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循环miR-122对日本非酒精性脂肪性肝病组织学特征和肝细胞癌的影响

Impact of circulating miR-122 for histological features and hepatocellular carcinoma of nonalcoholic fatty liver disease in Japan.

作者信息

Akuta Norio, Kawamura Yusuke, Suzuki Fumitaka, Saitoh Satoshi, Arase Yasuji, Kunimoto Hideo, Sorin Yushi, Fujiyama Shunichiro, Sezaki Hitomi, Hosaka Tetsuya, Kobayashi Masahiro, Suzuki Yoshiyuki, Kobayashi Mariko, Ikeda Kenji, Kumada Hiromitsu

机构信息

Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.

Liver Research Laboratory, Toranomon Hospital, Tokyo, Japan.

出版信息

Hepatol Int. 2016 Jul;10(4):647-56. doi: 10.1007/s12072-016-9729-2. Epub 2016 Apr 13.

Abstract

BACKGROUND AND AIM

Relationships between circulating microRNA-122 (miR-122) and histological features of nonalcoholic fatty liver disease (NAFLD) are unclear.

METHODS

The impact of serum miR-122 levels for histological features and hepatocellular carcinoma (HCC) was investigated in 305 Japanese patients with histological proven NAFLD. Twenty-three patients were with HCC at the time of diagnosis of NAFLD, and four patients developed HCC during the follow-up. The cross-sectional or longitudinal evaluations were performed to investigate the impact for HCC.

RESULTS

Serum miR-122 levels (calibrated relative to the median levels of patients) partly affected severity of steatosis, ballooning, lobular inflammation, and stage. Multivariate analysis identified HCC and/or histological components of NASH as morphological factors that independently influenced serum miR-122 levels at the diagnosis of NAFLD. There was a strong correlation between serum miR-122 levels and AST, ALT levels. In cross-sectional evaluation, serum miR-122 levels of patients without HCC were significantly higher than those with HCC in patients of stage 3 but not stage 4. In longitudinal evaluation of one patient with follow-up time of 25 years, from the diagnosis of NAFLD until HCC, serum miR-122 levels had already tended to decrease before the progression of fibrosis stage.

CONCLUSIONS

HCC and/or histological components of NASH affected serum miR-122 levels, independently. In longitudinal evaluation of HCC patients, serum miR-122 levels had already tended to decrease before the progression of fibrosis stage. Further prospective studies are needed to investigate the impact of serum miR-122 for histological features and hepatocarcinogenesis of NAFLD.

摘要

背景与目的

循环微小RNA-122(miR-122)与非酒精性脂肪性肝病(NAFLD)组织学特征之间的关系尚不清楚。

方法

在305例经组织学证实为NAFLD的日本患者中,研究血清miR-122水平对组织学特征和肝细胞癌(HCC)的影响。23例患者在NAFLD诊断时已患有HCC,4例患者在随访期间发生HCC。进行横断面或纵向评估以研究对HCC的影响。

结果

血清miR-122水平(相对于患者中位数水平进行校准)部分影响脂肪变性、气球样变、小叶炎症和分期的严重程度。多变量分析确定HCC和/或NASH的组织学成分是在NAFLD诊断时独立影响血清miR-122水平的形态学因素。血清miR-122水平与AST、ALT水平之间存在强相关性。在横断面评估中,3期但非4期患者中,无HCC患者的血清miR-122水平显著高于有HCC患者。在对一名随访时间为25年的患者进行纵向评估时,从NAFLD诊断到HCC,血清miR-122水平在纤维化阶段进展之前就已趋于下降。

结论

HCC和/或NASH的组织学成分独立影响血清miR-122水平。在HCC患者的纵向评估中,血清miR-122水平在纤维化阶段进展之前就已趋于下降。需要进一步的前瞻性研究来调查血清miR-122对NAFLD组织学特征和肝癌发生的影响。

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