Cao Yu-Tian, Xiang Liu-Lan, Qi Fang, Zhang Yu-Juan, Chen Yi, Zhou Xi-Qiao
The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China.
Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
EClinicalMedicine. 2022 Jul 10;51:101547. doi: 10.1016/j.eclinm.2022.101547. eCollection 2022 Sep.
Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, and among the non-invasive tests, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) have shown better diagnostic performance in NAFLD. This meta-analysis aimed to evaluate the performance of CAP and LSM for assessing steatosis and fibrosis in NAFLD.
We searched the PubMed, Web of Science, Cochrane Library, and Embase databases for relevant articles published up to February 13, 2022, and selected studies that met the inclusion and exclusion criteria, and evaluated the quality of evidence. Then we pooled sensitivity (SE), specificity (SP), and area under receiver operating characteristic (AUROC) curves. A random effect model was applied regardless of heterogeneity. Meta-regression analysis and subgroup analysis were performed to explore heterogeneity, and Fagan plot analysis was used to evaluate clinical utility. This meta-analysis was completed in Nanjing, Jiangsu and registered on PROSPERO (CRD42022309965).
A total of 10537 patients from 61 studies were included in our meta-analysis. The AUROC of CAP were 0·924, 0·794 and 0·778 for steatosis grades ≥ S1, ≥ S2 and = S3, respectively, and the AUROC of LSM for detecting fibrosis stages ≥ F1, ≥ F2, ≥ F3, and = F4 were 0·851, 0·830, 0·897 and 0·925, respectively. Subgroup analysis revealed that BMI ≥ 30 kg/m² had lower accuracy for diagnosing S ≥ S1, ≥ S2 than BMI<30 kg/m². For the mean cut-off values, significant differences were found in CAP values among different body mass index (BMI) populations and LSM values among different regions. For diagnosing S ≥ S1, ≥ S2 and = S3, the mean CAP cut-off values for BMI ≥ 30 kg/m² were 30·7, 28·2, and 27·9 dB/m higher than for BMI < 30 kg/m² ( = 0·001, 0·001 and 0·018, respectively). For diagnosing F ≥ F2 and = F4, the mean cut-off values of Europe and America were 0·96 and 2·03 kPa higher than Asia ( 0·027, 0·034), respectively. In addition, the results did not change significantly after sensitivity analysis and the trim and fill method to correct for publication bias, proving that the conclusions are robust.
The good performance of CAP and LSM for the diagnosis of mild steatosis (S ≥ S1), advanced liver fibrosis (F ≥ F3), and cirrhosis (F = F4) can be used to screen for NAFLD in high-risk populations. Of note, the accuracy of CAP for the detection of steatosis in patients with obesity is reduced and requires specific diagnostic values. For LSM, the same diagnostic values can be used when the appropriate probes are selected based on BMI and the automated probe selection tool. The performance of CAP and LSM in assessing steatosis in patients with obesity, moderate to severe steatosis, and low-grade fibrosis should be further validated and improved in the future.
The study was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
非酒精性脂肪性肝病(NAFLD)是一种常见的慢性肝病,在非侵入性检查中,受控衰减参数(CAP)和肝脏硬度测量(LSM)在NAFLD中显示出更好的诊断性能。本荟萃分析旨在评估CAP和LSM在评估NAFLD中的脂肪变性和纤维化方面的性能。
我们检索了截至2022年2月13日发表的PubMed、Web of Science、Cochrane图书馆和Embase数据库中的相关文章,选择符合纳入和排除标准的研究,并评估证据质量。然后我们汇总了敏感性(SE)、特异性(SP)和受试者操作特征曲线下面积(AUROC)。无论异质性如何,均应用随机效应模型。进行了Meta回归分析和亚组分析以探索异质性,并使用Fagan图分析来评估临床实用性。本荟萃分析在江苏南京完成,并在PROSPERO(CRD42022309965)上注册。
我们的荟萃分析共纳入了来自61项研究的10537名患者。CAP对于脂肪变性分级≥S1、≥S2和=S3的AUROC分别为0.924、0.794和0.778,LSM对于检测纤维化分期≥F1、≥F2、≥F3和=F4的AUROC分别为0.851、0.830、0.897和0.925。亚组分析显示,体重指数(BMI)≥30kg/m²诊断S≥S1、≥S2的准确性低于BMI<30kg/m²。对于平均临界值,不同体重指数(BMI)人群的CAP值和不同地区的LSM值存在显著差异。对于诊断S≥S1、≥S2和=S3,BMI≥30kg/m²的平均CAP临界值分别比BMI<30kg/m²高30.7、28.2和27.9dB/m(P分别为0.001、0.001和0.018)。对于诊断F≥F2和=F4,欧美地区的平均临界值分别比亚洲高0.96和2.03kPa(P分别为0.027、0.034)。此外,敏感性分析和用于校正发表偏倚的修剪和填充方法后结果无显著变化,证明结论可靠。
CAP和LSM在诊断轻度脂肪变性(S≥S1)、晚期肝纤维化(F≥F3)和肝硬化(F=F4)方面表现良好,可用于高危人群的NAFLD筛查。值得注意的是,CAP检测肥胖患者脂肪变性的准确性降低,需要特定的诊断值。对于LSM,当根据BMI选择合适探头并使用自动探头选择工具时,可使用相同的诊断值。CAP和LSM在评估肥胖患者、中重度脂肪变性患者和轻度纤维化患者脂肪变性方面的性能未来应进一步验证和改进。
本研究由江苏省高等教育机构优势学科建设工程资助项目(PAPD)资助。