SAN FRANCISCO, CA—Coffee consumption might reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve survival following orthotopic liver transplantation (OLT), suggest study findings reported at the The Liver Meeting® 2015.  

“Coffee consumption appears associated with a decreased risk of tumor recurrence and improved survival following OLT for HCC,” concluded lead study author Georg Wiltberger, MD, of the Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, in Leipzig, Germany, and colleagues. 

“Experimental data suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects in HCC cells,” reported Dr. Wiltberger. “Our findings might have implications for future recommendations for HCC patients after OLT.”

There is “increasing evidence” suggesting that coffee consumption might decrease liver cirrhosis mortality and the risk for HCC, he noted. “Caffeine is a competitive antagonist at adenosine receptors.”

To determine if coffee consumption decreases HCC recurrence or affects survival, the research team interviewed a total of 90 patients and close relatives of patients who had undergone OLT for histologically-confirmed HCC between 2002 and 2012, to learn the number of cups of coffee consumed daily before and after liver transplantation. Then patients’ self-reported coffee-consumption data were analyzed alongside HCC recurrence and survival outcomes.

Separately, to study the possible mechanisms involving coffee consumption interactions with HCC cells, the authors conducted in vitro analyses of HepG2 HCC cell expression of adenosine receptors and ectoenzymes, and cells were treated with adenosine “in the presence or absence of 8-(3-Chlorostyryl)-caffeine (CSC) or alloxazine, followed by analyses of proliferation, metastasis and alterations in key adenosine-mediated cancer pathways inclusive of MAPK (ERK and JNK) and NF-kappa B.”

The team found that patients with high coffee intake experienced lower rates of HCC recurrence. 

“In patients with a high preoperative or postoperative coffee intake (more than 3 cups), HCC recurrence was observed less frequently when compared to those with low coffee intake (P=0.018),” Dr. Wiltberger reported. 

In multivariate analysis, only postoperative consumption of ≥3 cups of coffee daily was independently associated with recurrence-free survival.

“HepG2 cells express abundant levels of A2A and A2B as well as several key ectoenzymes, including ENTPD3, ENTPD5, ENTPD8, CD73, and adenosine deaminase 1 (ADA1),” Dr. Wiltberger reported. “These cells show intrinsic capacity to generate extracellular adenosine.”

Exogenous adenosine promoted HCC cell growth and metastasis in vitro, an effect that was halted by CSC but not alloxazine, he noted. “Moreover, adenosine induces activation of MAPK (ERK and JNK) and NF-kappaB pathways, which can be prevented by antagonism of A2A and A2B receptors,” he noted.