Download Alcoholic Liver Disease Alcoholic Hepatitis

Alcoholic Liver Disease
Alcohol Effects
1. Alcohol through action of alcohol DH &
acetaldehyde DH  excess NADH + H+ 
increased lipid biosynthesis
2. Impaired assembly & secretion of lipoproteins +
increased peripheral fat catabolism  fatty liver
3. Impaired hepatic methionine catabolism  dec.
intrahepatic glutathione (GSH) levels  inc.
sensitivity to oxidative injury
Alcoholic Liver Disease
Alcohol Effects
4. Induction of cytochrome P450
(a) CYP2E1  inc. alcohol catabolism in ER & inc.
conversion of other drugs to toxic metabolites
(b) production of reactive O2 species  damage
membrane hepatocellular dysfunction
5. Impaired microtubular and mitochondrial function
6. Alcohol  acetaldehyde  (+) lipid peroxidation
 disrupt cytoskeletal and membrane function
Alcoholic Liver Disease
Alcohol Effects
7. Become a major caloric source  displace other
nutrients  (+) malnutrition and vitamin deficiencies
8. Lead to chronic gastritis, intestinal mucosal damage
and pancreatitis  impaired digestive function
9. Induce release of bacterial endotoxin into portal
circulation from gut  (+) liver inflammation
10.Induce release of endothelins from sinusoidal
endothelial cells  (+) vasoconstriction & contraction
of stellate cells  dec. hepatic sinusoidal perfusion
 regional hypoxia
DIAGNOSIS OF ALCOHOL ABUSE
 The diagnosis of alcohol abuse is based on a history of heavy
alcohol intake and the presence of other organ system
damage or an excessive frequency of falls, lacerations, and
fractures.
 Biomarkers of alcohol abuse:
1- The most specific of these biomarkers is carbohydratedeficient transferrin (CDT).CDT levels increase in serum with
ingestion of 50 to 80 g/day of ethanol for two to three weeks
and decline gradually during abstinence, with a half-life of
approximately 15 days.
2-Increased Mean corpuscular erythrocyte volume
(MCV),increased serum gamma glutamyl transpeptidase
(GGTP) levels, and the ratio of mitochondrial aspartate
aminotransferase (AST) to total AST (mitochondrial
AST/total AST) and combinations of these markers have been
touted as more accurate measures of alcohol abuse.
Alcoholic Liver Disease
Hepatic Steatosis
• Alcoholic fatty liver
• Moderate alcohol intake  microvesicular
• Chronic alcohol intake  macrovesicular
• Enlarged, soft, yellow, greasy liver
• Completely reversible
Alcoholic Liver Disease
Alcoholic Hepatitis
• Characteristics:
1. Hepatocyte swelling & necrosis  ballooning due
to accumulation of fat, water & proteins
2. Mallory bodies – eosinophilic cytoplasmic
inclusions in degenerating hepatocytes
3. Neutrophilic reaction – accumulate around
degenerating hepatocytes (“satellitosis”)
4. Fibrosis – (+) activation of sinusoidal stellate cells
& portal tract fibroblasts
Histological features
of alcoholic hepatitis.
(A) Low- power view
demonstrating the
cardinal features of
steatosis, fibrosis,
inflammation, and
hepatocellular injury.
Histological features of
alcoholic hepatitis.
(B) (Black arrows) Mallory
bodies are irregular
eosinophilic cytoplasmic
structures with a rope-like
appearance. (Open
arrow) Ballooning
degeneration of
hepatocytes.
Histological features
of alcoholic hepatitis.
(c) (Open arrow)
Pericellular fibrosis,
also termed 'chickenwire' fibrosis
surrounds individual
degenerate
hepatocytes; (Black
arrow) Perivenular
fibrosis extends from
the central vein.
Histological features of alcoholic hepatitis. (d) The unit
lesion (also termed satellitosis) comprises a
degenerating hepatocyte with (arrow) a surrounding
cuff of neutrophils. Marked steatosis is also evident.
Alcoholic Liver Disease
Alcoholic cirrhosis
• Final, irreversible; 10 – 15% of alcoholics
• Micronodular with scattered larger nodules 
“hobnail” appearance of liver surface
• Broad expanses of tough, pale scar tissue due to
ischemic necrosis & fibrous obliteration of
nodules  Laennec cirrhosis
Liver enzymes
 Serum AST levels are almost always less than
300 to 500 U/L and typically are associated
with trivial elevation of serum ALT levels,
resulting in an AST/ALT ratio greater than 2,
which is characteristic of alcoholic liver
disease, in part because of deficiency of
pyridoxal 5′ phosphate (a cofactor of
aminotransferases) in alcoholic patients.
Alcoholic Liver Disease
 Short-term ingestion of up to 80 gm of
alcohol (~8 beers) over one to several days
 FATTY LIVER
 daily intake of 20-40 gm in female and 60-80
gm in male for 7 years  alcoholic cirrhosis
.
Daily intake of 160 gms or more for 10-20
years  SEVERE INJURY
Gynecomastia due to
alcoholic cirrhosis
A 32 year old male patient
with normal secondary sex
characteristics, no testicular
mass, no hystory of drug
ingestion, no other endocrine
abnormalities and a normal
neurological examination.
Nevertheless, he had a
history of more than 15 years
of large amounts of alcohol
intake and a liver biopsy
confirm alcoholic cirrhosis
(Laennec's Cirrhosis).
Alcoholic Liver Disease
• Cause of death:
1. Hepatic coma
2. Massive gastrointestinal hemorrhage
3. Intercurrent infection
4. Hepatorenal syndrome following alcoholic
hepatitis
5. Hepatocellular carcinoma
Metabolic Disorders
Non-alcoholic Fatty Liver Disease
(NAFL)
•
•
•
•
•
Occurs in patients who are not heavy drinkers
Strong association with obesity, dyslipidemia
and insulin resistance, and overt type 2 DM
May present only with elevated serum aminotransferases and/or GGT
(+) accumulation of triglycerides within
hepatocytes
Progress to non-alcoholic steatohepatitis
(NASH)  CIRRHOSIS
 Obesity is the condition most often reported in
association with NAFLD(overweight (defined as a body
mass index [BMI] > 25 kg/m2) , obese (BMI > 30 kg/m2)
and morbidly obese patients (BMI > 35 kg/m2) ).
 NAFLD also is strongly associated with type 2 diabetes
mellitus and glucose intolerance, with or without
superimposed obesity. Type 2 diabetes mellitus,
hyperglycemia, or glucose intolerance has been described
in 20% to 75% of adult patients with NASH and may
increase the risk of NASH more than twofold compared
with that for nondiabetic persons.
 NAFLD is now recognized as the hepatic component of
the metabolic syndrome, which includes hyperlipidemia,
glucose intolerance, obesity, and systemic hypertension.
The risk and severity of NAFLD increase with the
number of components of the metabolic syndrome.
Liver enzymes
 Two- to fourfold elevation of serum
ALT and AST levels. AST/ALT ratio less
than 1 in most patients.
 The serum ALT level usually is greater
than the AST level, in contrast with the
pattern of alcoholic hepatitis, in which
the AST level is at least twofold higher
than the ALT level .