Wang J-Y, Mao R-C, Zhang Y-M, Zhang Y-J, Liu H-Y, Qin Y-L, Lu M-J, Zhang J-M
Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
J Viral Hepat. 2015 Feb;22(2):128-36. doi: 10.1111/jvh.12284. Epub 2014 Aug 8.
Patients with chronic hepatitis B virus (HBV) infection and normal or mildly increased transaminases may have sustained significant liver damage, as verified by liver biopsy. However, no suitable noninvasive method exists for identifying liver necroinflammation in such patients. We aimed to investigate the power of microRNA-124 as a novel biomarker for liver necroinflammation. A total of 131 recruited patients with chronic HBV infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S). Thirty healthy individuals were included as controls (HCs). Serum microRNA-124 and microRNA-122 levels were measured using qRT-PCR. Forty-five patients from the study population receiving entecavir therapy were monitored for changes in serum microRNA-124 levels in association with improved liver histology. The capacity of serum microRNA-124 levels in discriminating the grade of liver necroinflammation was compared with alanine aminotransferase (ALT) with liver biopsy validation. Serum microRNA-124 levels were significantly higher in patients with chronic HBV infection than in HCs (P < 0.0001). Patients with considerable liver necroinflammation (G ≥ 2) had significantly higher serum miRNA-124 levels than those without or with mild necroinflammation (P < 0.0001). After 48 weeks of antiviral therapy, serum microRNA-124 levels considerably declined in 45 patients (P < 0.0001), which were associated with histological improvement. In patients with normal ALT and a serum HBV DNA load >10(4) copies/mL, receiver operating characteristic (ROC) curve of serum microRNA-124 levels yielded an area under ROC curve (AUC) of 0.840, with 58.3% sensitivity and 91.7% specificity in discriminating between moderate-to-severe liver necroinflammation (G ≥ 2).
慢性乙型肝炎病毒(HBV)感染且转氨酶正常或轻度升高的患者可能存在持续的显著肝损伤,肝活检已证实这一点。然而,目前尚无合适的非侵入性方法来识别此类患者的肝脏坏死性炎症。我们旨在研究微小RNA - 124作为肝脏坏死性炎症新型生物标志物的作用。总共131例招募的慢性HBV感染患者接受了肝活检,以进行坏死性炎症分级(G)和纤维化分期(S)。纳入30名健康个体作为对照(HC)。使用qRT - PCR检测血清微小RNA - 124和微小RNA - 122水平。对研究人群中接受恩替卡韦治疗的45例患者监测血清微小RNA - 124水平的变化及其与肝脏组织学改善的关系。将血清微小RNA - 124水平区分肝脏坏死性炎症分级的能力与经肝活检验证的丙氨酸氨基转移酶(ALT)进行比较。慢性HBV感染患者的血清微小RNA - 124水平显著高于健康对照(P < 0.0001)。存在明显肝脏坏死性炎症(G≥2)的患者血清微小RNA - 124水平显著高于无或轻度坏死性炎症的患者(P < 0.0001)。抗病毒治疗48周后,45例患者的血清微小RNA - 124水平显著下降(P < 0.0001),这与组织学改善相关。在ALT正常且血清HBV DNA载量>10⁴拷贝/mL的患者中,血清微小RNA - 124水平的受试者工作特征(ROC)曲线下面积(AUC)为0.840,在区分中度至重度肝脏坏死性炎症(G≥2)时灵敏度为58.3%,特异性为91.7%。