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Page 2 of 6 Carvalho et al. Hepatoma Res 2020;6:6 I http://dx.doi.org/10.20517/2394-5079.2019.027

Coffee is one of the most consumed beverages in the world. Coffee consists of several components, such as
caffeine, triacylglycerol, tocopherols, chlorogenic acid, cafestol, and kahweol, with relevant antioxidant and
anti-inflammatory properties. Because of their biological properties, these substances can have beneficial
[4]
effects on metabolism .
For many years, coffee intake has been related to adverse effects, mainly cardiovascular, but recent studies
show that daily coffee consumption, in addition to being harmful, can be beneficial and protective, especially
against the development of chronic liver diseases such as HCC. This protection seems to be associated with
[5]
the habit and frequency of coffee consumption .

As most studies on this subject have been observational, the mechanisms of coffee protection against various
diseases remain uncertain. However, some hypotheses have been suggested: polyphenols, antioxidants
[6]
found in coffee, may protect cells against oxidative stress and damage to DNA molecules . The protection
conferred by coffee is believed to occur through antioxidant components, which would influence the lower
liver enzymatic activity. Gamma-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) in
[7]
these studies showed lower serum levels in coffee drinkers versus nondrinkers .
The importance of hepatocarcinogenic pathways for the development of HCC has also been discussed, and
molecular mechanisms that generate liver aggression and metabolic changes in hepatocytes related mainly to
oxidative stress have been observed. The accumulation of several oxidative metabolites directly attacks DNA
molecules or makes the general functioning of the cell unfeasible, generating apoptosis. Thus, it is observed
that the protective mechanisms of substances present in coffee antagonize the hepatic carcinogenic pathways,
which theoretically supports the findings of coffee consumption as a protector of the liver.

Even with the accumulation of evidence in favor of coffee consumption, its dietary prescription remains
controversial. It is estimated that 36% of health professionals still believe that coffee consumption increases
the risk of cancer. Thus, research that reinforces the benefits of coffee is still needed, especially when the
[8]
outcomes are more impactful and chronic, such as the incidence of hepatocellular carcinoma .

This literature review aims to evaluate the role of coffee consumption in protecting against the development
of HCC.

METHODOLOGY
Scientific articles indexed through PubMed, including Medline, SciELO, and Lilacs, published in English
were used as search methods.

The terms used in English were: “hepatocellular carcinoma” or “liver cancer” or “HCC and “coffee”.
According to the study design or review article, cross-sectional, longitudinal, or descriptive investigations
were included, showing site and year of publication until 2019.

This literature review included articles that evaluated the role of coffee consumption in protecting against
the development of HCC and included the following topics: HCC pathogenesis; caffeine and HCC; amount
of coffee consumed and protective effect on hepatocarcinogenesis; impact of coffee consumption on HCC
mortality; and coffee consumption and recurrence of HCC after liver transplantation.

HCC PATHOGENESIS
The pathogenesis of HCC is multifactorial, which initially includes an inflammatory process mediated
by Kupffer cells in the liver or macrophages, which stimulate the production of proinflammatory