血清Ⅳ型胶原相对值及其组合模型在代谢相关脂肪性肝病肝脏炎症与纤维化评估中的应用价值

肝脏 ›› 2026, Vol. 31 ›› Issue (6): 886-890.

血清Ⅳ型胶原相对值及其组合模型在代谢相关脂肪性肝病肝脏炎症与纤维化评估中的应用价值

许城英, 孙璐, 毛成洁, 王敏英, 陆忠华

214000 无锡江南大学无锡医学院(许城英,王敏英);
214000 无锡南通大学无锡临床学院(孙璐,毛成洁);
214000 无锡江南大学附属无锡五院(无锡市第五人民医院肝病科)(陆忠华)

收稿日期:2025-11-27 出版日期:2026-06-30 发布日期:2026-07-29
通讯作者: 陆忠华,Email:Lu_z_h@jiangnan.edu.cn
基金资助:
无锡市医学重点学科建设项目-创新团队(CXTD2021009)

Clinical value of serum type Ⅳ collagen relative to the upper limit of normal and its combination model in the assessment of hepatic inflammation and fibrosis in metabolic dysfunction-associated steatotic liver disease

Xu Chengying¹, Sun Lu², Mao Chengjie¹, Wang Minying¹, Lu Zhonghua³

1. Wuxi Medical College, Jiangnan University, Wuxi 214000, China;
2. Wuxi Clinical College of Nantong University, Wuxi 214000, China;
3. Department of Hepatology, Affiliated Wuxi Fifth Hospital of Jiangnan University (the Fifth People′s Hospital of Wuxi), Wuxi 214000, China

Received:2025-11-27 Online:2026-06-30 Published:2026-07-29
Contact: Lu Zhonghua, Email: Lu_z_h@jiangnan.edu.cn

摘要/Abstract

摘要： 目的探讨基于Ⅳ-C及由病理生理动力学构建的新型无创诊断模型代谢反应病理指数(MRPI)在评估代谢相关脂肪性肝病(MASLD)显著肝纤维化(≥F2)中的应用价值。方法回顾性分析2017年1月至2025年12月于无锡市第五人民医院就诊并经肝穿刺活检确诊的202例MASLD患者的临床资料。基于肝脏微结构重塑、线粒体损伤与代谢负荷的非线性关系,构建MRPI模型。以纤维化-4指数(FIB-4)为对照,通过受试者工作特征(ROC)曲线分析MRPI诊断显著肝纤维化的效能。结果显著纤维化组血清Ⅳ型胶原中位数显著高于非显著组[80.00 ng/mL vs. 37.00 ng/mL,P<0.001]。MRPI模型诊断显著肝纤维化的曲线下面积(AUC)为0.857(95% CI: 0.808~0.904),显著优于FIB-4的0.749(95% CI: 0.688~0.817)(P<0.001)。在最佳截断值2.442下,MRPI的特异度为93.1%、灵敏度为61.4%,其特异度显著高于FIB-4(65.3%)。结论血清Ⅳ型胶原联合代谢与炎症指标构建的MRPI模型,能有效反映MASLD纤维化进展的病理生理过程,具有较高的特异度与诊断效能。

Abstract: Objective To investigate the application value of the Metabolic reaction pathological index (MRPI), a novel non-invasive diagnostic model constructed based on serum type Ⅳ collagen (Ⅳ-C) and pathophysiological dynamics, in evaluating significant liver fibrosis (≥F2) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods A retrospective analysis was conducted on the clinical data of 202 MASLD patients who underwent liver biopsy at the Fifth People′s Hospital of Wuxi from January 2017 to December 2025. The MRPI model was established based on the non-linear relationship among hepatic microstructural remodeling, mitochondrial injury, and metabolic load. Using the FIB-4 index as a control, the diagnostic efficacy of MRPI for significant liver fibrosis was analyzed using receiver operating characteristic (ROC) curves. Results The median serum type Ⅳ collagen in the significant fibrosis group was significantly higher than that in the non-significant group[80.00 ng/mL vs. 37.00 ng/mL, P<0.001]. The area under the curve (AUC) of the MRPI model for diagnosing significant liver fibrosis was 0.857 (95% CI: 0.808~0.904), which was significantly superior to that of the FIB-4 index[0.749 (95% CI: 0.688~0.817), P<0.001]. At the optimal cut-off value of 2.442, the specificity and sensitivity of MRPI were 93.1% and 61.4%, respectively, with its specificity being significantly higher than that of FIB-4 (65.3%). Conclusion The MRPI model, constructed by combining serum type Ⅳ collagen with metabolic and inflammatory indicators, effectively reflects the pathophysiological process of fibrosis progression in MASLD and demonstrates high specificity and diagnostic efficacy.

Key words: Metabolic dysfunction-associated steatotic liver disease, Liver fibrosis, Type IV collagen, Non-invasive diagnostic model, Pathophysiology

许城英, 孙璐, 毛成洁, 王敏英, 陆忠华. 血清Ⅳ型胶原相对值及其组合模型在代谢相关脂肪性肝病肝脏炎症与纤维化评估中的应用价值[J]. 肝脏, 2026, 31(6): 886-890.

Xu Chengying, Sun Lu, Mao Chengjie, Wang Minying, Lu Zhonghua. Clinical value of serum type Ⅳ collagen relative to the upper limit of normal and its combination model in the assessment of hepatic inflammation and fibrosis in metabolic dysfunction-associated steatotic liver disease[J]. Chinese Hepatolgy, 2026, 31(6): 886-890.

/ 推荐

参考文献

[1] 陈思彤, 卫小蝶, 韦新焕, 等. 代谢功能障碍相关脂肪性肝病诊疗进展[J]. 实用肝脏病杂志, 2024, 27(4): 481-483.
[2] Mejía-Guzmán J E, Belmont-Hernández R A, Chávez-Tapia N C, et al. Metabolic-dysfunction-associated steatotic liver disease: molecular mechanisms, clinical implications, and emerging therapeutic strategies[J]. Int J Mol Sci, 2025, 26(7): 2959.
[3] Sharma A, Godinez Leiva E, Kalavalapalli S, et al. Improving MASLD risk stratification in young adults with cardiometabolic risk factors and insulin resistance assessment[J]. J Endocr Soc, 2026, 10(1): bvaf209.
[4] Heyens L J M, Malde D P A van, Us G D, et al. Is FIB-4 the right tool for screening for liver fibrosis?[J]. Ann Hepatol, 2025: 102176.
[5] Sung S, Al-Karaghouli M, Tam M, et al. Age-dependent differences in FIB-4 predictions of fibrosis in patients with MASLD referred from primary care[J]. Hepatol Commun, 2025, 9(1): e0609.
[6] Gan C, Yaqoob U, Lu J, et al. Liver sinusoidal endothelial cells contribute to portal hypertension through collagen type Ⅳ-driven sinusoidal remodeling[J]. JCI insight, 2024, 9(11): e174775.
[7] Mak K M, Chen L L, Lee T F. Codistribution of collagen type Ⅳ and laminin in liver fibrosis of elderly cadavers: immunohistochemical marker of perisinusoidal basement membrane formation[J]. Anat Rec (Hoboken), 2013, 296(6): 953-964.
[8] Lønsmann I, Grove J I, Haider A, et al. Biomarkers of type Ⅳ collagen turnover reflect disease activity in patients with early-stage non-alcoholic fatty liver (NAFL)[J]. Biology (Basel), 2023, 12(8): 1087.
[9] Botros M, Sikaris K A. The de ritis ratio: the test of time[J]. Clin Biochem Rev, 2013, 34(3): 117-130.
[10] Moore M P, Cunningham R P, Meers G M, et al. Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD[J]. Hepatology, 2022, 76(5): 1452-1465.
[11] Chu Q, Gu X, Zheng Q, et al. Mitochondrial mechanisms of apoptosis and necroptosis in liver diseases[J]. Anal Cell Pathol (Amst), 2021, 2021: 8900122.
[12] Kamiike W, Fujikawa M, Koseki M, et al. Different patterns of leakage of cytosolic and mitochondrial enzymes[J]. Clin Chim Acta, 1989, 185(3): 265-270.
[13] Xuan Y, Wu D, Zhang Q, et al. Elevated ALT/AST ratio as a marker for NAFLD risk and severity: insights from a cross-sectional analysis in the United States[J]. Front Endocrinol (Lausanne), 2024, 15: 1457598.
[14] Meyer J, Balaphas A, Fontana P, et al. Platelet interactions with liver sinusoidal endothelial cells and hepatic stellate cells lead to hepatocyte proliferation[J]. Cells, 2020, 9(5): 1243.
[15] Szafranska K, Kruse L D, Holte C F, et al. The whole story about fenestrations in LSEC[J]. Front Physiol, 2021, 12: 735573.
[16] 范建高, 徐小元, 南月敏, 等. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J]. 实用肝脏病杂志, 2024, 27(4): 494-510.
[17] Qu J, Wang L, Li Y, et al. Liver sinusoidal endothelial cell: an important yet often overlooked player in the liver fibrosis[J]. Clin Mol Hepatol, 2024, 30(3): 303-325.
[18] 魏海梁, 司明明, 郭辉, 等. 线粒体与肝细胞损伤的关系[J]. 临床肝胆病杂志, 2020, 36(3): 687-689.
[19] 潘萌, 史晓燕. 线粒体自噬在肝脏相关疾病发生发展中的作用[J]. 临床肝胆病杂志, 2024, 40(2): 413-418.
[20] Wang G. A more holistic view of the logarithmic dose-response curve offers greater insights into insulin responses[J]. J Biol Chem, 2025, 301(1): 108037.
[21] 郭海清, 李明亮, 刘峰, 等. 北京市体检人群代谢相关脂肪性肝病的患病率、影响因素和纤维化风险分层分析[J]. 临床肝胆病杂志, 2025, 41(4): 643-649.