In Reply

EASL Clinical Practice Guidelines: Management of hepatitis C virus infection

HCV Can and Should Be Eliminated From Dialysis Units

Rethinking hepatitis C viral kinetics: Insights into host-virus interactions in ‘difficult-to-treat’ groups and implications for novel treatment approaches

The coming wave of HCV-related liver disease: Dilemmas and challenges

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

Chronic Ethanol Consumption Impairs Cellular Immune Responses Against HCV NS5 Protein Due to Dendritic Cell Dysfunction

Hepatitis C virus (HCV) infection is associated with an increase in proinflammatory cytokine levels. Similar changes are seen in maintenance hemodialysis patients with malnutrition-inflammation-cachexia syndrome (MICS), which is associated with poor clinical outcomes in this population. We hypothesized that HCV transcription-mediated amplification (TMA), a sensitive qualitative molecular test for HCV RNA, may identify maintenance hemodialysis patients with HCV infection not detected by means of antibody enzyme immunoassay (EIA), particularly in those with MICS. We evaluated HCV status in 314 maintenance hemodialysis patients by using HCV antibody EIA (version 2.0; Abbott Laboratories, Abbott Park, IL) and HCV TMA (Bayer Diagnostics Laboratories, Berkeley, CA). Twenty-five patients (8%) were EIA positive (EIA+)/TMA+; 4 patients (1%), EIA+/TMA negative (TMA-), and 22 patients (7%), EIA-/TMA+. In the 47 TMA+ patients, the sensitivity of EIA for HCV infection was only 53%. TMA+ patients had lower albumin levels and higher tumor necrosis factor alpha and serum glutamic oxaloacetic transaminase levels than TMA- patients. EIA+/TMA+ patients were more likely than EIA-/TMA+ or EIA-/TMA- patients to have hypoalbuminemia and higher iron and transaminase levels. Of all TMA+ patients, EIA- patients were more likely to have diabetes, be on dialysis therapy longer, and have lower liver enzyme levels and higher proinflammatory cytokine levels, including tumor necrosis factor alpha and interleukin 6. Maintenance hemodialysis patients infected with HCV according to TMA have clinical features suggestive of MICS. In this population, HCV EIA appears to have a low sensitivity for the identification of HCV infection, which may be caused by the confounding effect of MICS or other demographic or clinical factors. These apparently false-negative HCV antibody test results are seen in persons with a longer time on hemodialysis therapy, mirroring observations in other populations with serious progressive conditions, such as human immunodeficiency virus infection.

The molecular basis of the failed immune response in chronic HBV: Therapeutic implications

A Novel Immunocompetent Rat Model of HCV Infection and Hepatitis

Bone Marrow Iron in CKD: Correlation With Functional Iron Deficiency

Innate immunity and HCV

IL28B single nucleotide polymorphisms in the treatment of hepatitis C

Are HIV-infected patients candidates for liver transplantation?

Paving the way for T cell-based immunotherapies in chronic hepatitis E

Hepatitis C virus (HCV) replication complex resides in detergent-insoluble subcellular domains or lipid rafts. We used two proteomics approaches to characterize the protein content of lipid rafts isolated from Huh7 cells and its modification upon HCV replication. Using two-dimensional electrophoresis and mass spectrometry, we identified approximately 100 protein spots in the isolated lipid rafts; among them, 39 were reproducibly modified in HCV replicon cell lines as compared with control cell lines. We also used stable isotope labeling by amino acids in cell culture (SILAC) combined with one-dimensional electrophoresis separation and mass spectrometry. Using this approach, we identified 1036 individual proteins based on peptides selected with at least 95% confidence; among them, 413 proteins were identified with at least two peptides. Quantification analysis identified 150 proteins modified by at least 2.5-fold (110 up-regulated and 40 down-regulated) in HCV-replicating cells compared with controls. Protein identifications and quantifications obtained by both proteomics approaches were largely concordant. Modulated proteins included a majority of proteins involved in vesicular and protein trafficking and in cell signaling. Remarkably for a large number of proteins, their up-regulation in lipid rafts of HCV replicon cells was due to their relocalization. By using small interfering RNAs directed to the modulated small GTPases Cdc42 and RhoA, we observed an increase in HCV replication, whereas reduction of syntaxin 7 expression resulted in decreased replication of HCV. Our findings indicate that protein subcellular relocalization occurs in HCV-containing cells that can directly affect HCV replication.