Cirrhosis Liver in children

Introduction
• Cirrhosis is a diffuse hepatic process characterised by
fibrosis and the conversion of normal liver
architecture into structurally abnormal nodules.

• Cirrhosis represents the final histological pathway for

a wide variety of liver diseases.
 Essentials of Diagnosis & Typical Features

• Underlying liver disease.

• Hard nodular liver.

• Nodular liver on abdominal imaging.

• Liver biopsy demonstrating cirrhosis.

Cirrhosis is a histologically defined condition and
not a disease per se

• Diffuse hepatocyte injury and regeneration,

• An increase in connective tissue (bridging fibrosis),
• Disorganization of the lobular and vascular
architecture (regenerative nodules).
• Micronodular or macronodular
• Vasculature distortion leads to portal hypertension
and its consequences.
 Net effects
1. Portal hypertension:
1. Oesophageal varices
2. Hypoperfusion of the kidneys,
3. Water and salt retention
4. Increased cardiac output.
2. Damage to liver cells:
1. Derangement of synthetic functions
2. Derangement of detoxifying functions
 Etiology
1. Post necrotic:
1. Infective
2. Toxic
2. Biliary:
 Causes of cirrhosis
• Postnecrotic cirrhosis:
1. Idiopathic neonatal giant-cell hepatitis,
2. Viral hepatitis [HBV, HCV],
3. Autoimmune or drug-induced hepatitis);
4. Nonalcoholic fatty liver disease (NAFLD)
5. Inborn errors of metabolism
6. Wilson disease,
7. Hemochromatosis,
8. A 1-antitrypsin deficiency
 Biliary cirrhosis
1. Biliary atresia,

2. Choledochal cyst),

3. Tumors of the bile duct,

4. Caroli disease,

5. Cystic fibrosis
• Drugs: hypersensitivity reaction to phenytoin.
• Parasites : Fasciola, and Ascaris
 Clinical Findings
History
• Asymptomatic early in the course.
• Malaise, loss of appetite, failure to thrive, and
nausea
• Easy bruising
• Jaundice may or may not be present.
 Symptoms and Signs
• The first indication of cirrhosis:
1. Ascites
2. Gastrointestinal hemorrhage
3. Hepatic encephalopathy
O/E:
1. Variable hepatosplenomegaly,
2. spider angiomas,
3. warm skin,
4. palmar erythema,
5. Digital clubbing
6. Shrunken liver or is
7. Mild hepatomegaly: firm to hard; irregular edge.
8. Ascites may be detected as shifting dullness
9. Gynecomastia in males.
10.Digital clubbing in 10–15% of cases.
11.Pretibial edema reflecting hypoproteinemia.
12.In adolescent girls, irregularities of menstruation
or/and amenorrhea
 Biliary cirrhosis
1. Jaundice
2. Dark urine
3. Pruritus
4. Hepatomegaly
5. Xanthomas
6. Malnutrition
7. Failure to thrive due to steatorrhea
 Blood tests
• LFTs: hepatocyte damage
– aspartate transaminase (AST),
– alanine transaminase (ALT),
– alkaline phosphatase (ALP),
– bilirubin,
– gamma-glutamyltransferase (gamma-GT) in alcoholics.
• Albumin: hypoalbuminaemia
• Anemia, thrombocytopenia, and leukopenia in
hypersplenism
• Ferritin: is raised in haemochromatosis.
• Viral antibody screen for hepatitis B or C infection.
• Fasting glucose/insulin/triglycerides levels: NALD
• Autoantibody screen: anti-mitochondrial antibodies
are a very strong indicator of primary biliary
cirrhosis.
• Alpha-1-antitrypsin level: to assess for alpha-1-
antitrypsin deficiency.
• Ceruloplasmin and urinary copper for Wilson's
disease.
• Renal function tests and electrolytes:
– Hyponatraemia may be present (due to increased
activity of antidiuretic hormone).
– Poor renal function may represent hepatorenal
syndrome.
• Variable increase in the level of r-globulins.
• Prolonged PT unresponsive to vitamin k
In biliary cirrhosis:
• Elevated conjugated bilirubin, bile acids, GGT,
alkaline phosphatase, and cholesterol
 Imaging

• Hepatic ultrasound, CT, or MRI:

abnormal hepatic texture and nodules.

• Biliary cirrhosis:
abnormalities of the biliary tree may be apparent.
 Pathology
• Liver biopsy:
– regenerating nodules and surrounding fibrosis are
hallmarks of cirrhosis.
• Biliary cirrhosis:
– canalicular and hepatocyte cholestasis,
– plugging of bile ducts.
– The interlobular bile ducts may be increased or
decreased, depending on the cause and the stage
of the disease process.
 Differential Diagnosis
• Idiopathic neonatal giant-cell hepatitis:
1. unknown cause; presents with cholestasis
2. Forms 25–40% of neonatal intrahepatic cholestasis
3. patent extrahepatic tree
4. Stools with some pigment
5. Giant cells: +++
6. Portal reaction: Inflammation, minimal fibrosis
Neonatal Hepatitis Resulting from Infection

Cytomegalovirus Culture and PCR, liver

histology, IgM/IgG
Rubella Culture, IgM/IgG

Treponema pallidum Serology; darkfield exam

Toxoplasma gondii IgM/aIgG, PCR, culture

Herpes simplex PCR and culture, histology

 Viral hepatitis HBV, HCV
HBV HCV

Type of virus Hepadnavirus (DNA) Flavivirus (RNA)

Transmission routes Parenteral, sexual, Parenteral, sexual,

vertical vertical

Diagnostic test HBsAg, anti-HBc IgM Anti-HCV, PCR-RNA

test
 Autoimmune hepatitis
• Acute or chronic hepatitis.
• Hypergammaglobulinemia.
• Positive antinuclear antibodies (ANA)
• Serum IgG levels are elevated
• Low levels of C3 complement
• autoantibodies present:
– type 1—ASMA (antiactin);
– type 2—anti-LKM (anti–cytochrome P-450); and
– type 3—anti-SLA.
– HLA-A1 and HLA-B8.
– Liver biopsy shows loss of the lobular limiting plate, and interface
hepatitis ("piecemeal" necrosis).
 Non alcoholic Fatty Liver Disease (NAFLD)

• Hepatomegaly in patient with BMI > 95th

percentile.
• Elevated ALT > AST.
• Detection of fatty infiltration of the liver on
ultrasound.
• Histologic evidence of fat in the liver.
• Insulin resistance
 Inborn errors of metabolism
Inborn Error Diagnostic Studies
Galactosemia Galactose-1-phosphate Galactose-1-phosphate
uridylyltransferase uridylyltransferase assay of red
blood cells
Fructose Fructose-1-phosphate Liver fructose-1-phosphate
intolerance aldolase aldolase assay or genotyping of
leukocyte DNA
Tyrosinemia Fumarylacetoacetase Urinary succinylacetone,
fumarylacetoacetase assay of
red blood cells
Cystic fibrosis Cystic fibrosis Sweat test and genotyping of
transmembrane leukocyte DNA
conductance regulator gene
α1-Antitrypsin Abnormal 1-antitrypsin Serum 1-antitrypsin
deficiency molecule (PiZZ phenotype or genotype
phenotype)

Gaucher disease β -Glucosidase β-Glucosidase assay in

leukocytes
Niemann-Pick Lysosomal Sphingomyelinase assay
disease sphingomyelinase of leukocytes or liver or
fibroblasts (type C);
genotyping of leukocyte
DNA

Glycogen storage Branching enzyme Branching enzyme

disease type IV analysis of leukocytes or
liver, genotyping of
leukocyte DNA
 Wilson disease
• Acute or chronic liver disease.
• Deteriorating neurologic status.
• Kayser-Fleischer rings.
• Elevated liver copper.
• Abnormalities in levels of ceruloplasmin and serum
and urine copper
• Caused by mutations in the gene ATP 7B on
chromosome 13 coding for a specific adenosine
triphosphatase involved in copper transport.
• Impaired bile excretion of copper and incorporation
of copper into ceruloplasmin by the liver.
 Hemochromatosis
• Hereditary:
– Defect in a gene HFE, which helps regulate the
amount of iron absorbed from food
– Excessive accumulation of iron in the parenchymal
tissues
– Multi organ dysfunction
• Acquired:
– Multiple blood transfusions
 Alpha-1 antitrypsin deficiency
• Mutations in the SERPINA1 gene on chromosome 14
which codes alpha-1 antitrypsin.
• It is produced in the liver and released into the blood
• Protects the lungs from attack by neutrophil elastase,
produced by white blood cells in response to infection;
lung develops emphysema as neutrophil elastase
destroys alveloar wall.
• Abnormal alpha-1 antitrypsin protein accumulates and
damage the liver
 Biliary atresia
1. Incidence: 1:10,000–1:18,000 births
2. The perinatal form (80%): perinatal insult;
inflammatory obstruction and fibrosis of the biliary
tree, autoimmune reaction or rheo virus infection
3. Fetal-embryonic form (20% ), extrahepatic biliary
system do not develop normally; + or – heterotaxia.
4. Greenish yellow jaundice and pale stools
5. Hepatoportoenterostomy (kasai procedure)
 Indian Childhood Cirrhosis
• Occurs predominantly in rural areas in india and
presents with jaundice, pruritus, lethargy, and
hepatosplenomegaly.
• Increased hepatic copper content, usually >700 μg/g
dry weight.
• Excess dietary ingestion of copper through the use
of copper utensils used to cook food
• Untreated ICC has a mortality of 45%
• ?Genetic susceptibility to copper toxicosis
• Incidence of ICC decreased as families found
alternate feeding utensils
 Complications
1. Progressive nutritional disturbances,

2. Hormonal disturbances,

3. Portal hypertension and its complications.

4. Hepatocellular carcinoma:
1. Chronic form of hereditary tyrosinemia

2. Long-standing HBV or HCV disease.

 Treatment
• Specific treatment for the underlying cause.
• Ensure adequate nutrition, including calorie and
protein intake.
• Zinc deficiency is often seen in patients with
cirrhosis and treatment with zinc supplements may
be helpful.
• Pruritus:
– antihistamines
– Colestyramine
• protect them against hepatitis A, influenza and
pneumococci.
• Liver transplantation is the ultimate treatment
for cirrhosis and end-stage liver disease.

• Stem-cell or hepatocyte transplantation

aimed at restoring liver function is also being
investigated.
 Child-Pugh (Child-Pugh-Turcotte) Classification

Criterion Score 1 Score 2 Score 3

Serum albumin (g/L) >35 28-35 <28

<34 μmol/L (<2 34-50 μmol/L (2-3 >50 μmol/L (>3

Serum bilirubin (total)3
mg/dL) mg/dL) mg/dL)
International
<1.7 1.7-2.2 >2.2
Normalized Ratio (INR)
Controlled
Ascites Absent Poorly controlled
medically
Controlled
Encephalopathy Absent Poorly controlled
medically

A score of 5-6 is class A (life expectancy 15-20 years); a score of 7-9 is class B (life
expectancy 4-14 years); a score of 10-15 is class C (life expectancy 1-3 years).