A 10 Yrs.

old boy has presented with

hematemesis. His mother had noticed
anorexia, wt. loss, easy bruisability and a
few episodes of malena over the last 6
months. His school performance and hand
writing has deteriorated. Has been showing
some behavioral problems as well. On
general physical examination you find signs
of:
CHRONIC LIVER DISEASE
 FOCUS QUESTIONS
1. What are the principal varieties of chronic liver
disease?
2. Which infections produce chronic liver disease?
3. What metabolic abnormalities produce chronic
liver disease?
4. How are the various causes of chronic liver
disease differentiated?
5. What therapies are useful in the management
of chronic liver disease?
 CHRONIC HEPATITIS
Chronic hepatitis is defined as ongoing
Inflammation, with evidence of continued
hepatic inflammatory activity for a period of
at least 6 months, that is capable of
progression to cirrhosis, liver failure, and
death.
Two major categories of chronic
hepatitis are recognized:
• Chronic Persistent (CPH)
• Chronic Active (CAH)

Based on the location of the inflammatory

lesion found histologic specimens.
CPH:
• Limitation of the inflammatory
cells to the portal triads
• The lobular architecture is
preserved
• No significant fibrosis
CAH:
• The inflammatory lesion is not restricted to
the portal tract but enters the lobule
• The inflammatory process often disturbs
the lobular architecture
• Hepatic necrosis may be present with
increased fibroblastic activity and collagen
deposition within the areas of necrosis
CAUSES OF CHRONIC HEPATITIS:
• Viral Hepatitis:
 Hepatitis B
 Hepatitis C
 Delta hepatitis
 Cytomegalovirus

• Autoimmune Hepatitis:
 Anti-smooth muscle antibody-positive
 Anti-liver-kidney microsomal antibody-
positive
• Metabolic / Genetic Disorders:
 Wilson disease
 Alpha-1-antitrypsin deficiency
 Cystic fibrosis
 Steatohepatitis

• Toxic Hepatitis:
 Drugs
 Hepatotoxins
 Radiation
 CIRRHOSIS
• Cirrhosis is a clinico-pathologic state
representing the end stage of any chronic liver
disease
• Morphologically the liver displays regenerating
nodules devoid of central veins, surrounded by
variable amounts of connective tissue
• May be ‘Compensated’ or ‘Decompensated
 HEPATITIS C
• An RNA virus
• Transmission:

1) Parenteral – Blood and blood products,

Haemodialysis
2) Vertical - 7- 9%
3) Sporadic - Route of acquisition obscure
• Clinical Presentation:

 Incubation period 6-12 wks

 Acute Hepatitis – Very rare
 Chronic Hepatitis – Usually
asymptomatic
 Cirrhosis – Symptomatic with
complications
• Diagnosis:

Serum Aminotransferases:
- Fluctuating level is Characteristic of
Ch. HCV
- Normal Transaminases do not
exclude on going hepatic damage
• Serology:
Anti HCV Antibodies by:
-- ELISA (Enzyme Linked Immuno Sorbent
Assay)
-- RIBA (Recombinent Immono Blot
Assay)
Detection of Anti HCV Antibodies
indicates exposure
• HCV RNA by PCR:

- Establishes the presence of viremia and

thus confirms both infection & infectivity.

- Virus titers appear to correlate with

histological activity.
Clinical Course:
• Treatment:
Combination therapy with:

-- Interferon &
-- Ribavirin
• Prevention:

Development of an effective vaccine is

hampered by:
 Absence of a neutralizing antibody
 Heterogeneity of virus
 Failure to characterize the viral
antigenic determinants
 WILSON DISEASE
• Autosomal recessive disorder of copper
metabolism
• Biliary excretion of copper is reduced
resulting in the accumulation of
copper by the hepatocyte
• A defect in hepatocellular lysosomes is
responsible with impaired transport of
copper across the lysosomal membrane.
• The liver disease may range from
asymptomatic transaminemia to end-
stage cirrhosis with its associated
sequelae
• Clinical disease rarely is manifest before 5
years of age
Manifestations of Wilson Disease
• Hepatic:
 Acute hepatitis
Chronic active hepatitis
Cirrhosis
Fulminant hepatic failure

• Ophthalmologic:
Kayser-Fleischer rings
• Neurologic:
 Tremor
 Incoordination
 Dysarthria
 Gait disturbances

• Psychiatric
 Depression
 Neurosis
 Psychosis
• Other:
 Hemolytic anemia
 Proximal renal tubular dysfunction
 Cholelithiasis
• Investigations:
 LFTs
 Serum Ceruloplasmin (Decreased)
 Serum Copper (Elevated)
 24 Hr. Urinary Copper (Elevated)
 Liver Biopsy
• Treatment:
 Restrict copper intake to <1 mg/day
 D- Penicillamine
 Zinc
 Trientene
 Ammonium tetrathiomolybdate
 Liver Transplant
 Diagnostic Evaluation of
Children With CLD
Relevant historical information includes:
 Maternal and patient risk factors for
hepatitis (transfusion, intravenous drug
usage, and ethnic background)
 Presence of jaundice during infancy
 History of acute hepatitis
 Family history of liver disease
• Symptoms:
 Jaundice, dark urine, and light-colored
stools in acute phase
 Fatigue
 Malaise
 Abdominal pain
 Weight loss
 Hematemesis, malena, bruisability
 Hepatic Encephalopathy
 Common Presentations of CLD

Asymptomatic Chronic End

Chronic hepatitis Portal stage
elevation of
progressive hypertension disease
ALT / AST Gall
cholestasis stones

Neonatal
cholestasis Incidental
Hepatomegaly Hepatic Acute Liver
hepatomegaly±
and metabolic mass failure
splenomegaly
acidosis
 Hepatic Encephalopathy
Stage I:
• Periods of lethargy, euphoria
• Reversal of day-night sleeping
• May be alert
• Trouble drawing figures & performing
mental tasks
Stage II:
• Drowsiness
• Inappropriate behavior
• Agitation
• Wide mood swings
• Disorientation
• Asterixis
• Fetor hepaticus
• Incontinence
Stage III:
• Stupor but arousable
• Confused
• Incoherent speech
• Hyperreflexia
• Upgoing Plantar response
• Rigidity
Stage IV:
• Coma
 IV a: Responds to noxious stimuli
 IV b: No Response
• Areflexia
• No Asterixis
• Flaccidity
A 10 Yrs. old boy has presented with
hematemesis. His mother had noticed
anorexia, wt. loss, easy bruisability and a
few episodes of malena over the last 6
months. His school performance and hand
writing has deteriorated. Has been showing
some behavioral problems as well. On
general physical examination you find signs
of:
• Signs:
• Palmar erythema
• Spider angiomata
• Muscle wasting
• Ascites
• Enlarged firm liver and spleen
• Splenomegaly in this setting signifies the
presence of portal hypertension and the
likelihood of gastroesophageal varices.
A STORY……………..
 INVESTIGATIONS:
• Complete blood count, erythrocyte
sedimentation rate
• Serum aminotransferases (AST, ALT)
• Bilirubin (total and fractionated)
• Synthetic function (serum albumin,
prothrombin time, and cholesterol)
• HBsAg, anti-HBclgM, anti-HBc IgG,
HBeAg, and anti-HBe
• Serologic titers for cytomegalovirus and
Epstein Barr virus
• Alpha-1-antitrypsin level and protease
inhibitor phenotype
• Serum ceruloplasmin and 24-hour urinary
copper excretion
• Sweat Chloride test
• Antinuclear antibody titer
• Antimitochondrial antibody titer
• Anti-smooth muscle antibody titer
• Anti-liver-kidney microsomal antibody
titer
• Abdominal ultrasonography ± color flow
doppler of portal venous system
• Radionuclide liver-spleen scan
• Percutaneous liver biopsy
 Liver biochemical tests can be divided into 5
categories:

Tests that
detect liver Tests that Tests of liver Tests of Tests of
injury: detect synthetic hepatic hepatic
imapaired function:
ALT excretory metabolic
bile flow i.e
Albumin function: function:
AST cholestasis:
PT (INR) Bilirubin Glucose
LDH Alk phosph
S. Bile acids Ammonia
GGT
s. Bile acids
 Space of Disse

Hepatocyte Hepatocyte

ALT / AST Bile canaliculus

ALP GGT

AST(m) GGT

Mitochondria Microsomes

Location of liver enzymes

 MANAGEMENT
• TREAT THE UNDERLYING CAUSE
• Nutritional Rehabilitation
• Fat soluble Vitamin (A, D, E, K)
supplementation
• Protein restriction
• Management of coagulopathy by FFP
• Management of Portal HTN
• Banding of Esophageal Varices plus
treatment of acute bleeding episodes with
I/V fluids, Blood, Octreotide, Emergency
Shunting Procedure
• Drainage of significant Ascites alongwith
albumin infusion
• Management of Hepatic Encephalopathy
with:
-- Endotracheal intubation in advanced
stages (to prevent aspiration, reduce
cerebral edema by hyperventilation, and
to facilitate pulmonary toilet)
-- Fluid & Electrolyte Balance
-- TPN
-- Flumazenil
-- Lactulose Enemas
-- Management of raised ICP
-- Management of Infections
-- Rectal Neomycin
 SPECIFIC TREATMENT
LIVER TRANSPLANTATION
Indications:
• Severe chronic fatigue and weakness
Malnutrition
• Growth failure
• Bone disease
• Ascites refractory to medical therapy
• Recurrent gastroesophageal variceal
bleeding
• Spontaneous bacterial peritonitis
• Recurrent hepatic encephalopathy
• Prothrombin time > 20 sec unresponsive
to parenteral vitamin K
• Indirect bilirubin >6 mg/dL
• Cholesterol < 100 mg/dL
THE END…………