Increased levels of serum leptin are a risk factor for the recurrence of stage I/II hepatocellular carcinoma after curative treatment

Abstract

Obesity and related adipocytokine disbalance increase the risk of hepatocellular carcinoma. To determine the impact of increased levels of leptin, an obesity-related adipocytokine, on the recurrence of hepatocellular carcinoma, we conducted a prospective case-series analysis. Eighty-five consecutive primary hepatocellular carcinoma patients at our hospital from January 2006 to December 2008 were analyzed. Serum leptin level significantly correlated with Body Mass Index, total body fat, and the amount of subcutaneous fat. They included 33 with stage I/II, who underwent curative treatment. The factors contributing to recurrence of hepatocellular carcinoma, including leptin, were subjected to univariate and multivariate analyses using the Cox proportional hazards model. Body Mass Index (p = 0.0062), total body fat (p = 0.0404), albumin (p = 0.0210), α-fetoprotein (p = 0.0365), and leptin (p = 0.0003) were significantly associated with the recurrence of hepatocellular carcinoma in univariate analysis. Multivariate analysis suggested that leptin (hazard ratio 1.25, 95% CI 1.07-1.49, p = 0.0035) was a sole independent predictor. Kaplan-Meier analysis showed that recurrence-free survival was lower in patients with greater serum leptin concentrations (>5 ng/mL, p = 0.0221). These results suggest that the serum leptin level is a useful biomarker for predicting the early recurrence of hepatocellular carcinoma.

Keywords: carcinogenesis; hepatocellular carcinoma; insulin resistance; leptin; obesity.

Fig. 1

Correlation between the serum levels of leptin and (a) BMI, (b) total body fat, (c) amount of visceral fat, and (d) amount of subcutaneous fat in patients with HCC (n = 85). For BMI analysis, we excluded 7 patients with CT-detected ascites.

Fig. 2

Kaplan-Meier curves for recurrence-free survival in (a) total patients and in (b) subgroups divided on the basis of the serum leptin concentration (≤5 or >5 ng/mL).