prospective multicenter validation of preoperative plasma ceramides as novel predictive biomarkers for clinically relevant post-hepatectomy liver failure

Hanbiao Liang; Haiqing Liu; Jieyuan Li; Biao Wang; Pengxiang Huang; Weiyi Guo; Baoxiong Zhuang; Leyi Liao; Qingping Li; Xianqiu Wu; Tianzhou Peng; Zhanhong Lai; Shanhua Tang; Bijuan Zhu; Jing Gao; Shaokui Lin; Can Huang; Cuiting Liu; Minghui Zeng; Jianping Qian; Qifan Zhang; Jie Zhou; Xuesong Deng; Chuanjiang Li; Kai Wang

doi:10.1097/JS9.0000000000002791

prospective multicenter validation of preoperative plasma ceramides as novel predictive biomarkers for clinically relevant post-hepatectomy liver failure

Int J Surg. 2025 Jun 24. doi: 10.1097/JS9.0000000000002791. Online ahead of print.

Authors

Hanbiao Liang^{1

2}, Haiqing Liu¹, Jieyuan Li³, Biao Wang¹, Pengxiang Huang^{1

4}, Weiyi Guo⁵, Baoxiong Zhuang⁶, Leyi Liao¹, Qingping Li¹, Xianqiu Wu¹, Tianzhou Peng¹, Zhanhong Lai¹, Shanhua Tang¹, Bijuan Zhu¹, Jing Gao¹, Shaokui Lin¹, Can Huang¹, Cuiting Liu⁷, Minghui Zeng⁸, Jianping Qian¹, Qifan Zhang¹, Jie Zhou¹, Xuesong Deng⁹, Chuanjiang Li¹, Kai Wang¹

Affiliations

¹ Department of General Surgery, Division of Hepatobiliopancreatic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
² Department of General Surgery, Binhaiwan Central Hospital of Dongguan, (The Fifth People's Hospital of Dongguan), Dongguan, Guangdong, China.
³ Department of Hepatobiliary Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
⁴ Department of Hepatobiliary Surgery, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China.
⁵ Department of Gastroenterology, Dongguan People's Hospital, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China.
⁶ Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
⁷ Central Laboratory, Southern Medical University, Guangzhou, Guangdong, China.
⁸ Institute of Scientific Research, Southern Medical University, Guangzhou, China.
⁹ Department of Hepatobiliary Surgery, the First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

PMID: 40557443
DOI: 10.1097/JS9.0000000000002791

Abstract

Background: Circulating ceramides (CERs) are associated with liver diseases and dysfunction. The utility of plasma CERs in predicting post-hepatectomy liver failure (PHLF) remains unclear. This study aimed to evaluate the clinical utility of preoperative plasma CERs for predicting clinically relevant PHLF (CR-PHLF).

Methods: This study included 736 patients who underwent hepatectomy across four independent hospitals in China. The training set included 392 patients from 2019 to 2021, and the prospective internal and external validation sets included 195 patients from 2022 to 2024 and 149 patients from 2023 to 2025, respectively. Preoperative plasma CERs were measured using targeted lipidomics. Grade B/C PHLF was classified by the criteria of the International Study Group of Liver Surgery and defined as CR-PHLF. Predictors for CR-PHLF were identified by least absolute shrinkage and selection operator (LASSO) logistic regression and receiver operating characteristic (ROC) analysis. The study is registered on ClinicalTrials.gov (NCT********) and the Research Registry (******).

Results: Plasma CER(d18:1/20:1) demonstrated a positive correlation with preoperative liver dysfunction and superior predictive power for CR-PHLF, with an AUROC of 0.837 (95% CI: 0.782-0.892; P < 0.001). Major hepatectomy, direct bilirubin, and CER(d18:1/20:1) were identified as independent PHLF predictors and integrated into an innovative CR-PHLF prediction model (Hpx-CER model). The model exhibited commendable discrimination in the training set (AUROC = 0.896; 95% CI: 0.851-0.941; P < 0.001), and the prospective internal (AUROC = 0.907; 95% CI: 0.845-0.970; P < 0.001) and external validation sets (AUROC = 0.862; 95% CI: 0.707-1.000; P < 0.001). Across all high-risk subgroups of CR-PHLF, including major hepatectomy, difficult hepatectomy, cirrhosis, malignant liver diseases, and preoperative liver dysfunction, our model consistently outperformed conventional models in predicting CR-PHLF.

Conclusion: Plasma CER(d18:1/20:1) is a novel predictor of CR-PHLF. The Hpx-CER model performs commendably in predicting CR-PHLF and provides reliable preoperative risk estimations.

Keywords: biomarker; ceramides; nomogram; post-hepatectomy liver failure.