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*

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。

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

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.