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Thierry Poynard

Publications and source records attributed to Thierry Poynard.

At least 73 records · Page 4Linked to original sources
PubMed2003

Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma using two different schedules.

BACKGROUND: New therapies are needed to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Various gemcitabine-oxaliplatin combinations have been tested recently in patients with ovarian and pancreatic carcinoma, yielding interesting results with little toxicity. Therefore, the authors evaluated the activity and toxicity of two such combinations in patients with HCC. METHODS: Twenty-one patients were enrolled prospectively in the study. Eleven patients received gemcitabine 1000 mg/m2 on Day 1 and oxaliplatin 100 mg/m2 on Day 2 (GEMOX-1), and 10 patients received gemcitabine 1500 mg/m2 on Day 1 followed by oxaliplatin 85 mg/m2 on Day 1 (GEMOX-2). Treatment was repeated every 2 weeks until disease progression developed or until unacceptable adverse effects occurred. RESULTS: All patients were assessable for response and toxicity. Four patients (19%) achieved objective responses (95% confidence interval, 13-26%), including 3 patients in the GEMOX-1 group and 1 patient in the GEMOX-2 group. Ten patients (48%) had stable disease, and 7 patients (33%) experienced disease progression. The median progression-free survival was 5 months, and the median overall survival was 12 months. Fifty-four percent of patients in the GEMOX-1 group and 50% of patients in the GEMOX-2 group had received previous systemic chemotherapy or cisplatin-based chemoembolization. Grade 3-4 hematologic toxicity, according to National Cancer Institute Common Toxicity Criteria, consisted of thrombocytopenia (GEMOX-1 vs. GEMOX-2, 18% vs. 40%) and neutropenia (0% vs. 30%). No Grade 3-4 nonhematologic toxicity was observed, except for 1 episode of Grade 3 diarrhea. Grade 1 neurotoxicity and Grade 2 neurotoxicity (specific scale), respectively, were observed in 4 patients and 7 patients receiving GEMOX-1 and in 7 patients and 1 patient receiving GEMOX-2. CONCLUSIONS: Gemcitabine-oxaliplatin combination therapy is feasible in patients with advanced HCC. The GEMOX-1 regimen was tolerated better than the GEMOX-2 regimen. Currently, the GEMOX-1 regimen is being evaluated in a Phase II study in previously untreated patients with HCC.

Adult↗
PubMed2003

Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients.

OBJECTIVE: Liver biopsy, the gold standard for assessing hepatitis C virus (HCV)-related fibrosis, is invasive and prone to complications. Our aim was to determine the operating characteristics of a non-invasive index of biochemical markers for the prediction of fibrosis in patients with HIV/HCV co-infection. DESIGN: In a cross-sectional, cohort study in a French tertiary-care hospital 130 HIV/HCV-co-infected patients with a liver biopsy and serum were tested for markers of liver fibrosis. METHODS: An index incorporating age, sex, alpha(2)-macroglobulin, apolipoprotein A1, haptoglobin, bilirubin, and gamma-glutamyl-transpeptidase (GGT), derived using multivariate logistic regression, was compared with liver histology. HIV-specific indices including the CD4 cell count and HIV-RNA load were also constructed. The diagnostic values of the indices were compared using receiver operating characteristic (ROC) curves. MAIN OUTCOME MEASURE: Septal fibrosis (F2-F4) by the METAVIR classification. RESULTS: By multivariate analysis, the most informative markers were alpha(2)-macroglobulin, apolipoprotein A1, GGT, and sex. The area under the ROC curve of the five-marker index was 0.856 +/- 0.035; not significantly different from the HIV-specific indices. On a scale from zero to 1.00, the five-marker index had a positive predictive value of 86% for scores greater than 0.60, and a negative predictive value of 93% for scores of 0.20 or less. These thresholds could reduce the necessity for liver biopsy by 55% while maintaining an accuracy of 89%. CONCLUSION: An index including five biochemical markers accurately predicts significant fibrosis in patients with HIV/HCV co-infection, and may substantially reduce the necessity for liver biopsy.

Adult↗
PubMed2003

A comparison of fibrosis progression in chronic liver diseases.

BACKGROUND/AIMS: No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies. METHODS: A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)-HCV co-infection (HIV-HCV [n=180]), hepatitis B (HBV [n=777]), alcoholic liver disease (ALD [n=701]), primary biliary cirrhosis (PBC [n=406]), genetic hemochromatosis (GH [n=383]) auto-immune hepatitis (AIH [n=57]) and delta hepatitis (n=35). The fibrosis progression rates were estimated from birth and from the date of exposure, when known, to the first biopsy. RESULTS: There were highly significant differences in the rates of fibrosis progression, the most rapid being HIV-HCV co-infection (50% cirrhosis percentile at 52 years of age) and the slowest being PBC (50% cirrhosis percentile at 81 years). There was an acceleration of fibrosis progression with aging. Fibrosis progression was slower in females compared with males for HCV, HBV, GH, and PBC. In contrast, in ALD, the fibrosis progression was more rapid in females. CONCLUSIONS: Rates of fibrosis progression differ markedly between the predominant causes of chronic liver disease, and according to age and gender. Patients with HIV-HCV co-infection are at particularly high risk of fibrosis progression.

Adult↗
PubMed2003

Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B.

BACKGROUND AIMS: Liver biopsy is the gold standard for assessing hepatitis B virus (HBV)-related histology. The aim was to determine the diagnostic utility of noninvasive serum markers in patients with chronic hepatitis B. METHODS: The aminotransferases and indices including alpha(2)-macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase (GGT), and total bilirubin (Fibrotest), and ALT (Actitest) were compared with liver histology. The primary outcomes were A2-A3 activity and F2-F4 fibrosis (METAVIR). RESULTS: Two hundred and nine patients were included. Forty-one patients (20%) had A2-A3 activity and 61 (29%) had F2-F4 fibrosis. AST and GGT (P<0.001) were independently associated with A2-A3 activity. AST, ALT, and Actitest accurately predicted activity ((areas under receiver operating characteristic (ROC) curves (AUROC), 0.81-0.82+/-0.04)); an AST or ALT< or =30IU/l excluded significant activity with 96% certainty. Fibrotest accurately predicted F2-F4 fibrosis (AUROC, 0.78+/-0.04). Fibrotest scores (range, 0-1.0) < or =0.20 and >0.80 had negative and positive predictive values of 92%, respectively. Restricting biopsy to patients with intermediate scores (>0.20 and < or =0.80) may prevent liver biopsies in 46% of patients while maintaining 92% accuracy. CONCLUSIONS: The aminotransferases and an index including five biochemical markers are accurate noninvasive markers of HBV-related activity and fibrosis, respectively.

Adult↗
PubMed2003

Fibrogenic impact of high serum glucose in chronic hepatitis C.

BACKGROUND/AIMS: There is considerable variability in the rate of fibrosis progression in patients with chronic hepatitis C, most of which is related to factors so far unknown. We tested the hypothesis that high serum glucose and overweight might contribute to this variability. METHODS: Seven hundred and ten patients with chronic hepatitis C with a known duration of infection and no hepatitis B virus or human immunodeficiency virus coinfection were studied. Significant fibrosis was defined as bridging fibrosis including cirrhosis. Variables were tested for their association with significant fibrosis. RESULTS: In univariate analyses both serum glucose and body mass index were associated with fibrosis. In multivariate analyses, age at infection, duration of infection, serum glucose and daily alcohol intake but not body mass index were independently associated with significant fibrosis. Patients with high serum glucose had been contaminated at an older age and had features of the metabolic syndrome, including steatosis more frequently, as well as faster fibrosis progression rates. High serum glucose was associated with intermediate and advanced, but not with early, fibrosis stages. A high serum glucose was associated with a higher relative risk for significant fibrosis than overweight. CONCLUSIONS: High serum glucose, is an independent co-factor of fibrosis in chronic hepatitis C with a higher pro-fibrogenic impact than overweight.

Adolescent↗
PubMed2003

Sarcoidosis and interferon therapy: report of five cases and review of the literature.

BACKGROUND: Sarcoidosis is a multi-system disease of unknown etiology. Interferons (IFN) have been implicated in its pathogenesis. The objective of this study was to examine the causal relationship between sarcoidosis and IFN therapy. METHODS: Patients admitted for sarcoidosis (n=60) were reviewed for a history of IFN therapy. In addition, all cases of sarcoidosis in a cohort of hepatitis C-infected patients treated with IFN-alpha (n=1159) were analyzed. RESULTS: Five patients with prior IFN-alpha therapy and sarcoidosis were identified; an additional 23 have been reported in the literature. The median age of the 28 reported patients was 50 years, 16 (57%) were female, and 16 (57%) had isolated cutaneous disease. The median time to diagnosis was 4 months (range 1-16 months) following the introduction of IFN. A remission was observed in all patients with adequate follow-up (n=27): 15 (53%) upon dosage reduction or IFN discontinuation, seven (25%) with systemic corticosteroids, three (11%) with topical treatment, and three (11%) despite ongoing IFN therapy. Relapse was observed in both of the patients rechallenged with IFN. CONCLUSIONS: There is a potential causal relationship between IFN therapy and sarcoidosis. In patients with sarcoidosis in the setting of IFN therapy, the majority respond to IFN withdrawal or dosage reduction; however, some require corticosteroid therapy.

Journal Article↗
PubMed2003

Biochemical markers of fibrosis in patients with chronic hepatitis C: a comparison with prothrombin time, platelet count, and age-platelet index.

As an alternative to liver biopsy, an index of five biochemical markers (alpha2-macroglobulin, apolipoprotein A1, haptoglobin, total bilirubin, gamma-glutamyl-transpeptidase) has been shown to predict the severity of hepatitis C-related fibrosis. The objective of this study was to compare this index with other markers frequently used for this purpose (prothrombin time, platelets, age-platelet index). In 323 hepatitis C-infected patients, the discriminative values of these markers for F2-F4 fibrosis (by the METAVIR classification) were compared. By multiple logistic regression analysis, only the five-marker index (P < 0.0001) and prothrombin time (P = 0.02) were independently predictive of F2-F4 fibrosis. For this outcome, the area under the receiver operating characteristic curve was significantly higher for the five-marker index (0.836 +/- 0.024) than the age-platelet index (P = 0.002), and the platelet count and prothrombin time (P < 0.001), indicating greater diagnostic value. The addition of the latter markers to the five-marker index proved unhelpful for increasing its accuracy. In conclusion, an index of five biochemical markers accurately predicts significant hepatitis C-related fibrosis and is superior to traditional markers.

Adult↗
PubMed2003

Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C.

It has been suggested that hepatitis C virus (HCV) and especially genotype 3 is associated with steatosis. We assess the effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis. We analyzed 1,428 naïve patients included in a randomized trial. A single pathologist scored steatosis at baseline and 24 weeks after the treatment. At baseline, steatosis was present in 935 of 1,428 patients (65%), including 175 (83%) of 210 patients with genotype 3 versus 760 (62%) of 1,218 with other genotypes (P <.001). The variables associated with steatosis in logistic regression were genotype 3 (P <.001), triglycerides greater than 1.7 mmol/L (P <.001), body mass index greater than 27 (P <.04), age greater than 40 years (P <.001), and septal fibrosis (P =.007). In genotype 3-infected patients, steatosis was associated with high viral load and with lower serum cholesterol. Steatosis was associated with lower sustained response rate, even after taking into account other factors (P <.001). Among virologic responders, steatosis was much improved in genotype 3, improvement of at least 1 grade in 77%, and disappearance in 46% compared with other genotypes, 46% and 29%, respectively (P <.001 both comparisons). In genotype 3 responders, the baseline low serum cholesterol was corrected by treatment (P <.001). Steatosis was associated with HCV genotype 3, triglycerides, high body mass index, age, fibrosis stage, and lower virologic response to treatment. In conclusion, sustained disappearance of the virus is associated with reduction of steatosis in genotype 3 as well as a correction of baseline low serum cholesterol.

Adult↗
PubMed2003

Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin.

Liver fibrosis and activity indexes were validated in patients infected by hepatitis C virus (HCV) nontreated and treated by interferon. The aim was to validate their usefulness as surrogate markers of histologic features using the data of a randomized trial of combination peginterferon alfa-2b and ribavirin. Three hundred fifty-two patients who had had 2 interpretable liver biopsies and stored serum sample before and after treatment were selected. Two hundred eight patients received peginterferon alfa-2b 1.5 mcg per kg and ribavirin and 144 patients interferon alfa-2b 3 MU three times a week and ribavirin for 48 weeks. A fibrosis and an activity index combining 5 and 6 biochemical markers were assessed at baseline and at end of follow-up (24 weeks after treatment). The biochemical markers have significant predictive values both for the diagnosis of fibrosis and for activity. For the diagnosis of bridging fibrosis and/or moderate necroinflammatory activity, the area under the receiver operating characteristics curve of the activity index was 0.76 +/- 0.03 at baseline and 0.82 +/- 0.02 at end of follow-up. A cutoff of activity index at 0.30 (range, 0.00-1.00) had 90% sensitivity and 88% positive predictive value for the diagnosis of bridging fibrosis or moderate necroinflammatory activity. Sensitivity analyses with biopsy specimens of size greater than 15 mm suggest that a part of discordances between biochemical markers and histology were due to biopsy specimen sampling error. In conclusion, these biochemical markers of fibrosis and activity could be used as surrogate markers for liver biopsy in patients with chronic hepatitis C, both for the initial evaluation and for follow-up.

Adult↗
PubMed2002

A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease.

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.

Journal Article↗
PubMed2002

Truth survival in clinical research: an evidence-based requiem?

PURPOSE: Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. The authors hypothesized that conclusions derived from studies using better methodology should have a longer half-life. DATA SOURCES: MEDLINE and hand searches of journals with studies on cirrhosis and hepatitis. STUDY SELECTION: Original articles and meta-analyses published from 1945 to 1999 about cirrhosis or hepatitis in adults. DATA SYNTHESIS: In 2000, 285 of 474 conclusions (60%) were still considered to be true, 91 (19%) were considered to be obsolete, and 98 (21%) were considered to be false. The half-life of truth was 45 years. The 20-year survival of conclusions derived from meta-analysis was lower (57% +/- 10%) than that from nonrandomized studies (87% +/- 2%) (P < 0.001) or randomized trials (85% +/- 3%) (P < 0.001). The survival of conclusions was not different when studies of high methodologic quality were compared with those of low quality. In randomized trials, the 50-year survival rate was higher for 52 negative conclusions (68% +/- 13%) than for 118 positive conclusions (14% +/- 4%) (P < 0.001). CONCLUSIONS: Contrary to the authors' hypothesis, conclusions based on recognized, good methodology had no clear survival advantage. To better convince clinicians of the long-term utility of evidence-based medicine, better prognostic factors should be developed.

Clinical Trials as Topic↗
PubMed2002

Uses of error.

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Evidence-Based Medicine↗