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T Poynard

Publications and source records attributed to T Poynard.

At least 55 records · Page 3Linked to original sources
PubMed2001

Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study.

BACKGROUND: Liver biopsy is thought mandatory for management of patients with hepatitis C virus (HCV) infection, especially for staging fibrosis. We aimed, in our prospective study, to assess the predictive value of a combination of basic serum biochemical markers for diagnosis of clinically significant fibrosis (including early stages). METHODS: We assessed liver-biopsy patients with detectable HCV by PCR, for eligibility, and took a blood sample on the day of the procedure. The analysis was done in a first-year period for 205 patients and then tested in a second period on 134 patients. We devised a fibrosis index that included the most informative markers (combined with age and sex) for the first-year group. 11 serum markers were assessed as well as fibrosis stage: F0=no fibrosis and F1=portal fibrosis; and for clinically significant fibrosis, F2=few septa, F3=many septa, and F4=cirrhosis. Statistical analysis was by logistic regression, neural connection, and receiver-operating characteristic (ROC) curves. FINDINGS: First-year and second-year patient-group characteristics and biochemical markers did not differ. The overall frequency of clinically significant fibrosis was 40% (138 patients). The most informative markers were: alpha2 macroglobulin, alpha2 globulin (or haptoglobin), gamma globulin, apolipoprotein A1, gamma glutamyltranspeptidase, and total bilirubin. The areas (SD) under the ROC curves for the first-year (0.836 [0.430]) and second-year groups (0.870 [0.340]) did not differ (p=0.44). With the best index, a high negative predictive value (100% certainty of absence of F2, F3, or F4) was obtained for scores ranging from zero to 0.10 (12% [41] of all patients), and high positive predictive value (>90% certainty of presence of F2, F3, or F4) for scores ranging from 0.60 to 1.00 (34% [115] of all patients). INTERPRETATION: A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection.

Apolipoprotein A-I↗
PubMed2001

Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis c.

BACKGROUND AIMS: In hepatitis C there is controversy over the linearity of the rate of progression and the significance of gender, mode of infection and viral factors. METHODS: 2313 untreated patients with a reliable estimated duration of infection and liver fibrosis were included. Fibrosis progression was calculated using the Kaplan-Meier method and the rate of fibrosis progression using the hazard function. Seven risk factors were assessed: age at biopsy, gender, alcohol consumption, mode of infection, activity grade, hepatitis C virus genotype and RNA level. RESULTS: The percentage of patients without cirrhosis was 91% after 20 years of infection (95% CI:90-92%) and 56% after 40 years (95% CI:48-64%). Three independent factors were associated (P < 0.001) with a faster progression rate: age at infection, alcohol consumption of 50 g or more per day, and male gender. The mode of infection, histologic activity, genotype and viral load were not independently associated with fibrosis. Fibrosis progression was mainly dependent on age and the duration of infection and can be divided into four successive periods with very slow, slow, intermediate and rapid progression rates. CONCLUSION: In patients infected with hepatitis C, the majority of fibrosis progression occurred in those aged fifty years or older.

Adult↗
PubMed2001

Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome.

AIM: To update previous overviews of placebo-controlled double-blind trials assessing the efficacy and tolerance of smooth muscle relaxants in irritable bowel syndrome. METHODS AND TRIALS: A total of 23 randomized clinical trials were selected for meta-analyses of their efficacy and tolerance. Six drugs were analysed: cimetropium bromide (five trials), hyoscine butyl bromide (three trials), mebeverine (five trials), otilium bromide (four trials), pinaverium bromide (two trials) and trimebutine (four trials). The total number of patients included was 1888, of which 945 received an active drug and 943 a placebo. RESULTS: The mean percentage of patients with global improvement was 38% in the placebo group (n=925) and 56% in the myorelaxant group (n=927), in favour of myorelaxants with a mean odds ratio of 2.13, P < 0.001 (95% CI: 1.77--2.58) and a mean risk difference of 22% P < 0.001 (95% CI: 13--32%). The percentage of patients with pain improvement was 41% in the placebo group (n=568) and 53% in the myorelaxant group (n=567): odds ratio 1.65, P < 0.001 (95% CI: 1.30--2.10) and risk difference 18%, P < 0.001 (95% CI: 7--28%). There was no significant difference for adverse events. CONCLUSION: Myorelaxants are superior to placebo in the management of irritable bowel syndrome.

Abdominal Pain↗
PubMed2001

Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C in naive patients: 1999 update.

The aim of this study was to update our previous meta-analysis of interferon (IFN) in the treatment of hepatitis C and to analyse new factors, namely, HCV RNA end-point, patients with cirrhosis and patients with normal ALT. We use the Der Simonian and Laird method, with heterogeneity and sensitivity analyses. Seventy-six randomized control trials (RCTs) in naive patients were found but we focused our analysis on 59 RCTs with chronic hepatitis C (26 vs. controls and 33 comparing different regimens) and on seven RCTs in acute hepatitis. Interferon-alpha (IFN-alpha) at 3 MU thrice weekly (TIW) for 12 months exhibited 39% of virological end-of-treatment response (ETR) and 17% of virological sustained response (SR), respectively, vs. 1% and 3% in untreated controls (all P < 0.001). There was a significant dose effect (in favour of 6 vs. 3 MU TIW): the virological SR at 6 months were 35% in the 6 MU group (95% CI: 24-47) and 16% in the 3 MU group (95% CI: 8-27) and were at 12 months 43% in the 6 MU group (95%CI: 31-56) and 25% in the 3 MU group (95% CI: 16-37). There was a significant duration effect (12 vs. 6 months) upon the virological SR rate both at 3 and 6 MU: 3 MU provided 14% of virological SR (95% CI: 11-19) in the 12 months group vs. 7% (95% CI: 5-11) in the 6 months group and 6 MU provided 22% (95% CI: 17-29) and 16% (95% CI: 11-22) virological SR in the 12 and 6 months groups, respectively. Cirrhotic treated patients had 17% of virological SR (95 CI: 9-24%; P < 0.001) vs. 0% in controls and provided a 20% reduction rate (95 CI: -2% to -37%, P=0.03) in hepatocellular carcinoma incidence. In acute hepatitis C, a 3-month treatment with IFN-alpha showed significant efficacy vs. controls upon the virological SR rate (32% vs. 4%, P < 0.001). In conclusion, we confirm the dose and duration effect of IFN in chronic hepatitis C, and the efficacy of IFN-alpha in the treatment of acute hepatitis and in cirrhotic patients.

Acute Disease↗
PubMed2001

Factors affecting liver fibrosis in human immunodeficiency virus-and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy.

Hepatitis C virus (HCV)-related liver fibrosis progression is accelerated in human immunodeficiency virus (HIV)-infected patients. The effect of protease inhibitor (PI) therapy on liver fibrosis is unknown. The aim of this work was to analyze the impact of PI therapy on HCV-related liver fibrosis in HIV/HCV coinfected patients. We evaluated in a long-term follow-up retrospective cohort study the influence of antiretroviral therapy containing PI on liver fibrosis in 182 consecutive HIV/HCV coinfected patients. At liver biopsy, 63 patients had received PI and 119 patients had never been treated with PI. Relationships between liver histologic features, age, alcohol consumption, CD4 cell count, HIV-RNA load, and antiretroviral regimens were analyzed. Liver fibrosis stage was lower in patients receiving PIs by comparison with patients who had never received PIs (P =.03). The 5-, 15-, and 25-year cirrhosis rates were 2% versus 5%, 5% versus 18%, and 9% versus 27%, respectively, in patients who had received PIs compared with PI-untreated patients (P =.0006). Multivariate analysis identified 4 independent predictors of progression to cirrhosis: absence of protease inhibitor therapy (relative risk [RR] = 4.74, 95% confidence interval [CI], 1.34-16.67), heavy alcohol consumption (> or = 50 g daily) (RR = 4.71, 95% CI, 1.92-11.57), low CD4 cell count (<200/microL) (RR = 2.74, 95% CI, 1.17-6.41), and age at HCV contamination (> or = 20 years) (RR = 2.37, 95% CI, 1.04-5.38). In conclusion, protease inhibitor therapy might not accelerate progression to HCV-related cirrhosis. Furthermore, chronic use of antiretroviral therapy containing PI together with reduction of alcohol consumption and maintenance of high CD4 count could have a beneficial impact on liver fibrosis progression in HIV/HCV coinfected patients.

Adult↗
PubMed2001

Mechanisms of alcoholic liver disease: cytokines.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Manuela G. Neuman. The presentations were (1) New aspects of hepatic fibrosis, by D. A. Brenner; (2) Cellular immune response in hepatitis C models, by B. Rehermann; (3) The role of interleukin-10 in acute alcoholic hepatitis, by J. Taieb, S. Chollet-Martin, M. Cohard, J. J. Garaud, and T. Poynard; (4) Cytokine-mediated apoptosis in vitro, by M. G. Neuman; (5) Signaling for apoptosis and repair in vitro, by G. G. Katz, R. G. Cameron, N. H. Shear, and M. G. Neuman; (6) Interferons activate the P42/44 mitogen-activated protein kinase and Janus Kinase signal transducers and activation of transcription (JAK-STAT) signaling pathways in hepatocytes: Differential regulation by acute ethanol via a protein kinase C-dependent mechanism, by B. Gao; (7) Genetic polymorphisms of interleukin-1 in association with the development of Japanese alcoholic liver disease, by M. Takamatsu, M. Yamauchi, M. Ohata, S. Saito, S. Maeyama, T. Uchikoshi, and G. Toda; and (8) Increased levels of macrophage migration inhibitory factor in sera from patients with alcoholic liver diseases, by T. Kumagi, S. M. F. Akbar, M. Abe, K. Michitaka, N. Horiike, and M. Onji.

Alcohol Drinking↗
PubMed2001

[CagA status and virulence of Helicobacter pylori strains. Results of a French multicentric prospective study].

UNLABELLED: Previous experimental and epidemiological studies with few patients suggested that the presence of the cagA gene was a virulence factor for Helicobacter pylori (H. pylori). AIM: To establish in this large epidemiological cohort study the relationship between the histological virulence of H. pylori infection and the cagA status of the bacteria. METHODS: This prospective cohort study (6 month follow-up) was conducted on adult patients undergoing endoscopy for upper gastrointestinal symptoms. The cagA status of H. pylori-positive patients was established using the polymerase chain reaction (PCR) method on an antral biopsy. A score of histological virulence (inflammation, activity) was recorded on the basis of the Sydney system (on antral, angular and fundic biopsies). Eradication treatment given was not imposed and a clinical follow-up was performed at 3 and 6 months. H. pylori eradication was verified by a 13C urea breath test at 3 months. RESULTS: Four hundred and twenty two centers recruited 652 patients (mean age: 51 +/- 15 years, 55% female). Upper GI endoscopy was abnormal in 80% of the patients of whom 68% had a gastritis aspect; 38% were infected by H. pylori, and among them 51% were cagA-positive. The histological virulence scores associated with the cagA-positive strains were significantly higher than those associated with the cagA-negative strains, globally (P = 0.0035), in the antrum (P = 0.0063), and in the angulus (P = 0.046), but not in the fundus (P = 0.05). The cagA status was correlated neither with the symptom severity at inclusion and at 6 months (P > 0.05), nor with the H. pylori eradication rate at 3 months (75% in cagA-positive and 70% in cagA-negative strains, P = 0.52). CONCLUSION: This study on a large cohort of patients confirms the greater histological virulence of H. pylori cagA-positive strains. However, this virulence was not associated with more severe symptoms nor with an increase in resistance to H. pylori eradication treatment.

Adult↗
PubMed2000

[Treatment and prevention of hepatitis C].

Hepatitis C is a chronic disease with lethal complications and recent treatments have a strong efficacy. Ribavirin and alpha interferon combination allows obtaining a sustained viral response in 40% of patients who are theoretically protected against the progression to cirrhosis and its complications. In non responders prospective trials are in progress assessing the efficacy of stronger regimen or using sustain-release interferons. It is also possible that in non responders interferon reduces the progression of liver fibrosis permitting to reduce cirrhosis incidence and to wait for new drugs. Patients who need definitively a treatment are patients with fibrosis progression, patients with extrahepatic manifestations and those who can transmit the virus. Treatment of HCV should be systematically discussed in patients coinfected with HIV and HCV.

Antiviral Agents↗
PubMed2000

Is an "a la carte" combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALGOVIRC Project Group.

UNLABELLED: Randomized trials have shown the enhancement of efficacy with interferon alfa-2b and ribavirin (IFN-R) in comparison with interferon monotherapy (IFN) as first line treatment of chronic hepatitis C. Further definition of response based on disease, patient, and treatment characteristics is needed to determine the degree of benefit for the various patient subgroups. The aim of this study was to answer this question by analyzing the data from 1,744 naive patients included in trials that compared 24- or 48-week IFN-R treatment. Response factors were identified by logistic regression and receiver operating characteristics curves. Five independent characteristics were associated with a sustained loss of hepatitis C virus (HCV) RNA (<100 copies/mL) 24 weeks after the end of treatment: genotype 2 or 3, baseline viral load less than 3.5 million copies/mL, no or portal fibrosis, female gender, and age younger than 40 years. There was a significant advantage for IFN-R in comparison with IFN alone whatever the combination of factors. The most efficient strategy is to treat all patients for 24 weeks. If the 24-week polymerase chain reaction (PCR) is positive, treatment can be stopped. If the 24-week PCR is negative, patients with fewer than 4 favorable factors should be treated for an additional 24 weeks. CONCLUSION: The combination of IFN-R is better as first line treatment than IFN monotherapy. For patients who are PCR negative after 24 weeks of treatment, genotyping and baseline viral load, fibrosis stage, gender, and age are useful predictive factors in determining whether to continue an additional 24 weeks of treatment.

Adult↗
PubMed2000

Liver fibrosis in overweight patients.

BACKGROUND & AIMS: A common clinical issue is whether overweight patients with abnormal liver function test results should undergo liver biopsy. Although serious liver injury can occur, its prevalence and risk factors are not well known. METHODS: Ninety-three consecutive patients with abnormal liver function tests (but without overt liver disease), body mass index (BMI) > 25 kg/m(2), and no alcoholic, viral, autoimmune, drug-induced, or genetic liver disease were retrospectively studied. Clinical, biological, and histological variables were tested for association with septal fibrosis or cirrhosis. RESULTS: Septal fibrosis was present in 28 patients (30%) including cirrhosis in 10 (11%). Age >/= 50 years (odds ratio [OR], 14.1), BMI >/= 28 kg/m(2) (OR, 5.7), triglycerides >/= 1.7 mmol/L (OR, 5), and alanine aminotransferase (ALT) >/= 2N (OR, 4.6) were independently associated with septal fibrosis. Among histological features, septal fibrosis was strongly associated with necroinflammatory activity (OR, 44). A score combining age, BMI, triglycerides, and ALT had 100% negative predictive value for septal fibrosis when scoring 0 or 1 (100% sensitivity for a specificity of 47%). CONCLUSIONS: Septal fibrosis occurs frequently in overweight patients with abnormal liver function tests. A clinicobiological score combining BMI, age, ALT, and triglycerides could improve selection of patients for liver biopsy.

Adult↗
PubMed2000

Impact of human immunodeficiency virus infection on the histological features of chronic hepatitis C: a case-control study. The MULTIVIRC group.

Hepatitis C virus (HCV) is frequently encountered in human immunodeficiency virus (HIV)-infected patients because of common routes of transmission. Previous studies suggested that HIV infection impaired the natural course of chronic hepatitis C, with a more rapid progression to cirrhosis. However, these studies did not assess the HIV infection impact on chronic hepatitis C by taking into account the risk factors for liver fibrosis progression: alcohol, sex, age at the contamination, and duration of HCV infection. We studied liver biopsy specimens of 2 groups of 58 patients that were infected by both HCV and HIV or by HCV alone. The 2 groups were matched according those risk factors, and liver biopsy responses were evaluated with the METAVIR items. The METAVIR activity was higher in HIV-positive than HIV-negative patients. Cirrhosis was more frequent: (1) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-negative patients (10%) (P = .003), (2) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-positive patients with CD4 > 200 cells/microL (17%) (P = .04). These differences, which were linked to HIV status, might be related to the enhanced HCV replication during HIV infection or other immune mechanisms that need further studies.

Adult↗
PubMed2000

Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids.

BACKGROUND/AIMS: Several observations point to an important role of interactions between polymorphonuclear neutrophils and cytokines in severe alcoholic hepatitis. The polymorphonuclear neutrophil activation status and the local and systemic pro- and anti-inflammatory cytokine responses were quantified. The effect of corticosteroids, widely used in this setting, was evaluated using these parameters. METHODS: We studied blood polymorphonuclear neutrophil functions in terms of L-selectin and beta2-integrin expression, H2O2 production and IL-8 and tumor necrosis factor alpha synthesis capacity. We also measured IL-8, tumor necrosis factor alpha and IL-10 plasma and liver tissue levels. Fifteen patients with alcoholic hepatitis were compared to 15 patients with alcoholic cirrhosis without alcoholic hepatitis, and to 10 healthy volunteers. The impact of a 28-day course of corticosteroids on blood neutrophils activation status and cytokine levels was evaluated in patients with alcoholic hepatitis. RESULTS: Blood polymorphonuclear neutrophils were activated, as shown by increased H2O2 production (48+/-6 vs 29+/-6 MFI in healthy controls), and decreased L-selectin expression (300+/-61 vs 449+/-59 in healthy controls). Upon stimulation, polymorphonuclear neutrophils synthesized large amounts of IL-8 (21.7+/-9.2 ng/ml vs 8.8+/-10 ng/ml in healthy controls) and tumor necrosis factor alpha (524+/-132 pg/ml vs 79+/-144 pg/ml in healthy controls). Tumor necrosis factor alpha and IL-8 plasma and tissue levels were markedly increased as IL-10 was barely detectable in alcoholic hepatitis patients, compared to cirrhotic patients and healthy controls. During steroid therapy, plasma levels of the pro-inflammatory cytokine IL-8 fell as early as day 14, while levels of the anti-inflammatory cytokine IL-10 increased on day 21. Finally, polymorphonuclear neutrophil functions returned to normal after treatment. CONCLUSION: Severe alcoholic hepatitis appears to be associated with polymorphonuclear neutrophil activation and an imbalance between pro- and anti-inflammatory cytokines; during steroid therapy a normalization of these parameters was observed.

Adrenal Cortex Hormones↗
PubMed2000

Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections.

In patients with multiple hepatotropic viral infections (B and C, or B, C and D), the reciprocal influence of each virus remains controversial. The aims of this study were twofold: first, to determine the impact of multiple infection on the replication status of B, C and D viruses and on histological features; and second, to compare patients with multiple infection to patients infected only with the hepatitis C virus (HCV). We retrospectively included 50 patients with multiple infection and 50 control HCV patients, who were matched on independent factors associated with fibrosis, such as age, gender, alcohol consumption and duration of infection. The replication status of hepatitis B virus (HBV), HCV and hepatitis D virus (HDV), and histological lesions, were determined. In patients with multiple infection, HCV RNA was present less frequently (44% vs 98%, P < 0.001) and the prevalence of cirrhosis was higher (35% vs 8%, P < 0.001). Among patients with triple infection (n = 16), HBV replication was observed in 25%, HCV RNA was detectable in only two (P < 0.0001) and HCV viremia was significantly lower than in the matched HCV patients (0 vs 54.7, P < 0.0001). Among patients with dual infection (n = 34), HCV RNA was present less frequently in those with serological markers of active HBV infection than in those without (30% vs 79%, P = 0.01). Hence, multiple infection is associated with a decrease of HCV replication. Cirrhosis seems to be more frequently observed in patients with multiple infection. In patients with triple infection, serum HCV RNA and markers of HBV replication were absent in 80%, suggesting that HDV acts as a dominant virus. In patients with dual infection, HBV and HCV exert an alternative, dominant replication.

Adult↗
PubMed2000

Natural history of HCV infection.

Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. These individuals are at risk of developing both hepatological and non-hepatological manifestations. HCV is usually only fatal when it leads to cirrhosis, the final stage of liver fibrosis. Therefore, an estimate of fibrosis progression represents an important surrogate end-point for the evaluation of the vulnerability of an individual patient. In untreated patients, the median expected time to cirrhosis is 30 years; 33% of patients have an expected median time to cirrhosis of less than 20 years and 31% will only progress to cirrhosis after more than 50 years, if ever. Several factors are associated with fibrosis progression rate: duration of infection, age, male gender, consumption of alcohol, HIV co-infection and low CD4 count. Non-hepatological manifestations are frequent with more than 70% of HCV patients experiencing fatigue or at least one extrahepatic clinical manifestation involving primarily the joints, skin and muscles. Several immunological abnormalities are frequently observed, including cryoglobulins (40%),anti-nuclear antibodies (10%) and anti-smooth muscle antibodies (7%). In contrast severe extrahepatic manifestations are rare, with 1% for systemic vasculitis.

Antibodies, Antinuclear↗