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

Abstract

The aim of the present study was to assess the long-term impact of entecavir (ETV) on T, B and natural killer (NK) cell immunity in patients with suboptimal responses to adefovir (SRA) chronic hepatitis B (CHB). Thirty SRA CHB patients and 20 age- and gender-matched healthy controls (HC) completed at least 6 months of ETV treatment. Hepatitis B virus (HBV) DNA loads, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the frequency of different subsets of T, B and NK cells in individual subjects were measured. There were smaller numbers of CD3(-) CD56(+) and CD244(+) NK cells, CD3(+) CD8(+) T cells and cytokine-secreting CD4(+) T cells, but greater numbers of CD3(+) CD4(+) , CD4(+) CD25(+) Foxp3(+) , CD4(+) CD25(+) CD127(low) T cells and CD19(+) CD27(+) B cells, detected in SRA patients. After switching to ETV monotherapy, the levels of HBV DNA and hepatitis B s antigen, as well as hepatitis B e antigen seropositivity, decreased gradually, accompanied by decreases in ALT and AST levels. Furthermore, the number of NK, CD8(+) and cytokine-secreting CD4(+) T cells increased, whereas the number of CD4(+) , CD4(+) CD25(+) Foxp3(+) , CD4(+) CD25(+) CD127(low) T cells and CD19(+) CD27(+) B cells decreased, in SRA CHB patients. The frequency of CD4(+) interferon-γ-positive T cells was negatively associated with serum HBV DNA levels. Thus, treatment with ETV inhibits HBV replication, modulates T and NK cell immunity and improves liver function in SRA CHB patients.

Anti–PD-1/PD-L1 Blockade Immunotherapy Employed in Treating Hepatitis B Virus Infection–Related Advanced Hepatocellular Carcinoma: A Literature Review

“…Antiviral treatment could alter T-cell function, as CD8 + tumor-infiltrating lymphocytes from patients who received antiviral treatment (entecavir) did express higher effector T-cell markers and lower T-cell exhaustion markers. Antiviral drugs could activate T cells and strengthen their immune function, resulting in a better prognosis and decreased recurrence rates of HBV-related HCC (27,86,87). Peripheral expansion of Treg levels was also negatively correlated with HBV viral load, and the percentage of Tregs expressing PD-1 was significantly decreased when HBV replication was controlled (76).…”

Effect and Influencing Factors of Programmed Cell Death Protein-1 Inhibitor on Hepatitis B Virus Related Hepatocellular Carcinoma Undergoing Hepatic Arterial Chemotherapy

“…progression. The overall progression of the tumor was not related to baseline HBV DNA levels, age, gender, ECOG, HBeAg, PD-1 inhibitor type, and hepatic arterial chemotherapy type (p>0.05) as shown in Table 6 [21][22][23][24][25] .…”

Natural killer cells in hepatitis B virus infection

“…43,44,46,47 Viral load reduction through anti-viral therapy partly restores NK cells numbers, cytokine production and inhibitory receptor expression. 43,45,48,49 Although these studies are mostly consistent, there are discordances in some details such as the changes in the expression of some receptors 33,[43][44][45][46] and changes in cytolytic activity. The reasons for these differences are not clear yet, but may be ascribed to ethnic variations, sample size, disease process and severity.…”