CHAPTER 1

Alcoholic Liver Disease

Major Lesions of Alcoholic Liver Disease

Alcoholic fatty liver - >90% of binge and chronic

drinkers

Alcoholic hepatitis precursor of cirrhosis

Alcoholic cirrhosis end result of chronic heavy

drinking
Incidence of Alcoholic Hepatitis

Develops in only 10 to 20% of chronic drinkers

Risk factors include female gender, heredity and

immunity
Etiology and Pathogenesis

Quantity and duration of alcohol intake are most

important
Type of drink and pattern of drinking are less
important
Thresholds
- Males - 60 80 g/day for 10 years
- Females - 20 40 g/day for 10 years
Etiology and Pathogenesis

Contributing factors include;

- chronic viral hepatitis
hepatitis C more than hepatitis B
- non-alcoholic steatohepatitis (NASH) with or
without obesity
Alcohol a direct hepatotoxin involves release of
pro-inflammatory cytokines and TNF
Pathology
Alcoholic fatty liver
- macrovesicular steatosis starts with the peri-
venular hepatocytes
- accumulation of fat due to inability of the
hepatocyte to process and transport fat
- benign and reversible
Pathology
Alcoholic hepatitis
- characterized by ballooning degeneration,
hepatocyte necrosis, polymorphonuclear infiltration
and fibrosis
- Mallory bodies may be seen but is not specific
- reversible unless with cirrhosis
Clinical Features
Alcoholic fatty liver
- most often asymptomatic except for hepatomegaly
Alcoholic hepatitis
- may present with fever and abdominal pain but may
also be asymptomatic
- may also present with hepatic parenchymal dysfunction
(e.g. spider angiomas, jaundice) or portal hypertension
(e.g. ascites, variceal bleeding) in the absence of cirrhosis
Laboratory Findings
Elevated AST and ALT (<400 IU/L)
AST/ALT ratio usually of > 2
Elevated gamma glutamyl transpeptidase (GGTP)
sensitive but not specific to alcoholic liver disease
Ultrasound detects hepatic enlargement and change in
echogenicity
Hepatic synthetic functional derangements (e.g. decreased
albumin and prolonged protime) seen in cirrhosis
Prognosis in Alcoholic Hepatitis
Discriminant function
4.6 x protime prolongation (sec) + serum bilirubin
(mg%)
- poor prognosis if > 32
Treatment of Alcoholic Hepatitis
Alcohol abstinence include nutritional and
psychological counseling
Pharmacologic
- prednisone 40 mg/day or prednisolone 32 mg/day
for 4 weeks then taper for 4 weeks
- TNF inhibitor pentoxifylline 400 PO TID for 4
weeks
What is cirrhosis?

A chronic or prolonged liver inflammation

of various causes, characterized by:
fibrosis (scar tissue) with
architectural distortion
disordered blood flow
regenerative nodules
alcoholic cirrhosis is usually
micronodular unlike in post-
hepatitis cirrhosis
Cirrhosis

Has always been thought to be irreversible

but recent evidence state that early
cirrhosis is reversible when the underlying
insult is removed
What causes cirrhosis?

viral hepatitis B and C

alcohol
biliary cirrhosis
NASH
cardiac cirrhosis
inherited metabolic (hemochromatosis,
Wilsons disease, 1 anti-trypsin deficiency)
Pathological and Clinical Features
of Cirrhosis

hepatic dysfunction jaundice, spider angioma,

palmar erythema,
testicular atrophy,sparse axillary
hair
edema, ascites,
hepatic encephalopathy

esophageal varices
portal hypertensive gastropathy
portal hypertension hypersplenism
Child- Pugh Classification

Score 1 2 3
bilirubin (micromol/l) < 34 34-50 > 50

albumin (g/l) > 35 28-35 < 28

PT (sec prolonged) <4 4-6 >6

encephalopathy none mild marked

ascites none mild marked

The individual scores are summed and then grouped as:

<7 = A 7-9 = B >9 = C
Prevention of Acute Complications

Upper GI bleeding

Hepatic Encephalopathy

Subacute bacterial peritonitis

Hepato-renal syndrome

Infections
Hepatic Encephalopathy

A syndrome observed in patients with

cirrhosis characterized by personality
changes, intellectual impairment and a
decreased level of consciousness.
Pathogenesis of HE

Several theories had been proposed for the

development of Hepatic Encephalopathy

Ammonia Hypothesis

False Neurotransmitter Hypothesis

GABA Hypothesis
Grading of the Symptoms of
Hepatic Encephalopathy

Clinically normal mental status but minimal changes in memory,

Grade 0 concentration, intellectual function, and coordination

Mild confusion, euphoria, or depression; decreased attention; slowing of

Grade 1 ability to perform mental tasks; irritability; and disordered sleep pattern,
such as inverted sleep cycle

Drowsiness, lethargy, gross deficits in ability to perform mental tasks,

Grade 2 obvious personality changes, inappropriate behavior, and intermittent
disorientation, usually about time

Somnolent but can be aroused, unable to perform mental tasks,

Grade 3 disorientation about time and place, marked confusion, amnesia, occasional
fits of rage, present but incomprehensible speech

Coma with or without response to painful stimuli.

Grade 4
Prevention of Decompensation

Prevent ongoing liver damage

- nucleoside analoques (lamivudine,
entecavir,adefovir)
- alcohol abstinence
- avoidance of certain drugs
- bile duct decompresssion
- steroids
- prophylactic band ligation
Prevent deterioration of nutritional status