse intracytoplasmic staining with perinuclear accumulation. This study suggests that the escape of tumoral hepatocytes from control of cell proliferation by TGF-beta 1, despite its overexpression by these cells, might be related to a defect in TGF-beta 1 receptor II processing on the liver cell membrane.

Carcinoma, Hepatocellular↗
PubMed1995

Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer.

OBJECTIVE: The aim was to compare the clinical efficacy of lansoprazole with the efficacies of ranitidine and famotidine in order to rank this drug in the hierarchy of duodenal ulcer treatments. METHODS: All randomized clinical trials in which lansoprazole was used to treat patients with duodenal ulceration were reviewed. The meta-analysis included a quality assessment for each trial. The main criterion chosen for the meta-analysis was the endoscopic healing rate at 4 weeks; other criteria were the healing rate at 2 weeks and the absence of pain at 2 and 4 weeks. Statistical methods used were the Der Simonian and Laird method and the method of Peto et al. A sensitivity analysis was performed according to the H2 blocker type (famotidine or ranitidine). Odds ratios against histamine-receptor blockers were used to compare lansoprazole indirectly with omeprazole and other drugs. RESULTS: Five double-blind trials were identified including 848 patients. The mean 4-week healing rate in patients treated with lansoprazole was 85%, which was significantly higher than the healing rate in patients treated with H2-receptor blockers (75%). This difference of 10% was significant (P < 0.01) according to the Der Simonian method, and the corresponding odds ratio of 2.27 (95% confidence interval 1.5-3.2) was significant according to the Peto method (P < 0.01). There was also a significant difference in favour of lansoprazole for 2-week healing rates (mean difference 20%, P < 0.01) and for the percentage of patients without pain at 2 weeks (mean difference 8%; P < 0.02). Indirect comparisons of 4-week healing rates showed no difference between 30 mg lansoprazole and 20 mg omeprazole and confirmed that both drugs had a greater efficacy than ranitidine, famotidine, nizitidine, cimetidine or sucralfate. CONCLUSION: This meta-analysis showed that 30 mg lansoprazole was more effective in producing healing at 2 and 4 weeks than ranitidine or famotidine. Lansoprazole also led to a greater reduction in the percentage of patients free of pain at 2 weeks. The efficacy of lansoprazole was not different from that of omeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

[Medico-economic aspects of the treatment of duodenal ulcer: from antisecretory treatment to eradication of Helicobacter pylori].

OBJECTIVES: Radical changes are currently taking place in the treatment of duodenal ulcer, where strategies of eradication of Helicobacter pylori are replacing traditional antisecretory treatment. The aim of this study is to present the economic aspects of the different therapeutic approaches. METHODS: A critical analysis based on a selected number of clinical trials and medical economic analyses published in the international literature. RESULTS: A comparative analysis of traditional ranitidine/omeprazole treatments shows that ranitidine is more cost-effective in France at short term. With regard to traditional strategies, there are no French studies comparing H2-antagonists to proton pump inhibitors. Comparative studies seem in favour of eradication of Helicobacter pylori over traditional therapies, both in terms of cost and effectiveness. CONCLUSION: Arguments comparing the effectiveness of proton pump inhibitors versus H2-antagonists have become obsolete. In current therapeutic approaches of duodenal ulcer, the level of inhibition of the acid secretion no longer plays an important role.

Anti-Ulcer Agents↗
PubMed1994

Evaluation of efficacy of liver transplantation in alcoholic cirrhosis by a case-control study and simulated controls.

To assess the efficacy of liver transplantation in patients with alcoholic cirrhosis, we compared 2-year survival of 169 liver transplantation patients in 12 French centres with survival of two control groups treated conservatively. The matched group was 169 patients of similar age, cirrhosis severity, and bleeding history; the simulated group was 169 patients whose theoretical survival was determined in a cohort of 797 patients with alcoholic cirrhosis. The probability of survival to 2 years in transplanted patients was 73 (95% confidence interval 67-79%) versus 67% (59-75) in the matched and 67% (63-71) in simulated controls. When prognostic factors were taken into account, transplantation was associated with survival (r = 0.527; p = 0.069). Patients with severe liver disease (high-risk group) benefited most for 2-year survival: 64% (42-86) vs 41% (23-59) in the matched and 23% (19-27) in the simulated control groups (p < 0.01). There was no difference for patients at low and at medium risk. Liver transplantation increases the 2-year survival of patients with severe alcoholic cirrhosis. In patients with less severe disease, further studies should be done by non-randomised controlled studies with longer follow-up or by randomised trials.

Adult↗