循环骨形态发生蛋白 (BMP) 8B 是非酒精性脂肪性肝炎 (NASH) 诊断的无创性预测生物标志物。

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complex disease which is characterized by the deposition of fats in the hepatocytes. Further, it progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. The increasing prevalence of NAFLD urges to find the non-invasive predictive biomarkers. In this study, we sought to determine increased BMP8B levels as predictors for the progression of NAFLD. METHODS: In the present cross-sectional study, circulatory BMP8B levels were measured in healthy controls (n = 56), NAFL patients (n = 72) and NASH patients (n = 77) by using an ELISA kit. Human hepatic BMP8B mRNA expression was measured in the liver tissue of control and NASH patients. In addition, BMP8B expression was confirmed by immunohistochemistry analysis. Furthermore, hepatic BMP8B mRNA expression was measured in wild type (WT) mice, WT mice fed with choline deficient high fat diet (WT+CDHF), iNOS (inducible nitric oxide synthase) knockout (iNOS-/-) mice, iNOS-/- fed with CDHF diet (iNOS-/-+CDHF). RESULTS: Increased circulatory BMP8B levels and BMP8B mRNA expression in hepatic tissue were significantly higher in NASH patients as compared with the control subjects. BMP8B expression was increased parallel to the fibrosis score in the hepatic tissues of NASH patients. It was observed that increased BMP8B levels have shown a significant positive correlation between aspartate aminotransferase (r = 0.31, p = 0.005), alanine aminotransferase (r = 0.23, p = 0.045), APRI (r = 0.30, p = 0.009), and Fib-4 score (r = 0.25, p = 0.036) in NASH patients. BMP8B has maintained a significant association with NASH and shown high sensitivity (92.91%) and specificity (92.73%) in NASH patients. Furthermore, increased BMP8B mRNA expression levels were observed in iNOS-/-+CDHF mice. CONCLUSION: Our study findings confirmed that BMP8B increases with the severity of the disease and BMP8B shows potential as a non-invasive predictive biomarker to identify NAFLD progression. However, future studies should investigate circulatory BMP8B levels in a large number of patients and also its impact on liver during NAFLD progression.

背景：非酒精性脂肪性肝病（NAFLD）是一种复杂的疾病，其特征是肝细胞内脂肪沉积。此外，它会进展为非酒精性脂肪性肝炎（NASH）、纤维化和肝细胞癌。NAFLD 的患病率不断增加，促使我们寻找非侵入性的预测生物标志物。在本研究中，我们试图确定 BMP8B 水平升高作为 NAFLD 进展的预测因子。

方法：在这项横断面研究中，我们使用 ELISA 试剂盒测量了健康对照组（n=56）、NAFL 患者（n=72）和 NASH 患者（n=77）的循环 BMP8B 水平。我们还测量了对照组和 NASH 患者肝组织中的人肝 BMP8B mRNA 表达。此外，我们通过免疫组织化学分析证实了 BMP8B 的表达。此外，我们还在野生型（WT）小鼠、给予胆碱缺乏高脂肪饮食的 WT 小鼠（WT+CDHF）、诱导型一氧化氮合酶（iNOS）敲除（iNOS-/-）小鼠、给予 CDHF 饮食的 iNOS-/-小鼠（iNOS-/-+CDHF）中测量了肝组织中的 BMP8B mRNA 表达。

结果：与对照组相比，NASH 患者的循环 BMP8B 水平和肝组织中的 BMP8B mRNA 表达显著升高。BMP8B 的表达与 NASH 患者肝组织中的纤维化评分呈平行增加。观察到在 NASH 患者中，升高的 BMP8B 水平与天冬氨酸转氨酶（r=0.31，p=0.005）、丙氨酸转氨酶（r=0.23，p=0.045）、APRI（r=0.30，p=0.009）和 Fib-4 评分（r=0.25，p=0.036）之间存在显著正相关。BMP8B 与 NASH 保持显著相关性，在 NASH 患者中具有高灵敏度（92.91%）和特异性（92.73%）。此外，在 iNOS-/-+CDHF 小鼠中观察到 BMP8B mRNA 表达水平升高。

结论：我们的研究结果证实，BMP8B 随着疾病的严重程度而增加，BMP8B 有望成为识别 NAFLD 进展的非侵入性预测生物标志物。然而，未来的研究应该在大量患者中研究循环 BMP8B 水平，并研究其在 NAFLD 进展过程中对肝脏的影响。