Georg Wiltberger1, Yan Wu2, Undine Lange3, Hans-Michael Hau3, Elliot Tapper2, Felix Krenzien4, Georgi Atanasov4, Christian Benzing4, Linda Feldbrügge4, Eva Csizmadia2, Johannes Broschewitz2, Michael Bartels5, Daniel Seehofer2, Sven Jonas6, Thomas Berg7, Phillip Hessel8, Rudi Ascherl9, Ulf P Neumann1, Johann Pratschke4, Simon C Robson2, Moritz Schmelzle4. 1. Department of General, Visceral, and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany. 2. Liver Center and The Transplant Institute, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 3. Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. 4. Departmentof Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany. 5. Department of General- and Visceral surgery, Helios Clinic Leipzig, Leipzig, Germany. 6. Department of Hepato-, Pancreato- and Biliary Surgery, 310Klinik Nürnberg, Nuremberg, Germany. 7. Section of Hepatology, Department of Internal Medicine, Neurology, Dermatology, University Hospital Leipzig, Leipzig, Germany. 8. Center for Population and Development Studies, Harvard University, Cambridge, Massachusetts. 9. Hospital for Children and Adolescents, University Hospital Leipzig, Leipzig, Germany.
Abstract
BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.
BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.
Authors: Safak Gül-Klein; Anika Kästner; Philipp Konstantin Haber; Felix Krenzien; Simon Wabitsch; Alexander Krannich; Andreas Andreou; Dennis Eurich; Frank Tacke; David Horst; Johann Pratschke; Moritz Schmelzle Journal: J Hepatocell Carcinoma Date: 2021-03-18