To assess the impact of sequential therapy with adefovir dipivoxil (ADV) and pegylated interferon alfa-2a (PEG-IFN) on virological (serum HBV-DNA) and serological (serum HBsAg) response in 20 consecutive HBeAg-negative patients. Patients received ADV for 20 weeks, then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks. Serum HBV-DNA and HBsAg were assessed at baseline, during therapy (weeks 20, 44 and 68) and follow-up (weeks 92 and 116). Sustained virological response (SVR) was defined as serum HBV-DNA < 10 000 copies/mL (partial) or < 70 copies/mL (complete) 24 weeks after stopping treatment. A serological response was defined as a serum HBsAg decrease >= 1 log(10)IU/mL at the end of treatment. Baseline median serum HBV-DNA and HBsAg levels were 7.6 log(10)copies/mL and 3.8 log(10)IU/mL, respectively. Ten patients (50%) achieved SVR, six of them had partial response and four complete response. Four patients (20%) achieved serological response. Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0 log(10)IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at weeks 20, 44 and 68, respectively). On-treatment serum HBsAg decrease had a high accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients. Serum HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials are needed to explore this strategy with more potent analogues.

Improvements in hygienic and sanitary conditions, especially in developing countries, have lead to a progressive shift in the epidemiologic pattern of hepatitis A. This infection, most commonly transmitted via feco-oral route, is now observed in adult patients reflecting the reduced circulation of the hepatitis A virus in many countries. Paradoxically, the risk of more severe disease forms and outbreaks is increased. Vaccination against hepatitis A appears as an effective way to reduce hepatitis A incidence, HAV could be eradicated if routine vaccination of children is implemented in all countries. However, this vaccination is not presently recommended for areas with high overall and age-specific incidence.

Results: 38 HCV genotype lb isolates originated in Camporeale have been associated in a unique "transmission cluster".A Monte Carlo Markov simulation, has been used to construct a "bayesian skyline plot" starting from the sequences alignment of the "transmission cluster" isolates.The obtained results have permitted to calculate the date of virus introduction in the population between the end of the 1940s and the begin of the 1950s.Conclusions: The combination of data obtained from classic phylogenesys and from the application of the Bayes' theorem on the study of the coalescence of genealogical tree are useful to define the spread and possibly the modality of transmission of a pathogen over time.Our data showed that in a small area, such as the Camporeale town, HCV can spread with few circulating strains as a direct consequence of particular events and method of transmission (e.g.glass syringe and transfusion).These data have also shown that the increased medicalization associated to low level of knowledge of the linked risks, as in Italy after world-war II, could have contributed to the diffusion of the hepatitis C infection.

Le virus de l'hépatite A (VHA) est la première cause d'hépatite virale aiguë dans le monde. Cette infection généralement bénigne se traduit parfois par des formes sévères voire mortelles, en particulier chez les sujets de plus de 50 ans. L'amélioration des conditions d'hygiène s'est accompagnée d'une diminution de l'immunisation naturelle contre le VHA qui rend possible la survenue d'épidémies touchant des adultes. Cette évolution épidémiologique a conduit à la modification ou à la mise en place de systèmes de surveillance et à la modification des recommandations vaccinales. Le diagnostic de l'infection aiguë est crucial quand des mesures de contrôle épidémique doivent être prises. Ce diagnostic est fondé sur la détection d'IgM d'anti-VHA. Dans certains cas, des IgM peuvent être détectées en l'absence d'infection par le VHA. La mesure de l'avidité d'IgG d'anti-VHA peut alors aider au diagnostic. L'épidémiologie moléculaire contribue à l'identification des cas groupés et des sources de contamination. Un observatoire de la diversité des souches circulantes permet de mieux appréhender l'épidémiologie du VHA, en particulier ses modes de diffusion au sein d'une communauté ou d'un pays à l'autre, et permet également d'adapter les outils de détection du virus.

Aim - Diagnosis of acute hepatitis A virus (HAV) infection is classically based on the detection of HAV-19M. Nevertheless, HAV-19M can be positive for patients with polyclonal stimulation of their immune system (i.e. immune reactivation). To improve the diagnostic yield, an avidity test for HAV-IgG antibodies was developed and tested.Methods - Avidity tests were performed in 128 sera: 11 selected samples from patients with past infection, 15 acute hepatitis A, 10 vaccinated subjects and 4 patients with immune reactivation as well as 84 HAV-19M positive unselected sera, provided by routine laboratories.Results - Patients with past infection had avidities over 70%, whereas avidities in patients with acute hepatitis A were below 50% during the first month following the onset of symptoms. As expected, patients with immune reactivation had avidities over 70% consistent with past infection. The results obtained for the 84 unselected sera allowed reconsidering the diagnosis of acute hepatitis A for nearly a third of patients.Conclusion - This test could improve the diagnosis of acute hepatitis A infection, particularly in elderly patients.

Investigation of hepatitis A virus (HAV) outbreaks often implies nucleotide sequence analysis. As an alternative method for the identification of related strains, single strand conformation polymorphism method (SSCP) was compared to sequence analysis. Twenty-three strains from sporadic and outbreak cases were studied retrospectively. SSCP, sequence identity and phylogenetic analyses were conducted on a 267 bp fragment of the VP1-2A variable region. The results of SSCP pattern comparison and sequence identity were highly correlated (r = 0.92, P < 0.001). If SSCP showed similar patterns, the VP1-2A fragments had a high and significant probability to have a sequence identity over 99.6%. Results were concordant for outbreak strains. The only discordant result concerned a cluster of three sporadic cases evidenced by phylogenetic analysis while SSCP showed similar patterns for only two of these three cases. A prospective SSCP analysis of a recent HAV outbreak confirmed the reliability of this technique. SSCP may thus provide a rapid and cost-effective tool for preliminary investigation of HAV outbreaks, before undertaking exhaustive nucleotide sequence analysis.

TransfusionVolume 44, Issue 7 p. 1121-1122 Silent transfusion-transmitted hepatitis A virus infection in an infant Olivier Garraud MD, PhD, Olivier Garraud MD, PhD 1e-mail: [email protected]Search for more papers by this authorRachel Conductier MD, Rachel Conductier MD 2Etablissement Français du Sang Auvergne-Loire 25 Boulevard Pasteur 42023 Saint-Etienne Cedex 02, France;Search for more papers by this author Hélène Odent-Malaure MD, Hélène Odent-Malaure MD 2Etablissement Français du Sang Auvergne-Loire 25 Boulevard Pasteur 42023 Saint-Etienne Cedex 02, France;Search for more papers by this authorJacques Carrières MD, Jacques Carrières MD 2Etablissement Français du Sang Auvergne-Loire 25 Boulevard Pasteur 42023 Saint-Etienne Cedex 02, France;Search for more papers by this authorPhilippe Chopart MD, Philippe Chopart MD 3Centre Hospitalier Emile Roux Boulevard Chantemesse 43000 Le Puy-en-Velay, FranceSearch for more papers by this authorFrançois Brenas MD, François Brenas MD 3Centre Hospitalier Emile Roux Boulevard Chantemesse 43000 Le Puy-en-Velay, FranceSearch for more papers by this authorVincent Mackiewicz DPharm, Vincent Mackiewicz DPharm 4CNR des virus des hèpatites à transmission enterique Laboratoire de Virologie Hôpital Paul Brousse 94804 Villejuif cedex, FranceSearch for more papers by this author Elisabeth Dussaix MD, PhD, Elisabeth Dussaix MD, PhD 4CNR des virus des hèpatites à transmission enterique Laboratoire de Virologie Hôpital Paul Brousse 94804 Villejuif cedex, FranceSearch for more papers by this authorBruno Pozzetto MD, PhD, Bruno Pozzetto MD, PhD 5Départment of Bactériologie, Virologie, and Hygiène CHU de Saint-Etienne 42055 Saint-Etienne Cedex 02, FranceSearch for more papers by this author Olivier Garraud MD, PhD, Olivier Garraud MD, PhD 1e-mail: [email protected]Search for more papers by this authorRachel Conductier MD, Rachel Conductier MD 2Etablissement Français du Sang Auvergne-Loire 25 Boulevard Pasteur 42023 Saint-Etienne Cedex 02, France;Search for more papers by this author Hélène Odent-Malaure MD, Hélène Odent-Malaure MD 2Etablissement Français du Sang Auvergne-Loire 25 Boulevard Pasteur 42023 Saint-Etienne Cedex 02, France;Search for more papers by this authorJacques Carrières MD, Jacques Carrières MD 2Etablissement Français du Sang Auvergne-Loire 25 Boulevard Pasteur 42023 Saint-Etienne Cedex 02, France;Search for more papers by this authorPhilippe Chopart MD, Philippe Chopart MD 3Centre Hospitalier Emile Roux Boulevard Chantemesse 43000 Le Puy-en-Velay, FranceSearch for more papers by this authorFrançois Brenas MD, François Brenas MD 3Centre Hospitalier Emile Roux Boulevard Chantemesse 43000 Le Puy-en-Velay, FranceSearch for more papers by this authorVincent Mackiewicz DPharm, Vincent Mackiewicz DPharm 4CNR des virus des hèpatites à transmission enterique Laboratoire de Virologie Hôpital Paul Brousse 94804 Villejuif cedex, FranceSearch for more papers by this author Elisabeth Dussaix MD, PhD, Elisabeth Dussaix MD, PhD 4CNR des virus des hèpatites à transmission enterique Laboratoire de Virologie Hôpital Paul Brousse 94804 Villejuif cedex, FranceSearch for more papers by this authorBruno Pozzetto MD, PhD, Bruno Pozzetto MD, PhD 5Départment of Bactériologie, Virologie, and Hygiène CHU de Saint-Etienne 42055 Saint-Etienne Cedex 02, FranceSearch for more papers by this author First published: 28 June 2004 https://doi.org/10.1111/j.1537-2995.2004.00403.xCitations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES 1 Diwan AH, Stubbs JR, Carnahan GE. Transfusion of hepatitis A via WBC-reduced RBCs and FFB from a single donation. Transfusion 2003; 43: 536- 40. 2 Roseff SD, Luban NL, Manno CS. Guidelines for assessing appropriateness of pediatric transfusion. Transfusion 2002; 42: 1398- 413. 3 Rezende G, Roque-Afonso AM, Samuel D, et al. Viral and clinical factors associated with the fulminant course of hepatitis A infection. Hepatology 2003; 38: 613- 8. 4 Hollinger FB, Khan NC, Oeflinger PE, et al. Posttransfusion hepatitis type A. JAMA 1983; 250: 2313- 7. 5 Andreu G, Morel P, Forestier F, et al. Hemovigilance network in France: organization and analysis of immediate trans-fusion incident reports from 1994 to 1998. Transfusion 1994; 42: 1356- 64. Citing Literature Volume44, Issue7July 2004Pages 1121-1122 ReferencesRelatedInformation

ABSTRACT Hepatitis A virus (HAV) is shed in feces but also in saliva. HAV RNA was detected in saliva in five out of six acutely infected patients with HAV viremia. Serum and saliva sequences were identical. The simplicity of obtaining material allows the recommendation of the use of saliva for investigation of outbreaks.

ABSTRACT Diagnosis of acute hepatitis A virus (HAV) infection is based on the detection of HAV immunoglobulin M (IgM). However, IgM could be detected due to nonspecific polyclonal activation of the immune system. An avidity test for anti-HAV IgG was developed to distinguish acute infection, where low-avidity antibodies are detected, from immune reactivation. The assay was tested on 104 samples, including 11 sera from patients with past infection, 15 sera from patients with acute infection and 4 collected after recovery, 10 sera from vaccinated subjects, 4 sera from patients with suspected immune reactivation, and 60 unselected HAV-IgM positive sera, collected over 1 year in a routine laboratory. The avidity index (AI) was expressed as percentage. The results were provided as the mean ± one standard deviation. Patients with a history of prior infection had AIs of >70% (mean, 86% ± 10), whereas the mean AI was 36% ± 16 during acute HAV infection ( P < 0.001). Within the first month after the onset of hepatitis, avidity was either noncalculable due to a very low IgG titer or <50%. In patients with immune reactivation, avidity was >70% (88% ± 10%), a finding consistent with a prior infection. Among the 60 unselected sera, 35 (58%) had a noncalculable or <50% avidity, and most of them had a detectable HAV RNA, confirming HAV infection. In contrast, 16 (27%) had an avidity of >70%, and none was reverse transcription-PCR positive, suggesting immune reactivation. These 16 patients were significantly older than the others (50 ± 16 years versus 26 ± 14 years). The new anti-HAV IgG avidity assay we developed could improve HAV infection diagnosis, particularly in elderly patients.

Sera from 12 patients infected with human immunodeficiency virus and hepatitis B virus (HBV), on lamivudine as part of an antiretroviral therapy, were retrospectively analysed for the presence of HBV polymerase mutations by the line probe assay, INNO-LiPA HBV DR, and by the direct sequencing assay, TRUGENE HBV genotyping kit. Results at codons 180, 204 and 207 were compared for 44 samples. Full concordance was observed for 81.4% of the 129 analysed codons. Discordance involved only mixed populations: LiPA detected additional species in 19 codons and TRUGENE in five. Viral breakthrough occurred in seven patients, 12-33 months after lamivudine initiation. In five cases with close sampling available, both assays detected mutations before the rise in viral load, although earlier by LiPA for three patients. The time interval between the first mutant detection and viral escape ranged from 2 to 22 months. Mutations were detected in four of the five remaining patients: 1) at therapy initiation in a primary non-responder; 2) after 37 months, but replication became undetectable after tenofovir introduction; 3) transiently at 6 months by LiPA but treatment was ceased thereafter; 4) after 23 months but replication levels remained low during a 5-year follow-up. Interestingly, TRUGENE sequencing identified on late samples from three patients a variant carrying rtV173L plus rtL180M plus M204V mutations, having the in vitro characteristics of 'vaccine escape' mutants. Both assays appear to be valuable tools for the early detection of mutated HBV strains. The detection of genotypic therapeutic decision-making, although clinical or other virological factors may determine the rapidity of the viral breakthrough.