ALCOHOL INDUCED LIVER
Presented By: NAGARAJU
India : alcohol
The prevalence of use of alcohol
Ranges from a low of 7% in Gujarat, to 75% in
The per capita consumption is 4 lit/adult/year
It accounts for 50% of CLD
ALD cause of mortality M: 11/100000
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Symptoms of Alcoholic Liver Disease may not appear
until the condition is relatively advanced. They vary
with the severity of the disease and worsen after a bout
of heavy drinking.
Alcoholics are at an increased risk for gastrointestinal
disorders, heart diseases and high blood pressure.
Excessive alcohol use can also cause peptic
ulcers, aggression, anxiety and depression.
A number of cancers can be developed as a result of
alcoholism. Cancer of
mouth, throat, oesophagus, stomach and liver are the
few commonly- occurring ones.
Fatigue/nausea /loss of appetite
Swollen abdomen due to an enlarged liver
Pain in the abdomen
Fluid build-up in legs (oedema) and abdomen in case of
Pain/numbness in hands and legs
Hypo /hyper pigmentation on the skin
Small spider like blood vessels on skin
Red colouration on hands /feet
Yellow colouration of skin /eyes in case of jaundice
Bleeding nose /gums
Changing moods /confusion/hallucinations/decreased
Impaired memory /poor judgment
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Serious complications of alcohol
It include advanced diseases such as brain
damage (Alcoholic Encephalopathy) and
hypertension (high blood pressure within
The disease usually affects those who are
older than 30 years.
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Liver is the Largest solid organ,
Main Metabolic organ of the Body
The liver is located in the upper right-hand portion of the abdominal
cavity, beneath the diaphragm, and on top of the stomach, right
kidney, and intestines. Shaped like a cone, the liver is a dark reddish-
brown organ that weighs about 3 pounds.
Liver is Made up of different cell types however 4 important cell types are
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They are rich in Organelle such as ER,
Golgi complex, Mitochondria.
Participate in Protein, Carbohydrate & Lipid
Produce serum protein such Albumin, Coagulation
Sinusoidal endothelial cell lines the walls of
Filtration due to presence of Fenestration.
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They are located within sinusoidal cell.
Upon activation they secrete Inflammatory mediator:
Stellate cell: Play central role in storage of Vitamin
Overall functions of Liver:
As a Detoxifying Organ
As a Metabolic Organ
As an Immunological Organ,
As an Emulsifying agent(Bile salts) Producing Organ.
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Ethanol: is a small two carbon alcohol that, due to its small
size and alcoholic hydroxyl group is soluble in both aqueous
and lipid environments.
This allows ethanol to freely pass from bodily fluids into cells.
Since the portal circulation from the gut passes first through
the liver, the bulk of ingested alcohol is metabolized in the
The process of ethanol oxidation involves at least three
distinct enzymatic pathways.
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Microsomal ethanol oxidizing system (MEOS) which
involves the cytochrome P450 enzyme CYP2E1 and requires
NADPH instead of NAD+ as for ADH. The MEOS pathway is
induced in individuals who chronically consume alcohol.
Fatty acid ethyl ester (FAEE) synthase. This latter
pathway results in the formation of fatty acid ethyl esters and
takes place primarily in the liver and pancreas, both of which
are highly susceptible to the toxic effects of alcohol.
Acute Effects of Ethanol Metabolism
The metabolism of ethanol via the CYP2E1 pathway results in
increased ROS production, including superoxide, hydrogen peroxide
(H2O2), and hydroxyl radicals.
ROS production is associated with cancer
development, atherosclerosis, diabetes, inflammation, aging, and other
The cell regulates ROS levels via numerous defense systems involving
a variety of different antioxidant compounds (e.g. glutathione, GSH).
During ethanol oxidation ROS production increases dramatically due to
induction of CYP2E1 and by activation of Kupffer cells in the liver.
Both acute and chronic alcohol consumption can increase ROS
production and lead to oxidative stress.
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Chronic Effects of Ethanol Metabolism
In addition to the negative effects of the altered NADH/NAD+
ratio on hepatic gluconeogenesis, fatty acid oxidation is also
reduced as this process requires NAD+ as a cofactor.
Concomitant with reduced fatty acid oxidation is enhanced
fatty acid synthesis and increased triacylglyceride production
by the liver.
In the mitochondria, the production of acetate from
acetaldehyde leads to increased levels of acetyl-CoA. Since
the increased generation of NADH also reduces the activity of
the TCA cycle, the acetyl-CoA is diverted to fatty acid
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The reduction in cytosolic NAD+ leads to reduced activity of
glycerol-3-phosphate dehydrogenase (in the glycerol 3-phosphate
to DHAP direction) resulting in increased levels of glycerol 3-
phosphate which is the backbone for the synthesis of the
Both of these two events lead to fatty acid deposition in the liver
leading to fatty liver syndrome and excessive levels of lipids in
the blood, referred to as hyperlipidemia.
Because ethanol metabolism by ADH and ALDH occurs
essentially only in the liver, any of the adverse effects described
above that are associated with ethanol metabolism by these
enzymes, and the associated ROS production, primarily affect that
In contrast, CYP2E1 is found in many tissues in addition to the
liver, including the brain, heart, lungs, neutrophils, and
Accordingly, metabolic consequences of CYP2E1-mediated
ethanol oxidation will affect numerous tissues. The harmful
effects associated with CYP2E1-mediated ethanol metabolism
are primarily related to the production of ROS, mainly
superoxide and hydroxyl radicals.
In the liver, the oxidative stress resulting from CYP2E1-
mediated ethanol metabolism plays an important role in
alcohol-related development of liver cancer.
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Chronic ethanol consumption and alcohol metabolism also
negatively affects several other metabolic pathways, thereby
contributing to the spectrum of metabolic disorders
frequently found in alcoholics.
These disorders include fatty liver syndromes such as
NAFLD and NASH, hyperlipidemia, lactic
acidosis, ketoacidosis, and hyperuricemia.
The first stage of liver damage following chronic alcohol
consumption is the appearance of fatty liver, which is
followed by inflammation, apoptosis, fibrosis, and finally
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In the home, methanol is most frequently found in the form
of "canned heat" or in windshield-washing products.
Poisonings occur from accidental ingestion of methanol-
containing products or when it is misguidedly ingested as an
Methanol poisoning causes visual disturbance, frequently
described as "like being in a snowstorm.
Methanol (methyl alcohol, wood alcohol) is widely used in
the industrial production of synthetic organic compounds and
as a constituent of many commercial solvents.
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Risk for the development of ALD.
Time to develop ALD = to amount of alcohol
Men: 60-80 gm/day for 10 years
Women:20-40 gm/day for 10 years
Develops ONLY in 10 to 20% of those who are
chronically heavy drinkers.
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WINE: ml/10 Gms of alcohol
HARD LIQOUR : ml/3
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ALCOHOL ABUSE VS. ALCOHOL DEPENDENCE
ALCOHOL abuses as those who drink despite
recurrent social, interpersonal, and legal problems
Dependence- presence of 3 or more symptoms
b) Withdrawal symptoms
c) Loss of control over drinking
d) Strong desire to drink
e) Drinking despite harm
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DETECTION OF ALCOHOL ABUSE
CAGE(Cut down,annoyed by criticism, guity about
drinking, Eye-opener in the morning)
AUDIT (Alcohol use Disorders Identification Test) 10-
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SYMPTOMS PHYSICAL EXAMINATION
Jaundice stigma of CLD
Fatigue Tender hepatomegaly
Weight loss decompensation
Pain in RHC Eso.varies
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Both AST and ALT are INC., <300IU/ml
AST>ALT of 2 (80%)
Inc in GGT
Macocytosis with anemia
Leukocytosis –correlates with degree of injury.
Increasing Bilrubin and PT correlate with severity of liver
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Life style Medication
EtoH intake : 80% survival rate in those who
Smoking: Cigarette smoking is an independent
risk factore for cirrhosis in ALD
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Nutritional supplement improves hepatic
function, and out come in AH,
•Patients consuming > 3000kcal/d had virtually
•Whereas those consuming <1000 kcal/d had >
80% 6-month mortality
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Decrease the immune response
Increase production of albumin
Improve caloric intake by improving
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Prednisolone: 32 mg Po for 4 week followed
Active form prednisolone, rather than the in
active precursor prednisone, is preferred
No long term survival benefits
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It attenuates TNF-a release and action
Exertes an antifibrinogenic action
Lower portal hypertention
Decrease blood viscosity
Improve organ microcirculation
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Side-effects: Epigastric pain, vomiting, and
Dose: 400 mg TID
Improvement in short-term (4-week)
Decrease in the rate of development of
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s-adenosylmethionine: Benefits of SAM in
ALD include roles as an
Critical methyl donor
Decreasing TNF levels, and Glutathionine
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No siginificant effects of PTU vs Placebo
on mortality, complications of liver disease
No beneficial effect on overall mortality
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OLT for alcoholic hepatitis is not currently
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All Alcoholic patients should be screened for alcoholic liver
disease. The diagnosis of alcoholic liver disease requires a
detailed patient history, with supportive laboratory and
Liver biopsy may be useful to confirm the diagnosis, rule
out other diseases, and prognosticate. All patients with
alcohol-related liver disease should abstain from alcohol.
For those with severe disease and no contraindications to
their use, steroids should be considered. Liver
transplantation remains an option for select patients with
end-stage liver disease due to alcohol.