Effects Of Antiviral Therapy On Peripheral CD4~+T Cell Balance And HSCs In CHB Patients

Background & AimsWeak host immunity to hepatitis B virus (HBV) is responsible for chronic HBV infection. Several lines of experimental evidence suggest that treatment with telbivudine increases the rate of HBV e antigen (HBeAg) loss, undetectable HBV DNA, and normalization of serum alanine amino-transferase (ALT) in chronic hepatitis B (CHB) patients. However, it is still unclear whether antiviral therapy affects CD4+T cell responses/alance and function of hepatic stellate cells (HSCs) during sustained telbivudine treatment.Methods and Major FindingsThirty CHB patients who seropositive for hepatitis B e antigen are naive for antiviral therapy and received telbivudine treatment (600mg/d) for 12 months were enrolled in this study. At 0,12,24,48,52 weeks after treatment, peripheral blood were collected to longitudinally analyze the frequencies of CD4+T cell lineages (Th1, Th2, Treg and Th17) and evaluate detailed virological, and biochemical parameters. And we found the telbivudine-induced HBV suppression and ALT normalization was accompanied by a significant increase in the percentages of Th1 and Th17 cells, together with a dramatic decrease in Th2 and Treg cells, with the Treg/Th17 balance shifted toward Th17 and the Th1/Th2 balance shifted toward Th1. In addition, we also detected the difference of therapeutic responses between HBeAg-positive and HBeAg-negative groups were significantly correlated with the changes in peripheral CD4+T cell responses.Furthermore, serum were collected and peripheral CD4+T cells were purified at five therapeutic points during therapy for further in vitro incubation and co-culture experiments with human hepatic stellate cell (HSCs) line (LX-2), and Cell-IQ monitoring, Real-time PCR and Western-blot were used to investigate cell proliferation, synthesis of extracellular matrix (ECM), and activation level of LX-2. Results turned out that, compared to the blood with high HBV loads, those with undetectable HBV DNA had the serum or CD4+T cells which could significantly inhibit the pro-fibrotic features of LX-2. ConclusionsTelbivudine therapy could dramatically inhibit HBV replication and shape CD4+T cell response,and these effects could inhibit the pro-fibrotic features of HSCs.