Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis

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 a major factor of hazard reduction in a multivariate analysis (HR = 0.29, 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.Georg Wiltberger and Yan Wu share first authorship. Simon Robson and Moritz Schmelzle share senior authorship.

Identifying Potential Prognostic Biomarkers Associated With Clinicopathologic Characteristics of Hepatocellular Carcinoma by Bioinformatics Analysis

“…Delia Hoffmann group have identified the expression of Tryptophan 2,3-Dioxygenase expression in human hepatocellular carcinoma cells, which indicated that TDO might be an immunotherapeutic target in hepatocellular carcinoma [28]. Besides, caffeine has shown tumouricidal activity in HCC cells and was associated with decreased risk of HCC recurrence [29]. Quinone oxidoreductase1 (NQO1) transcription might be inhibited by promoter hypermethylation in HCC, which might be involved in HCC pathogenesis [30].…”

Effects of Caffeine Treatment on Hepatopulmonary Syndrome in Biliary Cirrhotic Rats

“…The coffee or caffeine consumption has many other effects on the liver and lung. We summarize these emerging findings in the Table 2 [6,28,29,30,31,32,33,34,35,36,37,38,39,40,41] and Table 3 [24,26,42,43,44,45,46,47,48,49,50].…”

Progress in Phytochemical and Bioactivities of Coffea arabica L.

“…Ratanamarno et al [5] reported that catechin (C, 6), epicatechin (EC, 7), epicatechin gallate (ECG, 8) and epigallocatechin gallate (EGCG, 9) in fresh C. arabica L. leaves. Chen et al identified delphinidin 3,5-diglucoside (10) and delphinidin 3-(6"-malonyl-glucoside) (11) in the young leaves of C. arabica L. [6] Besides the above mentioned constituents, flavonoids and their glycosides were also isolated from the leaves of C. arabica L., which were named as cyanidin-3-O-Glu (12), cyanidin-3-O-rutinoside (13), kaempferol (14), kaempferol-3-O-Glc (15), kaempferol-3-O-Glc-Hex-DeHex (16), kaempferol-3-O-Glc-Hex (17), kaempferol-3-O-Glc-(6''-Rha) (18), quercetin (19), quercitrin (20), isoquercitrin (21), rutin (22), hyperoside (23), quercetin-3-O-Glc-Hex-DeHex (24), quercetin-3-O-Glu (25), luteolin (26), patuletin (27), fisetin (28), myricetin (29) and apigenin (30). [6][7][8][9] Their structures are shown in Figure 2.…”

“…Ginsenoside Rb1 and trigonelline could prevent the development of diabetic renal lesions by regulating the expression of miR-3550 and further associating with the Wnt/β-catenin signaling. [24] Live protection activity Wiltberger et al [25] reported that coffee consumption is associated with a decreased risk of hepatocellular carcinoma recurrence and provides for increased survival following orthotopic liver transplantation. Multivariate analysis showed that coffee intake emerged as a major factor of hazard reduction for overall survival postoperative.…”