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基于新型血清标志物评估非酒精性脂肪性肝病(NAFLD)严重程度的初步研究。

Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study.

机构信息

Department of Clinical Biochemistry, Royal Free Hospital, London, United Kingdom.

UCL Research Department of Infection & Population Health, Royal Free Hospital, London, United Kingdom.

出版信息

PLoS One. 2021 Nov 23;16(11):e0260313. doi: 10.1371/journal.pone.0260313. eCollection 2021.

Abstract

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD.

METHODS

This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity.

RESULTS

Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8.

CONCLUSIONS

Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

摘要

背景/目的:非酒精性脂肪性肝病(NAFLD)是一个重大的公共卫生问题。从非酒精性脂肪性肝炎(NASH)患者中鉴别出单纯性脂肪变性患者非常重要,因为 NASH 与发病率和死亡率的增加相关。血清标志物,包括脂肪因子和细胞因子,在 NAFLD 的发病机制和进展中起重要作用。在此,我们评估了这些标志物在 NAFLD 患者中的应用价值。

方法

这是一项前瞻性、横断面研究,纳入了 105 例不同严重程度的 NAFLD 成年患者。通过 3 种生物芯片平台和 2 种酶联免疫吸附测定(ELISA)方法检测了 12 种血清标志物。我们还使用与纤维化严重程度最相关的血清标志物开发了一种 NAFLD 个体纤维化指数(NIFI)。

结果

105 例患者中 61 例(58.1%)为男性,平均年龄为 53.5 岁。多变量回归分析显示,白细胞介素 6(IL-6)水平升高(p=0.0321)和基质金属蛋白酶 9(MMP-9)血清水平降低(p=0.0031)与 Fibroscan®检测到的更高纤维化程度相关。使用 NIFI 的 ROC 曲线分析,预测 Fibroscan 值≥7.2kPa 的曲线下面积为 0.77(95%CI:0.67,0.88,p<0.001),敏感性为 89.3%,特异性为 57.9%,阳性似然比为 2.8。

结论

NAFLD 纤维化程度的增加与 IL-6 和 MMP-9 的差异表达相关。NIFI 可能对预测晚期 NAFLD 纤维化有价值,并可能有助于避免对低风险患者进行不必要的干预,如肝活检。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8d5/8610238/b58f84ec6d1b/pone.0260313.g001.jpg

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