Matsuura Kentaro, Aizawa Nobuhiro, Enomoto Hirayuki, Nishiguchi Shuhei, Toyoda Hidenori, Kumada Takashi, Iio Etsuko, Ito Kyoko, Ogawa Shintaro, Isogawa Masanori, Alter Harvey J, Tanaka Yasuhito
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Open Forum Infect Dis. 2018 Oct 22;5(11):ofy268. doi: 10.1093/ofid/ofy268. eCollection 2018 Nov.
Evaluating the progression of hepatic fibrosis in chronic hepatitis C (CHC) is critical, and identifying a predictive biomarker for fibrosis will be helpful for implementing personalized surveillance of hepatocellular carcinoma after the elimination of hepatitis C virus by antiviral therapy. This study aimed to investigate the association of circulating let-7a-5p levels with severity of hepatic fibrosis.
We analyzed circulating let-7a-5p levels in serum and serum-derived extracellular vesicles (EVs) in 84 Japanese CHC patients who underwent a liver biopsy by quantitative real-time polymerase chain reaction, and investigated the association of its levels with histological hepatic fibrotic stage, liver stiffness, and several hepatic fibrotic markers.
The levels of let-7a-5p in serum and EVs were significantly lower in patients with liver cirrhosis. Additionally, the serum let-7a-5p level correlated significantly with hepatic fibrotic markers, Mac-2 binding protein glycan isomer (M2BPGi), fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and liver stiffness, evaluated by transient elastography. Furthermore, the serum let-7a-5p level was superior to M2BPGi, FIB-4, and APRI and was comparable to liver stiffness in discriminating liver cirrhosis.
These results provide evidence that circulating let-7a-5p in serum may serve as a surrogate marker for severity of hepatic fibrosis in CHC.
评估慢性丙型肝炎(CHC)中肝纤维化的进展至关重要,识别纤维化的预测生物标志物将有助于在通过抗病毒治疗消除丙型肝炎病毒后实施肝细胞癌的个性化监测。本研究旨在探讨循环中let-7a-5p水平与肝纤维化严重程度的关联。
我们通过定量实时聚合酶链反应分析了84例接受肝活检的日本CHC患者血清及血清来源的细胞外囊泡(EVs)中循环let-7a-5p水平,并研究其水平与组织学肝纤维化分期、肝脏硬度及几种肝纤维化标志物的关联。
肝硬化患者血清和EVs中let-7a-5p水平显著降低。此外,血清let-7a-5p水平与肝纤维化标志物、Mac-2结合蛋白聚糖异构体(M2BPGi)、纤维化-4(FIB-4)指数、天冬氨酸转氨酶与血小板比值指数(APRI)以及通过瞬时弹性成像评估的肝脏硬度显著相关。此外,血清let-7a-5p水平在区分肝硬化方面优于M2BPGi、FIB-4和APRI,与肝脏硬度相当。
这些结果提供了证据,表明血清中循环的let-7a-5p可能作为CHC中肝纤维化严重程度的替代标志物。