3.3.3.

Alcoholic Liver Disease

Definition
Alcoholic liver disease is a group of structural and functional
liver resulting from excessive alcohol
changes in the
consumption.
rate of liver injury depend on the amount of alcohol
The severity and progression
consumed and duration of
excessive drinking.
Pharmacotherapy of Diseases-II (Chapter 3)
91

Stages
1) Alcoholic Fatty Lver: lt is the initial and mildest form caused by prolonged
consumption of small amounts of alcohol (more than one alcoholic drink [14
grams of alcohol] per day for women and two alcoholic drinks [28 grams of
alcohol) per day for men). In liver, fat (triglycerides) is deposited by
increased lipogenesis, decreased fatty acid oxidation, fat metabolism by
hepatocytes, mobilisation of lipids from adipose tissue, or consumption of
dietary fat. Fatty liver is asymptomatic and reversible (i.e., the liver recovers
and the fat globules disappear on quitting alcohol consumption).

2) Alcoholic Hepatitis: It is the second stage of alcoholic liver disease.

Excessive alcohol consumption increases fatty changes in hepatocytes as
well as other degenerative changes, resulting in liver cell necrosis. The most
significant feature of severe alcoholic liver injury indicating that the liver
cells have been irreparably damaged is accumulation of Mallory bodies or
alcoholic hyaline (inregularly shaped. pink coloured deposits) within the
cytoplasm of liver cells. Neutrophilic leukocytes also deposit due to the liver
cell necrosis, and the injury is followed by progressive fibrous scarring
throughout the liver.
Alcoholic Cirrhosis: It is the third and most advanced stage of alcoholic
liver injury. The characteristic features are diffuse scarring of the liver which
obstructs liver function and also reduces blood flow through the liver.

Etiology
The primary cause of alcoholic liver disease is prolonged heavy drinking
resulting in scarring and cirrhosis of liver tissue (final phase of the disease).
Alcoholic liver disease does not occur in every heavy drinker. The chances of
getting the disease depend on how long the individual have been drinking.

The disease occurs more commonly in some families. Women are comparati vely
more affected than men.

Pathogenesis
In liver, alcohol metabolism
takes place by the following two pathways:
1) Alcohol Dehydrogenase Pathway: Liver cells metabolise alcohol to
acetaldehyde in the presence of alcohol
Acetaldehyde
dehydrogenase
is further metabolised to acetate in the enzyme.
mitochondria by
acetaldehyde dehydrogenase enzyme. Nicotinamide Adenine Dinucleotide
(NAD) reduced
is to NADH (reduced form of NAD) in the
the enzymes. Increased amount of NADH in presence of both
relation to NAD inhibits
gluconeogenesis and increases fatty acid oxidation, which consecutively
promotes fatty infiltration in the liver. duon,
2) Cytochrome P-450 2E1 Pathway: Alcohol
is metabolised to Nicotinamide
Adenine Dinucleotide Phosphate (NADP) and also generates free radicals
through oxidation of NADPH (roduced form of
NADP).
Long-term exposure to alcohol also activates
metabolism), which produce TNF-a and hepatic macrophages (third site of
reactive oxygen species in mitochondria.
92 D. Pharm. Second Year (Pharmacotherapeutics) PCI

Alcoholics have deficiency of some antioxidants (like glutathione and vitamin

E). Thus, the oxidative stress increases hepatocyte necrosis and apoptosis. Lipid
peroxidation is also induced by free radicals, resulting in inflammation and
Acetaldehyde (the alcohol metabolite) binds to cellular protein and
fibrosis.
produces antigenic adducts
and induces inflammation. Alcohol also causes
endotoxaemia by affecting the barrier function of intestinal mucosa. This
condition further leads to hepatic inflammation.
Clinical Manifestations
In the initial stage. the alcoholic liver disease remains asyrnptomatic or the
symptoms appear slowly, depending on how well the liver is working. But
conditions become severe after prolonged heavy drinking.

Symptoms occurring in the early stages are:

1) Fatigue and loss of energy,
2) Appetite and weight loss,
3) Nausea.
4) Pain in abdomen, and
5) Small. red coloured spider-like blood vessels on skin.

Symptoms occurring in the advanced stages (when the liver condition worsens) are:
1) Oedema and ascites (due to fluid
build-up in and legs abdomen
respectively),
2) Jaundice
3) Redness on palms of the hands,
4) Impotence, shrinking of testicles, and enlarged breasts in
men,
5) Bruising and bleeding easily
6) Confusion or difficulty in thinking, and
7) Pale or clay-coloured stools.

Non-pharmacological Management
The following
precautions should be taken by the patients:
1) Less consumption
2)
of alcohol,
Eating a healthy diet with low salt content, and
3) Vaccinations for influenza, hepatitis A and B, and
pneumococcal pneumonia
Pharmacological Management
Following medications are prescribed by the physician:
1) Diuretics to get rid
of
2) Vitamin K or blood fluid build-up,
3) Medicines products to prevent abnormal bleeding,
for mental confusion, and
4) Antibiotics to prevent infections.
Some other treatments which
can be
) Endoscopic treatments for enlargedrecommended
veins in the
are
2) Removal of fluid from throat,
the abdonien
3) Placing
a
Transjugular Intrahepatic
(paracentesis), and
blood flow in liver. Portosystemic Shunt (TIPS) to repa"
Liver transplantation is
required if cirrhosis progresses to the final
stage.