A new use for an old index: preoperative high-density lipoprotein predicts recurrence in patients with hepatocellular carcinoma after curative resections

Abstract

Background: Hepatocellular carcinoma has high incidence and mortality worldwide. Liver is the site of most metabolic biotransformation, which could reflect the status of cells. Most plasma apolipoproteins, endogenous lipids and lipoproteins are synthesized in the liver. Therefore, the effects of lipid metabolites on prognosis of HCC deserved to be explored.

Methods: We prospectively included 58 healthy donors (HD), 50 chronic hepatitis (CH) patients and a training cohort of 189 patients with HCC who underwent curative resections at Zhongshan Hospital from January 2012 to August 2012. We identified the optimal HDL_PO cutoff value at 0.98 mmol/L and used it to stratify patients into low- or high-HDL_PO groups for the entire cohort and four low-recurrent-risk subgroups. We also included an independent validation group of 182 HCC patients to validate this cutoff value. Prognostic values of HDL_PO and other factors were determined by Kaplan-Meier curves and the Cox proportional hazards model.

Results: The low-HDL_PO group had a higher median tumor grade (P = 0.020) and a higher recurrence rate (P = 0.032). Results of multivariate analysis showed that preoperative γ-glutamyl transpeptidase (GGT) and HDL_PO were independent predictors of recurrence. Moreover, the predictive value of HDL_PO was retained in four low-recurrent-risk subgroups. As expected, clinicopathologic characteristics and predictive values were similar in the validation and training cohorts.

Conclusions: HDL_PO is an accessible predictor of HCC recurrence after liver resections that can help identify patients who need more careful monitoring and follow-up care.

Keywords: HCC; HDL; Lipid metabolites; Prognosis.

Fig. 1

Lipid metabolites in different groups. Levels of total cholesterol (TC; a), triglycerides (TG; b), high-density lipoprotein (HDL; c) and low-density lipoprotein (LDL; d) in HCC patients,chronic hepatitis (CH) patients, and healthy donors (HD); and TG (e) as well as HDL (f) were analyzed in patients who suffered recurrences and those whose HCC did not recur

Fig. 2

Prognostic significance of HDL_PO in the training and validation cohorts. Kaplan–Meier analysis for time to recurrence (TTR) and overall survival (OS) for patients with low- vs high-HDL_PO in the training cohort (a, c) and the validation group (b, d)

Fig. 3

The predictive value of HDLPO shown in 4 low-risk subgroups in the training cohort. Kaplan–Meier analysis of TTR for HCC patients with negative AFP levels (a), ALT≤40 μg/L (b), with no satellite lesions (c), with encapsulated tumors (d), with BCLC stage 0 + A disease (e), and Child-Pugh A (f).

Fig. 4

The sourse and metabolism of HDL. The HDL mRNA level of tumor tissue and paratumor tissue (a); HDL concentration of HCC cell lines and normal live cell line (b)