Treatment with Telbivudine Positively Regulates Antiviral Immune Profiles in Chinese Patients with Chronic Hepatitis B

Abstract

dChronic infection with hepatitis B virus (HBV) is associated with impairment of T and NK cell immunity. This study was aimed at investigating the impact of treatment with telbivudine (LDT) on T and NK cell immunity in patients with chronic hepatitis B (CHB). A total of 54 CHB patients and 30 healthy controls (HC) were recruited. Individual patients were treated orally with 600 mg LDT daily for 13 months. The serum HBV DNA loads, the levels of the HBV-related biomarkers alanine aminotransferase (ALT) and aspartate transaminase (AST), and the numbers of different subsets of peripheral T and NK cells in subjects were measured before and longitudinally after LDT treatment. Following treatment with LDT, the serum HBV DNA loads and the percentages of HBsAg-or HBeAg-seropositive cases were gradually reduced, accompanied by decreased levels of serum ALT

Telbivudine therapy may shape CD4+ T‐cell response to prevent liver fibrosis in patients with chronic hepatitis B

“…Thus, the probable explanations are either the viruses could develop some unknown mutations or the host immunity just fails to recognize them. Though there are several researches demonstrating the restoration of host immunity during NAs therapy could effectively predict the final therapeutic response , they fail to draw a clear picture of longitudinal changes of CD4 + T subsets during this process and its potential associations with liver fibrosis progression. Here, during the 52‐week telbivudine therapy, from the thorough comparison of peripheral CD4 + T subsets in CHB patients with different responses to therapy, we found favourable responses to telbivudine are especially correlated with early and significant up‐regulation of Th1 and Th17 responses, and significant down‐regulation of Treg response, mostly before TW‐12, as shown in CR and PR groups.…”

“…This change of CD4 + T‐cell subsets in CR and PR groups during telbivudine therapy, suggests that NAs could partly restore defective anti‐HBV immunity through its ability to decrease virus loads. Besides, patients with better responses to telbivudine had remained a dramatic Th1‐polarization in Th1/Th2 balance and a dramatic Th17‐polarization in Th17/Treg balance during the whole therapeutic process, indicating that efficient CD4 + T‐cell responses against HBV require the clearance of intracellular antigens and the persistence of proinflammatory stimuli, which were almost consistent with several other researches .…”

Kinetics of Th17 Cytokines During Telbivudine Therapy in Patients With Chronic Hepatitis B

“…Telbivudine therapy increased the numbers/frequencies of CD4 + T cells (4), CD8 + T cell and NK cells (28), as well as improved the function of CD4 + T cells (47), myeloid dendritic cells (31), iNKT cells (36), and cytokines secretion (4). On the other hand, antiviral treatment with telbivudine reduced the proportion of CD4 + CD25 high regulatory T cells (30) and downregulated the expression of PD-1 and PD-L1 (8).…”

Effects of entecavir on peripheral blood lymphocyte profiles in chronic hepatitis B patients with suboptimal responses to adefovir

“…Reduced viral loads could have decreased the inhibitory effect of HBV on NK cell activity and increased NK cell responses in refractory CHB patients. The NK cell response to viral antigens is important for viral clearance during HBV infection . In addition, activated NK cells, particularly CD244 + NK cells, secrete high levels of IFN‐ γ , which is crucial for the clearance of HBV .…”

“…The NK cell response to viral antigens is important for viral clearance during HBV infection. [23][24][25][26] In addition, activated NK cells, particularly CD244 + NK cells, secrete high levels of IFN-c, which is crucial for the clearance of HBV. 19,20 The significant increase in CD244 + NK responses following treatment with ETV may inhibit HBV replication via negative feedback, contributing to anti-HBV immunity in refractory CHB patients.…”