1,307 research outputs found
COVID-19: Possible Impact of the Genetic Background in IFNL Genes on Disease Outcomes
No full textOpen-Access-Publikationsfonds 202
Hepatitis C Virus, Diabetes and Steatosis: Clinical Evidence in Favor of a Linkage and Role of Genotypes
No full textInfection with hepatitis C virus (HCV) primarily causes chronic liver disease with characteristic histopathologic features, including hepatic steatosis. Moreover, chronic hepatitis C is also closely related to insulin resistance (IR) and an increased risk of type 2 diabetes mellitus (DM). This review summarizes the available clinical evidence for a linkage of chronic HCV infection and developing IR or DM that comprises (i) retro- and prospective clinical studies, (ii) the excess risk of chronic hepatitis C patients to develop DM compared to hepatitis B patients, (iii) a preferential relationship of IR with HCV type-1, -2 or -4 infections, (iv) a correlation between IR, viral load and responsiveness to antiviral treatment and (v) a decreased incidence of DM in chronic hepatitis C after sustained virological response. This review further refers to the clinical evidence of a preferential relationship between hepatic steatosis and HCV type-3 infection, and that two distinct genotype-specific pathogenic mechanisms underlie steatosis in hepatitis C. In HCV type-3 infections, steatosis is related to viral load but not to metabolic factors, and, thus, is termed 'viral steatosis'. In HCV type-1, -2 or -4 infections, steatosis appears to be secondary to IR and regarded as 'metabolic steatosis'. In conclusion, multiple lines of clinical evidence support a linkage of HCV infection and both hepatic carbohydrate and lipid metabolism. The extent to which targeting the host's metabolism by drugs or by lifestyle change translates into an improvement of health or in a better response to interferon-alpha will provide further valuable insights into virus-host interactions, and is topic which is currently addressed in clinical studies. Copyright (C) 2010 S. Karger AG, Base
Activation of Type I and Type III Interferons in Chronic Hepatitis C
No full textInfection with hepatitis C virus (HCV) results in chronic and progressive liver disease. Persistency rates add up to 85%. Despite recognition of the virus by the human host in peripheral blood and in the liver, immune response appears to be ineffective in clearing infection. The ability to spontaneously eradicate the virus as well as the outcome of infection upon therapy with human recombinant interferon-alpha (IFN-alpha) was found to correlate most closely with genetic variations within the region encoding the IFN-lambda genes, as revealed by genome-wide association studies on main ethnic populations in 2009. This review summarizes the induction of type I and type III IFN genes and their effectors, the IFN-stimulated genes. It focusses on the in vivo situation in chronic HCV infection in man both in the peripheral blood compartment and in the liver. It also addresses the impact of genetic polymorphisms in the region of type III IFN genes on their activation. Finally, it discusses how antiviral drugs (i.e. IFN-alpha, ribavirin and the direct-acting antivirals) may complementarily control the activation of endogenous IFNs and succeed in combatting infections. (C) 2015 S. Karger AG, Base
Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-gamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B
No full textThe pathogenesis of hepatitis C virus-induced chronic liver disease is still poorly understood. Previous studies revealed enhanced hepatic expression of the Th1 prototype cytokine IFN-gamma in individuals with chronic hepatitis C. In accordance with several animal models of experimentally induced hepatitis, a Th1 lymphocyte driven inflammatory process, which involves newly infiltrated as well as resident monocytes/macrophages, has been proposed. An involvement of the interferon-gamma-inducible chemokine IP-10, which is chemoattractive for stimulated Th1 cells and monocytes, is also suggested. Using an HBV transgenic mouse model, a reduction of hepatic infiltration and liver disease was achieved recently by administration of antibodies directed against the interferon-gamma-inducible chemokine Mig and against IP-10. In the present study, expression of IP-10 was investigated both in serum and in the liver of patients with chronic hepatitis C and hepatitis B. Patients with liver diseases of non-viral etiologies served as controls. IP-10 expression was highest in hepatitis C. In chronic hepatitis C, but not in chronic hepatitis B nor in liver disorders unrelated to viral infections, IP-10 expression was strongly correlated with the amount of transcripts for IFN-gamma and to the amount of transcripts for the constitutively expressed macrophage derived cytokine IL-18. Hepatic inflammatory activity, however, was found to be associated more closely with IFN-gamma than with IP-10 or IL-18 mRNA expression. The data support the hypothesis that IP-10 is responsible for the recruitment of Th1 cells and monocytes in chronic hepatitis C, and suggest that its role in chronic hepatitis B is less determining. Moreover, they deliver additional support for the view that IFN-gamma still has to be considered as a mediator that determines the outcome of inflammation, e.g., via its ability to activate IL-18 expressing cells and to initiate a delayed type hypersensitivity reaction. (C) 2003 Wiley-Liss, Inc
Interferon-alpha therapy does not modulate hepatic expression of classical type I interferon inducible genes
No full textHepatitis C virus (HCV) infection is a major cause of chronic liver disease. Treatment with interferon-alpha(2) (IFN-alpha(2)) can induce viral clearance and marked biochemical and histological improvement. IFN-alpha(2) treatment has been shown to stimulate the expression of type I IFN regulated genes in peripheral blood mononuclear cells (PBMCs) of hepatitis C patients; however, whether it affects hepatic expression remains unknown. This study thus aimed at comparing hepatic gene expression with particular emphasis on type I IFN inducible genes in patients with chronic hepatitis C before and during an IFN-a2 monotherapy. Responsiveness to IFN-alpha(2) therapy was monitored by determining serum and hepatic viral load. Differential gene expression analysis was performed by two different techniques, namely suppression subtractive hybridization (SSH) and differential display (DD). Expression of two prototype type I IFN regulated genes was quantified in further PBMC and liver samples. Among different genes found to be up-regulated during an effective, that is, virus clearing, IFN-alpha treatment, only a single one was identified which can be accounted to type I IFN responsive genes. Parallel quantitative real time PCR analyses demonstrated significant induction of the type I IFN regulated genes MxA and PKR in PBMC, but not in the liver. Taken together, while IFN-alpha treatment leads to the induction of type I IFN regulated genes in PBMC, such an induction appears not to occur in the liver of hepatitis C patients. The mechanism by which IFN-a treatment causes viral clearance might be independent of hepatic activation of type I IFN regulated genes
Expression of the chemokine IP-10 correlates with the amount of hepatic IFN-gamma and IL-18 mRNA in chronic hepatitis C
No full textEndotoxin receptor CD14 gene variants and histological features in chronic HCV infection
No full textAIM: To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis C. METHODS: Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5'-nuclease assays using fluorescent dye-labeled allele-specific probes. RESULTS: Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers (39.6 +/- 12.5 vs 45.7 +/- 11.5, P = 0.008). Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers (21/37 vs 32/100, P = 0.008). The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation (P = 0.003) and with bile duct damage (P < 0.001). The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T polymorphism. CONCLUSION: The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C. (c) 2009 The WJG Press and Baishideng. All rights reserved.Deutsche Forschungsgemeinschaft [474/1-1]; Damascus University, Syri
Tolerization of human peripheral blood mononuclear cells by bacterially-derived minicells
No full textRelating Serum GGT to ALT Activity Enhances Its Predictability on Treatment Outcome in Chronic Hepatitis C
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