abnormal nodules. Alcoholic cirrhosis is mostly
micronodular in type, with a size of nodules from
1 to 5 mm. Macronodules with a size ranging from
5 to 50 mm may occur, especially in the late phases of
the disease. The loss of normal liver architecture, with
separation of the portal tracts and the central zones of
the liver by septa of fibrotic tissue, results in alter-
ations of the vascular supply and a disturbance of the
intrahepatic blood circulation.
0016 Morbidity and mortality resulting from alcoholic
cirrhosis are related principally to the loss of liver cell
function, to derangements in the vascular system of
the liver, or to both. The onset of cirrhosis is often
insidious and associated with nonspecific symptoms
such as fatigue, anorexia, weight loss, nausea, and
abdominal discomfort. As the disease progresses,
signs of hepatocellular failure became prominent.
The most severe complications are iron overload,
hepatic encephalopathy, and portal hypertension
with ascites and bleeding from esophageal varices.
0017 In association with cirrhosis of the liver, hepatocel-
lular carcinoma may develop. The pathogenesis of the
carcinomatous transformation is still unclear, espe-
cially because these tumor forms may also occur in
noncirrhotic livers.
0018 Ethanol leads to a number of metabolic and struc-
tural alterations in the liver that predispose this organ
to derangements in its functional integrity. These are
as follows: an increase in the ratio of NADH (the
reduced form of nicotinamide adenine dinucleotide,
or NAD) to NAD; interactions of ethanol with lipid
and protein metabolism; stimulation of fibrosis with
deposition of collagen; inhibition of liver cell regener-
ation; humoral and cellular immunological alter-
ations; and excessive production of free radicals and
cytokines. Alcohol induces cell death and inflamma-
tion, which can result in scarring that distorts the
liver’s internal structure and impairs its function.
Acetaldehyde, the first oxidation product of ethanol
metabolism, may exert some toxic effects of its own
in liver tissue; it activates stellate cells directly and
promotes liver scarring in the absence of inflamma-
tion.
0019 All stages of liver injury can be produced in the
baboon fed high-protein and vitamin-supplemented
diets. This evidence suggests that toxic effects of
alcohol, and not malnutrition, are the principal
causes for the development of cirrhosis in chronic
alcoholics. But alcohol abuse establishes only the
conditions for the generation of cirrhotic lesions,
which require the addition of some independent
factors emerging over time.
0020 Abstinence from alcohol is the essential factor for
prevention and treatment of alcoholic cirrhosis. If
irreversible liver damage is already established, some
complications of cirrhosis can be alleviated by nutri-
tional treatment. Portal-systemic encephalopathy, for
example, often responds to an application of amino
acid mixtures, enriched with branched-chain amino
acids, whereas ascites responds favorably to sodium
restriction.
Wernicke’s Encephalopathy and
Korsakoff’s Syndrome
0021Wernicke’s encephalopathy and Korsakoff’s psych-
osis are diseases of the central nervous system (CNS)
secondary to alcoholism. They represent a continuum
of the same neuropathological process and develop in
about 2–3% of alcoholics. Wernicke’s disease is often
followed by Korsakoff’s syndrome. Severe alcoholics
may have both diseases, but some of them show
Korsakoff’s psychosis without preceding Wernicke’s
encephalopathy. Wernicke’s disease is an acute or
chronic encephalopathy with a triad of clinical abnor-
malities: ophthalmoplegia, ataxia, and mental con-
fusion. Korsakoff’s syndrome is a psychosis with
marked abnormalities in cognitive function: the car-
dinal symptoms are anterograde amnesia, disorien-
tation, learning deficits, and confabulations. The
relationship between the two diseases is not entirely
clear. The neuropathological changes seen in autopsy
materials of Wernicke–Korsakoff patients consist of
circumscribed, symmetrical lesions in the diencepha-
lon and brainstem. Most affected are the mammillary
bodies and the dorsomedial nuclei of the thalamus. In
acute cases the lesions are widespread and severe. In
chronic cases the lesions are more restricted and show
great variations in extent and severity within the
affected area. There are corresponding variations of
the clinical symptoms.
0022Extreme deficiency of thiamin, induced by malnu-
trition and interaction of ethanol with thiamin ab-
sorption and metabolism, is regarded as the primary
cause of this syndrome. Patients with Wernicke’s dis-
ease often have a high energy intake, consisting
mainly of ethanol and/or carbohydrates, without suf-
ficient protein and vitamins. Beyond that a direct
toxic effect of alcohol on the brain has also been
implicated. The Wernicke–Korsakoff’s disease is not
confined to alcoholism, but is also present in other
conditions associated with thiamin malnutrition, e.g.,
hyperemesis gravidarum, Hodgkin’s lymphoma, car-
cinoma of the stomach, and anorexia nervosa. Thia-
min application can reverse Wernicke’s syndrome in
many but not all patients, at least when administered
early in the course of the disease. In contrast, Korsak-
off’s patients often show poor response to thiamin
therapy. Additional factors, of as yet unknown origin,
seem to be necessary for the full development of
1326 CIRRHOSIS AND DISORDERS OF HIGH ALCOHOL CONSUMPTION