Deng QY, Leng HQ, Wang TC, Hu C. Establishment and validation of an intratumoral fibrosis-based nomogram for predicting aggressive recurrence after liver resection in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(5): 116135 [DOI: 10.4240/wjgs.v18.i5.116135]
Corresponding Author of This Article
Chao Hu, Department of Radiology, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. huchao0101@csu.edu.cn
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Gastroenterology & Hepatology
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research-article
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Deng QY, Leng HQ, Wang TC, Hu C. Establishment and validation of an intratumoral fibrosis-based nomogram for predicting aggressive recurrence after liver resection in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(5): 116135 [DOI: 10.4240/wjgs.v18.i5.116135]
World J Gastrointest Surg. May 27, 2026; 18(5): 116135 Published online May 27, 2026. doi: 10.4240/wjgs.v18.i5.116135
Establishment and validation of an intratumoral fibrosis-based nomogram for predicting aggressive recurrence after liver resection in hepatocellular carcinoma
Qi-Yuan Deng, Hao-Qun Leng, Tian-Cheng Wang, Chao Hu
Qi-Yuan Deng, Hao-Qun Leng, Tian-Cheng Wang, Chao Hu, Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Co-first authors: Qi-Yuan Deng and Hao-Qun Leng.
Author contributions: Deng QY and Leng HQ wrote the manuscript, reviewed and analyzed the patients’ clinical data and contributed equally to this article as co-first authors of this manuscript; Deng QY and Wang TC reviewed the histological slides; Deng QY, Leng HQ, and Wang TC collected and provided the patients’ clinical information; Hu C edited and revised the manuscript; Hu C was the main contributor and is the guarantor of this work; All authors read and approved the final manuscript.
Supported by the Hunan Provincial Natural Science Youth Fund Project, No. 2023JJ40824.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the Second Xiangya Hospital of Central South University, approval No. Z0633-01.
Informed consent statement: The informed consent was waived by the Institutional Review Board.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The patient-derived datasets generated during this study are not publicly available due to patient privacy restrictions but are accessible from the corresponding author upon reasonable request. The underlying code for this study is available in a public GitHub repository (https://github.com).
Corresponding author: Chao Hu, Department of Radiology, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. huchao0101@csu.edu.cn
Received: November 4, 2025 Revised: January 10, 2026 Accepted: March 4, 2026 Published online: May 27, 2026 Processing time: 205 Days and 6.3 Hours
Abstract
BACKGROUND
Aggressive recurrence after liver resection (LRE) in hepatocellular carcinoma (HCC) is associated with unfavorable clinical outcomes. Intratumoral fibrosis (ITF) is mechanistically associated with aggressive recurrence, promoting immunosuppression, angiogenesis, and matrix stiffening, thereby supporting its potential as a predictive biomarker.
AIM
To develop and validate a competing risk nomogram incorporating ITF to predict aggressive HCC recurrence after LRE.
METHODS
This study included untreated patients with solitary HCC tumors from two retrospective datasets spanning August 2013 to November 2023. Patients were stratified into high-ITF (score ≥ 2) and low-ITF (score < 2) groups based on a semiquantitative Sirius red staining scale of 0-3. The cumulative incidence of aggressive recurrence, recurrence-free survival, and overall survival were compared between the groups. Variables associated with aggressive recurrence were identified using Fine-Gray regression analysis and incorporated into a predictive nomogram. The model performance was assessed in terms of calibration, discrimination, and clinical utility of the model.
RESULTS
A significant correlation was identified between ITF and aggressive recurrence. Multivariate Fine-Gray analysis revealed that preoperative neutrophil count, tumor size, ITF, and microvascular invasion were independent predictors of aggressive recurrence. A competing risk nomogram was developed to estimate the risk of aggressive recurrence after LRE in patients with HCC. The predictive nomogram demonstrated strong discrimination and calibration with concordance indices of 0.799 [95% confidence interval (CI): 0.770-0.830] and 0.779 (95%CI: 0.703-0.848), and areas under the receiver operating characteristic curves at 2 years of 0.850 (95%CI: 0.816-0.884) and 0.842 (95%CI: 0.765-0.919) in the training and validation cohorts, respectively.
CONCLUSION
ITF is a predictive marker of aggressive recurrence after LRE in patients with HCC. A nomogram integrating ITF with other clinical factors demonstrated robust efficacy in predicting aggressive recurrence.
Core Tip: Accurate risk stratification for aggressive recurrence is essential in patients with hepatocellular carcinoma undergoing liver resection. In this multicenter study we identified intratumoral fibrosis as a novel independent histopathological predictor of aggressive recurrence. We developed a competing risk nomogram by integrating intratumoral fibrosis with key clinical variables to provide individualized risk estimation. The model demonstrated robust performance across independent cohorts, offering a validated tool for improved postoperative prognostic stratification.
