Abstract
The aim of this study was to determine the correlation between dynamic changes in serum cytokine/chemokine expression levels in response to entecavir (ETV) treatment and HBV e antigen (HBeAg) seroconversion in patients with chronic hepatitis B (CHB). Four cytokines (interleukin [IL]-4, IL-6, IL-8, and interferon-γ) and five chemokines (macro-phage inflammatory protein [MIP]-1α, MIP-1β, platelet derived growth factor-BB, and interferon-inducible protein 10 [IP-10]) before ETV therapy and at 3, 6, 12, 24, 36 and 60 months during therapy in 105 CHB patients were analyzed. The results showed that the low decrease rate of IP-10 levels after 1 year of ETV treatment was an independent predictor of HBeAg seroconversion at year 5 (Hazard ratio = 0.972). The area under the receiver operating characteristic curves for the decrease rate of IP-10 levels after 1 year of treatment to discriminate a year-5 HBeAg seroconversion was 0.752 (p = 0.005). The results indicate that higher IP-10 level at year one of ETV treatment is associated with an increased probability of HBeAg seroconversion. Quantification of IP-10 during ETV treatment may help to predict long-term HBeAg seroconversion in patients with CHB.
Highlights
The exact mechanisms and factors that contribute to hepatitis B virus (HBV) e antigen (HBeAg) seroclearance and HBe antibody (HBeAb) production are not well described
Levels of hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA at baseline were significantly higher in patients without HBeAg seroconversion than in those with HBeAg seroconversion
ALT levels in all patients in the HBeAg seroconversion group decreased to normal values and HBV DNA in 89.6% (43/48) was below the detection limit; in the patient cohort without HBeAg seroconversion, there were ten patients (17.5%) whose ALT levels were abnormal, and the percentage of patients whose HBV DNA levels were below the detection limit was 56.1% (32/57), the HBV DNA levels in all other patients without HBeAg seroconversion were below 105 IU/mL
Summary
The exact mechanisms and factors that contribute to HBeAg seroclearance and HBeAb production are not well described. Cytokines inhibit viral replication, but determine the predominant pattern of the host immune response[9,10]. A previous study reported that the T-cell response and circulating cytokine profile were associated with viral replication and liver function in CHB13. Interleukin (IL)-10, IL-12, IL-21 have important roles during the immune clearance phase and are associated with HBeAg seroconversion[14,15]. The relationship between multiple cytokines and chemokines and responses to ETV therapy in patients with CHB has not been fully elucidated in the Chinese population.
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