Z Gastroenterol 2016; 54 - KV290
DOI: 10.1055/s-0036-1587066

Coffee consumption promotes survival and protects against hepatocellular carcinoma recurrence following liver transplantation: putative mechanisms involve modulation of adenosinergic signalling

G Wiltberger 1, R Maio 2, U Lange 1, R Ascherl 1, HM Hau 1, F Krenzien 3, G Atanasov 3, C Benzing 3, E Tapper 2, L Feldbrügge 2, J Broschewitz 1, M Bartels 1, S Jonas 4, J Pratschke 3, Y Wu 2, S Robson 2, M Schmelzle 3
  • 1Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig, Deutschland
  • 2Liver Center and The Transplant Institute, Div. of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
  • 3Departmentof General, Visceral, and Transplant Surgery, Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Deutschland
  • 4Department of Hepato-, Pancreato- and Biliary Surgery, 310Klinik, Nürnberg, Deutschland

Background: Increasing evidence suggests that coffee consumption might be associated with hepatocellular carcinoma (HCC) and liver cirrhosis death risk. Caffeine is a natural antagonist to extracellular adenosine-mediated receptor signaling with proposed tumoricidal activity in experimental settings.

Aim: To determine whether coffee consumption decreases HCC recurrence and promotes survival following orthotopic liver transplantation (OLT) and to examine putative mechanisms of action.

Methods: Patients who underwent OLT for HCC from January 2002 to December 2012 were interviewed on consumed cups of coffee per day before and after OLT. Coffee consumption was correlated with HCC recurrence and survival. For mechanistic studies in vitro, human HepG2 cells were analysed for expression of adenosine receptors and ectoenzymes. Cells were treated with adenosine, in the presence or absence of receptor antagonists.

Results: 90 patients with a median age of 60 years (range 73 – 37) underwent OLT for histologically confirmed HCC. 16 (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1 – 40.5) post-transplant. In patients with a high preoperative or postoperative coffee (≥3 cups per day) intake HCC recurrence was observed less frequently than in those with low coffee (less than ≤2 cups per day)intake (p = 0.018). In a multivariate Cox' proportional hazard model for those who consume no less than 3 cups daily may have a better chance of recurrence-free survival than those who do not drink coffee at all. HepG2 cells express abundant levels of A2A and A2B as well as several key ectoenzymes. These cells show intrinsic capacity to generate extracellular adenosine. Exogenous adenosine promotes HCC cell growth and metastasis in vitro, which is blocked by CSC, but not by alloxazine.

Conclusions: Coffee consumption is associated with a decreased risk of HCC recurrence and increased survival following OLT. Experimental data suggest that these results might be, at least in parts, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects in HCC cells. Our findings have implications for future recommendations for HCC patients after OLT.