慢性乙型肝炎肝纤维化变化及病毒载量对血清GP73、HIF-1α、miR-21、miR-148b水平的影响

Changes of liver fibrosis and effects of viral loads on serum levels of GP73, HIF-1α, miR-21 and miR-148b in patients with chronic hepatitis B

    摘要
  • 摘要:
    目的 探讨乙型肝炎病毒(HBV)感染所致慢性乙型病毒性肝炎(CHB)不同病毒载量患者血清中高尔基体蛋白73(GP73)、缺氧诱导因子1α(HIF-1α)、微小核糖核酸(miR)-21、miR-148b水平变化。
    方法 选取2019年1月-2023年12月牡丹江医学院附属红旗医院收治的92例HBV感染所致CHB患者(感染组)，96名健康体检者(对照组)，其中感染组根据病毒载量分为低载量组(49例)、中高载量组(43例)；比较感染组和对照组肝纤维化指标、GP73、HIF-1α、miR-21、miR-148b水平，不同病毒载量组GP73、HIF-1α、miR-21、miR-148b水平，分析GP73、HIF-1α、miR-21、miR-148b水平与病毒载量的相关性，分析GP73、HIF-1α、miR-21、miR-148b水平单一及联合检测对HBV感染所致CHB的诊断价值。
    结果 感染组透明质酸(HA)、Ⅳ型胶原(C Ⅳ)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)水平分别为(39.98±9.91)μg/L、(22.44±4.13)μg/L、(31.62±3.86)μg/L、(29.03±4.66)μg/L，血清GP73、HIF-1a、miR-21水平分别为(29.88±9.85)ng/ml、(48.92±16.29)μg/L、1.37±0.45，均高于对照组，miR-148b水平为0.98±0.32，低于对照组(P < 0.05)；中高载量组血清GP73、HIF-1a、miR-21水平分别为(46.32±11.22)ng/ml、(64.33±15.77)μg/L、1.68±0.51，高于低载量组，miR-148b水平为0.60±0.16，低于低载量组(P < 0.05)；血清GP73、HIF-1a、miR-21水平与病毒载量呈正相关，miR-148b水平与病毒载量呈负相关(r=0.722、0.683、0.716、-0.658，P < 0.05)；血清GP73、HIF-1a、miR-21、miR-148b水平联合检测对HBV感染所致CHB患者的诊断曲线下面积(AUC)值为0.941，高于单独检测的AUC值(分别为0.812、0.787、0.802、0.802)(P < 0.05)，且联合检测的敏感度为95.65%，特异度为84.37%。
    结论 HBV感染所致CHB患者肝纤维化指标与GP73、HIF-1α、miR-21水平呈高表达，miR-148b水平呈低表达；GP73、HIF-1α、miR-21、miR-148b水平与病毒载量有关，且GP73、HIF-1α、miR-21、miR-148b水平联合检测对HBV感染所致CHB患者具有较高的诊断价值。

     

    Abstract:
    OBJECTIVE To investigate the levels of golgi protein 73 (GP73), hypoxia-inducing factor 1α (HIF-1α), microRNA (MiR) -21 and miR-148b in patients with different HBV viral loads in chronic hepatitis B (CHB) infection.
    METHODS Ninety-two patients with CHB (the infected group) and 96 healthy healthcare examined subjects (the control group) were selected from Red Flag Hospital affiliated to Mudanjiang Medical College from Jan. 2019 to Dec. 2023. The infected group was further divided into the low load (49 cases) group and medium-high load group (43 cases) according to HBV loads. Liver fibrosis indexes and levels of GP73, HIF-1α, miR-21 and miR-148b were compared between the infected group and the control group, and levels of GP73, HIF-1α, miR-21 and miR-148b were compared between the different viral load groups. The correlation between GP73, HIF-1α, miR-21, miR-148b and viral load was analyzed, and their diagnostic values for single and combined detection of CHB was analyzed.
    RESULTS In the infected group, the levels of hyaluronic acid (HA), type Ⅳ collagen (CⅣ), type Ⅲ procollagen (PCⅢ) and laminin (LN) were (39.98±9.91) μg/L, (22.44±4.13) μg/L, (31.62±3.86) μg/L, and (29.03±4.66) μg/L, respectively, and serum levels of GP73, HIF-1a and miR-21 were (29.88±9.85) ng/ml, (48.92±16.29) μg/L and 1.37±0.45, respectively, all higher than those of the control group; miR-148b was 0.98±0.32 in the infected group, lower than that of the control group (P < 0.05). Serum levels of GP73, HIF-1a and miR-21 in the medium-high load group were (46.32±11.22) ng/ml, (64.33±15.77) μg/L and 1.68±0.51, respectively, higher than those in the low-load group, and miR-148b was 0.60±0.16 in the medium-high load group, lower than those in the low-load group (P < 0.05). Serum levels of GP73, HIF-1a and miR-21 were positively correlated with viral load, while miR-148b performed oppositely (r=0.722; 0.683; 0.716; -0.658, respectively, P < 0.05). The area under the diagnostic curve (AUC) value of combined detection of GP73, HIF-1a, miR-21 and miR-148b for CHB was 0.941, which was higher than that of single detection (0.812; 0.787; 0.802; 0.802, respectively) (P < 0.05), with the sensitivity 95.65% and the specificity 84.37%.
    CONCLUSIONS The liver fibrosis indexes and the GP73, HIF-1α and miR-21 in patients of CHB are highly expressed, while serum miR-148b level is low. The levels of GP73, HIF-1α and miR-21, miR-148b are related to viral loads. Moreover, the combined detection of GP73, HIF-1α, miR-21 and miR-148b has high diagnostic value for CHB.

     

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