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Subgroup-Specific Nomogram for Refined Risk Stratification in Hepatocellular Carcinoma Patients with Low LDL-C.

Bojun Liu¹, Zhixia Gu^2,3,4,5, Ling Li⁶

¹Hepatic Disease and Oncology Minimally Invasive Interventional Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.

Journal of Hepatocellular Carcinoma

|June 22, 2026

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Lowering low-density lipoprotein cholesterol (LDL-C) is linked to worse survival in hepatocellular carcinoma (HCC) patients. A new nomogram aids in personalized risk stratification for this high-risk group.

Area of Science:

Oncology
Cardiovascular Research
Biostatistics

Background:

Hepatocellular carcinoma (HCC) presents significant mortality and clinical variability.
Low low-density lipoprotein cholesterol (LDL-C) is a known risk factor for HCC, but its precise impact on overall survival (OS) and effective risk stratification strategies remain underexplored.
Current prognostic models lack the specificity needed for precise risk assessment in HCC patients with low LDL-C levels.

Purpose of the Study:

To investigate the continuous dose-response relationship between LDL-C levels and OS in HCC patients.
To develop and validate a precise prognostic model for secondary risk stratification in high-risk HCC patients with low LDL-C.

Main Methods:

Retrospective analysis of 486 HCC patients.

Keywords:

HCC LDL-C hepatocellular carcinoma low-density lipoprotein cholesterol nomogram os overall survival risk stratification

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Restricted cubic splines (RCS) and Cox regression to assess the LDL-C and OS relationship.

Development of a subgroup-specific nomogram using LASSO regression, validated with C-index, ROC curves, calibration, DCA, and KM curves.

Main Results:

A non-linear relationship was observed, with mortality risk increasing as LDL-C dropped below 2.2 mmol/L.
Lower baseline LDL-C was confirmed as an independent predictor of worse OS (HR=0.714, P=0.019).
The developed nomogram demonstrated good discrimination (C-index=0.686) and clinical utility for secondary risk stratification within the low LDL-C subgroup (P<0.0001).

Conclusions:

Reduced baseline LDL-C independently predicts poorer overall survival in HCC patients.
The novel subgroup-specific nomogram offers an objective tool for enhanced risk stratification, facilitating personalized treatment strategies for high-risk HCC populations.