Kawanaka Miwa, Fushimi Takashi, Tanikawa Tomohiro, Urata Noriiyo, Haruma Ken, Kawamoto Hirofumi, Otsuka Motoyuki
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Okayama, Japan.
Department of General Internal Medicine 2, General Medical Center, Kawasaki Medical School, Okayama, Japan.
Hepatol Res. 2025 Jul;55(7):994-1004. doi: 10.1111/hepr.14202. Epub 2025 Jun 11.
Liver fibrosis is a critical prognostic factor for chronic liver disease that influences morbidity and mortality. Type IV collagen 7S, measured using a chemiluminescent enzyme immunoassay, was evaluated as a novel noninvasive biomarker with its cutoff value determined via magnetic resonance elastography (MRE) to eliminate sampling bias. A two-step approach combining the fibrosis-4 (FIB-4) index and type IV collagen 7S demonstrated potential in enhancing risk stratification and clinical utility.
This study included 307 patients with chronic liver disease and 235 with metabolic dysfunction-associated steatotic liver disease. Type IV collagen 7S was compared with biomarkers such as FIB-4 index, M2BPGi, and hyaluronic acid. Diagnostic accuracy was assessed using AUROC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value, with cutoffs determined via the Youden Index. Subgroup analyses evaluated performance based on ALT levels (≤30 and >30 U/L) and age (≤60 and >60 years). A two-step risk stratification model incorporating type IV collagen 7S was developed for intermediate FIB-4 index groups (1.3-2.66) to assess its utility.
For liver stiffness assessed using MRE, type IV collagen 7S showed the highest correlation (ρ = 0.591, p < 0.001) and outperformed other biomarkers, particularly for F ≥ 2. Its performance was notable in patients with low ALT levels (≤30 U/L) and in elderly patients (>60 years). In the intermediate FIB-4 index group, the two-stage model reduced over triage by 20%, increased specificity from 55% to 78% and enhanced PPV by 13%.
The novel assay, type IV collagen 7S, is a highly effective and noninvasive biomarker for liver fibrosis. The performance of type IV collagen 7S tends to have robustness under the difference of ALT. Its combination with the FIB-4 index enhances diagnostic precision, particularly in intermediate-risk patients, reinforcing its role in refining fibrosis staging and optimizing patient management.
肝纤维化是影响慢性肝病发病率和死亡率的关键预后因素。通过化学发光酶免疫测定法检测的IV型胶原7S，被评估为一种新型无创生物标志物，其临界值通过磁共振弹性成像（MRE）确定，以消除抽样偏差。结合纤维化-4（FIB-4）指数和IV型胶原7S的两步法在增强风险分层和临床实用性方面显示出潜力。
本研究纳入了307例慢性肝病患者和235例代谢功能障碍相关脂肪性肝病患者。将IV型胶原7S与FIB-4指数、M2BPGi和透明质酸等生物标志物进行比较。使用受试者工作特征曲线下面积（AUROC）、敏感性、特异性、阳性预测值（PPV）和阴性预测值评估诊断准确性，通过约登指数确定临界值。亚组分析根据丙氨酸氨基转移酶（ALT）水平（≤30和>30 U/L）和年龄（≤60和>60岁）评估性能。为中间FIB-4指数组（1.3 - 2.66）建立了一个纳入IV型胶原7S的两步风险分层模型，以评估其效用。
对于使用MRE评估的肝脏硬度，IV型胶原7S显示出最高的相关性（ρ = 0.591，p < 0.001），并且优于其他生物标志物，尤其是对于纤维化程度≥2级的患者。其在低ALT水平（≤30 U/L）的患者和老年患者（>60岁）中表现显著。在中间FIB-4指数组中，两阶段模型将过度分诊减少了20%，特异性从55%提高到78%，PPV提高了13%。
新型检测方法IV型胶原7S是一种用于肝纤维化的高效无创生物标志物。IV型胶原7S的性能在ALT差异下往往具有稳健性。它与FIB-4指数的结合提高了诊断精度，特别是在中风险患者中，强化了其在细化纤维化分期和优化患者管理中的作用。
