166 log IU/mL/year were the optimal levels in predicting NA-related HBsAg seroclearance. Serum HBsAg measurements hence have a role in the clinical monitoring of CHB patients, and in prognosticating CHB patients for the probability of eventual HBsAg seroclearance during NA therapy. “
“Immunotolerance is maintained by regulatory T cells (Tregs), including CD4+CD25hi, CD8+CD28−, Talazoparib γδ, and CD3+CD56+ [natural killer T (NKT)] cells. CD4+CD25hi cells are impaired in children with autoimmune hepatitis (AIH). Little is
known about Tregs in adults with AIH. The aim of this study was to investigate the frequency and function of Treg subsets in adult patients with AIH during periods of active disease and remission. Forty-seven AIH patients (16 with active disease and 31 in remission) and 28 healthy controls were studied. Flow cytometry was used to evaluate surface markers and function-related intracellular molecules in γδ, CD8+CD28−, NKT, and CD4+CD25hi cells. CD4+CD25hi T cell function was determined by the ability to suppress proliferation and interferon gamma (IFN-γ) production by CD4+CD25− target cells. Liver forkhead box P3–positive (FOXP3+) cells were sought by immunohistochemistry.
In AIH patients, particularly during active disease, CD4+CD25hi T cells were fewer, expressed lower levels of FOXP3, and were less effective at inhibiting target cell proliferation versus healthy controls. Moreover, although the numbers of CD8+CD28− T cells were similar in AIH Epigenetics Compound Library in vitro CYTH4 patients and healthy controls, NKT cells were numerically reduced, especially during active disease, and produced lower quantities of the immunoregulatory cytokine interleukin-4 versus controls. In contrast, γδ T cells in AIH patients were more numerous versus
healthy controls and had an inverted Vδ1/Vδ2 ratio and higher IFN-γ and granzyme B production; the latter was correlated to biochemical indices of liver damage. There were few FOXP3+ cells within the portal tract inflammatory infiltrate. Conclusion: Our data show that the defect in immunoregulation in adult AIH is complex, and γδ T cells are likely to be effectors of liver damage. (HEPATOLOGY 2010) Autoimmune hepatitis (AIH) is an immune-mediated liver disease characterized by high levels of aminotransferases and gamma-globulins, circulating autoantibodies, and histological evidence of interface hepatitis.1-3 Two AIH subsets are conventionally recognized according to their autoantibody profile4: type 1 AIH (AIH-1), which is characterized by positivity for anti-nuclear antibody (ANA) and/or anti–smooth muscle antibody (anti-SMA),5 and type 2 AIH, the serological hallmarks of which are anti–liver/kidney microsomal antibody type 1 and anti–liver cytosol antibody type 1.