Background & Aims: Immune responses by CD8 T cells are essential for control of HBV replication. Although selection of escape mutations in CD8 T-cell epitopes has been previously described in HBV infection, its overall influence on HBV sequence diversity and correlation with markers of HBV replication remain unclear.
Methods: Whole-genome sequencing was applied to HBV isolates from 532 patients with chronic HBV infection and high-resolution HLA class I genotyping.
Background And Aims: There is growing interest in T cell-based immune therapies for a functional cure of chronic HBV infection including check-point inhibition, T cell-targeted vaccines or TCR-grafted effector cells. All these approaches depend on recognition of HLA class I-presented viral peptides. The HBV core region 18-27 is an immunodominant target of CD8+ T cells and represents the prime target for T cell-based therapies.
View Article and Find Full Text PDFInfection with the hepatitis D virus induces the most severe form of chronic viral hepatitis, affecting over 12 million people worldwide. Chronic HDV infection leads to rapid development of liver cirrhosis and hepatocellular carcinoma in ~70% of patients within 15 years of infection. Recent evidence suggests that an interplay of different components of the immune system are contributing to viral control and may even be implicated in liver disease pathogenesis.
View Article and Find Full Text PDFBackground & Aims: The hepatitis D virus (HDV) causes the most severe form of chronic hepatitis, often progressing to cirrhosis within 5 to 10 years. There is no curative treatment, and the mechanisms underlying the accelerated liver disease progression are unknown.
Methods: Innate and adaptive immune responses were studied in blood and liver of 24 patients infected with HDV and 30 uninfected controls by multiparameter flow cytometry in correlation with disease severity and stage.
Background & Aim: Hepatitis D virus (HDV) superinfection of patients with chronic HBV infection results in rapid progression to liver cirrhosis. Little is known about HDV-specific T cells and how they contribute to the antiviral immune response and liver disease pathogenesis.
Methods: We isolated peripheral blood mononuclear cells from 28 patients with chronic HDV and HBV infection, identified HDV-specific CD8 T-cell epitopes, and characterized HDV-specific CD8 T cells.
Simultaneous detection of anti-HBs and HBV DNA is a rare serological combination and has been described in acute and chronic HBV infection. To scrutinize viral and clinical patterns associated with concurrent detection of anti-HBs and HBV DNA. Simultaneous detection of anti-HBs and HBV DNA was observed in 64/1444 (4.
View Article and Find Full Text PDFUnlabelled: Activation of hepatitis B virus (HBV)-specific CD8 T cells by therapeutic vaccination may promote sustained control of viral replication by clearance of covalently closed circular DNA from infected hepatocytes. However, little is known about the exact targets of the CD8 T-cell response and whether HBV reproducibly evades CD8 T-cell immune pressure by mutation. The aim of this study was to address if HBV reproducibly selects substitutions in CD8 T-cell epitopes that functionally act as immune escape mutations.
View Article and Find Full Text PDFBackground & Aims: CD8(+) T cells are an essential component of a successful immune response against hepatitis B virus (HBV). Patients who spontaneously clear HBsAg after acute HBV infection have a strong CD8(+) T cell immune response, predominantly directed against the HBV core protein (HBcAg). However, the fate and phenotype of HBcAg-specific CD8(+) T cells after immune control are unclear.
View Article and Find Full Text PDFBackground: Nonsteroidal anti-inflammatory drugs (NSAIDs), conventional and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely used medications for the treatment of various inflammatory conditions. There is strong evidence of a possible association between the use of these drugs and the relapse of inflammatory bowel diseases (IBD).
Objective: Our objective was to examine the literature regarding the exacerbation of IBD associated with the use of conventional NSAIDs and selective COX-2 inhibitors and the underlying pathogenetic mechanisms.