A cross sectional survey on UK older adult's attitudes to ageing, dementia and positive psychology attributes.

Background: With an increasingly ageing population worldwide, the predominant attitude towards ageing is still negative. Negative stereotypes have detrimental effects on individuals' physical and mental health. Evidence is required about factors that may predict and change these views.

Baseline and post-treatment hepatitis C NS5A resistance in relapsed patients from a multicentric real-life cohort.

Background: Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors.

Methods: From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors.

First next-generation sequencing full-genome characterization of a hepatitis C virus genotype 7 divergent subtype.

We report the near-full-length genome sequence of a hepatitis C virus (HCV) isolate from a man originating from Democratic Republic of Congo, the genotype of which could not be determined by the routinely used sequencing technique. The near-complete genome sequence of this variant BAK1 was obtained by the association of two next-generation sequencing technologies. Evolutionary analysis indicates that this isolate, BAK1, could be the first reported strain belonging to a new HCV-7b subtype.

Hepatitis C virus whole genome sequencing: Current methods/issues and future challenges.

Therapy for hepatitis C is currently undergoing a revolution. The arrival of new antiviral agents targeting viral proteins reinforces the need for a better knowledge of the viral strains infecting each patient. Hepatitis C virus (HCV) whole genome sequencing provides essential information for precise typing, study of the viral natural history or identification of resistance-associated variants.

Amplification and pyrosequencing of near-full-length hepatitis C virus for typing and monitoring antiviral resistant strains.

Directly acting antiviral drugs have contributed considerable progress to hepatitis C virus (HCV) treatment, but they show variable activity depending on virus genotypes and subtypes. Therefore, accurate genotyping including recombinant form detection is still of major importance, as is the detection of resistance-associated mutations in case of therapeutic failure. To meet these goals, an approach to amplify the HCV near-complete genome with a single long-range PCR and sequence it with Roche GS Junior was developed.

Recent evidence of underestimated circulation of hepatitis C virus intergenotypic recombinant strain RF2k/1b in the Rhône-Alpes region, France, January to August 2014: implications for antiviral treatment.

Since the beginning of 2014, hepatitis C virus (HCV) recombinant forms RF2k/1b have been detected in the Rhône-Alpes French region in 10 patients originating from the Caucasus area. Circulation of this particular HCV strain is very likely to be underestimated. It is also prone to be misgenotyped when using genotyping methods based on the 5' region of the viral genome, which may lead to suboptimal treatment.

Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C.

During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-infected and NASH patients in physiological conditions as well as after stimulation using flow cytometric and immunohistochemical analyses.

Lymphocytes degranulation in liver in hepatitis C virus carriers is associated with IFNL4 polymorphisms and ALT levels.

Background: The polymorphisms of IFNL4 are strongly associated with both spontaneous hepatitis C virus (HCV) clearance and response to peg-IFN-α/ribavirin treatment. To further establish the biological effects of the IFNL4 and rs1297860 variations, we studied the activity of liver immune cells.

Methods: Fresh liver samples were collected from HCV-infected patients before any treatment and from NASH patients as controls.

Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis.

Background & Aims: In chronic hepatitis C (CHC), HCV-specific T-cell responses are often dysfunctionnal. In vitro data point out that regulatory T cells (Treg) are able to suppress HCV-specific lymphocyte proliferation and cytokine secretion but their implication in this pathology is still debated.

Methods: Three complementary approaches were performed to investigate phenotype, frequency or localization of intra-hepatic Treg in treatment naïve CHC patients.

Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin.

The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels.

Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C.

Background/aims: The fate of intrahepatic NK cell subsets in the course of HCV and HBV infections is not clearly understood.

Methods: Blood and intrahepatic CD56(+) NK cell subsets (expressing NKG2A, CD158a,h or CD158b,j receptors) from HCV or HBV patients were quantified by flow cytometry and localized by immunohistochemistry in liver biopsies.

Results: A significant reduction in NK cell frequency and a quantitative imbalance between CD56(bright) and CD56(dim) subsets were observed in chronic HCV patients as compared to HBV patients, underlining that the inflammatory environment is not the only cause of these phenomena.

IRES complexity before IFN-alpha treatment and evolution of the viral load at the early stage of treatment in peripheral blood mononuclear cells from chronic hepatitis C patients.

At the early stage of treatment, IFN alpha-2a induces inhibition of HCV replication. The viral load reflects mainly the degradation rate of the viruses. However, differences in the behavior of the viral population depend on changes, which occurred in the HCV-IRES genome.

Lack of clinical significance of variability in the internal ribosome entry site of hepatitis C virus.

The extreme 5'-proximal sequence of the hepatitis C virus (HCV) genome including the 5' non-coding region (5'NCR) of 341 nucleotide long and the first 30 nucleotides of the core region is highly conserved among different HCV genotypes. It contains a segment termed Internal Ribosome Entry Site (IRES) that regulates the cap-independent translation of HCV-RNA to polyprotein. Sequence variability in this region has important implications for structural organisation and function of the IRES element and could correlate with HCV RNA concentration or response to antiviral therapy.

Influence of three successive antiviral treatments on viral heterogeneity in nonresponder chronic hepatitis C patients.

The purpose of the present study was to assess the viral diversity of hepatitis C virus (HCV) in six nonresponder patients during three unsuccessful treatments. These patients were treated successively with IFN-alpha2a (IFN-alpha) at a posology of 3.10(6) units (MIU) three times a week, 10 MIU three times a week, and a combination of IFN-alpha (3 MIU) plus ribavirin (1,000 mg/day).

Dynamics of viral quasispecies during interferon therapy in non responder chronic hepatitis C patients.

Background: the reference method to study the HCV complexity was cloning and sequence analysis of a sufficient number of clones. The evolution of the viral complexity in chronic non responder patients during treatment with standard doses of interferon was not very well investigate because this method was expensive and labour intensive when large series of patients were concerned. Meanwhile, with the alternative Single-Strand Conformation Polymorphism (SSCP) method, a rough estimation of the quasispecies present in a given sample could be obtained.

Mosquito cells bind and replicate hepatitis C virus.

Several studies have demonstrated some hepatitis C virus (HCV) replication in lymphocyte and hepatocyte cell lines such as in African green monkey Vero cells. The aim of the present study was to select other cell lines able to bind and replicate HCV. Human hepatoma PLC/PRF/5 cells, human lymphoma Namalwa cells, Vero and mosquito AP61 cells were inoculated with HCV-positive plasma, washed six times and examined for the presence of the viral genome at different times post infection, using an RT-PCR method.

Hepatitis C virus RNA in plasma and blood mononuclear cells in patients with chronic hepatitis C treated with alpha-interferon.

Hepatitis C virus (HCV), a positive stranded RNA virus, is the main causative agent of post-transfusion and sporadic non-A non-B hepatitis worldwide. Paired samples of plasma and peripheral blood mononuclear cells (PBMC) from 11 patients with chronic hepatitis C treated with alpha-interferon (IFN) were tested, using a single step polymerase chain reaction (PCR), for the presence of HCV RNA. Before treatment, the viral genome was detected in all the plasma samples and 81.

Different prevalence of precore mutants in five members of a hepatitis-B-virus-infected family: evidence for a precore variant type in an asymptomatic anti-HBs patient.

Chronic active hepatitis B (CAH-B), anti-HBe (+) has been associated with a hepatitis B virus variant carrying a stop codon at the distal pre-C region that prevents HBeAg synthesis. We analyzed the HBV DNA pre-C region in five members of a Turkish family. The mother presented an anti-HBe (+) CAH-B and the four children different hepatitis B virus serological and clinical profiles.

Quantitative detection of hepatitis B virus DNA in serum using chemiluminescence: comparison with radioactive solution hybridization assay.

A quantitative, non-radioactive hybrid capture HBV DNA assay (Digene Diagnostics), which uses an efficient solution hybridization procedure coupled to a sensitive chemiluminescent signal amplification system, was compared with the quantitative, radioactive solution hybridization assay (Genostics, Abbott Laboratories), in hepatitis B virus carriers, particularly in those undergoing antiviral therapy. The qualitative reproducibility of the chemiluminescent method, tested on 30 sera, was acceptable, with a reproducibility rate of 93.3%.

c-Ha-ras polymorphism in patients with hepatocellular carcinoma. Comparison of healthy subjects and alcoholic patients with cirrhosis.

It has been observed that certain rare alleles of the c-Ha-ras gene occur more frequently in patients with certain malignant tumors than in healthy individuals, suggesting that these alleles may serve as markers for particular types of cancer. In this study, we compared the restriction fragment length polymorphism at the c-Ha-ras gene locus in 40 patients with cirrhosis and hepatocellular carcinoma with that in 39 patients with cirrhosis and in 42 normal subjects, all of Caucasian origin. Southern blotting of leukocyte DNA from the above patients, after digestion with either BamH1 or AvaII, revealed the presence of allele fragments of different sizes, corresponding to 4 common alleles and 3 rare alleles.

Interest of the detection of hepatitis C virus RNA in patients with alcoholic liver disease. Comparison with the HBV status.

HCV-RNA detection was investigated in 66 chronic alcoholic patients divided into 3 groups according to the severity of liver injury: group 1 included 22 chronic alcoholics without cirrhosis, group 2, 20 patients with alcoholic cirrhosis and group 3, 24 patients with alcoholic cirrhosis and hepatocellular carcinoma. The 'nested' polymerase chain reaction (PCR) technique amplifying the 5' non-coding region was used to detect HCV-RNA. For comparison, ELISA1, ELISA2 and RIBA2 tests (Ortho Diagnostics System) were also used to detect anti-HCV antibodies.

Advantage of PCR for detecting low amounts of HBV DNA in patients' sera.

Serum hepatitis B virus DNA (HBV DNA) is now the most important and reliable marker for monitoring viral replication. Quantitative detection of HBV DNA in serum is based on a commercial standardized solution hybridization assay (Genostics). In this work, we studied the sensitivity and specificity of this method, in comparison with the polymerase chain reaction (PCR) technique, for low-value HBV DNA serum samples.