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Page 12 of 16 Teschke. Hepatoma Res 2019;5:40 I http://dx.doi.org/10.20517/2394-5079.2019.0017

for ALD as compared to alcoholic men [5,8,70,71] . In particular, women have more advanced liver disease at
time of diagnosis, experience a more severe clinical course within a shorter time of alcohol abuse, and had
[72]
consumed less alcohol compared to men , in line with a lower thresholds for development of alcoholic
liver injury [71,72] . This gender difference can be traced back to higher blood alcohol concentrations in
woman compared to men who consume the same amount of alcohol, resulting from a lower proportion of
[50]
body water in females than in males of equal body weight and from a lower ADH dependent first pass
[73]
metabolism in the gastric mucosa . Under discussion are also gender based differences in the sensitivity
[50]
of hepatic Kupffer cells to endotoxins generated in the gut .
Immune system
Little is firmly established related to specific immune reactions that could assist initiate and perpetuate
AHCC although immune involvement is most likely , as known from other tumors. Alcohol can modify
[7]
both, the innate immune system (IIS) and the adaptive immune system (AIS) [8,15] . More specifically, IIS is
promoted by macrophages, Kupffer cells, neutrophils, and natural killer cells, whereby macrophages are
prepared to attack antigens of bacterial cell walls and respond by providing cytokines.

Amount of alcohol
[7]
An excessive alcohol consumption is a risk factor not only of AC [7,15] but also for AHCC . For both stages
of ALD, a rough linear dose-response relationship between the amount of alcohol consumption and the
[7]
respective risk is assumed . For AHCC, an alcohol use expressed as absolute ethanol is risky at and above
> 60-100 g per day, that compares with an odd ratio of 4.52 if the total amount of alcohol consumption
during lifetime is considered.

Diagnosis of AHCC and surveillance programmes
As an inexpensive method readily available in clinical settings, ultrasound is commonly used to diagnose
AC and AHCC [74,75] . Ultrasound parameters for AC include liver size, bluntness of the edge, coarsened of
[74]
the liver parenchyma, nodularity of the liver surface, and spleen size , while data of liver stiffness could be
[5]
supportive . In search for AHCC, ultrasound technique has been improved by introducing the contrast-
[75]
enhanced ultrasound (CEUS), considered as a major diagnostic breakthrough . CEUS is unique in that
it allows non-invasive assessment of liver perfusion in real time throughout the vascular phase and may
abandon previous methods such as magnetic resonance or computer tomography images. Under imaging
guidance, tissue from the suspected HCC may be obtained to verify histologically the diagnosis.

In line with other causes of cirrhosis, periodic screening for AHCC is recommended for patients with
[59]
AC, who should be included in respective surveillance programmes , which offer screenings at intervals
of 6 months. This allows early detection of AHCC and implementation of curative procedures. However,
[76]
contradictory recommendations suggest surveillance by biannual ultrasound .

Prevention
Clinical medicine should focus primarily on prevention of AHCC for the sake of the patient at risk, the
human society, and financials of the health system. Overall prevention of AHCC is most successful if
alcohol abuse can early be stopped. First of all, if physicians suspect that a patient may have an alcohol
[53]
problem, specific questionnaires could help rule out or confirm the problem, as summarized recently . A
better and more objective approach would be doing just two laboratory tests in search for a serum quotient
AST/ALT that may be > 1.0 if an alcohol problem exists independently from a specific ALD stage including
already AFL . The ratio is significantly increased in patients with AH and AC (2.85 ± 0.2). This led to the
[15]
proposal that a serum AST/ALT ratio > 2.0 is highly suggestive of alcoholic hepatitis and cirrhosis [15,77] .
Values of the AST/ALT ratio have been published for patients with AFL (1.64 ± 1.57), as compared with
a corresponding control group consisting of individuals with normal liver histology and normal values
of AST and ALT, showing a lower AST/ALT ratio (0.72 ± 0.24) [15,78] . In search for individuals with severe
alcohol abuse, other laboratory data show variable percentages of sensitivity: carbohydrate-deficient