Hepatitis: France

Fontaine H, Petitprez K, Roudot-Thoraval F, Trinchet JC, Anonymous00285, Anonymous00286, Anonymous00287, Anonymous00288, Anonymous00289, Anonymous00290, Anonymous00291. · Unité d'Hépatologie Médicale, Hôpital Cochin, Paris, France. · Gastroenterol Clin Biol. · Pubmed #17541342 No free full text.

This publication has no abstract.

Bossi P, Tegnell A, Baka A, Van Loock F, Hendriks J, Werner A, Maidhof H, Gouvras G, Anonymous00206. · Task Force on Biological and Chemical Agent Threats, Public Health Directorate, European Commission, Luxembourg. · Euro Surveill. · Pubmed #15677840 links to  free full text

Abstract: Q fever is a zoonotic disease caused by Coxiella burnetii. Its interest as a potential biological weapon stems from the fact that an aerosol of very few organisms could infect humans. Another route of transmission of C. burnetii could be through adding it to the food supply. Nevertheless, C. burnetii is considered to be one of the less suitable candidate agents for use in a bioterrorist attack; the incubation is long, many infections are inapparent and the mortality is low. In the case of an intentional release of C. burnetii by a terrorist, clinical presentation would be similar to naturally occurring disease. It may be asymptomatic, acute, normally accompanied by pneumonia or hepatitis, or chronic, usually manifested as endocarditis. Most cases of acute Q fever are asymptomatic and resolve spontaneously without specific treatment. Nevertheless, treatment can shorten the duration of illness and decrease the risk of complications such as endocarditis. Post-exposure prophylaxis is recommended after the exposure in the case of a bioterrorist attack.

Afef. · AFEF, 3, rue Troyon, 75017 Paris, France. · Gastroenterol Clin Biol. · Pubmed #19505784 No free full text.

This publication has no abstract.

Péron JM, Mansuy JM, Vinel JP, Kamar N. · Service d'hépato-gastroentérologie, fédération digestive, hôpital Purpan, CHU de Toulouse, place du Dr-Baylac, TSA 40031, 31059 Toulouse cedex 9, France. · Gastroenterol Clin Biol. · Pubmed #19481395 No free full text.

This publication has no abstract.

Halfon P, Ouzan D. · Laboratoire de Virologie Alphabio, Service de Maladies Infectieuses, Hôpital Ambroise Paré, Marseille, France. · Presse Med. · Pubmed #19157775 No free full text.

This publication has no abstract.

Vallet-Pichard A, Fontaine H, Pol S. · Unité d'Hépatologie et U-370, Hôpital Necker, Paris. · Gastroenterol Clin Biol. · Pubmed #12483129 No free full text.

This publication has no abstract.

Zoulim F. · INSERM Unité 271, et Service d'Hépatologie et de Gastroentérologie, Hôtel-Dieu, 151, cours Albert-Thomas, 69003 Lyon, France. · Gastroenterol Clin Biol. · Pubmed #11173726 No free full text.

This publication has no abstract.

Buffet C. · Hépatogastroentérologie, Hôpital de Bicêtre, 78, rue du Général Leclerc, 94270 Kremlin-Bicetre. · Bull Acad Natl Med. · Pubmed #19445377 No free full text.

Abstract: HBV cannot be fully eradicated from the body because of the persistence of covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. True cure is infrequent, but persistent suppression of HBV DNA slows liver disease progression and helps to prevent hepatocellular carcinoma. Treatment options for chronic hepatitis B include pegylated interferon and 4 licensed oral nucleosides/nucleotides (lamivudine, adefovir entecavir and tenofovir). Interferon is the only drug with a defined duration of treatment. It is effective in 30% to 40% of patients but is poorly tolerated. In contrast to interferon, nucleotide/nucleoside analogs have only minor adverse effects. However, a resurgence of the infection may occur when these drugs are withdrawn, implying that treatment may have to continue indefinitely. The onset of viral resistance to these agents also limits their long-term use but can be minimized by ensuring potent suppression of viral replication.

Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E. · Inserm, U, Villejuif, France. · Biochem J. · Pubmed #19426143 No free full text.

Abstract: Despite high expression levels at the plasma membrane or in intracellular vesicles, tetraspanins remain among the most mysterious transmembrane molecules 20 years after their discovery. Several genetic studies in mammals and invertebrates have demonstrated key physiological roles for some of these tetraspanins, in particular in the immune response, sperm-egg fusion, photoreceptor function and the normal function of certain epithelia. Other studies have highlighted their ability to modulate cell migration and metastasis formation. Their role in the propagation of infectious agents has drawn recent attention, with evidence for HIV budding in tetraspanin-enriched plasma membrane domains. Infection of hepatocytic cells by two major pathogens, the hepatitis C virus and the malaria parasite, also requires the tetraspanin CD81. The function of tetraspanins is thought to be linked to their ability to associate with one another and a wealth of other integral proteins, thereby building up an interacting network or 'tetraspanin web'. On the basis of the biochemical dissection of the tetraspanin web and recent analysis of the dynamics of some of its constituents, we propose that tetraspanins tightly regulate transient interactions between a variety of molecules and as such favour the efficient assembly of specialized structures upon proper stimulation.

Si Ahmed SN, Zoulim F. · INSERM, U871, 69003 Lyon, France. · Expert Rev Anti Infect Ther. · Pubmed #19344244 No free full text.

Abstract: HBV is the leading cause of liver cancer and frequently leads to cirrhosis and liver failure. The goals of nucleos(t)ide analog treatments are to suppress viral replication to as low as possible, to halt disease progression and to prevent the onset of complications. Due to the mechanism of viral genome persistence, chronic hepatitis B requires long-term therapy that exposes patients to the risk of selection of resistant mutants and treatment failure. Genotypic resistance is defined as the detection of resistant mutations that are known to confer resistance to antiviral drugs. Virologic rebound is defined as an increase in viral load of at least 1 log(10) copies/ml compared with the lowest value during therapy. Clinical breakthrough is defined as a rise in alanine aminotransferase levels and liver disease progression following the emergence of resistant mutants and the rise in viral load. Currently, the management of antiviral therapy should be based on precise virologic monitoring to enable an early diagnosis of partial response and treatment failure. An early treatment adaptation is recommended at least at the time of virologic breakthrough or in the case of insufficient viral suppression. The choice of drug for second-line therapy should be based on cross-resistance data to tailor therapy to the virologic situation of the patient. The addition of a complementary drug is the preferred strategy. Clinical experience shows that an optimal management of antiviral therapy allows the control of viral replication in the majority of patients in whom liver disease progression is halted.

Ossendza RA, Bréchot JF, Fimbel B, Bacq Y. · Hepatogastroenterology department, Trousseau hospital, CHRU de Tours, F-37044 Tours Cedex, France. · Presse Med. · Pubmed #19286345 links to  free full text

This publication has no abstract.

Zeisel MB, Barth H, Schuster C, Baumert TF. · Inserm, U748, Strasbourg, France. · Front Biosci. · Pubmed #19273272 No free full text.

Abstract: With an estimated 170 million infected individuals, hepatitis C virus (HCV) has a major impact on public health. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between the virus and the target cell that is required for successful entry into the cell and initiation of infection. Using recombinant HCV envelope glycoproteins and HCV pseudotype particles, several cell surface molecules have been identified interacting with HCV during viral binding and entry. These include CD81, highly sulfated heparan sulfate, the low-density lipoprotein receptor, scavenger receptor class B type I and claudin-1. Treatment options for chronic HCV infection are limited and a vaccine to prevent HCV infection is not available. Interfering with HCV entry holds promise for drug design and discovery as the understanding of molecular mechanisms underlying HCV interaction with the host cell is advancing. The complexity of the virus entry process offers several therapeutic targets.

Burlone ME, Budkowska A. · Pasteur Institute, Hepacivirus and Innate Immunity, 75724 Paris Cedex 15, France. · J Gen Virol. · Pubmed #19264629 No free full text.

Abstract: Hepatitis C virus (HCV), a major cause of chronic liver disease, is a single-stranded positive sense virus of the family Flaviviridae. HCV cell entry is a multi-step process, involving several viral and cellular factors that trigger virus uptake into the hepatocyte. Tetraspanin CD81, human scavenger receptor SR-BI, and tight junction molecules Claudin-1 and occludin are the main receptors that mediate HCV entry. In addition, the virus may use glycosaminoglycans and/or low density receptors on host cells as initial attachment factors. A unique feature of HCV is the dependence of virus replication and assembly on host cell lipid metabolism. Most notably, during HCV assembly and release from the infected cells, virus particles associate with lipids and very-low-density lipoproteins. Thus, infectious virus circulates in patient sera in the form of triglyceride-rich particles. Consequently, lipoproteins and lipoprotein receptors play an essential role in virus uptake and the initiation of infection. This review summarizes the current knowledge about HCV receptors, mechanisms of HCV cell entry and the role of lipoproteins in this process.

Belizna CC, Hamidou MA, Levesque H, Guillevin L, Shoenfeld Y. · Internal Medicine Department, CHU Rouen, Rouen, France. · Rheumatology (Oxford). · Pubmed #19258377 No free full text.

Abstract: Vasculitis may be associated with infection, immunization or anti-microbial drugs. Infections are responsible for a number of different types of vasculitis. Conversely, patients with vasculitis may develop infections, which sometimes mimic relapse. The aim of this review is to summarize the various aspects of the inter-relationship between vasculitis and infection, and the physiopathological mechanisms involved, in light of our current knowledge from animal models. Currently, a causal relationship between infection and vasculitis has only been established in a few instances and many mechanisms remain hypothetical. This inter-relationship is further assessed from the point of view of clinical presentation and therapeutic options, based on case reports and prospective observational data.

Castera L. · Department of Hepatology, Hôpital St André & Haut Lévêque, Bordeaux University Hospital, Bordeaux, France. · J Viral Hepat. · Pubmed #19254351 No free full text.

Abstract: The limitations of liver biopsy (invasive procedure, sampling errors, inter-observer variability and nondynamic fibrosis evaluation) have stimulated the search for noninvasive approaches for the assessment of liver fibrosis in patients with viral hepatitis. A variety of methods including the measurement of liver stiffness, using transient elastography, and serum markers, ranging from routine laboratory tests to more complex algorithms or indices combining the results of panels of markers, have been proposed. Among serum indices, Fibrotest has been the most extensively studied and validated. Transient elastography appears as a promising method but has been mostly validated in chronic hepatitis C with performance equivalent to that of serum markers for the diagnosis of significant fibrosis. The combination of both approaches as first-line assessment of liver fibrosis could avoid the performance of liver biopsy in the majority of patients with chronic hepatitis C, a strategy that deserves further evaluation in patients with hepatitis B or HIV-HCV coinfection. Transient elastography also appears to be an excellent tool for early detection of cirrhosis and may have prognostic value in this setting. Guidelines are now awaited for the use of noninvasive methods in clinical practice.

Traineau R, Elghouzzi MH, Bierling P. · Etablissement français du sang Ile-de-France, hôpital Saint-Louis, 75475 Paris Cedex 10, France. · Rev Prat. · Pubmed #19253889 No free full text.

Abstract: Many infectious diseases are transmissible by blood transfusion but the overall risk of transfusion transmitted infections is very low through the combination of restrictive donor selection and increasingly sensitive screening. The noninfectious risks (hemolytic transfusion reactions, circulatory overload, transfusion related lung injury) are higher than the current infectious risks. Bacterial contamination of blood components remains the most frequent infectious risk from transfusion but are constantly declining. The estimated residual risk for transfusion transmitted HIV and hepatitis are lower 1/2 600 000 for HIV, 1/6 500 000 for HCV, 1/1 700 000 for HBV. For the future, the concerns are the risks of emerging or reemerging infections transmitted by blood as dengue, Chickungunya, West Nile Virus... Four transfusion transmissions of vCJD have been reported in UK, uncertainties about the incubation periods, the number of infected donors and the lack of sensitive assays for screening blood aggravate concerns about the transfusion transmission risks for vCJD. The ultimate strategy against infectious disease (all but vCJD) could be to develop inactivation methods. Pathogen inactivation have been implemented for plasma, are expected to become available for platelets, but for red blood cells are only in development.

Stoll-Keller F, Barth H, Fafi-Kremer S, Zeisel MB, Baumert TF. · Inserm, U748 et Laboratoire de Virologie des Hôpitaux Universitaires de Strasbourg, 3 rue Koeberlé 67000 Strasbourg, France. · Expert Rev Vaccines. · Pubmed #19249975 No free full text.

Abstract: Development of an effective vaccine against the hepatitis C virus (HCV) has long been defined as a difficult challenge due to the considerable variability of this RNA virus and the observation that convalescent humans and chimpanzees could be re-infected after re-exposure. On the other hand, progress in the understanding of antiviral immune responses in patients with viral clearance has elucidated key mechanisms playing a role in the control of viral infection. Studies investigating prophylactic vaccine approaches in chimpanzees have confirmed that the induction and maintenance of strong helper and cytotoxic T-cell immune responses against multiple viral epitopes is necessary for protection against viral clearance and chronic infection. A multispecific B-cell response, resulting in rapid induction of cross-neutralizing antibodies may assist cellular responses. Therapeutic vaccine formulations currently being evaluated in clinical trials are facing the fact that the immune system of chronic carriers is impaired and needs the restoration of T-cell functions to enhance their efficacy.

Inchauspe G, Bach G, Martin P, Bonnefoy JY. · Transgene SA, Strasbourg, France. · Int Rev Immunol. · Pubmed #19241251 No free full text.

This publication has no abstract.

Chevaliez S, Pawlotsky JM. · Department of Virology, Hopital Henri Mondor, Universite Paris 12, Creteil, France. · Ann Hepatol. · Pubmed #19221527 No free full text.

This publication has no abstract.

Zucman-Rossi J, Clément B, Buendia MA, Lerat H, Beers BV, Bedossa P, Taieb J, Rosenbaum J. · Inserm, U674 ; université Paris-Diderot-Paris-VII, 75010 Paris, France. · Bull Cancer. · Pubmed #19211359 No free full text.

Abstract: Hepatocellular carcinogenesis is usually the result of a muti-step process. It begins with an exposure to various risk factors; followed by the development of a chronic hepatitis and cirrhosis that is a pre-neoplastic step; and finally after the occurrence of an hepatocellular carcinoma (HCC), different molecular events control aggressiveness of the tumors. The aim of this work was to identify in the international context, forces and priorities of the fundamental and translational HCC research.

Zoulim F, Durantel D, Deny P. · INSERM, U871, Lyon, France. · Liver Int. · Pubmed #19207973 No free full text.

Abstract: The management of hepatitis B virus resistance to antivirals has evolved rapidly in recent years. The definition of resistance is now well established, with the importance of partial response and the improvement of assays to detect genotypic resistance and virological breakthrough. Data on phenotypic resistance have allowed to define the cross-resistance profile for the main resistant mutants, providing a rationale for treatment adaptation. Clinical studies have shown that an early treatment intervention in case of a virological breakthrough or a partial response with the addition of a second drug having a complementary cross-resistance profile allows one to maintain the majority of patients in clinical remission. The prevention of resistance should rely on the use of the most potent antivirals with a high genetic barrier to resistance as a first-line therapy. The future perspectives are to design strategies to hasten the HBsAg clearance, which should become a new treatment endpoint, to prevent drug resistance and to decrease the incidence of complications of chronic hepatitis B.

Asselah T, Benhamou Y, Marcellin P. · INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Service d'hépatologie, Hôpital Beaujon, Clichy, France. · Liver Int. · Pubmed #19207967 No free full text.

Abstract: Chronic hepatitis C is among the leading causes of chronic liver disease worldwide, with approximately 170 million people infected. The severity of disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Recently,advances have been made, with the combination of pegylated interferon (PEG-IFN) and ribavirin leading to a sustained virological response (SVR) in approximately 55% of cases. In genotypes 2 or 3, SVR rates reach 80%; in genotype 1 SVR rates is 50%. Furthermore, SVR appears to be long lasting, associated probably with a reduction in the risk of cirrhosis and hepatocellular carcinoma. Despite this progress, treatment failure still occurs in about half of the patients. Furthermore, therapy results in several side effects and high costs. These limitations have led to important development of novel compounds under the name of specifically targeted antiviral therapy for HCV (STAT-C). Also, considering side effects and treatment cost, prediction of virological non-response is mandatory. The management of chronic hepatitis C must include better knowledge of viral cycle and mechanisms of non response. The development of new molecules such as HCV enzyme inhibitors is ongoing. The aim of this review is to summarize results obtained with STATC: protease and polymerase inhibitors.

Bedossa P. · Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, INSERM, Paris-Diderot University, Paris, France. · Liver Int. · Pubmed #19207962 No free full text.

Abstract: Chronic viral hepatitis is a prolonged inflammatory disease of the liver that may lead to the development of fibrosis, necro-inflammation and other associated pathological features. Because fibrosis and its end-point cirrhosis are the main causes of morbidity and mortality, fibrosis assessment is considered as the most relevant information for the evaluation of the severity of the disease and as a useful indicator for prognosis and treatment decision. Because fibrosis implies morphological damage, liver biopsy has come to be the natural gold standard for staging the disease. However, the high prevalence of chronic hepatitis C in addition to the cost and constraints generated by this procedure have triggered an intensive search for alternative methods for fibrosis evaluation. In this article, the strengths and weaknesses of liver biopsy and of non-invasive markers will be reviewed and their respective roles in management of patients with chronic hepatitis C will be discussed.

Chevaliez S, Pawlotsky JM. · Department of Virology & INSERM U841, French National Reference Center for Viral Hepatitis B, C and delta, Hôpital Henri Mondor, Université Paris 12, Créteil, France. · Liver Int. · Pubmed #19207960 No free full text.

Abstract: Chronic hepatitis C is a global health problem that may cause cirrhosis and progression to hepatocellular carcinoma. Currently available antiviral treatments are moderately effective. Several virological assays are available to help diagnose and manage patients infected with the hepatitis C virus (HCV). These include the anti-HCV antibody assays, measurement of HCV RNA viral load and HCV genotyping. HCV RNA can be assayed by two types of molecular biology-based techniques: target amplification as in polymerase chain reaction methods and signal amplification such as the branched DNA assay. Monitoring of viral kinetics during the early phases of antiviral treatment is crucial in making treatment decisions such as early stopping rules and also in optimizing the length of treatment. The HCV genotype can be determined by several methods. Whatever the method, pretreatment determination allows treatment length and ribavirin dose to be optimized and also offers prognostic information on treatment outcomes as certain genotypes respond more favourably to treatment. Thus, virological assays are indispensable in the diagnosis and management of individuals infected with the HCV.

Marcellin P. · Service d'Hépatologie, AP-HP and INSERM U773, Centre de Recherche Biologique Bichat-Beaujon CRB3, Université Denis Diderot-Paris 7, Hôpital Beaujon, Clichy, France. · Liver Int. · Pubmed #19207959 No free full text.

Abstract: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections in humans, and represent a major global public health problem. HBV- and HCV-related chronic hepatitis are the main causes of cirrhosis and hepatocellular carcinoma (HCC) that are responsible for a high rate of morbidity and mortality. End-stage HBV- and HCV-related liver disease and HCC are the main causes of liver transplantation. In the last few years, knowledge of the epidemiology and the natural history of HBV and HCV infection has markedly improved. Furthermore, considerable progress has been made in the efficacy of therapy. New drugs and new therapeutic strategies that are currently under evaluation could further improve the efficacy of therapy in the near future.