Hepatitis: France

Roche B, Samuel D. · Assistance Publique-Hopitaux de Paris, Hopital Paul Brousse, Centre Hepato-Biliaire, Villejuif, France. · Best Pract Res Clin Gastroenterol. · Pubmed #19187873 No free full text.

Abstract: End-stage liver disease caused by the hepatitis B and C viruses (HBV and HCV) are major indications for liver transplantation. Outcome depends largely on the prevention of allograft reinfection. The advent of long-term hepatitis B immune globulin administration and the introduction of new antiviral agents were a major breakthrough in the management of these patients. Today, survival after orthotopic liver transplantation (OLT) is similar to that of patients transplanted for HBsAg-negative liver disease, and the risk of recurrence is below 10%. In contrast, HCV reinfection is almost constant and significantly impairs patient and graft survival. Factors that may influence disease severity and consequently progression of HCV graft injury remain unclear. Pre-transplantation and prophylactic post-transplantation antiviral treatments are limited by low applicability and poor tolerance. Treatment of established graft lesions with combination therapy gave promising results, with sustained virological response in 25-45% of patients, but indications, modality and duration of treatment should be assessed.

Chevaliez S, Pawlotsky JM. · Department of Virology & INSERM U955, French National Reference Centre for Viral Hepatitis B, C and delta, Hôpital Henri Mondor, Université Paris, Créteil, France. · Best Pract Res Clin Gastroenterol. · Pubmed #19187865 No free full text.

Abstract: Virological tools, including serological and molecular tools, are needed to diagnose chronic hepatitis B and C infections. They may also be useful to establish their prognosis, but they have found their principal application in guiding treatment decisions and assessing the virological responses to therapy. The goal of chronic hepatitis B therapy is to prevent progression of liver disease. This is achieved if HBV replication is durably abolished or significantly reduced. In HBeAg-positive patients, HBeAg clearance followed by the HBe seroconversion phase can be achieved. In HBeAg-negative patients, long-term antiviral suppression of viral replication is needed. The loss of HBsAg, eventually associated with an HBs seroconversion, is the most desirable endpoint of therapy but is rarely achieved. The efficacy endpoint of chronic hepatitis C treatment is the sustained virological response, defined by an undetectable HCV RNA in serum with a sensitive assay 24 weeks after the end of treatment. The HCV genotype and on-treatment viral kinetics can be used to tailor treatment dosages and duration.

Serfaty L, Capeau J. · UPMC University Paris 06, F-75005, Paris, France. · Liver Int. · Pubmed #19187069 No free full text.

Abstract: Epidemiological data indicate a strong risk for development of insulin resistance (IR), and, ultimately, overt diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection. Steatosis, or fatty liver, is closely linked with IR in persons without HCV, such as those with metabolic syndrome, primarily due to increased visceral fat leading to altered adipokine production and increased free fatty acid (FFA) release. Moreover, there is evidence that liver fat can have an impact on the development of hepatic IR independently of changes in adipose tissue. Multiple mechanisms can account for the development of IR in patients with chronic HCV. In particular, there is evidence for a triangular interaction between steatosis, inflammatory processes and IR. In patients infected by the genotype 1 virus, steatosis is strongly related to IR, leading to a metabolic steatosis, while, in genotype 3 patients, steatosis is related to viral load in the context of a viral steatosis. Chronic inflammatory processes in the liver may be mediated by persistently activated macrophages and other immune cells, with concomitant overproduction of pro-inflammatory cytokines such as tumour necrosis factor-alpha. Activation of inflammatory pathways, together with increased levels of FFAs, can disrupt hepatocyte intracellular pathways and inhibit insulin signalling, leading to IR. Molecular studies have also shown that the HCV core protein can directly inhibit the insulin signalling pathway and increase reactive oxygen species production, both of which can further exacerbate IR. The available data provide an understanding of chronic HCV whereby chronic inflammatory processes, steatosis and IR contribute to each other, leading to an increased risk of DM, and its associated poor outcomes, in persons with chronic HCV.

Adam F, Anonymous00118. · Département d'anesthésie réanimation, hôpital Ambroise-Paré, AP-HP, 9 avenue Charles-de-Gaulle, Boulogne-Billancourt, France. · Ann Fr Anesth Reanim. · Pubmed #19168319 No free full text.

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Underner M, Hadjadj S, Beauchant M, Bridoux F, Debiais F, Meurice JC. · Unité de Tabacologie, CHU de Poitiers, France. · Rev Mal Respir. · Pubmed #19107017 No free full text.

Abstract: INTRODUCTION: In addition to being a major cardiovascular risk factor, smoking promotes or worsens thyroid, digestive, renal and bone diseases. BACKGROUND: Smoking is positively associated with hyperthyroidism. It is associated with Graves' disease and it especially increases the risk of the development of severe exophthalmos. In contrast, smoking might exert a protective action for thyroid carcinoma. Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C. Smoking accelerates the progression of primary biliary cirrhosis and increases the risk of hepatocellular carcinoma. Smoking increases risk of both hyperplastic and adenomatous polyps. While Crohn's disease is associated with smoking, ulcerative colitis is largely a disease of non smokers. Smoking increases risk of development of both renal cell carcinoma and chronic nephropathies, particularly in types 1 and 2 diabetes. Smoking is a risk factor for decreased bone density and is associated with a significantly increased risk of fracture. Smoking is related to the development of rheumatoid arthritis and may adversely influence its severity. CONCLUSIONS: Smoking might be considered a risk factor for the development of several thyroid, digestive, renal and bone diseases. Consequently, smoking prevention and cessation programs must be strongly encouraged among the patients concerned.

Delhem N, Carpentier A, Moralès O, Miroux C, Groux H, Auriault C, Pancré V. · Laboratoire d'immunopathologie des cancers viro-induits, institut de biologie de Lille, UMR 8161, Lille, France. · Bull Cancer. · Pubmed #19091657 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and also the third most common cause of cancer-related death. HCC arises most frequently in males with cirrhosis, which is most often a consequence of chronic hepatitis infection (HBV and HCV) or alcohol abuse. To date, the only effective approaches for patients with HCC are resection or liver transplantation. Immunological mechanisms are important in the surveillance of malignancy and control of tumor progression. Tumor-infiltrating lymphocytes (TILs) have been described in HCC, and extensive infiltration has been associated with reduced tumor recurrence following resection. However continued tumor-growth, despite the presence of a lymphocytic infiltration, including tumor-specific T-cells within and surrounding tumors, suggests a failure of immune control. Although, many mechanisms have been proposed for this attenuated immune response, it becomes evident that direct suppression of effector cells, supported by regulatory T-cells could play a pivotal role in the suppression of immune response to tumors. Initially described in context of immune disorders such as inflammatory autoimmune pathologies, regulatory T lymphocytes are characterized by their capacity to inhibit T helper response. To date, several regulatory T-cells are described, however CD4+CD25+ regulatory T-cells and Tr1 subpopulations remain best characterized. Currently, there is no evidence for direct implication of CD4+CD25+ regulatory T-cells in the malignancy and control of HCC progression. However, recent studies showed that both regulatory T-cells subpopulations and particularly Tr1 have been implicated in the modulation of the immune response during HCV chronic infection, supporting HCC progression.

Asselah T, Bièche I, Sabbagh A, Bedossa P, Moreau R, Valla D, Vidaud M, Marcellin P. · INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Paris, France. · Gut. · Pubmed #19074178 links to  free full text

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide. Up to 70% of patients will have persistent infection after inoculation, making this disease a significant cause of morbidity and mortality. The severity of disease varies widely, from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Since the discovery of HCV, the treatment of hepatitis C has considerably improved. Recently, combination of pegylated interferons with ribavirin gives a response rate of about 55%. Treatment is indicated in patients with moderate or severe fibrosis. The tolerability of combination treatment is relatively poor, with a frequent flu-like syndrome and an impaired quality of life. In addition to viral and environmental behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in HCV infection. The sequencing of the human genome, together with the development of high-throughput technologies that measure the function of the genome, have afforded unique opportunities to develop profiles that can distinguish, identify and classify discrete subsets of disease, predict the disease outcome or predict the response to treatment. This paper reviews the published literature on gene expression associated with HCV infection (HCV infection, fibrosis progression), and also according to response to treatment.

Castera L. · Service d'Hépato-Gastroentérologie, CHU Bordeaux, Hôpital Haut Lévêque, Avenue Magellan, 33604 Pessac, France. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072402 No free full text.

Abstract: Prognosis and management of chronic liver diseases greatly depend on the amount and progression of liver fibrosis. Although liver biopsy is still considered as the gold standard to evaluate fibrosis in the liver, it is an invasive procedure, with rare but potentially life-threatening complications, and is prone to sampling errors. These limitations have stimulated the search for new noninvasive approaches. A number of methods, including serum indices and the measurement of liver stiffness using transient elastography, have been proposed for the noninvasive assessment of hepatic fibrosis, mainly in patients with chronic hepatitis C. It can be anticipated that these noninvasive methods will become an important tool in clinical practice in the near future. This review is aimed at discussing the advantages and limits of these methods and the perspectives for their rationale for use in clinical practice.

Chevaliez S, Pawlotsky JM. · French National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. · Handb Exp Pharmacol. · Pubmed #19048202 No free full text.

Abstract: In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN) by Isaacs and Lindenmann. Subsequently, the IFN-alpha gene was cloned, fully sequenced and IFN-alpha was produced in recombinant form. Recombinant IFN-alpha is now used as the basis for treatment of chronic hepatitis C virus infection and can also be used to treat certain forms of chronic hepatitis B virus infections. IFNs have also been used in other viral infections, although with less success. The antiviral mechanisms of IFNs are reviewed in this chapter as well as the utility of IFNs in the treatment of persistent viral infections.

Slama L, Le Camus C, Serfaty L, Pialoux G, Capeau J, Gharakhanian S. · Service des maladies infectieuses, hôpital Tenon, AP-HP, 4, rue de la Chine, 75970 Paris cedex 20, France. · Diabetes Metab. · Pubmed #19046914 No free full text.

Abstract: The importance of metabolic disorders in the pathophysiology of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections is becoming increasingly apparent. Metabolic anomalies, with their potential for multiple-organ involvement, are to be expected, given the chronic nature of these diseases, and the intracellular dysregulation associated with them. Not only have the endocrine and cytokine metabolic anomalies seen in HIV and HCV infections been linked with the metabolic syndrome, but they also appear to have some pathways in common. Studying the differences and similarities between these metabolic anomalies may add to our understanding of HIV and HCV infection, and provide guidance on how to treat these chronic diseases. This review highlights the principal underlying factors for metabolic disorders in these chronic viral diseases-namely insulin resistance and liver damage. Both the chronic viral state itself and the host immune response give rise to glucose and lipid metabolic disorders that, in turn, are risk factors for hepatic damage. The various interactions between HIV and/or HCV with insulin resistance, type 2 diabetes, steatosis and fibrogenesis should be considered when determining the treatment and long-term follow-up of patients. Recent data indicate that HCV clearance improves insulin resistance and hepatic function in HCV-infected patients treated with interferon with or without ribavirin.

Biagini P, de Micco P. · CNRS UMR 6578 équipe émergence et coévolution virale, établissement français du sang Alpes-Méditerranée, université de la Méditerranée, CTRS infectiopôle sud, 27, boulevard Jean-Moulin, 13005 Marseille, France. · Transfus Clin Biol. · Pubmed #19026582 No free full text.

Abstract: Ten years after their discovery, anelloviruses combine some characteristics making them particularly intriguing. In support of their extreme genetic diversity and high prevalence in various populations, their natural history is still poorly understood along with their implication in human health. These viruses have been identified in blood and blood-derived products, and are probably remarkable examples of co-existence and co-evolution in their various hosts. This article presents epidemiological and molecular characterizing this new viral family.

Million M, Lepidi H, Raoult D. · CNRS, UMR 6236, IRD 198, unité de recherche sur les maladies infectieuses et tropicales émergentes, faculté de médecine, université de la Méditerranée, 27, boulevard Jean-Moulin, 13385 Marseille cedex 05, France. · Med Mal Infect. · Pubmed #19013734 No free full text.

Abstract: Q fever is a zoonotic disease caused by the ubiquitous pathogen Coxiella burnetii responsible for acute and chronic clinical manifestations. Its geographically heterogeneous prevalence seems mainly related to the clinician interest and the availability of a reference center. Its polymorphic clinical expression imposes reference to diagnosis in presence of pneumonia, hepatitis, prolonged fever or endocarditis with no proof of its etiology. The diagnosis is mainly serological. If acute Q fever is most often benign, endocarditis is constantly fatal without treatment. The treatment is effective and well tolerated, but must be adapted to the acute or chronic pattern, the presence of a heart valve disease, an aneurysm or a vascular prosthesis, an immunodeficiency and the specific problem of pregnancy.

Asselah T, Lada O, Moucari R, Marcellin P. · Université Paris 7-Denis-Diderot, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Recherche Biomédicale Bichat Beaujon CRB3, INSERM U773. · Expert Opin Investig Drugs. · Pubmed #19012511 No free full text.

Abstract: Chronic hepatitis B virus (HBV) infection, affecting approximately 350 million people worldwide, is associated with significant morbidity and mortality. In the past 10 years, hepatitis B therapy research has led to a multitude of available antiviral therapies: IFN-alpha, pegylated IFN-alpha(2a), lamivudine, adefovir, entecavir, telbivudine and tenofovir. To further improve reductions in viral load and resistance profiles, development of new HBV therapeutic strategies has been an important focus. One such therapy is clevudine, an analogue of the beta-L configuration. Clevudine is already licensed in Korea for anti-HBV therapy (Bukwang Pharmaceuticals, Seoul, Korea). Unique to clevudine is its ability to maintain antiviral activity following discontinuation of therapy. Typically, hepatitis B treatment requires continuous therapy to prevent reactivation. Sustained response is uncommon except in hepatitis B antigen (HBeAg)-positive patients who developed HBeAg seroconversion. This article reviews chronic HBV and its therapy options. Specifically, it describes clevudine's potent and sustained antiviral activity as observed in vitro and in vivo.

Poynard T, Morra R, Ingiliz P, Imbert-Bismut F, Thabut D, Messous D, Munteanu M, Massard J, Benhamou Y, Ratziu V. · Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Université Paris VI, CNRS ESA 8067 Paris, France. · Adv Clin Chem. · Pubmed #19004189 No free full text.

Abstract: Liver biopsy, due to its limitations and risks, is an imperfect gold standard for assessing the severity of the most frequent chronic liver diseases. This chapter summarized the advantages and the limits of the available biomarkers of liver fibrosis. Among a total of 2237 references, a total of 14 validated biomarkers have been identified between 1991 and 2007. Nine were not patented and five were patented. FibroTest (FT) was the most studied test with 33 different populations including 6549 patients and 925 controls. The mean diagnostic value for the diagnosis of advanced fibrosis assessed using standardized area under the receiver operating characteristics (ROC) curves was 0.84 [95% confidence interval (CI), 0.83-0.86], without significant difference between the causes of liver disease, hepatitis C, hepatitis B, alcoholic or nonalcoholic fatty liver disease. High-risk profiles of false negative/positive of FT are present in 3% of populations, mainly Gilbert syndrome, hemolysis, and acute inflammation. FT has higher accuracy than aspartate aminotransferase/platelets ratio index (APRI), the most used nonpatented test. No significant difference has been observed between the five patented tests. A quality score has been assessed in order to compare the quality of fibrosis biomarkers. Neither biomarkers nor biopsy are sufficient alone to take definitive decision in a given patient and all the clinical and biological data must be taken into account. Due to the evidence-based data, health authorities in some countries have already approved validated biomarkers as first-line procedure for the staging of liver fibrosis. This overview of evidence-based data suggests that biomarkers could be used as an alternative to liver biopsy for the assessment of fibrosis stage in the four more common chronic liver diseases: C virus (HCV), hepatitis B virus (HBV), hepatitis nonalcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD). Neither biomarkers nor biopsy are sufficient alone to take definitive decision in a given patient and all the clinical and biological data must be taken into account.

Albert ML, Decalf J, Pol S. · The Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, Paris, France. · J Hepatol. · Pubmed #18929418 No free full text.

Abstract: Chronic hepatitis C is a major public health problem. Despite numerous clinical studies in humans and experimental observations made in chimpanzees, hepatitis C pathogenesis remains poorly understood. Here, we review the clinical features of acute and chronic disease, and discuss the role of the immune system in the pathogenesis of disease. Many are aware of the dual role of T cells: responsibility for clearance of the virus during acute phase; and liver injury during chronic phase. Nonetheless, there is an emerging belief that failure to prime HCV-specific T cells is responsible for the failure to spontaneously clear the virus, and possibly, for the lack of response to pegylated-IFNalpha(2a)/ribavirin therapy. We have focused on the latest suspects, plasmacytoid dendritic cells (pDCs), considered to be the professional type I IFNs producing cells. We review the somewhat contradictory data regarding the functional capacity of pDCs in chronic HCV patients and argue that, while lower in relative concentration as compared to healthy individuals, they are not defective in their ability to initiate an innate inflammatory response. Thus, instead of being the culprit, pDCs may in fact represent a novel therapeutic target in order to improve upon existing therapies for treating HCV patients.

Nicolas JF, Guy B. · University Lyon 1, UFR Lyon-Sud, IFR 128 BioSciences Lyon-Gerland, Institut National de la Santé et de la Recherche Médicale U503, 21 Avenue Tony Garnier, Lyon Cedex 07, Lyon 69365, France. · Expert Rev Vaccines. · Pubmed #18844594 No free full text.

Abstract: The dermis and epidermis are alternative sites for prophylactic vaccination that have received renewed interest in recent years, not only because of the ease of access to the skin, but also its unique immunological properties. This review discusses the characteristics of the skin, current knowledge on skin immunity and clinical experience with cutaneous immunization against infectious diseases, with a special focus on intradermal immunization. The most widely accepted paradigm explaining the efficacy of cutaneous immunization is reviewed and recent research suggesting where this paradigm may need some refinement is highlighted. Clinical investigations that have concentrated on the intradermal route to vaccinate against influenza, rabies or hepatitis B support the current knowledge on skin immunity and, when combined with recent progress made in the development of user-friendly injection systems, have stimulated the ongoing clinical development of novel vaccines.

Schramm F, Moenne-Loccoz R, Fafi-Kremer S, Soulier E, Royer C, Weitten T, Brignon N, Ellero B, Woehl-Jaegle ML, Meyer C, Wolf P, Doffoel M, Baumert TF, Gut JP, Stoll-Keller F, Schvoerer E. · Unité Inserm 748, 3, rue Koeberlé, 67000 Strasbourg, France. · Pathol Biol (Paris). · Pubmed #18842359 No free full text.

Abstract: Besides hepatocytes, representing the main replication site of hepatitis C virus, peripheral blood mononuclear cells also represent a crucial target for viral infection. Hepatitis C virus compartmentalization (i.e., non-random distribution) of viral variants between plasma and peripheral blood mononuclear cells, more frequently observed in liver transplant patients compared to non-transplanted patients, makes liver transplantation an interesting model for the analysis of hepatitis C leukotropism. This article aims to present, firstly, in clinical and biological features arguing favour of hepatitis C virus infection leukotropism and, secondly, to review current knowledge about compartmentalization between plasma and peripheral blood mononuclear cells, especially in the liver transplantation setting.

Zoulim F, Radenne S, Ducerf C. · INSERM, [corrected] U871 Lyon, France. · Liver Transpl. · Pubmed #18825719 No free full text.

Abstract: 1. Hepatitis B virus replication is associated with a severe outcome in patients with decompensated cirrhosis. 2. Viral suppression induced by antivirals results in a clinical improvement that allows liver transplantation to be delayed or avoided. 3. Early treatment intervention is mandatory in patients with decompensated cirrhosis because of the delay in the restoration of liver functions. 4. Lamivudine is no longer the drug of choice because the initial enthusiasm has been tempered by the high rate of resistance development. 5. Early add-on therapy with adefovir allows us to rescue lamivudine resistance, but its use may be limited by nephrotoxicity. 6. Studies are ongoing with the newer generation of antivirals (telbivudine, tenofovir, entecavir, and emtricitabine) in monotherapy or in combination to determine the best strategy for achieving rapid and prolonged suppression of viral replication. These improved strategies should enhance treatment success enough to obtain clinical stabilization, to delay or prevent the need for transplantation, and to reduce the risk of hepatitis B virus recurrence on the graft.AASLD.

Ichai P, Samuel D. · AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France. · Liver Transpl. · Pubmed #18825677 No free full text.

Abstract: 1. Establishing the cause of fulminant hepatitis is an important step in the management of acute liver failure, so that specific therapy can be initiated and any contraindications to liver transplantation can be eliminated. 2. The etiology of fulminant hepatitis varies in different countries and at different times. A viral etiology (in particular hepatitis B virus) is now less frequent, and paracetamol-induced fulminant hepatic failure is more common. 3. Many patients have miscellaneous causes of fulminant hepatitis. It is important to establish the main clinical and biological characteristics for specific management. 4. Assessment of the prognosis of fulminant hepatitis is important for distinguishing patients requiring liver transplantation from those whose will improve spontaneously. Prognosis depends on several factors, including the gold standard, the King's College Hospital criteria and Clichy's criteria.

Dufour B, Moutou F, Hattenberger AM, Rodhain F. · National Veterinary School of Alfort (Ecole Nationale Vétérinaire d'Alfort- ENVA), Maladies Contagieuses, Maisons-Alfort Cedex, France. · Rev Sci Tech. · Pubmed #18819676 No free full text.

Abstract: Global changes, including an increase in trade and global warming, which act on the environment, are likely to impact on the evolution of pathogens and hence of diseases. To anticipate the risks created by this new situation, a French group of experts has developed a method for prioritising animal health risks. This is a two-phase method: the first step is to identify the diseases whose incidence or geographical distribution could be affected by the changes taking place, and the second step is to evaluate the risk of each of these diseases. As a result of this process, six priority diseases were selected: bluetongue, Rift Valley fever, West Nile fever, visceral leishmaniasis, leptospirosis and African horse sickness. The main recommendations were: to develop epidemiological surveillance, to increase knowledge of epidemiological cycles, to develop research into these diseases and to pool cross-border efforts to control them.

Gould EA, Higgs S. · Unité des Virus Emergents, Faculté de Médecine Timone, 13385 Marseille, Cedex 05, France. · Trans R Soc Trop Med Hyg. · Pubmed #18799177 No free full text.

Abstract: While some skeptics remain unconvinced that global climate change is a reality, there is no doubt that during the past 50 years or so, patterns of emerging arbovirus diseases have changed significantly. Can this be attributed to climate change? Climate is a major factor in determining: (1) the geographic and temporal distribution of arthropods; (2) characteristics of arthropod life cycles; (3) dispersal patterns of associated arboviruses; (4) the evolution of arboviruses; and (5) the efficiency with which they are transmitted from arthropods to vertebrate hosts. Thus, under the influence of increasing temperatures and rainfall through warming of the oceans, and alteration of the natural cycles that stabilise climate, one is inevitably drawn to the conclusion that arboviruses will continue to emerge in new regions. For example, we cannot ignore the unexpected but successful establishment of chikungunya fever in northern Italy, the sudden appearance of West Nile virus in North America, the increasing frequency of Rift Valley fever epidemics in the Arabian Peninsula, and very recently, the emergence of Bluetongue virus in northern Europe. In this brief review we ask the question, are these diseases emerging because of climate change or do other factors play an equal or even more important role in their emergence?

Couzigou C, Voyer C, Shaghaghi CK, Bourée P, Vittecoq D. · Service des maladies infectieuses et tropicales, hôpital Paul-Brousse, AP-HP, 12, avenue Paul-Vaillant-Couturier, Villejuif 94800, France. · Med Mal Infect. · Pubmed #18723304 No free full text.

Abstract: Human immunodeficiency virus (HIV) positive international travelers are at higher risk of infectious complications. The pretravel assessment often provides an opportunity to update routine vaccinations and HIV patient specific vaccinations including pneumococcus, hepatitis A, hepatitis B, and influenza. Other vaccinations may be required or recommended. Decision for vaccination require considering the risk and severity of the vaccine, preventable diseases in the destination area, the nature of the vaccine (live attenuated vaccines or not), the patient's immune status, and the risk of virological rebound as a consequence of vaccination. The immunogenicity of vaccines is decreased in HIV patient with low CD4 cell counts (above 500 cells per cubic millimetres and particularly above 200 cells per cubic millimetres) and in patients with a persistent HIV RNA viral load. Vaccines should be administered to patients whose HIV infections are in the early stage or in patients receiving HAART with a satisfactory immune status and reduced HIV RNA level. Testing of postvaccination antibodies is useful if serological protective levels are defined. In case of non-response after vaccination, few studies suggest that additional revaccination, increase of vaccine dose, intradermic vaccination, or use of prime-boost combination may be successful. Further research is needed to define vaccination strategies, adapted to the immune status of the HIV patient.

Labbe G, Pessayre D, Fromenty B. · Sanofi-aventis recherche & développement, Drug Safety Evaluation, Alfortville, France. · Fundam Clin Pharmacol. · Pubmed #18705745 No free full text.

Abstract: Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects such as lactic acidosis and rhabdomyolysis in some patients. By severely altering mitochondrial function in the liver, drugs can induce microvesicular steatosis, a potentially severe lesion that can be associated with profound hypoglycaemia and encephalopathy. They can also trigger hepatic necrosis and/or apoptosis, causing cytolytic hepatitis, which can evolve into liver failure. Milder mitochondrial dysfunction, sometimes combined with an inhibition of triglyceride egress from the liver, can induce macrovacuolar steatosis, a benign lesion in the short term. However, in the long term this lesion can evolve in some individuals towards steatohepatitis, which itself can progress to extensive fibrosis and cirrhosis. As liver injury caused by mitochondrial dysfunction can induce the premature end of clinical trials, or drug withdrawal after marketing, it should be detected during the preclinical safety studies. Several in vitro and in vivo investigations can be performed to determine if newly developed drugs disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition (MPT) pore. As drugs can be deleterious for hepatic mitochondria in some individuals but not in others, it may also be important to use novel animal models with underlying mitochondrial and/or metabolic abnormalities. This could help us to better predict idiosyncratic liver injury caused by drug-induced mitochondrial dysfunction.

Imbert P, Guérin N, Sorge F, Anonymous00022. · Service des maladies infectieuses et tropicales, Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France. · Med Trop (Mars). · Pubmed #18689311 No free full text.

Abstract: Each year hundreds of thousands of children leave France to travel to developing countries where they are exposed to infectious agents that can be prevented by vaccination. During the child's pre-travel check-up, practitioners should check that all mandatory immunizations are up-to-date and provide advice on relevant vaccines in function of the epidemiological situation at the chosen destination. However various factors hinder full compliance with this approach and some vaccines are underused. Underused vaccines are referred to as neglected vaccines. In the French vaccination schedule three vaccinations can be considered as neglected. The first is the hepatitis B vaccine that has a low coverage level in France due to strong reluctance to its use despite the fact that the virus is widespread in tropical areas. The second is pneumococcal vaccine that should be administered to all infants less than 2 years of age, especially for travel to areas where pneumonia and meningitis are frequent. The third is BCG vaccine that is now at greater risk of being neglected in child travellers because its use has been downgraded from a general requirement to a recommendation only for children at risk. A serious limitation on the use of travel vaccinations is cost that can lead families to neglect some infectious risk such as hepatitis A that is a major risk for child travellers as well as for their relatives during or after the trip and typhoid fever that is essentially an imported disease. Rabies vaccine is also underused due to its cost and to poor understanding of the risk by many practitioners and families. The purpose of this article is to underline the need to improve information and access to vaccines that are all too often neglected in child travellers.

Wartelle-Bladou C, Rosenthal E, Ratziu V, De Lédinghen V, Lang JP, Poynard T. · Service d'Hépato-Gastroentérologie, Centre Hospitalier du Pays d'Aix, Avenue des tamaris, 13616 Aix-en-Provence cedex 1, France. · Gastroenterol Clin Biol. · Pubmed #18675187 No free full text.

Abstract: Adhesion to pegylated combination therapy is a key factor for therapeutic success in patients HCV infected. To optimize it, goals to reach are to limit dose reduction and premature discontinuation of treatment due to adverse events ; to improve the patient compliance to treatment, particularly during the first three months, particularly to ribavirin. Therapeutic education, management of psychiatric adverse events, epoetin alfa, have demonstrated their benefit in terms of sustained virologic response or quality of life. Preparing the treatment with the patient and a multi-disciplinary team, setting successive therapeutic goals with the predictive value of the early virologic response will promote adhesion to treatment. A hepatitis C training program for general practitioners (GP) allows an efficient follow-up of treated patients by a trio hepatologist - GP - nurse and a concrete implication of GP in the field of hepatitis C. Further developments are needed for : taking in account the patient quality of life during treatment to anticipate premature discontinuation, promotion of therapeutic education by specialized nurses, standardization of the diagnosis of depression during treatment, and regular updating of general practitioners on antiviral C treatment.