不同肝纤维化程度的慢性乙型肝炎患者血清FGF-21、PDGF-BB和FBRS水平变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2022.03.011

摘要/Abstract

摘要： 目的研究血清成纤维细胞生长因子21(FGF-21)和血小板衍生生长因子-BB(PDGF-BB)及外周血单个核细胞纤维化蛋白(FBRS)水平诊断慢性乙型肝炎(CHB)患者肝纤维化程度的效能。方法 2020年1月～2021年1月我院收治的CHB患者92例,行肝穿刺活检,采用ELISA法测定血清FGF-21和PDGF-BB水平,采用实时荧光定量PCR法测定外周血单个核细胞(PBMCs)FBRS mRNA水平,使用Fibroscan行肝脏硬度检测(LSM)。应用受试者工作特征(ROC)曲线下面积(AUC)分析各指标诊断显著性肝纤维化的效能。结果经肝组织病理学检查,发现非显著性肝纤维化(S_0~1期)49例,显著性肝纤维化(S_2~4期)43例;显著性肝纤维化组血清FGF-21水平为(228.8±52.6)ng/ml,显著低于非显著性肝纤维化组【(289.3±57.9)ng/ml,P<0.05】,血清PDGF-BB水平为(84.7±32.9)pg/ml,显著高于非显著性肝纤维化组【(44.7±18.5)pg/ml,P<0.05】,PBMCs FBRS水平为(8.7±3.2),显著高于非显著性肝纤维化组【(4.4±1.8),P<0.05】,LSM为(15.6±3.9)kPa,显著高于非显著性肝纤维化组【(7.6±1.8)kPa,P<0.05】;FGF-21、PDGF-BB、FBRS和LSM诊断显著性肝纤维化的最佳截断点分别为249.0(ng/ml)、63.5(pg/ml)、7.4和11.2(kPa),其AUC分别为0.800、0.714、0.690和0.960,诊断的敏感度和特异度分别为69.8%和79.6%、69.8%和69.4%、65.1%和73.5%及93.3%和98.0%,四项指标联合诊断的AUC为0.989,其敏感度和特异度分别为95.3%和63.3%。结论联合应用血清FGF-21、PDGF-BB、FBRS和LSM可以提高诊断CHB患者肝纤维化程度的灵敏性,但特异性仍不高,需要进一步研究。

关键词: 慢性乙型肝炎, 肝纤维化, 成纤维细胞生长因子21, 血小板衍生生长因子-BB, 纤维化蛋白, 肝脏硬度检测, 诊断

Abstract: Objective The aim of this study was to investigate the diagnostic performance of serum fibroblast growth factor 21 (FGF-21), platelet-derived growth factor-BB (PDGF-BB) and peripheral blood mononuclear cell (PBMC) fibrosin (FBRS) levels on significant liver fibrosis in patients with chronic hepatitis B (CHB). Methods 92 patients with CHB were enrolled in our hospital between January 2020 and January 2021, and all underwent liver biopsies and liver stiffness measurement (LSM). Serum FGF-21 and PDGF-BB were measured by ELISA, and PBMCs FBRS mRNA was assayed by real-time fluorescent quantitative PCR. The diagnostic performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). Results The liver histopathologic examination showed non-significant liver fibrosis in 49 cases, and significant liver fibrosis in 43 cases; in patients with significant liver fibrosis, serum FGF-21 level was (228.8±52.6)ng/ml, significantly lower than [(289.3±57.9)ng/ml, P<0.05], serum PDGF-BB level was (84.7±32.9)pg/ml, significantly higher than [(44.7±18.5)pg/ml, P<0.05], PBMCs FBRS mRNA load was (8.7±3.2), significantly higher than [(4.4±1.8), P<0.05], and the LSM was (15.6±3.9)kPa, significantly higher than [(7.6±1.8)kPa, P<0.05] in patients with non-significant liver fibrosis; the AUCs were 0.800, 0.714, 0.690 and 0.960 by the FGF-21, PDGF-BB, FBRS and LSM in predicting significant liver fibrosis when the cut-off-values were set at 249.0(ng/ml), 63.5(pg/ml), 7.4 and 11.2(kPa), respectively, with the sensitivities (Se) and specificities (Sp) of 69.8% and 79.6%, 69.8% and 69.4%, 65.1% and 73.5%, and 93.3% and 98.0%, but the AUC was 0.989 by the combination of the four parameters, with the Se and Sp of 95.3% and 63.3%. Conclusion The combination of serum FGF-21 and PDGF-BB, PBMCs FBRS mRNA and LSM in predicting liver fibrosis in patients with CHB could improve the Se, but the Sp is still not high, which needs further clinical investigation.

Key words: Hepatitis B, Liver fibrosis, Fibroblast growth factor 21, Platelet-derived growth factor-BB, Fibrosin, Liver stiffness measurement, Diagnosis

李春花, 李忠新, 张春雷, 曾学辉, 陈甜甜, 宋林立. 不同肝纤维化程度的慢性乙型肝炎患者血清FGF-21、PDGF-BB和FBRS水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2022, 25(3): 347-350.

Li Chunhua, Li Zhongxin, Zhang Chunlei, et al. Diagnostic performance of serum FGF-21, PDGF-BB and FBRS levels on significant liver fibrosis in patients with chronic hepatitis B[J]. Journal of Practical Hepatology, 2022, 25(3): 347-350.

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不同肝纤维化程度的慢性乙型肝炎患者血清FGF-21、PDGF-BB和FBRS水平变化及其临床意义探讨^*

Diagnostic performance of serum FGF-21, PDGF-BB and FBRS levels on significant liver fibrosis in patients with chronic hepatitis B

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