biopsy (ALT: 0/2, HBV-DNA: 8/20, TE: 7/23, ALT+TE: 3/3, HBV-DNA+TE: 5/10).Grading and staging did not differ significantly in patients with or without HBV-DNA > 2000 IU/mL and with or without stiffness > 6.5 kPa, but were higher in the 8 patients with ALT+TE/HBV-DNA+TE biopsy indications than in the remaining 15 patients (grading:3.9±1.0 vs 2.9±1.0,p = 0.056; staging:1.9±0.8 vs 0.9±0.8,p = 0.016).Moderate fibrosis (staging score = 2-3) was found in 7/23 (30%) patients (grading minimal/mild: 3/4) being more frequent in cases with than without ALT+TE/HBV-DNA+TE [5/8 (63%) vs 2/15 (13%), p = 0.026] or with than without ALT+TE/HBV-DNA+TE or stiffness > 9.5 kPa [6/9 (67%) vs 1/14 (7%), p = 0.005].Conclusions: Up to 30% of HBeAg-negative chronic HBV carriers without elevated both ALT and HBV-DNA levels may have relatively high stiffness values (>6.5 kPa) by TE.However, only the rare cases with very high stiffness (>9.5 kPa) or those with the combination of stiffness values >6.5 kPa with elevated ALT (>ULN) and/or HBV-DNA (>2000 IU/mL) may benefit from a liver biopsy usually showing moderate fibrosis with minimal-mild necroinflammatory activity.

Background:The treatment of chronic hepatitis C is based on pegylated interferon-alpha (PEG-IFN) and ribavirin.This treatment allows a sustained virological response (SVR) for about 55% of the patients.Optimizing interferon and ribavirin efficacy remains a real challenge as they will still be associated with the new molecules.A number of virological factors (e.g. the hepatitis C virus (HCV) genotype and baseline titer of HCV RNA) may influence the treatment response.Here, we have evaluated the influence of host factor on the IFN activity one month after starting the treatment.Methods: The study enrolled 44 patients who were eligible for therapy.The treatment was based on the combined therapy pegylated IFN and ribavirin.The interferon concentration was determined one month after the initiation of the treatment with a bioassay based on the human interferon-inducible MxA promoter linked to the chloramphenicol acetyl transferase reporter gene.Results: For each patient, the interferon concentration was measured in the serum at month 1.We observed a great variability in the IFN concentration between the patients.The median of the interferon concentration at month 1 was significantly higher for patients having a Rapid Virological Response (RVR) or having an Early Virological Response (EVR) (RVR-: 364 IU/mL, RVR+: 834 IU/mL (p < 0.01), EVR+: 488 IU/mL, EVR-: 121 IU/mL (p < 0.01)).Moreover, patients non responder (NR) 6 months after the end of the treatment had a lower interferon concentration than Sustained Virological Responder (SVR) (Median NR: 164 IU/mL, SVR: 451 IU/mL (p < 0.01).There was a correlation between the IFN concentration and the interferon exposition (defined as the dose of interferon reported to the bodyweight) (r = 0.64541, p < 0.001) as well as with the bodyweight (r = -0.378,p = 0.0109).Conclusions: These results suggest that the bodyweight could influence the interferon concentration in the serum.This effect was strongly important with pegylated IFN alpha 2a used at fixed doses.The IFN concentration, measured with a bioassay could influence the response.It could be interesting to monitor the IFN concentration in addition to ribavirin in order to increase the response rate.This seems to be particularly right for patients with high bodyweight.

Introduction: Le dépistage des varices oesophagiennes (VO) par l'endoscopie digestive est recommandé chez les patients cirrhotiques. Une méthode non invasive pourrait être proposée.

En France, les données sur la prévalence de l'AgHBs au cours de la grossesse sont anciennes [1]. Le dépistage de l'AgHBs durant la grossesse, obligatoire depuis 1992, n'a fait l'objet que d'une évaluation à partir de données de l'Assurance Maladie. La Picardie appartient à l'interrégion nord-ouest caractérisée par la plus forte prévalence de l'AgHBs en France (11,2 p. 1000, INVS 2004). Notre but a été d'étudier la prévalence de l'AgHBs au cours de la grossesse en Picardie, et la traçabilité du dépistage. La Picardie a enregistré 22 595 accouchements du 01/01 au 31/12/2006 sur toutes les maternités publiques et privées. Trois méthodes ont été utilisées : 1) le dépistage de l'AgHBs et sa traçabilité ont été étudiés sur un échantillon de 1 198 dossiers cliniques, avec randomisation et stratification sur les 20 établissements de la région ; 2) pour toutes les grossesses enregistrées dans les données de l'Assurance maladie (Urcam), la prescription du dosage de l'AgHBs a été recherchée ; 3) les dossiers des nouveau-nés séro-vaccinés ont été recherchés par interrogation de la base PMSI et l'examen des registres des pharmacies des établissements et des blocs obstétricaux. A partir de l'échantillonnage des dossiers cliniques, la prévalence de l'AgHBs au cours de la grossesse en Picardie était de 1,8 p. 1000, avec une traçabilité du dépistage à 92,9 % (extrêmes : 65-100 % selon les maternités). Les données de l'Urcam ont identifié 20 724 grossesses et la prescription du dosage l'AgHBs a été répertoriée dans 47,9 % des cas. Les résultats à partir de dossiers des nouveau-nés séro-vaccinés sont en cours de validation (la prévalence de l'AgHBs au cours de la grossesse apparaît très variable selon les territoires de santé couverts par les maternités). La prévalence de l'AgHBs chez les femmes enceintes de Picardie est comparable aux données nationales de l'INVS 2004 (2,1 p. 1000 chez la femme). La traçabilité du dépistage est supérieure à 90 % mais avec de fortes disparités selon les maternités. Les données de l'Assurance Maladie ne permettent pas une utilisation à des fins épidémiologiques et médicales. Financement : DHOS (FMESPP), CHU Amiens (DRRC), Laboratoire Sanofi-Pasteur-MSD, Laboratoire Roche, Laboratoire français du Fractionnement et des Biotechnologies (LFB-Biomédicaments).

Le dépistage des varices œsophagiennes (VO) par l'endoscopie digestive est recommandé chez les patients cirrhotiques. Une méthode non invasive pourrait être proposée. 1) Evaluer les performances diagnostiques de l'élastométrie impulsionnelle ultrasonore hépatique pour la prédiction des VO ≥ 2. 2) Etudier la valeur pronostique de l'élasticité du foie chez les patients cirrhotiques. 183 trois patients cirrhotiques ont bénéficié d'examens cliniques, biologiques et échographiques. Une endoscopie œso-gastro-duodénale, et une mesure de l'élasticité hépatique par le Fibroscan® étaient réalisées par 2 opérateurs différents, en aveugle. 183 patients (64,5 % hommes) de 55,2 ± 11,6 ans, présentaient une cirrhose (MELD médian 9) alcoolique, virale, autres dans 102 (56,3 %), 58 (31,7 %) et 22 (12 %) cas.41 (22,4 %) avaient des VO ≥ 2. L'élasticité médiane (n = 183) était à 33,66 kPa (extrêmes : 12-75), plus élevée en présence de VO ≥ 2 (51,24 ± 1,61 vs. 29,81 ± 1,82, p < 0,0001), et d'une cirrhose alcoolique versus non alcooliques (40,39 ± 1,75 vs. 25,73 ± 1,82 kPa, p < 0,0001). Globalement (n = 183) une élasticité ≥ 48 kPa prédisait des VO ≥ 2 avec des sensibilités, spécificités, VPP, VPN à 73,2, 73,2, 44,1 et 90,4 %, et une aire sous la courbe ROC (AUROC) à 0,75 (IC 95 % : 0,69-0,82). Pour la cirrhose alcoolique (n = 103), le cut off était à 47,2 kPa avec des sensibilités, spécificités, VPP, VPN à 84,6, 63,6, 44 et 92,5 %, AUROC à 0,77 (0,68-0,85). Pour la cirrhose virale (n = 58), un cut off à 19,8 kPa présentait les performances diagnostiques respectives à 88,9, 55,1, 26,7, 96,4 %, et 0,73 (0,60-0,84). Avec 1 an de recul, 16 (8,75 %) patients décédaient. En analyse multivariée, l'élasticité hépatique n'était pas prédictive de la mortalité. L'étiologie de la cirrhose a un impact important pour la détermination du cut off d'élasticité diagnostique des VO ≥ 2. L'élasticité hépatique n'est pas prédictive de la mortalité à 1 an.

Objective. - Screening for maternal hepatitis B surface antigen (HBsAg) is mandatory in France since 1992, however, no evaluation is available. We studied the traceability of HBsAg screening and its prevalence in pregnant women in Picardy for year 2006.Patients and methods. - Traceability of HBsAg screening was studied in a sample of 1198 hospital case files, which were randomized and stratified for all the 20 clinics of the region (22,114 deliveries), both public and private. HBsAg prevalence was also studied using various registries (PMSI national database of medical acts performed during hospitalization, central pharmacies and obstetric theatres).Results. - The traceability of the screening was lacking in 9.9% (range: 0-34.7%, depending on the maternity clinic). The prevalence of HBsAg during pregnancy was 1.8 per 1000 women (upper limit: 4.3 per 1000) from the case files sample. Registries examination showed large variations of HBsAg's prevalence from 0 to 12.0 per 1000 (mean: 2.9; CI 95%: 7 to 17) among the region.Discussion and conclusion. - HBsAg traceability during pregnancy must be improved. HBsAg prevalence largely varies among maternity clinics and is a significant issue which is underestimated in France. (C) 2009 Elsevier Masson SAS. All rights reserved.

Aucune publication française n’est disponible pour évaluer la prise en charge des nouveau-nés (NN) de mères porteuses de l’antigène HBs (Ag HBs). Le but de cette étude était d’évaluer la traçabilité et la conformité aux recommandations des injections d’immunoglobulines spécifiques (Igs) aux NN dans les maternités publiques et privées de Picardie en 2006.Les dossiers des mères susceptibles d’être Ag HBs+ ont été cherchés par une requête dans le Programme de Médicalisation des systèmes d’information (PMSI). Les NN ayant reçu des Igs ont été recherchés à partir des registres de pharmacie et/ou des blocs obstétricaux et/ou d’une requête PMSI.Dix-neuf des 20 maternités de Picardie ont fourni des données. Nous avons analysé 145 dossiers (65 mères Ag HBs+, 75 Ag HBs -, 5 de statut inconnu) et 81 injections d’Igs tracées et 5 non tracées dans les dossiers. Vingt pour cent des injections d’Igs tracées (16/81) ont été faites hors des indications des recommandations (mère Ag HBs -). Dans 85 % des cas la dose administrée était conforme aux recommandations (100 UI), et dans 79 % des cas l’horaire d’injection était conforme (dans les 12 h après l’accouchement). La traçabilité des Igs (numéro de lot) était présente dans le dossier dans 69 % des cas. Au total, 40 % (32/81) des injections d’Igs tracées ont eu une indication pertinente, une dose et un horaire conformes aux recommandations et un numéro de lot présent dans le dossier. Un courrier de suivi pour la prise en charge de la mère et/ou de l’enfant était noté dans 40 dossiers sur 145.La prévention de la transmission verticale de l’hépatite B doit faire l’objet d’actions d’amélioration qui nécessitent une stratégie nationale et une mobilisation pluri-professionnelle avec une mise en œuvre locale.No French publication is avalaible to assess the prevention of the hepatitis B transmission during delivery. The aim of this study was to evaluate the traceability and the compliance with the guidelines for administration of hepatitis B immune globulin (Ig) in public and private maternities of Picardy.We obtained the files of the mothers who were likely to be HBsAg + by a query in the medico-administrative data base (PMSI). New borns who received hepatitis B Ig were obtained by the pharmacies and the obstetrical wards's registers and a PMSI query.Nineteen of 20 maternities participated to the study. One hundred and forty five files were identified (65 mothers HBsAg +, 75 HBsAg -, 5 unknown) and 81 hepatitis B Ig injections were rated in the file and 5 unrated. Twenty percent of the rated Ig injections (16/81) were not pertinent (new born from HbsAg - mothers). Dose complied with the guidelines (100 UI) in 85 % of cases and the schedule (within the 12 first hours after delivery) in 79 %. The traceability was present in 69 % of the files. As a whole, only 40 % (32/81) of Ig injections follow the guidelines indications (indication, recommended dose and time, traceability). A letter (for general practioner, pediatrician or hepatologist) for follow up of the baby or/and the mother was found in 40 files out of 145.The prevention of the hepatitis B transmission during the delivery must be improved through a national strategy with a multi-professional mobilisation plus a local implementation.

In resource-poor countries, the high cost of user fees for deliveries limits access to skilled attendance, and contributes to maternal and neonatal mortality and the impoverishment of vulnerable households. A growing number of countries are experimenting with different approaches to tackling financial barriers to maternal health care. This paper describes an innovative scheme introduced in Ghana in 2003 to exempt all pregnant women from payments for delivery, in which public, mission and private providers could claim back lost user fee revenues, according to an agreed tariff. The paper presents part of the findings of an evaluation of the policy based on interviews with 65 key informants in the health system at national, regional, district and facility level, including policymakers, managers and providers. The exemption mechanism was well accepted and appropriate, but there were important problems with disbursing and sustaining the funding, and with budgeting and management. Staff workloads increased as more women attended, and levels of compensation for services and staff were important to the scheme's acceptance. At the end of 2005, a national health insurance scheme, intended to include full maternal health care cover, was starting up in Ghana, and it was not yet clear how the exemptions scheme would fit into it.Dans les pays pauvres, le montant élevé des contributions demandées aux patientes pour les accouchements limite l'accès à des soins de qualité, tout en contribuant à la mortalité maternelle et néonatale et à l'appauvrissement des ménages vulnérables. Un nombre croissant de pays expérimentent différentes méthodes pour lever les obstacles financiers aux soins de santé maternelle. Un projet novateur, introduit au Ghana en 2003, exonérait toutes les femmes enceintes du paiement des accouchements et prévoyait que les praticiens publics, privés et des missions pouvaient récupérer leurs honoraires perdus, conformément à un barème convenu. L'article présente une partie des conclusions d'une évaluation de cette politique, sur la base d'entretiens avec 65 informateurs clés dans le système de santé aux niveaux national, régional, des districts et des maternités, notamment des responsables politiques, des gestionnaires et des praticiens. Le mécanisme d'exonération a été bien accepté et était satisfaisant, mais il connaissait de graves problèmes de décaissement des fonds et de maintien du financement, ainsi que de budgétisation et de gestion. La charge de travail du personnel a augmenté car davantage de femmes ont demandé des soins, et les niveaux de compensation pour les services et le personnel étaient importants pour l'acceptation du projet. Fin 2005, un plan national d'assurance maladie, devant couvrir totalement les soins de santé maternelle, démarrait au Ghana et la manière dont le projet d'exonération s'y adapterait n'était pas encore claire.En los países con pocos recursos, el alto costo de las tarifas por partos limita el acceso a asistencia calificada y contribuye a la mortalidad materna y neonatal y al empobrecimiento de hogares vulnerables. En un creciente número de países se está experimentando con diferentes estrategias para afrontar los obstáculos financieros a los servicios de salud materna. En este artículo se describe un plan innovador presentado en Ghana en 2003 para eximir a todas las mujeres embarazadas de pagos por parto, mediante el cual los prestadores de servicios públicos, misioneros y privados pueden reclamar ingresos perdidos de tarifas de usuarias, de acuerdo con una tarifa acordada. Se expone parte de los resultados de una evaluación de la política basada en entrevistas con 65 informantes clave (incluidos formuladores de políticas, administradores y prestadores de servicios) del sistema de salud a nivel nacional, regional, distrital y local. El mecanismo de exención fue bien aceptado y apropiado, pero hubo problemas importantes con el desembolso y sustento del financiamiento, así como con los presupuestos y la administración. El volumen de trabajo del personal aumentó a medida que se atendían más mujeres, y los niveles de remuneración por servicios y personal fueron esenciales para la aceptación del plan. A fines de 2005, se estaba iniciando en Ghana un plan nacional de seguro médico, con el objetivo de incluir cobertura completa de servicios de salud materna, pero aún no era claro cómo el plan de exenciones se integraría a éste.

We read the article by Fraquelli et al ( Gut 2007; 56 :968–73) with great interest. In addition to the Fibroscan’s excellent reproducibility, the authors reported stiffness cut-offs for the non-invasive diagnosis of liver fibrosis with, notably, a value of 11.9 kPa for cirrhosis. This choice is arguable because the study population …

A clinical study was carried out to compare the response rate of two groups of non‐responder (NR) hepatitis C virus (HCV) genotype 1 chronically infected patients treated with interferon and ribavirin, with or without amantadine. The viral load decreased more markedly in the group treated by tritherapy including amantadine, but the response rate at the end of treatment was not significantly different between bitherapy and tritherapy. As amantadine could have an antiviral effect on the ion channel activity of the p7 HCV protein, the p7 quasispecies was characterized by cloning and sequencing. Sequence data were analyzed to determine the pattern and significance of p7 genetic heterogeneity and a possible relationship with therapy. Subtype differences were confirmed between p7 HCV genotypes 1a and 1b, and quasispecies analysis showed a reduction of genetic diversity in subtype 1a, but not 1b, during tritherapy. However, the absence of changes at numerous positions, as well as the conservative changes at other positions, indicated the high conservation of the p7 structure. Residue His‐17, proposed to interact with amantadine, was fully conserved in both subtypes 1a and 1b, independently of amantadine administration. In conclusion, although the analysis of the p7 sequences revealed a selective pressure during therapy, no specific residues appeared to be linked to the effect of amantadine on viral decline. These results suggest that the potential antiviral effect of amantadine might be non‐specific and related to a reduction in endosomal acidification and therefore reduced viral entry of HCV via its pH‐dependent pathway. J. Med. Virol. 79:144–154, 2007. © 2006 Wiley‐Liss, Inc.

Background/Aims: In patients with unexplained elevated transaminases, prognosis of the liver disease and factors associated with increased risk of liver fibrosis and normal/subnormal liver are unknown. The aim of this prospective study was to identify diagnosis and clinical and biological factors associated with significant (bridging) fibrosis and minimal lesions of the liver in patients with persistent unexplained elevated ALT levels.Methods: From July 2002 through October 2004, all consecutive asymptomatic patients with unexplained chronically elevated ALT levels were included. All patients had clinical, biological, ultrasonographic examination and a liver biopsy.Results: 272 patients (60.3% males, mean age 46.4 years, BMI 26.7) were included. Pathological findings were: minimal lesions (18.7%), steatosis (26.8%), NASH (32.7%), and miscellaneous (21.7%). Significant fibrosis was found in 27.4% of cases, including 9 cases of cirrhosis. By multivariate analysis, independent predictors of significant fibrosis were tobacco use (OR 2.5, 95% CI 1.34-4.74 p = 0.04), BMI > 25 (2.49, 1.31-4.73 p = 0.005) and diabetes (4.41, 1.73-11.29 p = 0.002). Independent factors associated with minimal lesions were female gender (OR 3.4 95% CI 1.73-6.75 p < 0.0001) and BMI < 25 (3.55, 1.8-6.98, p < 0.0001).Conclusions: In patients with unexplained chronically elevated transaminases, significant fibrosis is statistically associated with tobacco use, BMI > 25 and diabetes, and minimal lesions are significantly associated with female gender and BMI < 25. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Propos. – Les bases moléculaires à l’origine d’un phénotype de surcharge en fer héréditaire sont désormais mieux connues et conduisent à établir une nouvelle classification des hémochromatoses génétiques que nous présentons dans cette mise au point.

Background: Genetic testing can determine those at risk for hereditary haemochromatosis (HH) caused by HFE mutations before the onset of symptoms. However, there is no optimum screening strategy, mainly owing to the variable penetrance in those who are homozygous for the HFE Cys282Tyr (C282Y) mutation. The objective of this study was to identify the majority of individuals at serious risk of developing HFE haemochromatosis before they developed life threatening complications. Methods: We first estimated the therapeutic penetrance of the C282Y mutation in people living in la Somme, France, using genetic, demographic, biochemical, and follow up data. We examined the benefits of neonatal screening on the basis of increased risk to relatives of newborns carrying one or two copies of the C282Y mutation. Between 1999 and 2002, we screened 7038 newborns from two maternity hospitals in the north of France for the C282Y and His63Asp (H63D) mutations in the HFE gene, using bloodspots collected on Guthrie cards. Family studies and genetic counselling were undertaken, based on the results of the baby’s genotype. Findings: In la Somme, we found that 24% of the adults homozygous for the C282Y mutation required at least 5 g iron to be removed to restore normal iron parameters (that is, the therapeutic penetrance). In the reverse cascade screening study, we identified 19 C282Y homozygotes (1/370), 491 heterozygotes (1/14) and 166 compound heterozygotes (1/42) in 7038 newborns tested. The reverse cascade screening strategy resulted in 80 adults being screened for both mutations. We identified 10 previously unknown C282Y homozygotes of whom six (four men and two women) required venesection. Acceptance of neonatal screening was high; parents understood the risks of having HH and the benefits of early detection, but a number of parents were reluctant to take the test themselves. Neonatal screening for HH is straightforward. Reverse cascade screening increased the efficiency of detecting affected adults with undiagnosed haemochromatosis. This strategy allows almost complete coverage for HH and could be a model for efficient screening for other late onset genetic diseases.

PURPOSE:Recent discoveries in molecular mechanisms of iron metabolism have changed the classical view of hereditary iron overload conditions. We present natural mutations in newly discovered genes and related phenotypes observed in patients with different form of haemochromatosis.CURRENT KNOWLEDGE AND KEY POINTS:Most haemochromatosis patients are homozygous for the C282Y mutation in the HFE gene. Ferroportin, TFR2, hemojuvelin and hepcidin mutations also cause iron overload. Recent data support the hypothesis that haemochromatosis should no longer be considered a monogenic disease but rather an oligogenic disorder. Several results suggest that haemochromatosis could result from digenic inheritance of mutations in HFE and HAMP.FUTURE PROSPECTS AND PROJECTS:Other modifier genes probably influence penetrance in C282Y homozygous patients. Such genes could enhance or reduce the phenotypic expression in various iron overload conditions.

Propos. – Cette revue résume les données récentes de la littérature relatives aux nouveaux acteurs impliqués dans l’absorption et dans la régulation de l’homéostasie du fer.

PURPOSE:Advances towards the understanding of gene regulation and protein function recently discovered through iron metabolism disorders are the subject of this review.CURRENT KNOWLEDGE AND KEY POINTS:Within a few years the discovery of genes that determine heritable defects of cellular iron uptake or regulation in mice as in humans have provided new insights for investigation into iron metabolism pathways.FUTURE PROSPECTS AND PROJECTS:It is still unclear how connections are made between new proteins in iron uptake, trafficking and regulation of iron homeostasis. Gene expression studies using microarrays technology in different iron conditions should help to explore iron homeostasis further.

Background: Quantitation of hepatitis C virus (HCV) RNA has become an essential tool for monitoring antiviral therapies in chronically infected patients. Different quantitative HCV RNA assays have been reported, mainly using techniques based on signal amplification with branched DNA (bDNA) technology or target sequence amplification by reverse-transcription PCR method (RT-PCR). Objectives and study design: An RT-PCR assay using TaqMan (fluorescence-based real-time PCR) and minor groove binding (MGB) probes was designed for the quantitative determination of HCV RNA in the clinical samples. Calculation of the concentration of HCV RNA was based on an external standard curve in the presence of an internal positive control (IPC). Results: The assay detected 550 international units (IU)/mL with >95% probability of a positive result, with a linear range extending up to 10,000,000IU/mL. The test exhibited good reproducibility with intra-assay and inter-assay coefficients of variation (CV) of 1.6% and 3.2%, respectively. All the major HCV genotypes were quantified with equivalent efficiency and accuracy. HCV genotypes 5 and 6 have also been amplified but too few samples have been tested. The performance of this new assay for quantitation of HCV viremia was evaluated with 213 anti-HCV positive sera, 120 of which corresponded to 30 patients sampled during the therapy. We used the Amplicor HCV Monitor assay (Roche Diagnostics, France) and the bDNA VERSANT HCV RNA assay (Bayer Diagnostics, France) to analyze 173 and 40 samples, respectively. The assay described here was significantly correlated with both commercial assays (R2=0.9535, P<0.0001 and R2=0.8508, P<0.0001, respectively). Conclusion: The present study illustrated the high reproducibility and reliability of our TaqMan HCV assay. Moreover, the monitoring of viral decline with our assay gave the same results as those obtained with the commercial assays indicating that this new technique provides an attractive approach for measuring HCV viral load.