Genotype 1 hepatitis C virus envelope features that determine antiviral response assessed through optimal covariance networks

The poor response to the combined antiviral therapy of pegylated alfa-interferon and ribavarin for hepatitis C virus (HCV) infection may be linked to mutations in the viral envelope gene E1E2 (env), which can result in escape from the immune response and higher efficacy of viral entry. Mutations that result in failure of therapy most likely require compensatory mutations to achieve sufficient change in envelope structure and function. Compensatory mutations were investigated by determining positions in the E1E2 gene where amino acids (aa) covaried across groups of individuals. We assessed networks of covarying positions in E1E2 sequences that differentiated sustained virological response (SVR) from non-response (NR) in 43 genotype 1a (17 SVR), and 49 genotype 1b (25 SVR) chronically HCV-infected individuals. Binary integer programming over covariance networks was used to extract aa combinations that differed between response groups. Genotype 1a E1E2 sequences exhibited higher degrees of covariance and clustered into 3 main groups while 1b sequences exhibited no clustering. Between 5 and 9 aa pairs were required to separate SVR from NR in each genotype. aa in hypervariable region 1 were 6 times more likely than chance to occur in the optimal networks. The pair 531-626 (EI) appeared frequently in the optimal networks and was present in 6 of 9 NR in one of the 1a clusters. The most frequent pairs representing SVR were 431-481 (EE), 500-522 (QA) in 1a, and 407-434 (AQ) in 1b. Optimal networks based on covarying aa pairs in HCV envelope can indicate features that are associated with failure or success to antiviral therapy

Effets d'une alimentation parentérale sur l'adaptation des disaccharidases de la bordure en brosse jéjunale chez le rat adulte. Rôle des hormones thyroïdiennes

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Effets d'une émulsion lipidique administrée par voie entérale ou parentérale sur l'adaptation fonctionnelle intestinale chez le rat adulte

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Adaptation enzymatique intestinale en fonction de la composition et du mode d'administration de l'alimentation

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Alcohol, hepatitis C screening and hepatic fibrosis in drug users

Background: In drug users, viral hepatitis C, alcohol abuse, and drug use are three interconnected public health challenges.Methods: This study assessed the impact of alcohol on hepatitis C screening and hepatic fibrosis in this patient population. In total, 934 substance users were included and divided into three groups: Group A, alcohol use disorder only (n = 511); Group ISDU, intravenous and snorting drug users (n = 142); Group ISDAU, intravenous and snorting drug users with alcohol use disorder (n = 281). A FibroScan was performed first, after which participants were proposed to undergo screening for HCV.Results: The HCV screening rate was significantly lower in Group A (62%) than in the ISDAU or ISDU groups (81% and 85% respectively) (p&lt;0.001). The rate of HCV seropositivity was lower in Group A (4.4%), whereas it was significantly higher in the ISDAU group than ISDU group (42.3% vs 30.0%, p = 0.02). The rates of significant fibrosis and severe fibrosis were higher in Group A (34% and 21%) and the ISDAU group (29% and 18%) than in ISDU (15% and 7%) (p&lt;0.001). While entering, in addition to the group, age, gender, smoking status (cannabis and tobacco), drug consummation, HCV seropositivity, and BMI as co-variables in a multivariate model, only age correlated with fibrosis (p&lt;0.001). Considering age, there was no difference in impact among the different substances on the fibrosis score.Conclusion: Alcohol consumption impacts the health status of drug users. It is thus appropriate to early identify alcohol consumption in drug users and consider alcohol as a risk factor for severe fibrosis and HCV transmission. Alcohol consumption warrants the strengthening of HCV screening and hepatic fibrosis assessment.&nbsp;</p

[Physiopathology of bullous pemphigoid]

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