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As per the above studies, there is some epidemiological evidence for an inverse association between coffee consumption and liver cancer. The same may be the case for liver fibrosis and alcoholic cirrhosis. Clearly, a plausible biological mechanism is required to explain and confirm these associations.
The role of caffeine
Caffeine has been suggested as a key component in the observed associations between coffee consumption and a reduced risk of liver conditions 10,25,26,42,43. The precise mechanisms behind this effect are unclear, however a number of potential mechanisms have been proposed.
A number of papers have suggested that caffeine, and in particular its main primary metabolite, paraxanthine, can suppress the synthesis of CTGF (connective tissue growth factor) via a cascade of control cycles, thereby slowing down the growth of this type of tissue, which in turn slows down the progression of liver fibrosis, alcoholic cirrhosis and liver cancer9,25,26,42. However, some of the epidemiological studies did not find an association with tea, which suggests that the mechanism of action might be not dependent solely on caffeine (via paraxanthine).
It has also been suggested that caffeine may act via by blocking adenosine receptors, since the structure of caffeine mimics that of adenosine43, in turn inhibiting activation of liver cells.
However, it should be noted that caffeine may not be the most important component, as other caffeinated drinks do not appear to provide similar protection against liver disease41.
Other coffee constituents
A 2010 paper also mentions the potential role of the coffee components kahweol and cafestol in lowering the risk of liver cancer27. There is some evidence that they may have anti-carcinogenic properties27.
It has also been proposed that the polyphenols found in coffee, such as chlorogenic acid, may reduce oxidative stress in the liver, in turn reducing the risk of fibrosis and development of cancers43.
A further paper looks at the role of the chlorogenic acids and caffeic acid in coffee, which have been shown to be capable of preventing hepatitis B virus replication, both in vitro and in vivo41.
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