Coppola Nicola, Onorato Lorenzo, Panella Marta, de Stefano Giorgio, Mosca Nicola, Minichini Carmine, Messina Vincenzo, Potenza Nicoletta, Starace Mario, Alessio Loredana, Farella Nunzia, Sagnelli Evangelista, Russo Aniello
Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy.
Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy.
Front Immunol. 2018 Jun 13;9:1334. doi: 10.3389/fimmu.2018.01334. eCollection 2018.
To evaluate the correlation between the hepatic expression pattern of hsa-miR-125a-5p and HBV-DNA and the progression of fibrosis in patients with overt or occult HBV infection.
We enrolled all the HBsAg-positive treatment naive patients (overt HBV group) and all the HBsAg-negative patients with hepatocellular carcinoma and with a positive HBV-DNA in their hepatic tissue (occult HBV group), who underwent a diagnostic liver biopsy between April 2007 and April 2015. Tissue concentrations of HBV-DNA and hsa-miR-125a-5p were then analyzed by real-time quantitative PCR. Necroinflammatory activity and fibrosis were evaluated according to the Ishak score.
During the study period, we enrolled 64 patients with overt and 10 patients with occult HBV infection. In the overt HBV group, 35 of 64 (54.7%) showed a mild fibrosis (staging 0-2), 17 (26.6%) a moderate fibrosis (staging 3-4), while the remaining 12 (18.7%) had a cirrhosis. All patients in the occult HBV group were cirrhotic. Patients with more advanced fibrosis stage showed a higher mean age when compared with those with mild ( < 0.00001) or moderate fibrosis ( < 0.00001) and were more frequently male than patients with staging 0-2 ( = 0.04). Similarly, patients with occult B infection were older than HBsAg-positive patients. Liver concentrations of miR-125a-5p were significantly higher in patients with cirrhosis (9.75 ± 4.42 AU) when compared with patients with mild (1.39 ± 0.94, = 0.0002) or moderate fibrosis (2.43 ± 2.18, = 0.0006) and were moderately higher in occult than in overt HBV infection ( = 0.09). Moreover, we found an inverse correlation, although not statistically significant, between the tissue HBV-DNA levels and the staging of fibrosis.
This study suggests a correlation between the tissue expression of hsa-miR-125a-5p and the progression of liver damage in a group of patients with occult or overt HBV infection. If confirmed, these data suggest the hsa-miR-125a-5p may be a novel biomarker of hepatic damage.
评估hsa-miR-125a-5p在肝脏中的表达模式与乙肝病毒脱氧核糖核酸(HBV-DNA)以及显性或隐匿性HBV感染患者纤维化进展之间的相关性。
我们纳入了所有2007年4月至2015年4月间接受诊断性肝活检的HBsAg阳性初治患者(显性HBV组)以及所有肝细胞癌且肝组织中HBV-DNA阳性的HBsAg阴性患者(隐匿性HBV组)。然后通过实时定量聚合酶链反应分析组织中HBV-DNA和hsa-miR-125a-5p的浓度。根据Ishak评分评估坏死性炎症活动和纤维化情况。
在研究期间,我们纳入了64例显性HBV感染患者和10例隐匿性HBV感染患者。在显性HBV组中,64例患者中有35例(54.7%)表现为轻度纤维化(分期0-2),17例(26.6%)为中度纤维化(分期3-4),其余12例(18.7%)为肝硬化。隐匿性HBV组的所有患者均为肝硬化。与轻度(<0.00001)或中度纤维化患者相比,纤维化分期更高级的患者平均年龄更高(<0.00001),且男性比例高于分期0-2的患者(P=0.04)。同样,隐匿性HB感染患者比HBsAg阳性患者年龄更大。与轻度纤维化患者(1.39±0.94,P=0.0002)或中度纤维化患者(2.43±2.18,P=0.0006)相比,肝硬化患者肝脏中miR-125a-5p的浓度显著更高(9.75±4.42 AU),隐匿性HBV感染患者的该浓度略高于显性HBV感染患者(P=0.09)。此外,我们发现组织中HBV-DNA水平与纤维化分期之间存在负相关,尽管无统计学意义。
本研究表明hsa-miR-125a-5p的组织表达与一组隐匿性或显性HBV感染患者的肝损伤进展之间存在相关性。如果得到证实,这些数据表明hsa-miR-125a-5p可能是肝损伤的一种新型生物标志物。