Abstract：
BACKGROUND: Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (age, diabetes, PRO-C3, and platelet count) to detect patients with an LSM >8 kPa or >12 kPa in comparison to the Fibrosis-4 Index (FIB-4).
METHODS: Serum from patients with MASLD (n = 269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods. Liver stiffness measurement (LSM) by vibration-controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used.
RESULTS: An LSM >8 kPa was found in 108 (40.1%) patients. PRO-C3, PRO-C6, C4M, and PRO-C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI] = 0.67-0.79) to detect patients >8 kPa, compared to FIB-4 (0.71, (95%CI = 0.64-0.77, p = 0.35), and had a higher net benefit compared to FIB-4 from a probability threshold of 15%. FIB-4 and ADAPT performed equally well to detect patients with an LSM >12 kPa, AUC 0.76 versus 0.76, p = 0.93.
CONCLUSIONS: ADAPT seems to be marginally better than FIB-4 in identifying patients with an LSM >8 kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low-risk populations. The overall performance of FIB-4 was similar to that of ADAPT in detecting patients with an LSM of >12 kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB-4 remains a first-line test for advanced fibrosis.
METHODS: Serum from patients with MASLD (n = 269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods. Liver stiffness measurement (LSM) by vibration-controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used.
RESULTS: An LSM >8 kPa was found in 108 (40.1%) patients. PRO-C3, PRO-C6, C4M, and PRO-C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI] = 0.67-0.79) to detect patients >8 kPa, compared to FIB-4 (0.71, (95%CI = 0.64-0.77, p = 0.35), and had a higher net benefit compared to FIB-4 from a probability threshold of 15%. FIB-4 and ADAPT performed equally well to detect patients with an LSM >12 kPa, AUC 0.76 versus 0.76, p = 0.93.
CONCLUSIONS: ADAPT seems to be marginally better than FIB-4 in identifying patients with an LSM >8 kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low-risk populations. The overall performance of FIB-4 was similar to that of ADAPT in detecting patients with an LSM of >12 kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB-4 remains a first-line test for advanced fibrosis.
摘要：
背景：胶原蛋白形成和降解的裂解产物作为代谢功能障碍相关脂肪变性肝病（MASLD）患者晚期纤维化风险的一线生物标志物具有潜力。这里,我们评估了PRO-C3、PRO-C6、C4M、PRO-C18L,和临床评分ADAPT(年龄，糖尿病,PRO-C3和血小板计数）以检测与纤维化-4指数（FIB-4）相比LSM>8kPa或>12kPa的患者。
方法：使用基于酶联免疫吸附测定的方法分析了来自瑞典六所大学医院的MASLD患者（n=269）的血清。通过振动控制的瞬时弹性成像进行肝脏硬度测量（LSM）。曲线下面积（AUC），校正曲线,采用净效益分析。
结果：108例（40.1%）患者发现LSM>8kPa。PRO-C3,PRO-C6,C4M,PRO-C18L的AUC范围为0.48至0.62。ADAPT具有最高的AUC（0.73，95％置信区间[CI]=0.67-0.79）来检测>8kPa的患者，与FIB-4(0.71，(95CI=0.64-0.77，p=0.35)相比，与FIB-4相比，净收益更高，概率阈值为15%。FIB-4和ADAPT同样能很好地检测LSM>12kPa的患者，AUC0.76对0.76,p=0.93。
结论：ADAPT在识别LSM>8kPa的患者方面似乎比FIB-4略好。然而,ADAPT作为一线测试的临床实用性尚不确定，尤其是在低风险人群中。FIB-4在检测LSM>12kPa患者方面的总体性能与ADAPT相似。总之,结果表明，ADAPT可能有助于检测MASLD中纤维化的早期阶段，但FIB-4仍然是晚期纤维化的一线检测。
方法：使用基于酶联免疫吸附测定的方法分析了来自瑞典六所大学医院的MASLD患者（n=269）的血清。通过振动控制的瞬时弹性成像进行肝脏硬度测量（LSM）。曲线下面积（AUC），校正曲线,采用净效益分析。
结果：108例（40.1%）患者发现LSM>8kPa。PRO-C3,PRO-C6,C4M,PRO-C18L的AUC范围为0.48至0.62。ADAPT具有最高的AUC（0.73，95％置信区间[CI]=0.67-0.79）来检测>8kPa的患者，与FIB-4(0.71，(95CI=0.64-0.77，p=0.35)相比，与FIB-4相比，净收益更高，概率阈值为15%。FIB-4和ADAPT同样能很好地检测LSM>12kPa的患者，AUC0.76对0.76,p=0.93。
结论：ADAPT在识别LSM>8kPa的患者方面似乎比FIB-4略好。然而,ADAPT作为一线测试的临床实用性尚不确定，尤其是在低风险人群中。FIB-4在检测LSM>12kPa患者方面的总体性能与ADAPT相似。总之,结果表明，ADAPT可能有助于检测MASLD中纤维化的早期阶段，但FIB-4仍然是晚期纤维化的一线检测。
