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Thierry Poynard

Publications and source records attributed to Thierry Poynard.

At least 37 records · Page 2Linked to original sources
PubMed2005

Natural history and predictors of disease severity in chronic hepatitis C.

Cirrhosis is the end-stage consequence of fibrosis progression in patients with chronic hepatitis C. The median time from infection to cirrhosis is 30 years, with a high inter-individual variability, which is now better understood. Several factors have been clearly shown to be associated with fibrosis progression rate: duration of infection, age, male gender, alcohol consumption, HIV co-infection and low CD4 count. Metabolic conditions such as steatosis, being overweight and diabetes are emerging as independent co-factors of fibrogenesis. The recent validation of non-invasive biomarkers should facilitate the study of fibrosis progression in large populations.

Disease Progression↗
PubMed2005

Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1.

BACKGROUND/AIMS: Adefovir dipivoxil (10 mg once-daily) was added to antiretroviral therapy including lamivudine in 35 HIV/HBV co-infected patients. METHODS: Parameters evaluated included alanine aminotransferase (ALT), HBV DNA and serological markers, HIV-1 RNA, and CD4+ cell count. RESULTS: Twenty-nine patients (83%) completed 144 weeks. Serum HBV DNA declined from a baseline 9.76 log10 copies/mL (median) to 4.68, 5.24, and 5.90 log10 copies/mL at weeks 48, 96, and 144, respectively (P<0.0001 at all time points). Seven patients (25%) achieved HBV DNA<2.3 log10 copies/mL. No adefovir-associated resistance mutations in HBV DNA polymerase or HIV-1 reverse transcriptase were detected. ALT declined from 81 IU/L (median) at baseline by -16.0, -44.5, and -46.0 IU/L at week 48, 96 and 144, respectively (P=<0.05, respectively), and normalized in 71% of patients (20 of 28) by week 144. Two patients developed antibodies against HB 'e' antigen by week 48. No serious adverse events related to adefovir dipivoxil occurred during the study, and HIV-1 RNA and CD4+ cell counts were stable. CONCLUSIONS: Treatment with adefovir dipivoxil for 144 weeks was well tolerated and resulted in significant and sustained reductions in HBV DNA and ALT in HIV/HBV co-infected patients. Efficacy increased with treatment duration, with no loss of viral suppression.

AIDS-Related Opportunistic Infections↗
PubMed2005

A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B.

BACKGROUND & AIMS: A previous 4-week trial of telbivudine in patients with chronic hepatitis B indicated marked antiviral effects with good tolerability, leading to the present 1-year phase 2b trial. METHODS: This randomized, double-blind, multicenter trial evaluated the efficacy and safety of telbivudine 400 or 600 mg/day and telbivudine 400 or 600 mg/day plus lamivudine 100 mg/day (Comb400 and Comb600) compared with lamivudine 100 mg/day in hepatitis B e antigen (HBeAg)-positive adults with compensated chronic hepatitis B. RESULTS: A total of 104 patients were randomized 1:1:1:1:1 among the 5 groups. Median reductions in serum hepatitis B virus (HBV) DNA levels at week 52 (log(10) copies/mL) were as follows: lamivudine, 4.66; telbivudine 400 mg, 6.43; telbivudine 600 mg, 6.09; Comb400, 6.40; and Comb600, 6.05. At week 52, telbivudine monotherapy showed a significantly greater mean reduction in HBV DNA levels (6.01 vs 4.57 log(10) copies/mL; P < .05), clearance of polymerase chain reaction-detectable HBV DNA (61% vs 32%; P < .05), and normalization of alanine aminotransferase levels (86% vs 63%; P < .05) compared with lamivudine monotherapy, with proportionally greater HBeAg seroconversion (31% vs 22%) and less viral breakthrough (4.5% vs 15.8%) (P = NS for both). Combination treatment was not better than telbivudine alone. All treatments were well tolerated. In exploratory scientific analyses, clinical efficacy at 1 year appeared related to reduction in HBV DNA levels in the first 6 months of treatment. CONCLUSIONS: Patients with chronic hepatitis B treated with telbivudine exhibited significantly greater virologic and biochemical responses compared with lamivudine. Results with the combination regimens were similar to those obtained with telbivudine alone. These data support the ongoing phase 3 evaluation of telbivudine for treatment of patients with chronic hepatitis B.

Adolescent↗
PubMed2005

Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease.

BACKGROUND & AIMS: The aim of this study was to determine the diagnostic use of noninvasive markers of fibrosis in patients with chronic alcoholic liver disease. METHODS: A total of 221 consecutive patients with an alcohol intake of >50 g/day (median, 100 g/day) and available liver biopsy examination and FibroTest FibroSure (FT) results were included prospectively. Fibrosis was assessed blindly on a 5-stage histologic scale similar to that of the METAVIR scoring system. Hyaluronic acid was measured and used as a standard serum marker of fibrosis. RESULTS: Advanced fibrosis (F2-F4) was present at biopsy examination in 63% of patients. The mean FT value (SE) was F0 = .29 (.05); F1 = .29 (.03), F2 = .40 (.03), F3 = .53 (.04); and F4 = .88 (.02) (P < .05 between all groups, except between F0 and F1). As opposed to FT, there was no significant difference for hyaluronic acid between F2 and F1 and between F2 and F0. For F2-F4 vs. F0-F1, the FT area under the ROC curves (AUROC) = .84 (.03) and .79 (.03) for hyaluronic acid. For the diagnosis of F4, the AUROC was very high, .95 for FT and .93 for hyaluronic acid. The discordances of the 2 stages were attributed to biopsy failures in 26 cases and to FT failures in 13 cases. CONCLUSIONS: In heavy drinkers, FT is a simple and noninvasive quantitative estimate of liver fibrosis. The use of FT may decrease the need for liver biopsy examination.

Biomarkers↗
PubMed2005

Sampling variability of liver biopsy in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. METHODS: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test. RESULTS: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. CONCLUSIONS: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.

Adult↗
PubMed2005

A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients.

BACKGROUND & AIMS: Entecavir is a nucleoside analogue with potent in vitro activity against lamivudine-resistant hepatitis B virus (HBV). This randomized, dose-ranging, phase 2 study compared the efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients. METHODS: Hepatitis B e antigen (HBeAg)-positive and -negative patients (n = 182), viremic despite lamivudine treatment for > or =24 weeks or having documented lamivudine resistance substitutions, were switched directly to entecavir (1.0, 0.5, or 0.1 mg daily) or continued on lamivudine (100 mg daily) for up to 76 weeks. RESULTS: At week 24, significantly more patients receiving entecavir 1.0 mg (79%) or 0.5 mg (51%) had undetectable HBV DNA levels by branched chain DNA assay compared with lamivudine (13%; P < .0001). Entecavir 1.0 mg was superior to entecavir 0.5 mg for this end point (P < .01). After 48 weeks, mean reductions in HBV DNA levels were 5.06, 4.46, and 2.85 log(10) copies/mL on entecavir 1.0, 0.5, and 0.1 mg, respectively, significantly higher than 1.37 log(10) copies/mL on lamivudine. Significantly higher proportions of patients achieved normalization of alanine aminotransferase levels on entecavir 1.0, 0.5, and 0.1 mg (68%, 59%, and 47%, respectively) than on lamivudine (6%). One virologic rebound due to resistance occurred (in the 0.5-mg group). CONCLUSIONS: In HBeAg-positive and HBeAg-negative lamivudine-refractory patients, treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and resulted in significant reductions in HBV DNA levels and normalization of alanine aminotransferase levels. One milligram of entecavir was more effective than 0.5 mg in this population.

Adult↗
PubMed2005

FAS promoter polymorphisms correlate with activity grade in hepatitis C patients.

OBJECTIVE: Hepatocytes are susceptible to FAS-mediated apoptosis. The impact of polymorphisms in the FAS gene on histopathological features of HCV infection was therefore investigated. DESIGN/METHODS: Three single-nucleotide polymorphisms in the FAS promoter were assessed in 190 patients with chronic hepatitis C. Associations between FAS haplotypes and fibrosis stage and activity grade were tested by univariate and multivariate analyses. RESULTS: While there was no correlation between FAS promoter genotype and fibrosis stage, patients carrying the GCA haplotype (P=0.03, Fisher's exact test) and those homozygous for the GTG haplotype (P = 0.06) tended to have lower activity scores. Logistic regression showed that these associations were independent of patient age, sex and alcohol consumption. In a logistic regression model incorporating only male gender (odds ratio 2.1, 95% confidence interval 1.1-4.1 P = 0.04), the presence of the GCA haplotype (OR 0.31 95% CI 0.13-0.78 P = 0.01), and GTG homozygosity (OR 0.26 95% CI 0.08-0.83 P = 0.02), all three factors were independently correlated with activity grade. Furthermore, the GTG haplotype appeared to have lower promoter activity than the wild type GTA haplotype in a hepatocellular carcinoma cell line. CONCLUSIONS: Genetic polymorphism in the FAS gene may account for some of the histopathological variability in chronic hepatitis C.

Adult↗
PubMed2005

Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection.

OBJECTIVES: The noninvasive serum markers, FibroTest-ActiTest (FT-AT), are an alternative to liver biopsy in patients with chronic hepatitis C and B. The aim was to use these markers in a prospective study of patients treated with lamivudine in order to assess the impact of treatment, as well as the factors associated with fibrosis progression. METHODS: Two hundred and ninety-eight patients were included in a prospective longitudinal study in 50 hospitals across France. FT-AT were measured at baseline, and then after 6, 12, and 24 months of lamivudine 100-mg treatment. Epidemiological, clinical, and virologic characteristics were analyzed by univariate and multivariate analysis. RESULTS: Two hundred and eighty-three patients were included for analysis. The accuracy of FT-AT versus biopsy was validated with the area under the ROC curve, 0.77 (SE = 0.03) for bridging fibrosis and 0.75 (SE = 0.06) for severe activity (A3). At baseline, bridging fibrosis (METAVIR stages F2-F3-F4) was highly associated (p < 0.001) in multivariate analysis with male gender and age and marginally associated with anti-HBe presence (p= 0.05) and non-Asian ethnic origin (p= 0.046). Lamivudine treatment had a very significant impact overall. FT decreased significantly from 0.51 at baseline to 0.37 at 24 months (p < 0.001), and 85% of patients had improvement at 24 months. AT also decreased significantly from 0.56 to 0.13 (p < 0.0001), and 91% of patients had improvement at 24 months. A three-phase kinetics was observed for both fibrosis and activity; there was a marked improvement during the first 6 months, followed by a plateau between 6 and 12 months, and another improvement between 12 and 24 months. The occurrence of a YMDD variant does not entirely explain these three-phase variations. The first phase impact on fibrosis rates was higher in Asian patients (p= 0.01) and in patients younger than 40 yr (p < 0.001). CONCLUSIONS: In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT-AT should be useful in the noninvasive follow-up of lamivudine treatment.

Adult↗
PubMed2005

A reference material for traceability of aspartate aminotransferase (AST) results.

Standardization of aspartate aminotransferase (AST) determination is highly desirable for inter-laboratory comparison. Serum AST mean values for 20 patients suffering from viral hepatitis showed an inter-laboratory (n = 13) variation of 9.4%. Part of this variation was due to two laboratories using procedures without pyridoxal-5'-phosphate. A traceable AST value was assigned to an enzyme calibrator (EC) through the appropriate International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) primary reference procedure. The EC was commutable for seven routine methods. Common calibration using the EC reduced the inter-laboratory coefficient of variation (CV = 5.9% ) and allowed retention of a common reference interval for a set of routine procedures. Calibration made superfluous the expression of results in multiples of the upper reference limit, which increased inter-laboratory variation (CV = 18.5%). Furthermore, for 92% of patients, calibration with the EC allowed the correction of misclassifications when taking into account the reference interval of the reference procedure. Use of this EC could be proposed to complete the AST reference system.

Adult↗
PubMed2005

FibroTest-FibroSURE: towards a universal biomarker of liver fibrosis?

Among the noninvasive alternatives to liver biopsy, several studies have demonstrated the predictive value and superior benefit/risk ratio to biopsy of two combinations of simple serum biochemical markers in patients infected with hepatitis B and C virus. These include FibroTest (BioPredictive) for the quantitative assessment of fibrosis, and ActiTest (BioPredictive) for the quantitative assessment of necroinflammatory activity (HCV-FibroSURE, LabCorp). The possible causes of false negatives and positives are also better identified. These tests, which are now available in 12 countries, can facilitate the screening and management of the most frequent liver diseases.

Biomarkers↗
PubMed2004

Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C.

SUMMARY: BACKGROUND: Recent studies strongly suggest that due to the limitations and risks of biopsy, as well as the improvement of the diagnostic accuracy of biochemical markers, liver biopsy should no longer be considered mandatory in patients with chronic hepatitis C. In 2001, FibroTest ActiTest (FT-AT), a panel of biochemical markers, was found to have high diagnostic value for fibrosis (FT range 0.00-1.00) and necroinflammatory histological activity (AT range 0.00-1.00). The aim was to summarize the diagnostic value of these tests from the scientific literature; to respond to frequently asked questions by performing original new analyses (including the range of diagnostic values, a comparison with other markers, the impact of genotype and viral load, and the diagnostic value in intermediate levels of injury); and to develop a system of conversion between the biochemical and biopsy estimates of liver injury. RESULTS: A total of 16 publications were identified. An integrated database was constructed using 1,570 individual data, to which applied analytical recommendations. The control group consisted of 300 prospectively studied blood donors. For the diagnosis of significant fibrosis by the METAVIR scoring system, the areas under the receiver operating characteristics curves (AUROC) ranged from 0.73 to 0.87. For the diagnosis of significant histological activity, the AUROCs ranged from 0.75 to 0.86. At a cut off of 0.31, the FT negative predictive value for excluding significant fibrosis (prevalence 0.31) was 91%. At a cut off of 0.36, the ActiTest negative predictive value for excluding significant necrosis (prevalence 0.41) was 85%. In three studies there was a direct comparison in the same patients of FT versus other biochemical markers, including hyaluronic acid, the Forns index, and the APRI index. All the comparisons favored FT (P < 0.05). There were no differences between the AUROCs of FT-AT according to genotype or viral load. The AUROCs of FT-AT for consecutive stages of fibrosis and grades of necrosis were the same for both moderate and extreme stages and grades. A conversion table was constructed between the continuous FT-AT values (0.00 to 1.00) and the expected semi-quantitative fibrosis stages (F0 to F4) and necrosis grades (A0 to A3). CONCLUSIONS: Based on these results, the use of the biochemical markers of liver fibrosis (FibroTest) and necrosis (ActiTest) can be recommended as an alternative to liver biopsy for the assessment of liver injury in patients with chronic hepatitis C. In clinical practice, liver biopsy should be recommended only as a second line test, i.e., in case of high risk of error of biochemical tests.

Journal Article↗
PubMed2004

Intra-individual fasting versus postprandial variation of biochemical markers of liver fibrosis (FibroTest) and activity (ActiTest).

BACKGROUND: Biochemical marker combinations, including alpha2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase, and total bilirubin (all part of FibroTest) plus alanine aminotransferase (all part of ActiTest), are being developed as alternatives to liver biopsy in patients with chronic hepatitis C and other various chronic liver diseases. Considering this premise, the primary aim of this study was to assess the impact of meal intake on FibroTest and ActiTest results. Such studies are very important for patients, as many clinical errors have been related to the absence of baseline evidence. RESULTS: Intra-individual variation was assessed for the 6 above components and for FibroTest and ActiTest, by measuring time dependent variations before and one hour after a standard meal in 64 subjects. These consisted of 29 healthy volunteers and 35 patients with chronic liver diseases. Meal intake had no significant impact on any of the six components, or on FibroTest or ActiTest, as assessed by repeated measure variance analyses (ANOVA all p > 0.90); the Spearman correlation coefficient ranged from 0.87 (total bilirubin) to 0.995 (gamma-glutamyl transpeptidase). The coefficients of variation (CV) between fasting and postprandial measurements fluctuated for the six components from 0.09 (apolipoprotein A1) to 0.14 (alpha2-macroglobulin), and from 0.09 for FibroTest to 0.13 for ActiTest. In contrast, meal intake had a significant impact on triglycerides (ANOVA p = 0.01, CV = 0.65) and glucose (ANOVA p = 0.04, CV = 0.31). As for the prediction of liver injury, the concordance between fasting and postprandial predicted histological stages and grades was almost perfect, both for FibroTest (kappa = 0.91, p < 0.001) and ActiTest (kappa = 0.80, p < 0.001). CONCLUSIONS: The intra-individual variation of biochemical markers was low, and it was shown that measurements of FibroTest, ActiTest and their components are not significantly modified by meal intake. This fact makes the screening of patients at risk of chronic liver diseases more convenient.

Journal Article↗
PubMed2004

Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.

BACKGROUND: The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure. METHODS: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers. RESULTS: Only 74 of 537 patients (14%) had a biopsy size > or =25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failures attributable to markers were false negatives (1.3%) attributable to inflammation. The most frequent failures attributable to biopsy were false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False positives of fibrosis staging (3.5%) were associated with fragmented biopsies. CONCLUSION: In this series, the size of liver biopsy is adequate in only a minor proportion (approximately 14%) of patients with chronic hepatitis C. When biopsy and marker results are discordant, a reason can be identified in more than two-thirds of cases and, in those cases, biopsy failure is >7 times more common than diagnostic failure of markers.

Adult↗
PubMed2004

Pegylated interferon alpha 2b and ribavirin in HIV/hepatitis C virus-co-infected non-responders and relapsers to IFN-based therapy.

BACKGROUND: Pegylated interferon alpha (PEG-IFN-alpha) and ribavirin is the most effective available treatment for chronic hepatitis C virus (HCV) infection. Its role in HIV/HCV-co-infected patients who have failed IFN-based therapy is unclear. OBJECTIVE: The aim of this study was to determine the safety and efficacy of this therapy in HIV/HCV-co-infected non-responders and relapsers. DESIGN: An open-label cohort study of 32 non-responders and relapsers to IFN (with or without ribavirin). Patients were treated for 48 weeks with PEG-IFN-alpha 2b and ribavirin. MAIN OUTCOME MEASURE: A sustained virological response (SVR) defined as a negative HCV-RNA level 24 weeks after the end of treatment. RESULTS: The mean age of the patients was 40 years; 78% were men, 67% had genotype 1, and 36% had bridging fibrosis or cirrhosis. The majority had a CD4 cell count greater than 200 cells/microl (97%) and an undetectable HIV-RNA level (81%). Fifteen patients (47%) withdrew because of adverse events, predominantly neuropsychiatric. In an intention-to-treat analysis, a SVR was observed in five patients (16%); 9% with genotype 1 versus 29% with genotype 3 and 33% with genotype 4 (P = NS). Additional, but statistically non-significant, univariate predictors of response were lower serum HCV-RNA (P = 0.07) and higher alanine aminotransferase levels (P = 0.055) at baseline. No patient with bridging fibrosis or cirrhosis responded. Treatment had a minimal impact on HIV parameters. CONCLUSION: PEG-IFN-alpha 2b and ribavirin is a potentially useful therapy in HIV/HCV-co-infected patients who have failed standard IFN-based regimens. Strategies to improve adherence are vital so as to maximize long-term response rates.

Adult↗