慢性乙型肝炎与乙型肝炎肝硬化患者外周 血细胞因子水平及临床意义

Levels and Clinical Significance of Peripheral Blood Cytokines in Patients with Chronic Hepatitis B and Hepatitis B-Related Liver Cirrhosis

摘要: 【目的】本研究旨在比较慢性乙型肝炎(CHB)患者与乙型肝炎肝硬化(HBV-LC)患者外周血中关键细胞因子的表达水平，分析其差异及临床意义。【方法】回顾性分析2022年7月至2025年7月于青岛大学附属医院就诊的132例CHB、129例HBV-LC患者及66例健康志愿者的临床资料与血清样本。检测血清中IL-5、IFN-α、IL-2、IL-6、IL-1β、IL-10、IFN-γ、IL-8、IL-17、IL-4、IL-12p及TNF-α水平。采用SPSS 27.0进行统计分析，组间比使用Kruskal-Wallis秩和检验及Mann-Whitney U检验，相关性分析采用Spearman检验。【结果】CHB组与HBV-LC组在年龄、ALT、AST、TB、PLT、白蛋白、甲胎蛋白、凝血酶原时间均与健康对照组有显著差异(P < 0.001)。CHB组中IL-5、IL-6、IFN-γ、IL-4、IL-12p水平低于健康对照组(P < 0.05)，IFN-α水平升高(P < 0.05)；HBC-LC组中IFN-α、IL-2、IL-8显著高于健康对照组(P < 0.05)，IFN-γ、IL-4、IL-12p较健康对照组显著降低(P < 0.05)；HBV-LC组中IL-5、IL-2、IL-6、IL-1β、IL-8水平明显高于CHB组(P < 0.05)，而IFN-γIL-4 IL-12p水平进一步降低。相关性分析表明，CHB组患者TNF-α水平与AST、白蛋白有显著的相关性(P < 0.05)，HBV-LC组患者TNF-α水平与AST、ALT及TB均具有显著相关性(P < 0.05)；CHB组患者IFN-γ水平与AST、ALT及白蛋白有显著的相关性(P < 0.05)，HBV-LC患者IFN-γ水平与AST、ALT、TB、血小板及白蛋白没有显著相关性(P > 0.05)；CHB组患者IL-10水平与AST、ALT、TB、血小板及白蛋白没有显著相关性(P > 0.05)，HBV-LC患者IL-10水平与AST、ALT及TB有显著相关性(P > 0.05)。【结论】本研究表明，在CHB向HBV-LC进展中，外周血促炎因子(如IL-6、IL-8)升高而免疫调节因子(如IFN-γ、IL-4)降低，提示免疫失衡伴随疾病进展。IFN-γ、IL-10等与肝损伤指标显著相关，提示其作为评估肝纤维化进展的无创生物标志物潜力，本研究为理解HBV相关肝病免疫机制及临床分期提供了依据。

Abstract: Objective: This study aims to compare the expression levels of key cytokines in the peripheral blood of patients with Chronic Hepatitis B (CHB) and those with Hepatitis B-related Liver Cirrhosis (HBV-LC), and to analyze their differences and clinical significance. Methods: A retrospective analysis was conducted on the clinical data and serum samples of 132 CHB patients, 129 HBV-LC patients, and 66 healthy volunteers who visited Qingdao University Affiliated Hospital from July 2022 to July 2025. Key cytokine levels in the serum were measured. Statistical analysis was performed using SPSS 27.0; group comparisons were conducted using the Kruskal-Wallis rank-sum test and Mann-Whitney U test, and correlation analysis was performed using the Spearman test. Results: The CHB group and the HBV-LC group showed significant differences in age, ALT, AST, TB, PLT, albumin, alpha-fetoprotein, and prothrombin time compared with the healthy control group (P < 0.001). In the CHB group, levels of IL-5, IL-6, IFN-γ, IL-4, and IL-12p were lower than those in the healthy control group (P < 0.05), while IFN-α levels were elevated (P < 0.05); in the HBV-LC group, IFN-α, IL-2, and IL-8 were significantly higher than in the healthy control group (P < 0.05), whereas IFN-γ, IL-4, and IL-12p were significantly lower than in the healthy control group (P < 0.05); in the HBV-LC group, IL-5, IL-2, IL-6, IL-1β, and IL-8 levels were significantly higher than in the CHB group (P < 0.05), while IFN-γ, IL-4, and IL-12p levels decreased further. Correlation analysis showed that in CHB patients, TNF-α levels were significantly correlated with AST and albumin (P < 0.05), while in HBV-LC patients, TNF-α levels were significantly correlated with AST, ALT, and TB (P < 0.05); in CHB patients, IFN-γ levels were significantly correlated with AST, ALT, and albumin (P < 0.05), whereas in HBV-LC patients, IFN-γ levels were not significantly correlated with AST, ALT, TB, platelets, and albumin (P > 0.05); IL-10 levels in CHB patients were not significantly correlated with AST, ALT, TB, platelets, and albumin (P > 0.05), while in HBV-LC patients, IL-10 levels were significantly correlated with AST, ALT, and TB (P < 0.05). Conclusion: This study shows that during the progression from CHB to HBV-LC, pro-inflammatory factors in peripheral blood (such as IL-6 and IL-8) increase while immunoregulatory factors (such as IFN-γ and IL-4) decrease, suggesting that immune imbalance accompanies disease progression. IFN-γ, IL-10, and other factors are significantly associated with liver injury markers, indicating their potential as non-invasive biomarkers for assessing the progression of liver fibrosis. This study provides a basis for understanding the immune mechanisms of HBV-related liver disease and clinical staging.