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Page 2 of 16 Teschke. Hepatoma Res 2019;5:40 I http://dx.doi.org/10.20517/2394-5079.2019.0017

INTRODUCTION
The WHO considers cancer as the second leading cause of death globally, responsible for an estimated
[1]
9.6 million deaths in 2018, attributing about 1 in 6 deaths to cancer . More specifically, the most common
causes of cancer death are cancers of lung (1.76 million deaths), colon including rectum (862,000 deaths),
stomach (783,000 deaths), liver (782,000 deaths), and breast (627,000 deaths), whereby around one third
of deaths from cancer can be traced back to the 5 leading behavioral and dietary risks: high body mass
[1]
index, low fruit and vegetable intake, lack of physical activity, tobacco use, and alcohol use . Consequently,
identifying the cause of liver cancer or more specifically primary hepatocellular carcinoma (HCC) in a
[2-7]
patient with this type of cancer can be challenging and is variable among different countries or regions .
This article discusses current aspects of primary alcoholic hepatocellular carcinoma (AHCC) with focus on
potential mechanistic steps and risk factors closely related to alcohol metabolism, reactive oxygen species
(ROS), and the gut-liver axis in the context of the intestinal microbiome. In addition, clinical aspects with
diagnostic approaches and therapy options including the controversially disputed liver transplantation will
be considered.

LITERATURE SEARCH AND SOURCE
The PubMed database was used to identify publications for the following terms: alcohol, ethanol, DNA,
ROS, alcoholic liver injury, and alcoholic hepatocellular carcinoma. Terms were used alone or combined.
Limited to the English language, publications of the first 50 hits from each searched segment were
analyzed for suitability of this review article. Publications were also derived from the large private archive.
The search for publications was completed on 4 October 2019. The final compilation consisted of original
papers, consensus reports, and review articles. The most relevant publications were included in the
reference list of this review.

ALCOHOL AS CHEMICAL
Ethanol is a short length chemical and a synonym to the term alcohol that is commonly used in a clinical
setting. In the human gastrointestinal tract, alcohol can be produced from sugar with the help of intestinal
bacteria and commonly undergoes rapid degradation by ubiquitous enzymes, for which alcohol serves as
natural endogenous substrate keeping the respective enzymes active at low levels and prepared for larger
amounts of exogenous alcohol eventually consumed as alcoholic beverage. Endogenous ethanol may be of
clinical interest as “auto-brewery syndrome”, a drunk-driving defence challenge [8-10] , with details provided
in a case control study .
[10]

Clearly, alcohol is otherwise a product found in beverages such as wine prepared from the sugar containing
grapes with the help of baker’s yeast alcohol dehydrogenase (ADH) [11,12] . Interestingly, a different ADH type
is also present in humans and partly involved when the alcohol consumed as beverage is oxidized in the
[13]
human gastrointestinal tract and the liver [8,14,15] .

ALCOHOL AND ACETALDEHYDE OXIDATION IN THE LIVER
After drinking of alcoholic beverages, alcohol is quickly taken up by the mucosa of the upper
[16]
gastrointestinal tract , as evidenced by the prompt appearance in the blood with higher blood alcohol
levels if the alcoholic beverage was consumed before a meal as long as the stomach is empty, as compared to
[17]
lower blood alcohol levels found if the alcohol is consumed during or right after a meal . As an exogenous
compound lacking an option of storage within any organ, alcohol must be removed for which several
[16]
possibilities exist . Whereas only small amounts of the ingested alcohol leave the body by exhalation or
with the urine, most of the alcohol must undergo enzymatic degradation in the liver [4,5,8,14-18] . The human