Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study

BACKGROUND AND AIMS: The natural course of chronic hepatitis B virus (HBV) infection is widely studied; however, follow-up studies of the same patients are scanty. Here, we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen (HBeAg)-positive patients treated with entecavir (ETV) to explore the relationship between the HBV serum viral nucleic acids and host immunity. METHODS: Thirty-three chronic hepatitis B patients who are HBeAg-positive, with high virus load (HBV DNA >20,000 IU/mL), and received standard nucleos(t)ide analogue (NA) antiviral therapy (ETV) for more than 48 weeks were included. The serum levels of HBV nucleic acids and selected cytokines were measured at 0, 12, 24, and 48 weeks respectively. RESULTS: Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV. There was a strong positive correlation between HBV RNA and HBeAg, with a concomitant decrease in the secretion of cytokines from type 1 helper T (Th1)/type 2 helper T (Th2)/interleukin (IL)-17 producing T (Th17) cells. IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA. CONCLUSIONS: HBeAg can be used to reflect the load of HBV RNA indirectly, because serum HBV RNA has not been widely used in clinical practice. Meanwhile, serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.