Introduction

Over 2 billion people worldwide are obese. There is strong evidence of an association between obesity and hepatocellular (HCC) cancer.This effect is mediated through an abnormal production of adipose-derived adipocytokines (leptin and adiponectin). In-situ leptin has been shown to accelerate HCC growth and dissemination and adiponectin has been shown to oppose its effects.

Orthotopic liver transplant (OLT) represents a potentially curative procedure for HCC patients. However, no data are currently available on the mechanistic role of leptin, adiponectin and other adipocytokines on oncologic outcomes of HCC patients undergoing OLT.

Hypothesis

We hypothesize that obese patients with HCC undergoing OLT have higher levels of leptin and lower adiponectin and this correlates with increased tumor grade, and recurrence than non-obese patients.

Methods

Between January 2011-May 2015 60 HCC+OLT patients were prospectively enrolled into a cohort study of patients with a BMI<25 and BMI≥25. We collected serum prior to transplant. Serum samples were analyzed for leptin, adiponectin, IL-6, TNF-alpha, IL-8, IP-10, VEGF, and HGF. These biomarkers were correlated with outcome variables including HCC recurrence and explant pathology. Statistics were analyzed using Sigmastat software.

Results

Median age of all patients was 59years and 75% were male. Etiology was 81.7% HCV; 11.7% HBV; 3.3% NAFLD; 3.3% Cryptogenic. Mean lab MELD was 16. No differences were noted in etiology or MELD across spectrum of BMI.

Conclusions

These data show that in patients within Milan criteria obesity is associated with poorer tumor grade on explant pathology and an increased recurrence. Furthermore, this effect is mechanistically caused by elevated pro-tumorogenic leptin and attenuated adiponectin production in obesity. Therefore, we propose that adipocytokines are a meaningful prognostic biomarker in patients with HCC and further studies need to be done to evaluate their potential role in the appropriate allocation of precious donor livers.

CITATION INFORMATION: Mathur A, Presbyskowski E, Carpenter D, Zorn E, Guarrera J, Samstein B, Griesemer A, Halazun K, Veras Y, Tomoaki K, Emond J. Dysfunctional Production of Adipocytokines in Obesity Results in Inferior Oncologic Outcomes from Hepatocellular Carcinoma Following Liver Transplantation. Am J Transplant. 2016;16 (suppl 3).

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