Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-alpha in NAs-suppressed chronic hepatitis B patients

Objective: The aim of this study was to explore the profile of cytokine changes during the combination therapy with pegylated interferon alpha (PEG-IFN-alpha) and its relationship with HBsAg loss in nucleos(t)ide analogs (NAs)-suppressed chronic hepatitis B patients.Methods: Seventy-six patients with chronic hepatitis B with HBsAg less than 1,500 IU/ml and HBV DNA negative after receiving >= 1-year NAs therapy were enrolled. Eighteen patients continued to take NAs monotherapy (the NAs group), and 58 patients received combination therapy with NAs and PEG-IFN-alpha (the Add-on group). The levels of IFNG, IL1B, IL1RN, IL2, IL4, IL6, IL10, IL12A, IL17A, CCL2, CCL3, CCL5, CXCL8, CXCL10, TNF, and CSF2 in peripheral blood during treatment were detected.Results: At week 48, 0.00% (0/18) in the NAs group and 25.86% (15/58) in the Add-on group achieved HBsAg loss. During 48 weeks of combined treatment, there was a transitory increase in the levels of ALT, IL1RN, IL2, and CCL2. Compared to the NAs group, CXCL8 and CXCL10 in the Add-on group remain higher after rising, yet CCL3 showed a continuously increasing trend. Mild and early increases in IL1B, CCL3, IL17A, IL2, IL4, IL6, and CXCL8 were associated with HBsAg loss or decrease > 1 log, while sustained high levels of CCL5 and CXCL10 were associated with poor responses to Add-on therapy at week 48.Conclusions: The serum cytokine change profile is closely related to the response to the combination therapy with PEG-IFN-alpha and NAs, and may help to reveal the mechanism of functional cure and discover new immunological predictors and new therapeutic targets.