Wei Huan, Bi Yanhua, Liao Chunhong, Huang Yuehua, Lian Yifan
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
School of Public Health, Sun Yat-sen University, Guangzhou, China.
Noncoding RNA Res. 2024 Aug 15;9(4):1342-1350. doi: 10.1016/j.ncrna.2024.08.004. eCollection 2024 Dec.
The lack of effective non-invasive diagnostic methods for liver fibrosis hinders timely treatment for chronic hepatitis B (CHB) patients, leading to the progression of advanced liver disease. Circulating microRNAs offer a non-invasive approach to fibrosis assessment. MicroRNA-15a/16-1 (miR-15a/16) was reported to be implicated in fibrosis development, but the role of plasma miR-15a/16 in liver fibrosis assessment remains poorly understood. This study explored the importance of plasma miR-15a/16 in assessing liver fibrosis severity of CHB patients.
Quantitative PCR was utilized to measure the levels of plasma miR-15a/16 in 435 patients with CHB and 74 healthy controls. We assessed the correlation between plasma miR-15a/16 levels and liver fibrosis and cirrhosis using Pearson correlation coefficients, multivariate linear and logistic regression models, and smooth curve fitting. Utilizing the receiver operating characteristic (ROC) curve, we examined the diagnostic potential of plasma miR-15a/16 in severe fibrosis and cirrhosis.
Plasma levels of miR-15a/16 in patients with CHB were significantly reduced compared to those in healthy controls. In the CHB cohort, levels were notably decreased in individuals with severe fibrosis or cirrhosis compared to those without severe fibrosis or cirrhosis. Plasma miR-15a/16 levels exhibited a negative relationship with the severity of liver fibrosis, gradually decreasing as the histological fibrosis stage progressed from S0 to S4. Reduced levels of plasma miR-15a/16 were linked to an elevated risk of severe liver fibrosis (miR-15a: odds ratio [OR] = 0.243; 95 % confidence interval [CI]: 0.138, 0.427; miR-16: OR = 0.201; 95 % CI: 0.097, 0.417) and cirrhosis (miR-15a: OR = 0.153; 95 % CI: 0.079, 0.298; miR-16: OR = 0.064; 95 % CI: 0.025, 0.162). MiR-15a achieved an area under the ROC curve of 0.886 and 0.832 for detecting moderate-to-severe fibrosis (S2-S4) and cirrhosis, respectively. MiR-16 demonstrated similar diagnostic values.
Plasma miR-15a/16 levels were negatively correlated with the severity of liver fibrosis in CHB patients and could serve as a new non-invasive indicator in evaluating liver fibrosis.
缺乏有效的肝纤维化非侵入性诊断方法阻碍了慢性乙型肝炎（CHB）患者的及时治疗，导致晚期肝病的进展。循环微RNA提供了一种用于纤维化评估的非侵入性方法。据报道，MicroRNA-15a/16-1（miR-15a/16）与纤维化发展有关，但血浆miR-15a/16在肝纤维化评估中的作用仍知之甚少。本研究探讨了血浆miR-15a/16在评估CHB患者肝纤维化严重程度中的重要性。
采用定量PCR检测435例CHB患者和74例健康对照者血浆miR-15a/16水平。我们使用Pearson相关系数、多元线性和逻辑回归模型以及平滑曲线拟合评估血浆miR-15a/16水平与肝纤维化和肝硬化之间的相关性。利用受试者工作特征（ROC）曲线，我们检验了血浆miR-15a/16在严重纤维化和肝硬化中的诊断潜力。
与健康对照者相比，CHB患者血浆miR-15a/16水平显著降低。在CHB队列中，与无严重纤维化或肝硬化的个体相比，严重纤维化或肝硬化个体的水平显著降低。血浆miR-15a/16水平与肝纤维化严重程度呈负相关，随着组织学纤维化阶段从S0进展到S4逐渐降低。血浆miR-15a/16水平降低与严重肝纤维化（miR-15a：比值比[OR]=0.243；95%置信区间[CI]：0.138，0.427；miR-16：OR=0.201；95%CI：0.097，0.417）和肝硬化（miR-15a：OR=0.153；95%CI：0.079，0.298；miR-16：OR=0.064；95%CI：0.025，0.162）风险升高相关。miR-15a检测中度至重度纤维化（S2-S4）和肝硬化的ROC曲线下面积分别为0.886和0.832。miR-16显示出类似的诊断价值。
CHB患者血浆miR-15a/16水平与肝纤维化严重程度呈负相关，可作为评估肝纤维化的一种新的非侵入性指标。
