关键词: 慢性乙型肝炎, 聚乙二醇干扰素α-2a, Toll样受体4, 协同刺激分子B7家族1, 治疗

Abstract: Objective The aim of this study was to investigate the antiviral response and changes of Toll-like receptor 4 (TLR4) and costimulatory molecule B7-H1 ( B7-H1) in peripheral blood mononuclear cells (PBMCs) by peginterferon α-2a (peg-IFN α-2a) and entecavir combination therapy in patients with chronic hepatitis B (CHB). Methods A total of 96 patients with CHB were enrolled in our hospital between July 2019 and July 2021, and were divided into control group (n=48) and observation group (n=48), receiving entecavir or entecavir and peg-IFN α-2a combination treatment for 48 weeks. Serum collagen type IV (IV-C), laminin (LN), procollagen type III (PG III) and hyaluronic acid (HA) levels, and serum interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and IL-6 levels were detected by ELISA. The percentages of TLR4 and B7-H1 on the surface of PBMCs were detected by flow cytometry. Results At the end 48 weeks of treatment, the negative conversion rate of serum HBeAg in the observation group was 37.5%, significantly higher than 14.6%(P＜0.05), and HBeAg seroconversion rate was 25.0%, significantly higher than 0.0%(P＜0.05) in the control group; serum ALT and AST levels in the two groups were back to normal and there was no significant differences between them(P>0.05); serum Ⅳ-C level in the observation was (83.9±17.7)μg/L, serum LN level was (89.2±25.5)μg/L and serum HA level was (124.9±22.7)μg/L, all significantly lower than [(106.5±20.3)μg/L, (124.1±32.7)μg/L and (179.2±38.4)μg/L, respectively, P＜0.05] in the control; serum IL-10 level in the observation was (30.6±5.7)pg/mL, significantly higher than [(20.4±8.6)pg/mL, P＜0.05], while serum TNF-α level was (28.8±7.4)mg/L, significantly lower than [(39.1±9.7)mg/L, P＜0.05], and serum IL-6 level was (19.1±3.8)pg/mL, significantly lower than [(27.5±5.4)pg/mL, P＜0.05] in the control; the percentage of TLR4 expression in the surfaces of PBMCs was (10.2±3.1)%, significantly lower than [(15.8±4.6)%, P＜0.05] and the percentage of B7-H1 expression was (8.9±1.5)%, significantly lower than [(11.6±2.2)%, P＜0.05] in the control group. Conclusion The efficacy of peg-IFN α-2a and entecavir combination in the treatment of patients with CHB is promising, which might inhibit HBV replication, promote the recovery of liver function tests, alleviate the process of liver fibrosis, and improve inflammatory response.

Key words: Hepatitis B, Peginterferon α-2a, Entecavir, Toll-like receptor 4, Costimulatory molecule B7-H1, Therapy