Rethinking Liver Fibrosis Staging in Patients with Hepatocellular Carcinoma: New Insights from a Large Two-Center Cohort Study

Abstract

Background

Hepatocellular carcinoma (HCC) is a prevalent and aggressive malignancy closely related to background chronic liver disease. This study aimed to explore predictive factors associated with background liver fibrosis burden in patients with HCC and sought to construct a practical predictive model for clinical use.

Methods

This large two-center retrospective cohort study evaluated data from Chinese medical centers. Uni- and multivariate ordinal logistic regression analyses were performed to identify variables associated with liver fibrosis stages. Predictive models based on variables identified by multivariate analysis were established in the Derivation Cohort and subjected to internal and external validation. Model performance was evaluated for discriminative and calibration abilities.

Results

Multivariate ordinal logistic regression analysis identified liver fibrosis severity score (LFSS), portal hypertension (PH) severity, plateletcrit (PCT) and model for end-stage liver disease-sodium (MELD-Na) as independent predictors of liver fibrosis stage in HCC patients. Nomograms that integrated these factors disclosed that the area under receiver operating characteristic curves (AUROCs) to predict S1 in the Derivation and External Validation cohorts were 0.850 and 0.919, respectively. Internal validation disclosed C-indexes of 0.823 and 0.833 in the Derivation and External Validation cohorts, respectively, indicating that the nomogram had good and excellent performance for distinguishing between S1 and non-S1 patients. Nomogram performance in the Derivation and External Validation cohorts, respectively, was fair and good to predict stage S2 (AUROCs 0.726, 0.806; C-indexes 0.713, 0.791); poor for S3 (AUROCs 0.648, 0.698; C-indexes 0.616, 0.666); good for S4 (AUROCs 0.812, 0.824; C-indexes 0.804, 0.792); and good for S3+S4 (AUROCs 0.806, 0.840; C-indexes 0.795, 0.811).

Conclusion

We propose new predictive models for the staging of background liver fibrosis in patients with HCC that can be implemented into clinical practice as important complements to hepatic imaging to inform HCC management strategy.

Keywords:

• hepatocellular carcinoma
• liver fibrosis
• portal hypertension
• MELD-Na
• plateletcrit

Data Sharing Statement

All data relevant to the study are included in the article or uploaded as Supplementary Information. The associated data are available from the corresponding authors, Wei Xu and Jingdong Li, upon reasonable request. The associated data are not publicly available due to privacy and ethical restrictions.

Ethics Approval and Consent to Participate

This study was reviewed and approved by the Institutional Review Board of Hunan Provincial People’s Hospital (The First Hospital Affiliated with Hunan Normal University; approval no. 2021-045) and Affiliated Hospital of North Sichuan Medical College (approval no. 2021-015). The informed written consent requirement was waived in view of the retrospective study design; patient privacy was ensured, and the data were anonymized or maintained with confidentiality.

Disclosure

The authors declare that they have no conflicts of interests.

Additional information

Funding

This study was funded by the Health Commission (project no. 20200074) and Education Department (project no. 20A313) of Hunan Province.