Traitement des hépatites B, C, D

Les hépatites virales sont un problème majeur de santé publique au niveau international. Environ 2 milliards de sujets dans le monde ont été en contact avec le VHB, soit qu\u27ils aient une infection, soit qu\u27ils aient éliminé partiellement le virus [1]. Quatre cents millions d\u27individus sont porteurs chroniques d\u27une infection par le virus de l\u27hépatite B (VHB) et parmi ceux-ci, environ à 15 millions sont co-infectés par un virus satellite du virus de l\u27hépatite B appelé le virus de l\u27hépatite Delta (VHD).Dans le monde, près de 200 millions de sujets sont également infectés par le virus de l\u27hépatite C [2]. Les chiffres concernant la mortalité et la morbidité globale de ces infections sont partiellement connus. L\u27OMS estime qu\u27environ 2 millions de décès par an sont dus aux infections par les virus des hépatites C (http://www.who.int/fr/). On sait également que les patients porteurs d\u27une infection chronique ont un risque majeur d\u27évoluer vers la cirrhose du foie et le carcinome hépato-cellulaire (le risque serait de 200 par rapport à un sujet non infecté [3, 4] ). Dans les pays développés, les hépatites B et C sont également responsables d\u27une grande partie des transplantations hépatiques [1] . L\u27objectif de cette revue est de faire le point sur le traitement des hépatites B, C et Delta en envisageant les schémas thérapeutiques les plus adaptés à l\u27Afrique. Nous aborderons d\u27abord le traitement des hépatites B, le traitement des co-infections B-Delta, le traitement des hépatites B chez les patients VIH puis le traitement des hépatites C et celui des hépatites C chez les patients vivant avec le VIH

Les mutants précore et du promoteur basal du core du virus de l’hépatite B

Le virus de l’hépatite B (VHB) est le seul virus à ADN qui possède une étape de reverse transcription au cours de son cycle de réplication. L’absence d’activité 3’-5’ exonucléasique de la fonction reversetranscriptase de l’ADN polymérase du virus génère une accumulation de mutations sur l’ensemble du génome viral. Ainsi, chez un même individu vont coexister des populations virales sauvages et mutées qui pourront évoluer tout au long de l’histoire naturelle de l’infection. La variabilité génétique du VHB s’observe dans toutes les régions du génome viral. La mutation la plus fréquemment décrite dans la région précore (PC) du VHB est la mutation G1896A qui induit la formation d’un codon stop dans l’ARN précore et abolit la synthèse de l’antigène HBe. Dans la région du promoteur basal du core (PBC), la double mutation (A1762T-G1764A) est associée à une baisse de la synthèse de l’antigène HBe. L’impact des mutants PC et du PBC dans l’histoire naturelle de l’hépatite B et dans la sévérité des lésions hépatiques n’est pas clairement établi

Systemic diseases and biotherapies: Understanding, evaluating, and preventing the risk of hepatitis B reactivation

Hepatitis B virus (HBV) reactivation can occur in chronic carriers of the HBV surface antigen (HBsAg) and constitutes a well-known complication of immunosuppressive therapy. HBV reactivation has also been reported after contact with the HBV. The increasing use of biological agents (TNFα antagonists, rituximab, abatacept, and tocilizumab) to treat systemic diseases has resulted in numerous publications about the risk of HBV reactivation. The relevant scientific societies have issued recommendations designed to prevent HBV reactivation. The main measures consist of screening for markers indicating chronic HBV infection (HBsAg) or HBV infection in the distant past (antibodies to the HBV core antigen) before initiating biological therapies, vaccinating marker-negative patients, and considering close follow-up or antiviral treatment before immunosuppressive treatment initiation or in the event of HBV reactivation. Here, we discuss the pathophysiological mechanisms underlying HBV reactivation during biological treatments, most notably in patients with occult HBV infection or markers for remote HBV infection, whose hepatocyte nuclei may contain a resistance form of HBV DNA known as covalently closed circular DNA (cccDNA). Assessment of the risk of reactivation relies on the HBV status, drugs used, and data from the literature. Finally, we discuss the various recommendations and modalities for HBV vaccination, preemptive treatment, and patient management, according to the level of risk and to the circumstances in which reactivation occurs

Quantification de l’antigène HBs : intérêts et limites dans le suivi des patients infectés par le virus de l’hépatite B

Hepatitis B surface antigen (HBsAg) is usually used as a qualitative marker for the diagnosis of hepatitis B virus (HBV) infection, ant its persistence for more 6 months defines chronic hepatitis B (CHB) infection. HBsAg quantification was introduced several years ago. Commercial quantitative assays are now available and studies have suggested its interest for the monitoring patients with chronic hepatitis B. Indeed, HBsAg titers can correlate with intrahepatic cccDNA levels. Several studies have shown that HBsAg titers vary in the different phases of the natural history of the CHB infection. The kinetic of serum HBsAg seems to have a predictive value of HBsAg clearance after treatment or of reactivation, in the case of lack of response to treatment. However, interpretation has to take into account the phase of CHB infection, the HBV genotype, HBeAg status and serum HBV DNA

Methylation of the Gpat2 promoter regulates transient expression during mouse spermatogenesis

Spermatogenesis is a highly regulated process that involves both mitotic and meiotic divisions, as well as cellular differentiation to yield mature spermatozoa from undifferentiated germinal stem cells. Although Gpat2 was originally annotated as a glycerol-3-phospate acyltransferase by sequence homology to Gpat1 , GPAT2 is highly expressed in testis but not in lipogenic tissues and is not up-regulated during adipocyte differentiation. New data show that GPAT2 is required for the synthesis of piRNAs, a group of small RNAs that protect the germ cell genome from retrotransposable elements. In order to understand the relationship between GPAT2 and its role in the testis, we focused on Gpat2 expression during the first wave of mouse spermatogenesis. Gpat2 expression was analyzed by qPCR, in situ hybridization, immunohistochemistry and Western blot. Gpat2 mRNA content and protein expression were maximal at 15 dpp and restricted to pachytene spermatocytes. To achieve this transient expression, both epigenetic mechanisms and trans-acting factors are involved. In vitro assays showed that Gpat2 expression correlates with DNA demethylation and histone acetylation and that it is up-regulated by retinoic acid. Epigenetic regulation by DNA methylation was confirmed in vivo in germ cells by bisulfite sequencing of the Gpat2 promoter. Consistent with the initiation of meiosis at 11 dpp, methylation decreased dramatically. Thus, Gpat2 is expressed at a specific stage of spermatogenesis, consistent with piRNA synthesis and meiosis I prophase, and its on-off expression pattern responds predominantly to epigenetic modifications.Fil: Garcia Fabiani, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Montanaro, Mauro Aldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Lacunza, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Cattaneo, Elizabeth Renee. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Coleman, Rosalind A.. University of North Carolina; Estados UnidosFil: Pellon Maison, Magali. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Gonzalez-Baró; MR. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; Argentin

Population Characteristics of Selected Small Pelagic Fish Species along the Tanzanian Coast

Although small pelagic fishing in Tanzania is rising, lack of information on population structure has been a significant concern in its management. This study aimed to determine the species composition, length-weight relationship and length at first maturity of Amblygaster sirm, Encrasicholina heteroloba, Encrasicholina punctifer, Stolephorus commersonii, and Spratelloides gracilis landed at Kilwa Kivinje, Kipumbwi and Shangani along the Tanzanian coast. These landing sites were chosen because of their locations and importance in the small pelagic fishery. Sampling was done monthly from October 2018 to June 2020. The catch composition was site specific such that  E. heteroloba dominated at Kilwa Kivinje and Shangani, while E. punctifer dominated at the Kipumbwi site. Further analysis shows allometric coefficient to be greater than 3 for A. sirm and E. punctifer, indicating positive allometric growth, while for S. commersonii and S. gracilis, the allometric coefficient was less than 3, indicating negative allometric growth. Our findings showed that length at first maturity (L50) differed, implying that these species start spawning at different sizes, an essential biological reference for sustainable small pelagic fish exploitation. We recommend seasonal closure of the fishery to maintain reproductive seasons since many species are multiple spawners. Keywords: Population; Small pelagic; Maturity; Tanzani

Time trend of Legionella colonization in the waterline of a hospital of Rome, Italy

Background: In many hospital’s Legionella outbreaks, hot water systems are the most frequent source of infection. Objectives: Considering the old age of the hospital waterline, an investigation on Legionella spp. water colonization was performed to evaluate the system weakness and to implement environmental preventive measures. Methods: From 2004 to 2010, a total of 5 sampling campaigns were performed, collecting 99 water samples from 13 wards and 3 other points of the water line (boilers, point of connection with public water line, hospital waterworks). The samples were analyzed, following national Legionella spp. standard methods. Results: A total of 28 samples (28.3%) were positive for Legionella spp. There has been an increasing time trend until 2008, from 4.5% to 75% in 2008; in the first month of 2010 only 26.3% of the samples were positive. The boiler was positive in 45.5% of samples collected since 2006. In total, surgeries were positive in 38% of cases (8/21): 100% of positive samples in 2006 and 2008, reduced at 50% in the first month of 2010. Only in these wards Legionella spp. were found four times to be >10,000 cfu/L. Among other wards, emergency medicine and oncology are the most contaminated (31% of positive samples). The worst year was 2008 with 75% of positive samples. Conclusion: Hospital water system seems to be affected by Legionella spp. colonization most frequently from 2006 to 2010. The high percentage of positivity in 2008 was related to the presence of a building yard in the hospital. In 2010 there was an improvement, although boilers, surgery, medicine and oncology are still contaminated. It is necessary now to investigate the temperature level mantained in hot-water system and also to observe if the structural characteristics of water ducts could have influenced the colonization observed

Spread of activation and deactivation in the brain: Does age matter?

Cross-sectional aging fMRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and ROI analyses