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Thierry Poynard

Publications and source records attributed to Thierry Poynard.

At least 19 recordsLinked to original sources
PubMed2006

Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Liver biopsy is considered the gold standard for assessing histologic lesions of non-alcoholic fatty liver disease (NAFLD). The aim was to develop and validate a new biomarker of non alcoholic steato hepatitis (NASH) the NashTest (NT) in patients with NAFLD. METHODS: 160 patients with NAFLD were prospectively included in a training group, 97 were included in a multicenter validation group and 383 controls. Histological diagnoses used Kleiner et al's scoring system, with 3 classes for NASH: "Not NASH", "Borderline", "NASH"). The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV, NPV) were assessed. RESULTS: NT was developed using patented algorithms combining 13 parameters: age, sex, height, weight, and serum levels of triglycerides, cholesterol, alpha2macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase, transaminases ALT, AST, and total bilirubin. AUROCs of NT for the diagnosis of NASH in the training and validation groups were, respectively, 0.79 (95%C I 0.69-0.86) and 0.79 (95% CI 0.67-0.87; P = 0.94); for the diagnosis of borderline NASH they were: 0.69 (95% CI 0.60-0.77) and 0.69 (95% CI 0.57-0.78; P = 0.98) and for the diagnosis of no NASH, 0.77 (95% CI 0.68-0.84) and 0.83 (95% CI 0.67-0.90; P = 0.34). When the two groups were pooled together the NashTest Sp for NASH = 94% (PPV = 66%), and Se = 33% (NPV = 81%); for borderline NASH or NASH Sp = 50% (PPV = 74%) and Se = 88% (NPV = 72%). CONCLUSION: In patients with non-alcoholic fatty liver disease, NashTest, a simple and non-invasive biomarker reliably predicts the presence or absence of NASH.

Algorithms↗
PubMed2006

Fibrosis as an end point for clinical trials in liver disease: a report of the international fibrosis group.

Deaths due to the consequences of advanced liver fibrosis and cirrhosis remain a significant cause of mortality worldwide. Biologically plausible pathways involved in hepatic fibrogenesis have also led to the identification of numerous preclinical and clinical compounds that have received great interest as potential future therapeutic agents for patients with liver fibrosis. With this in mind, stake holders from academia, regulatory agencies, clinicians, and the pharmaceutical industry met to understand and discuss the many complex issues involved in developing potential therapeutic agents which act primarily through modifying fibrosis and to discuss appropriate end points for clinical trials in these patient populations. In this article, we summarize those discussions and attempt to highlight many of the hurdles and unanswered questions as we attempt to move forward and develop therapies to combat liver fibrosis.

Animals↗
PubMed2006

A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C.

BACKGROUND: FibroTest, a noninvasive method of measuring biomarkers of liver fibrosis, is an alternative to liver biopsy for determining the severity of chronic hepatitis C virus (HCV) infection. We compared the 5-year prognostic value of the FibroTest with biopsy staging for predicting cirrhosis decompensation and survival in patients with chronic HCV infection. METHODS: Fibrosis stage was assessed on the same day by FibroTest and biopsy in a prospective cohort of 537 patients. Disease classification at baseline was 157 patients with severe fibrosis (FibroTest >0.58), 137 with moderate fibrosis (FibroTest 0.32-0.58), and 243 with no or minimal fibrosis (FibroTest <0.32). RESULTS: In 64 untreated patients with severe fibrosis, survival without HCV complications was 73% [95% confidence interval (CI), 59%-086%; 13 complications], and survival without HCV-related death was 85% (95% CI, 73%-96%; 7 HCV deaths). Survival rates were higher in patients with moderate fibrosis, [99% (95% CI, 97%-100%; 1 complication; P <0.001) and 100% (no HCV death; P <0.001) for patients with and without HCV-related complications, respectively], and in patients with minimal fibrosis [100% (no complication; P <0.001 vs severe) and 100% (no HCV death; P <0.001 vs severe), respectively]. FibroTest was a better predictor than biopsy staging for HCV complications, with area under the ROC curves (AUROC) = 0.96 (95% CI, 0.93%-0.97%) vs 0.91 (95% CI, 0.85%-0.94%; P = 0.01), respectively; it was also a better predictor for HCV deaths: AUROC = 0.96 (95% CI, 0.93%-0.98%) vs 0.87 (95% CI, 0.70%-0.94%; P = 0.046), respectively. The prognostic value of FibroTest was still significant (P <0.001) in multivariate analyses after taking into account histology, treatment, alcohol consumption, and HIV coinfection. CONCLUSION: The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy.

Alanine Transaminase↗
PubMed2006

The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steato-hepatitis in patients with chronic alcoholic liver disease.

BACKGROUND/AIMS: The aim was to identify a panel of biomarkers (AshTest) for the diagnosis of alcoholic steato-hepatitis (ASH), in patients with chronic alcoholic liver disease. METHODS: Biomarkers were assessed in patients with an alcohol intake>50 g/d, in a training group, and in two validation groups. Diagnosis of ASH (polymorphonuclear infiltrate and hepatocellular necrosis) and its histological severity (four classes: none, mild, moderate and severe) were assessed blindly. RESULTS: Two hundred and twenty-five patients were included, 70 in the training group, 155 in the validation groups, and 299 controls. AshTest was constructed using a combination of the six components of FibroTest-ActiTest plus aspartate aminotransferase. The AshTest area under the ROC curves for moderate-severe ASH was 0.90 in the training group, 0.88 and 0.89 in the validation groups. The median AshTest value was 0.005 in controls, 0.05 in patients without or with mild ASH, 0.64 in moderate, and 0.84 in severe ASH grade 3, (P<0.05 between all groups). At a 0.50 cut-off, the sensitivity of AshTest was 0.80 and the specificity was 0.84. CONCLUSIONS: In heavy drinkers, AshTest is a simple and non-invasive quantitative estimate of alcoholic hepatitis. The use of AshTest may reduce the need for liver biopsy, and therefore allow an earlier treatment of alcoholic hepatitis.

Adult↗
PubMed2006

Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions. The aim of this study was to determine the diagnostic utility of non-invasive markers of fibrosis, validated in chronic viral hepatitis and alcoholic liver disease (FibroTest, FT), in patients with NAFLD. METHODS: 170 patients with suspected NAFLD were prospectively included in a reference center (Group 1), 97 in a multicenter study (Group 2) and 954 blood donors as controls. Fibrosis was assessed on a 5 stage histological scale validated by Kleiner et al from F0 = none, F1 = perisinusoidal or periportal, F2 = perisinusoidal and portal/periportal, F3 = bridging and F4 = cirrhosis. Histology and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) were assessed. RESULTS: In both groups FT has elevated and not different AUROCs for the diagnosis of advanced fibrosis (F2F3F4): 0.86 (95%CI 0.77-0.91) versus 0.75 (95%CI 0.61-0.83; P = 0.10), and for F3F4: 0.92 (95%CI 0.83-0.96) versus 0.81 (95%CI 0.64-0.91; P = 0.12) in Group 1 and Group 2 respectively. When the 2 groups were pooled together a FT cutoff of 0.30 had a 90% NPV for advanced fibrosis (Se 77%); a FT cutoff of 0.70 had a 73% PPV for advanced fibrosis (Sp 98%). CONCLUSION: In patients with NAFLD, FibroTest, a simple and non-invasive quantitative estimate of liver fibrosis reliably predicts advanced fibrosis.

Age Factors↗
PubMed2006

A novel dendritic cell subset involved in tumor immunosurveillance.

The interferon (IFN)-gamma-induced TRAIL effector mechanism is a vital component of cancer immunosurveillance by natural killer (NK) cells in mice. Here we show that the main source of IFN-gamma is not the conventional NK cell but a subset of B220(+)Ly6C(-) dendritic cells, which are atypical insofar as they express NK cell-surface molecules. Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220(+)NK1.1(+) dendritic cells secrete high levels of IFN-gamma and mediate TRAIL-dependent lysis of tumor cells. Adoptive transfer of these IFN-producing killer dendritic cells (IKDCs) into tumor-bearing Rag2(-/-)Il2rg(-/-) mice prevented tumor outgrowth, whereas transfer of conventional NK cells did not. In conclusion, we identified IKDCs as pivotal sensors and effectors of the innate antitumor immune response.

Adoptive Transfer↗
PubMed2006

Irinotecan as first-line chemotherapy in patients with advanced hepatocellular carcinoma: a multicenter phase II study with dose adjustment according to baseline serum bilirubin level.

This study assessed the clinical activity and safety of irinotecan (CPT-11) in patients with advanced hepatocellular carcinoma (HCC) using dose adjustment according to baseline serum bilirubin level. Patients with advanced HCC received CPT-11 at a dose of 350 mg/m(2) when total bilirubin level was 1.5 times upper limit of normal (ULN) (group A), or 200 mg/m(2) when total bilirubin level was between 1.51 and 3 ULN (group B). No objective response, one minor response and 12 disease stabilizations were observed in the 29 patients (group A, 23; group B, 6) enrolled. Median time to progression and overall survival were 3.1 months (95% confidence interval [CI]: 2.0-4.0) and 7.4 months (95% CI: 3.9-12.0), respectively. Grade 3-4 adverse events (mostly neutropenia [47%], anaemia [24%], and diarrhoea [17%]) were more frequent in group A (74%) than in group B (33%) (P = 0.086). This study found favourable toxicity profile using dosage adjustment to the baseline total bilirubin level in patients with bilirubin level comprised between 1.51 and 3 ULN. However, the antitumour activity of single agent CPT-11 was not significant in advanced HCC.

Adolescent↗
PubMed2006

Successful rescue therapy with tenofovir in a patient with hepatic decompensation and adefovir resistant HBV mutant.

BACKGROUND: Prolonged adefovir therapy exposes to the emergence of adefovir resistant hepatitis B virus mutants. Initial reports of the rtN236T mutation showed preserved sensitivity to lamivudine; however, complex mutations are emerging with reduced susceptibility to lamivudine. CASE PRESENTATION: After 2 years of therapy, a cirrhotic patient developed the rtN236T and rtA181T adefovir resistant mutations. He had been previously treated with lamivudine, developed lamivudine resistance and, despite good compliance, had an incomplete response to adefovir. Adefovir resistance resulted in viral breakthrough with hepatitis flare-up and liver decompensation. Tenofovir had an excellent antiviral effect allowing sustained control of viral replication and reversal of hepatic failure. CONCLUSION: In patients with cirrhosis, adefovir resistance can lead to severe hepatitis. Tenofovir appears to be an effective treatment of adefovir resistant mutants. Incomplete control of viral replication with adefovir requires monitoring for viral resistance and should prompt a change in antiviral treatment.

Journal Article↗
PubMed2006

Intrahepatic virus-specific IL-10-producing CD8 T cells prevent liver damage during chronic hepatitis C virus infection.

CD8 T cell killing of hepatitis C virus (HCV)-infected hepatocytes is thought to contribute to liver damage during chronic HCV infection, whereas the participation of HCV-nonspecific immune cells is unclear. To visualize the spatial relationship of HCV-specific CD8 T cells with parenchymal target cells, and to examine their local functional activity in relation to hepatocellular necrosis and fibrosis, we used HLA tetramers and confocal microscopy in biopsies from 23 HLA-A2 or HLA-B7 patients with chronic HCV infection. Intrahepatic tetramer+ (HCV-specific) CD8 T cells protected from hepatic necroinflammatory disease activity, independently of age, gender, viral load, and viral genotype. Indeed, tetramer+ cells were scattered in the liver within regions of weak fibrosis (low laminin expression) and low hepatocellular apoptosis (TUNEL method), and expressed IL-10 but not IFNgamma. By contrast, tetramer-negative CD8 T cells were associated with active necroinflammatory liver disease, colocalized with strong laminin expression and hepatocellular apoptosis, and expressed more frequently IFNgamma than IL-10. Overall, liver regions harboring HCV-specific CD8 T cells tended to be healthier than areas containing only inflammatory cells of undefined specificity. In conclusion, HCV-specific IL-10-producing CD8 T cells, although not cytotoxic and unable to control viral replication, can attenuate hepatocellular necrosis, liver fibrosis, and inflammation mediated by bystander T cells, and may thus represent antigen-induced regulatory CD8 T cells. Therapeutic modulation of the intrahepatic balance between specific and bystander CD8 T cells might be beneficial in patients with chronic hepatitis C.

Adult↗
PubMed2006

Biological markers of liver fibrosis and activity as non-invasive alternatives to liver biopsy in patients with chronic hepatitis C and associated mixed cryoglobulinemia vasculitis.

OBJECTIVE AND METHODS: We assessed the reliability of non-invasive biological scoring indexes (Fibrotest-Actitest [FT-AT], Forns, APRI, age-platelet, platelet, hyaluronic acid) as non-invasive alternatives to liver biopsy (LB) in 138 HCV-infected patients. RESULTS: Thirty-six of 138 (26%) patients had systemic vasculitis, 27% significant serum inflammation, 47% fibrosis (F2F3F4) on LB. The diagnostic value of FT (F2F3F4 vs. F0F1) was assessed by an AUC of 0.83, without difference regarding to systemic vasculitis or serum inflammation. A discordance between FT-AT and the Metavir scoring indexes, present in 29% of patients, was associated with serum hemolysis and male but not with systemic vasculitis or serum inflammation. The other non-invasive biological tests were not influenced by serum inflammation or systemic vasculitis but were less reliable than FT (P <or= 0.05). CONCLUSION: The FT-AT is a reliable non-invasive biochemical alternative to LB in HCV-infected patients with systemic vasculitis and is more reliable than other non-invasive biological indexes.

Adult↗
PubMed2006

Impact of irritable bowel syndrome (IBS) on health-related quality of life (HRQOL).

AIMS: To assess the impact of irritable bowel syndrome (IBS) on patient-reported health-related quality of life (HRQOL). METHODS: Two HRQOL instruments were administered by telephone interviews to a sample of 253 IBS French patients recruited from the general population. IBS was diagnosed according to the Manning, Rome I and Rome II criteria. Patients with organic diseases were excluded from the study. A generic instrument, the Short Form 36 (SF-36), and an IBS disease-specific instrument, the IBSQOL, were used. RESULTS: Patients with IBS had statistically significant (P<0.05) lower scores for all SF-36 QOL domains compared with the general French population. Women (N=192) reported significantly (P<0.05) poorer HRQOL on both the SF-36 and the IBSQOL scores than men (N=61) for all domains except energy on the SF36 and the sleep on the IBSQOL. HRQOL deteriorated with time since onset of IBS symptoms for some domains such as diet. For both instruments, a positive correlation was observed between low scores and intensity of pain and discomfort. IBS patients with a predominance of diarrhea (N=72) exhibited significantly greater impairment of HRQOL in the emotional domain than IBS persons with constipation predominance (N=65) (P<or=0.05). CONCLUSION: IBS has a significant impact on HRQOL of patients. In addition, specific characteristics such as gender, symptom severity and time since onset of symptoms are predictive of more impaired health-related quality of life.

Adolescent↗
PubMed2006

Non-invasive diagnosis of large oesophageal varices with FibroTest in patients with cirrhosis: a preliminary retrospective study.

BACKGROUND AND AIMS: Primary prevention of variceal bleeding with beta-blockers improves survival in patients with large oesophageal varices (LOV). Therefore, cirrhotic patients frequently undergo screening endoscopy. As portal hypertension is related to liver fibrosis, this study aimed to assess the predictive value of FibroTest, a non-invasive marker of liver fibrosis, for the diagnosis of LOV in cirrhotic patients. METHODS: Ninety-nine cirrhotic patients had clinical examination, blood sample (liver function tests, platelet count, FibroTest) and upper endoscopy. Measurements of endoscopic and biochemical parameters were made blindly. Sensitivity, specificity, predictive values and area under the receiver operating characteristic curves were assessed for FibroTest, platelet count and Child-Pugh score. The main endpoint was the presence of LOV. RESULTS: Platelet count, prothrombin time, ascites, FibroTest and Child-Pugh class were significantly different among patients with or without LOV. FibroTest had the highest discriminative power with an area under receiver operating characteristics curves of 0.77 (SE=0.06), compared with 0.64 (0.08) and 0.68 (0.08) for platelet count and Child-Pugh score, respectively (P=0.08). A cut-off at 0.80 had a 86% negative predictive value for the diagnosis of LOV (Se=92%, Sp=21%). CONCLUSION: FibroTest could aid in the diagnosis of LOV and may therefore reduce the indication of endoscopic screening in cirrhotic patients.

Adult↗
PubMed2006

Hepatitis C in 6,865 patients 65 yr or older: a severe and neglected curable disease?

BACKGROUND: Few data are available on chronic hepatitis C (CHC) in elderly patients. The aim of this study was to compare the features and severity of CHC and the efficacy/safety of antiviral therapy in patients<65, between 65 and 80, and >80 yr old, and to determine the usefulness of biochemical markers (Fibrotest-Fibrosure/ActiTest [FT-AT]) in aged patients. METHODS: This was a retrospective study with two groups of patients: Group 1: prospective cohort including all hepatitis C virus patients from our institution (N=4,182); Group 2: all consecutive patients who had FT-AT performed in France between 2002 and 2004 (N=33,738). RESULTS: A total of 6,865 patients>or=65 yr old was included (Group 1=881, Group 2=5,984). Group 1: patients>or=65 had a longer duration of and a higher age at infection, more genotype 1, and a history of transfusion (p<0.001). Among the 2,169 patients who underwent liver biopsy, bridging fibrosis (F2,F3,F4) was more frequent in patients>or=65 yr old, regardless of the duration of infection. In multivariate analysis, ages at biopsy and at infection were associated with F2,F3,F4. Discovery of CHC by a complication was more frequent in patients>or=65 yr (p<0.001). One hundred seventy patients>or=65 yr received antiviral therapy. A sustained virologic response was obtained in 45% of patients>or=65 yr treated with pegylated interferon/ribavirin. Group 2: At FT, 58% of patients>80 yr, 37% of patients between 65 and 80 yr, and 14% of patients<65 yr (p<0.001) had cirrhosis. Patients>80 yr (43%) with cirrhosis had nonelevated alanine amino transferase (ALT), compared with 31% of patients<65 yr (p<0.001). CONCLUSION: In patients>or=65 yr, CHC is more severe and presents with lower ALT than in younger patients. Treatment is effective. Biochemical markers seem particularly useful as a noninvasive alternative to liver biopsy in this population.

Aged↗
PubMed2006

Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of "a" determinant variants.

In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the "a" determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (P = 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.

Carrier State↗
PubMed2006

Intermethod calibration of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) results: application to Fibrotest and Actitest scores.

Two multi-component scores (Fibrotest and Actitest) have been proposed to evaluate liver fibrosis or necro-inflammatory lesions as an alternative to liver biopsy. This approach requires standardization of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) determinations. For this purpose, ALT and GGT values were assigned to a multi-enzyme material using the appropriate primary reference procedure. This material was used as a common calibrator for sera from 20 patients with viral hepatitis. Measurements were carried out in 11 laboratories, using their own automated routine methods and compared to results obtained using the primary reference procedure. The expression of results in multiples of the upper reference limit worsened the inter-laboratory variation for both enzymes. The multi-enzyme material was commutable for ALT and GGT determination carried out with six analytical systems. Common calibration significantly improved inter-laboratory consistency, which finally reached 1.8% and 3.3% for ALT and GGT, respectively. For each enzyme, it also permitted the retention of a common reference interval for a set of calibrated methods and the improvement of inter-laboratory coherency of Fibrotest and Actitest scores.

Adult↗
PubMed2005

The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis.

BACKGROUND: Biopsy is the usual gold standard for liver steatosis assessment. The aim of this study was to identify a panel of biomarkers (SteatoTest), with sufficient predictive values, for the non-invasive diagnosis of steatosis in patients with or without chronic liver disease. Biomarkers and panels were assessed in a training group of consecutive patients with chronic hepatitis C and B, alcoholic liver disease, and non-alcoholic fatty liver disease, and were validated in two independent groups including a prospective one. Steatosis was blindly assessed by using a previously validated scoring system. RESULTS: 310 patients were included in the training group; 434 in three validation groups; and 140 in a control group. SteatoTest was constructed using a combination of the 6 components of FibroTest-ActiTest plus body mass index, serum cholesterol, triglycerides, and glucose adjusted for age and gender. SteatoTest area under the ROC curves was 0.79 (SE = 0.03) in the training group; 0.80 (0.04) in validation group 1; 0.86 (0.03) in validation group 2; and 0.72 (0.05) in the validation group 3 - all significantly higher than the standard markers: gamma-glutamyl-transpeptidase or alanine aminotransferase. The median SteatoTest value was 0.13 in fasting controls; 0.16 in non-fasting controls; 0.31 in patients without steatosis; 0.39 in grade 1 steatosis (0-5%); 0.58 in grade 2 (6-32%); and 0.74 in grade 3-4 (33-100%). For the diagnosis of grade 2-4 steatosis, the sensitivity of SteatoTest at the 0.30 cut-off was 0.91, 0.98, 1.00 and 0.85 and the specificity at the 0.70 cut-off was 0.89, 0.83, 0.92, 1.00, for the training and three validation groups, respectively. CONCLUSION: SteatoTest is a simple and non-invasive quantitative estimate of liver steatosis and may reduce the need for liver biopsy, particularly in patients with metabolic risk factor.

Journal Article↗