About coffee, cappuccino and connective tissue growth factor-Or how to protect your liver!?

Several epidemiological studies suggest that coffee drinking is inversely correlated with the risk of development of liver fibrosis. However, a causal, mechanistic explanation has long been pending. New results indicate that the methylxanthine caffeine, major component of coffee and the most widely consumed pharmacologically active substance in the world, might be responsible for this phenomenon as it, and even more potently its derived primary metabolite paraxanthine, inhibits transforming growth factor (TGF)-β-dependent and -independent synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal cells in vitro and in vivo. CTGF plays a crucial role in the fibrotic remodeling of various organs which has therefore frequently been proposed as therapeutic target in the management of fibrotic disorders. This article summarizes the clinical-epidemiological observations as well as the pathophysiological background of the antifibrotic effects of coffee consumption and provides suggestions for the therapeutic use of caffeine and its derived metabolic methylxanthines as potentially powerful drugs in patients with chronic fibrogenic liver disease by their inhibitory effect on (hepatocellular) CTGF synthesis.