Transcript Hepatobiliary Disorders

Hepatobiliary Disorders
Dr. Mohamed Hesham Sayed
Professor of Pediatrics
Rabigh Faculty of Medicine, KAU
Objectives
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Define and classify causes of cholestasis.
Describe the consequence of cholestasis
Correlate the abnormalities in LFT with cholestasis.
Recognize feature of biliary atresia.
Discuss viral hepatitis
Recognize feature and causes of chronic liver
disease.
• Describe end stage of liver disease
Clinical presentations of liver diseases
1) Hepatomegaly
• Infections: viral hepatitis, abscess, Bilharziasis
• Congestive: CHF, veno-occlusive disease
• Metabolic : Glycogen storage, Wilson disease
• Malignant : liver tumors, neuroblastoma
2) Jaundice
• Hemolytic anemias
• Acute and chronic liver diseases
3) Portal hypertension
• Collateral circulation(abd veins &varices)
• Splenomegaly
• Ascites
4) Acute liver cell failure
• Progressive jaundice
• Bleeding
• Rapidly developing coma
5) Chronic liver cell failure
• General: anorexia, wt loss
• Jaundice
• Ascites
• Bleeding
• Skin : palmar erythema &
spider nevi
• Encephalopathy
Reasons for a Delay in Referral of Infants
Who Have Liver Disease
• Lack of follow-up of neonatal jaundice (including
failure to fractionate serum bilirubin)
• Inadequate investigation of hemorrhagic disease/
coagulopathy
• Misdiagnosis of cholestasis (conjugated
hyperbilirubinemia) as human milk jaundice
(unconjugated hyperbilirubinemia)
• False security due to a fall in serum bilirubin
concentrations or presence of pigmented stools
Causes of Liver Diseases
• The causes of liver disease in pediatric
patients vary with age:
• Neonates and infants
– Biliary atresia and idiopathic neonatal hepatitis
• older children/adolescents
– Acetaminophen intoxication and Wilson disease
Causes of Liver Disease in Pediatric
Patients According to Age
Neonates and Infants
• Cholestatic disorders
—Biliary atresia
—Choledochal cyst
—Paucity of intrahepatic bile ducts (eg, Alagille
syndrome)
—Progressive familial intrahepatic cholestasis
syndromes (Byler disease and syndrome)
• Idiopathic neonatal hepatitis and mimickers
—Cystic fibrosis
—Alpha 1-antitrypsin deficiency
• Viral hepatitis or other infectious diseases
—Cytomegalovirus
—Herpes simplex virus/herpes zoster virus/human
herpesvirus 6
• Metabolic disease
– Tyrosinemia, galactosemia, fructosemia
• Others
– Total parenteral nutrition
Causes of Liver Disease in Pediatric
Patients According to Age Older
• Hepatitis
Children and Adolescents
—Viral hepatitis (hepatitis B virus, hepatitis C virus)
—Autoimmune hepatitis
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Wilson disease
Liver disease associated with inflammatory bowel disease
Parasitic infections
Toxins and pharmacologic remedies
Malignancies
Portal hypertension
Fatty liver of obesity (nonalcoholic steatohepatitis)
Hypotension/ischemia/cardiac failure
Neonatal Cholestasis
Definition
• Failure of bile to reach duodenum due to
Liver or
biliary disorder
Prolonged elevation of serum
conjugated bilirubin
beyond the first 14 days of life
Causes of cholestasis
1) Idiopathic neonatal hepatitis
The commonest cause due to unknown etiology
2) Infections : Bacterial, viral or protozoal
3) Metabolic
- Carbohydrate (galactosemia),
- Amino acids (tyrosinemia),
- Others (alpha-1-antitrypsin deficiency)
4) Bile duct obstruction: Extrahepatic biliary atresia (EHBA),
Choledochal cyst
5) Familial syndromes as paucity of intrahepatic bile ducts
(Allagile syndrome)
Allagile syndrome
Consequences of cholestasis
1) Decreased bile excretion
- Fat malabsorption
- Pale or clay colored stool
2) Retention of bile
- Jaundice
- Pruritis
- Progressive liver damage
Clinical features
* The diagnosis is considered in case of
- Persistent neonatal jaundice > 2 wks
- Hepatomegaly,
- Pale stools, and
- Dark urine
* Signs of the cause may include
- Low birth weight (TORCH),
- Cataract (galactosemia or rubella), or
- Abnormal facies in Allagile syndrome
1) α1-antitrypsin deficiency
Neonatal Cholestasis - History
• Jaundice in any infant after 2 weeks of age
should raise the suspicion of liver disease and
prompt appropriate evaluation.
• Onset related to diet….inborn error/metabolism
• Family history…. Alagille syndrome, IEM
• Male/LBW….neonatal hepatitis
• Female……EHBA
• Early onset/acholic stool….EHBA
Goals of timely evaluation
• Diagnose and treat known medical and/or lifethreatening conditions.
• Identify disorders amenable to surgical
therapy within an appropriate time-frame.
• Avoid surgical intervention in intrahepatic
diseases.
• Surgical correction of biliary atresia
ideally should occur within the first 2
months of life.
• Rx- Kasai portoenterostomy
– Age < 8wks 90% clear jaundice
Age 8-12 wks 45%
Age>12wks 22%
Rapid diagnosis of
biliary atresia
Extrahepatic biliary atresia
• Generally acholic stools with onset at about 2
weeks-old
• Average birth weight
• Hepatomegaly with firm to hard consistency
• Female predominance
• No well-documented familial cases
Extrahepatic biliary atresia
• Increased incidence of polysplenia syndrome
and intra-abdominal vascular anomalies
• Normal uptake on radionucleotide scan with
absent excretion
• Biopsy shows bile duct proliferation, bile
plugs, portal or perilobular fibrosis and
edema, and intact lobular structure
Idiopathic neonatal hepatitis
• Generally normal stools or acholic stools with
onset at one month-old
• Low birth weight
• Normal liver on exam or hepatomegaly with
normal to firm consistency
• Male predominance
• Familial cases (15-20%)
Idiopathic neonatal hepatitis
• Impaired uptake on radionucleotide scan with
normal excretion
• Biopsy shows intralobular inflammation with
focal hepatocellular necrosis and disruption of
the hepatic architecture. No alteration of the
bile ducts. Giant cell transformation occurs
but is non-specific.
Infantile Cholestasis - Objectives
• Aim 1: Identify a treatable cause
• Aim 2: Recognise complications
• Aim 3: Early referral to specialist unit when
necessary
Etiologies
• Basic distinction is between:
– Extrahepatic etiologies
– Intrahepatic etiologies
Extrahepatic etiologies
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Extrahepatic biliary atresia
Choledochal cyst
Bile duct stenosis
Spontaneous perforation of the bile duct
Cholelithiasis
Inspissated bile/mucus plug
Extrinsic compression of the bile duct
Intrahepatic etiologies
• Idiopathic Neonatal Hepatitis
• Toxic
– TPN-associated cholestasis
– Drug-induced cholestasis
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Genetic/Chromosomal
Infectious
Metabolic
Miscellaneous
CONJUGATED HYPERBILIRUBINAEMIA
(direct/total bilirubin > or = 20%)
CLOTTING SCREEN
Normal
Deranged
1mg vitamin K
i.v.
Examine stools
Pigmented
Repeat clotting studies after 4
hours
Acholic/Pale
Derangement persists
Severe Cholestatic Liver
Disease
 Urgently Exclude
Biliary Atresia
EXCLUDE FOLLOWING:
 Infective
 Haematological
 Inborn errors of metabolism
 Parenteral nutrition
 Endocrinopathy
 Storage disorders
 Genetic/Familial
 Vascular
 Idiopathic
NO
YES
*Age <6 weeks
Kasai
portoenterostomy
*Age > 6 weeks
liver
transplantation
Stabilise infant:
 Assess airway , breathing and
circulation
 Broad Spectrum antibiotics
 Regular Vit K iv
 N-acetyl- cysteine
100mcg/kg/24 hours
 Ranitidine iv
 Save urine & serum (especially
if transfusing)
 Blood if Hb <8
 Platelets if count <20
 FFP 10mls/kg if bleeding
Presentation
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Jaundice-  conjugated bilirubin
Pale stools
Dark urine
Abnormal LFTs - high or low GGT
Bleeding
Hepatosplenomegaly
Abdominal mass
Failure to thrive
Investigations of cholestasis
A) To document diagnosis of cholestasis
- Total and direct serum bilirubin
- Liver enzymes:
ALT (more liver specific), AST, alkaline phosphatase
and gamma glutamyl transpeptidase
- Serum proteins (total and albumin)
- Prothrombin time and concentration
B) To define the cause of cholestasis
1) Look for treatable conditions
- Galactosemia (reducing substance in urine);
- Septicemia (sepsis screen)
2) Look for congenital infections
- TORCH screenig
3) Look for metabolic conditions
- Tyrosinemia and alpha one antitrypsin deficiency
4) Look for choledochal cyst : by abdominal US
5) Differentiate between idiopathic hepatitis and
extrahepatic atresia:
A) Radionuclide scanning (HIDA scan)
- If dye in intestine  hepatitis
- If no dye in intestine  EHBA
B) Liver biopsy Most helpful but not 100% conclusive
- Giant cell transformation  hepatitis
- Fibrosis of portal tracts/bile duct proliferation  EHBA
C) Operative cholangiogram
- To demonstrate patency or obstruction of bile ducts
Biliary Atresia
• Radioisotope
scan (TBIDA) of
liver showing
good hepatic
uptake of
isotope and no
excretion into
bowel.
Biliary Atresia
Liver biopsy of biliary atresia showing bands of
fibrous tissue with bile duct proliferation.
Neonatal Hepatitis
Liver biopsy in neonatal hepatitis showing inflammatory infiltrate
throughout the liver, and giant cell and rosette formation of liver cells.
Biliary cirrhosis
Biliary cirrhosis
Kasai Portoenterostomy
Formation of Roux-en-Y to re establish bile flow by
anastomising bowel to ductal remnant
Management of cholestasis
1) Specific treatment
- Sepsis  antibiotics
- Galactosemia  Lactose free milk
- Choledochal cyst  surgical correction
- EHBA Kasai operation (hepatic portoenterostomy)
Should be done before 60 days to obtain good results
as the obliterative process is progressive Delay in
operation reduces the chances to find any patent
biliary ductules.
Procedure: a loop of jejunum is anastomosed to the
transected porta hepatis.
2) Nutritional support
Medium chain triglycerides and fat soluble vitamins
3) Treatment of complications
- Pruritis: ursodeoxycholic acid or bile acid binders as
cholestyramine
- Varices: sclerotherapy
- Hepatic encephalopathy: 10% glucose infusion, bowel
wash by enema, oral neomycin, lactulose,….
4) Liver transplantation
- For EHBA who have failed Kasai.
Cholestasis in Older Children
• HAV infection (anorexia, fever, vomiting,
abdominal pain, darkening of the urine with
elevated aminotransferase values in the absence
of other known hepatotoxic exposures).
• HCV infection (increased exposure to IV blood
products (hemodialysis, hemophilia, surgery).
• Hepatotoxic medications(isoniazid,
nitrofurantoin, sulfonamides, and NSAID , such as
acetaminophen and ibuprofen.
Cholestasis in Older children
• A history of sore throat in an individual who also
has jaundice, splenomegaly, and
lymphadenopathy suggests Epstein-Barr virus.
• Gall bladder disease, right upper quadrant colicky
pain and nausea (following ingestion of fatty
foods).
• Cholestasis may lead to complaints of pruritus
and a particularly dark and foamy urine. The color
is due to choluria (bile pigments in the urine); the
foaminess suggests the presence of choleuria
(bile salts in the urine).
Viral Hepatitis
HAV
HBV
HCV
HDV
Type
RNA
DNA
RNA
RNA,
RNA
incomplete
Transmission
Oral
Parenteral
Parenteral Parenteral
Oral
Incubation, day 15-40
50-150
30-150
20- 90
15-60
Carrier state
No
yes
yes
yes
No
Diagnosis
Anti-HAV HBsAg,
Anti-HCV, Anti-HDV
IgM
Anti-HBcIgM HCV-RNA
Anti-HEV
Vaccine
Yes
Yes
No
No
Treatment
Not
needed
Interferonalpha/
Lamivudine
Interferon- Interferonalpha/
alpha
Ribavirin
Yes
HEV
No
Diagnosis of viral hepatitis
1) Clinical forms of acute hepatitis (4 forms)
a) Icteric hepatitis: the most common
Pre - icteric phase :
- Mild fever , anorexia , vomiting and abdominal pain
- Urine is dark ( bilirubinuria )
Icteric phase :
- Jaundice appears
- Liver is tender and enlarged
- Anorexia is common
Convalescent phase :
- Gradual decline of symptoms and signs.
- This is the rule in hepatitis A.
b) Cholestatic hepatitis obstruction to bile flow,
jaundice, and pruritis and pale stool are common
c) Anicteric hepatitis
- Common in infants featured by GIT manifestations like
gastroenteritis
d) Fulminant hepatitis
- Not common and very serious
- Causing acute liver failure (progressive jaundice,
bleeding and rapidly developing coma)
2) Investigation to confirm acute liver injury
- Marked increase of serum bilirubin (direct or mixed)
- Marked elevations of transaminases (ALT and AST) to very
high levels.
- Bilirubin in urine
- Evidence of acute hepatic failure
1) Rising serum bilirubin
2) Low serum albumin
3) Prolonged prothrombin time
4) High blood ammonia, and electrolyte imbalance
3) Identification of the virus
HAV
HBV
HCV
HDV
HEV
Onset
Acute
Insidious
More insidious
With HBV
As HAV
Course
Short
prolonged
More
prolonged
Severe
As HAV
Chronicity
No
possible
Very possible
possible
No
Fulminant
failure
Rare
May occur
rare
With HBV
In
pregnant
females
Laboratory
diagnosis
Anti-HAV IgM
(acute),
Anti-HAVIgG
(recovery)
HBsAg/
antiHBc IgM
(acute),
Anti-HBs
(recovery),
HBsAg/
antiHBc IgG
(chronicity)
Anti-HCV
(exposure),
Anti-HCV/
HCVRNA
(chronic)
Anti-HCV and
–ve HCVRNA
(recovery)
Prevention
Hepatitis A
- Fecal - oral hygiene
- Hepatitis A vaccine
Hepatitis B
- Measures for blood products (use disposable syringes and
needles), screening of pregnant mothers, immunization
- Passive : gammaglobulin
- Active : hepatitis B vaccine.
Complications : in types B,C,D:
(1) Fulminant hepatitis & hepatic failure
(2) Chronic hepatitis ( persistent - active )
(3) Cirrhosis
(4) Hepatocellular carcinoma
(5) Aplastic anemia
Acute liver failure (fulminant hepatitis)
 Massive hepatic necrosis with subsequent loss of liver
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function,
Uncommon, but has a high mortality.
The child may present within hours or weeks with
jaundice, encephalopathy, coagulopathy,
hypoglycaemia and electrolyte disturbance.
Early signs of encephalopathy include alternate
periods of irritability and confusion with drowsiness.
Older children may be aggressive and unusually
difficult.
Complications include cerebral oedema, haemorrhage
from gastritis or coagulopathy, sepsis and pancreatitis.
Acute liver failure (fulminant hepatitis)
Causes
1.Infection…HAV, HBV, HCV, non-A to G
2.Drugs/Poisons…Paracetamol, isoniazide,…
3.Metabolic…Wilsons disease, tyrosinemia…
4.Autoimmune hepatitis
5.Reye’s syndrome
Acute liver failure (fulminant hepatitis)
• Management
– Maintaining the blood glucose (>4mmol/L) by IV
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dextrose.
preventing sepsis with broad-spectrum antibiotics
preventing haemorrhage IV vitamin K, FFP and
H2-blockers
treating cerebral oedema by fluid restriction and
mannitol diuresis.
Acute liver failure (fulminant hepatitis)
• Poor prognosis is likely
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when the liver begins to shrink in size,
if there is a rising bilirubin with falling transaminases,
an increasing coagulopathy or
progression to coma.
• Without liver transplantation, 70% of children
who progress to coma will die.
Reye's syndrome and Reye-like syndrome
 Acute non-inflammatory encephalopathy with
microvesicular fatty infiltration of the liver.
 Aetiology is unknown, there is a close association
with aspirin therapy.
 Stop give aspirin to children as an antipyretic to
avoid it
 Reye-like syndrome
• Beta oxidation defect, medium chain acyl-CoA
•
dehydrogenase deficiency (MCAD).
Many of these patients would have presented with acute
liver failure and a Reye-like syndrome later in life.
Chronic hepatitis
Causes
1) Chronic infection:
HBV, HDV, and HCV (not with HAV or HEV)
2) Autoimmune hepatitis
3) Drug-induced:
Rifampicin, isoniazid, nitrofurantoin
4) Inborn errors of metabolism
As Wilson disease and alpha-one anti-trypsin deficiency
Autoimmune Hepatitis
• The mean age is 7-10 years. More common in girls.
• May present as
– an acute hepatitis,
– as fulminant hepatic failure or
– chronic liver disease with autoimmune features such as skin
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rash, lupus erythematosus, arthritis, haemolytic anaemia or
nephritis.
Diagnosis is based on
– hypergammaglobulinaemia (IgG >20g/L);
– positive autoantibodies, e.g. smooth muscle antibodies
(SMAs), antinuclear antibodies (ANAs) or liver/kidney
microsomal antibodies.
– a low serum complement (C4); and typical histology.
Most children respond to prednisolone and azathioprine.
Wilson’s Disease
Kayser-Fleischer rings from copper in the cornea in a
child with Wilson's disease.
Clinical presentations
1) Unresolved hepatitis
Acute hepatitis unresolving in 6 months
2) Slowly progressive liver disease
Manifestations of chronic liver cell failure
Investigations
1. Liver functions tests: usually abnormal
2. Abdominal ultrasound: to define size of liver and
spleen and check for ascites
3. Liver biopsy: is very helpful for diagnosis, it shows
chronic inflammatory cell infiltrate
4. Investigations for the cause such as serological
markers for hepatitis B and C; autoantibodies for
autoimmune hepatitis and low seruloplasmin and
high copper in Wilson disease.
Complications
1. Liver cirrhosis and hepatic carcinoma
2. Portal hypertension causing varices and ascites
3. Chronic liver cell failure
Treatment
1) Treatment of cause if possible
• Interferon for chronic HBV and HCV
• Prednisolone and azathioprine for autoimmune
hepatitis
• D- penicillamine for Wilson disease
2) Liver transplantation
Good option for end stage liver disease with good
results
Liver Cirrhosis
• Definition : Irreversible condition with widespread liver
fibrosis & nodule formation. There is disturbed vascular
arrangement leading to portal hypertension
• Causes :
1 - Post-hepatitis cirrhosis
2 - Biliary cirrhosis eg. biliary atresia
3 - Metabolic e.g. Wilson's disease .
4 - Cardiovascular: Constrictive pericarditis- Budd
chiari synd.
• Diffuse fibrosis occur in :
- Schistosomiasis
- Cong. hepatic fibrosis
Complications
(1) Parenchymal Failure (liver call failure)
* Failure of synthetic function of liver
- Decrease S. albumin, prothrombin, coagulation factors
* Failure of detoxication
A - encephalopathy
B - hormonal changes
C - infection
(2) Vascular failure i.e. Portal hypertension Splenomegaly,
Ascites and
Portosystemic anastomosis (oesophageal varices)
Portal hypertension
• Definition: When the portal venous pressure exceeds 12
mmHg (normal variation 5 – 10 mmHg)
• Causes of portal hypertension:
1) Pre hepatic = portal vein obstruction/thrombosis due to
- umbilical sepsis
or - umbilical vein catheterization
* Clinically:
1 - Portal hypertension
2 - Marked splenic enlargement with NORMAL liver
2) Intra hepatic portal hypertension :
Hepatic - Chronic hepatitis - Cirrhosis
- Bilharzial fibrosis - Wilson disease
- Congenital hepatic fibrosis
- Veno-occlusive disease
Biliary - Extrahepatic biliary atresia
- Sclerosing cholangitis
* Clinically : - History of hepatic/biliary disease
- Portal hypertension
- Liver size is variable, usually shrunken with
sharp edge.
3) Post hepatic portal hypertension : (postsinusoidal)
- Budd-Chiari ( hepatic vein obstruction)
- Constrictive pericarditis .
* Clinically : - Portal hypertension
- Marked liver enlargement
- Spleen may be normal or enlarged in late
cases
Clinical features
1) Esophageal varices: due to opening of collateral circulation.
Also, dilated abdominal veins (caput medusa). Varices lead to
hematemesis which may be mild or massive.
2) Splenomegaly:
More evident with prehepatic and hepatic causes
3) Ascites: Due to
- Hypoproteinemia,
- Na retention,
- Renal impairment and fluid redistribution .
It can be complicated by bacterial peritonitis.
4) Hepatic encephalopathy: induced by GIT hemorrhage,
sepsis, electrolyte imbalance and high protein intake. The
mechanisms of CNS manifestations include
hyperammonemia, false neurotransmitters, high
aromatic amino acid levels and GABA accumulation
5) Renal failure: hepatorenal syndrome.
Cirrhosis and Portal Hypertension
Cirrhosis and portal
hypertension.
(i) malnutrition with loss
of fat and muscle bulk
(ii) distended abdomen
from ascites and
hepatosplenomegaly
(iii) scrotal swelling from
ascites
(iv) no jaundice despite
advanced liver disease.
Ascites
This infant has
• A grossly distended
abdomen from ascites
• Dilated abdominal veins
secondary to portal
hypertension and
• An umbilical hernia from
increased abdominal
pressure
• A surgical scar.
Cirrhosis and Portal Hypertension
Cirrhosis and Portal Hypertension
Portal Hypertension, Varices
Portal Hypertension, Varices
Portal Hypertension, Varices
Investigations
1) Upper endoscopy: to detect varices
2) Abdominal ultrasound: may show shrunken liver
and splenomegaly
3) Splenoportography to locate site of obstruction
4) Liver function tests
5) Screening for causes of chronic liver disorders
Management
• Aim: to prevent or treat bleeding varices
A) Emergency treatment of bleeding varices
1. Hospitalization
2. IV fluid resuscitation and blood transfusion
3. H2 blockers as ranitidine
4. If bleeding persists: vasopressin infusion
B) Endoscopic management by
- Sclerotherapy or
- Band ligation of the varices
C) Surgical treatment by portosystemic shunt (bypass)
- Transjugular intrahepatic porto-systemic shunt
(TIPSS)
- Surgical portosystemic shunts as porticaval shunts
D) Prevention of bleeding
- Prevention of first bleeding attack:
• Avoid aspirin
• Beta blockers as propranolol(reduces portal venous
pressure)
• prophylactic sclerotherapy or band ligation
- Prevention of rebleeding: beta blockers,
sclerotherapy, band ligation, surgical portosystemic
shunts and liver transplantation
Liver transplantation
• Indications include acute or chronic end stage liver
failure.
• Contraindications include sepsis, untreatable
cardiopulmonary disease or cerebrovascular disease.
• Most children receive part of an adult’s liver of a
living person.
• Complications after transplantation are not
uncommon such as hepatic artery thrombosis, biliary
leaks, rejection, VOD and sepsis
• Outcome: Children who survive the initial
postoperative period usually do well.
• Short and long term results are much promising for
this kind of therapy for previously hopeless cases.
Clinical and laboratory
evaluation of liver disease
Physical Examination
• The liver span is the distance between the
liver edge and the upper margin of dullness
obtained by percussion at the right
midclavicular line.
• The mean span changes from 4.5 to 5 cm at 1
week of age to 6 to 7 cm in early adolescence.
• If the spleen is enlarged:
– Portal hypertension or storage disease
• Tender hepatomegaly:
– Viral hepatitis or heart failure
• Massive hepatomegaly
– Congenital hepatic fibrosis
• Ascites:
– Portal hypertension or liver failure
• Massive hepatosplenomegaly:
– Storage disorder or malignancy
• Intense pruritus in obstructive liver disease,
that primarily is manifested by irritability.
• Alagille syndrome
– Characteristic facies (beaked nose, high forehead),
butterfly vertebrae, a murmur on auscultation due
to peripheral pulmonic stenosis, and a posterior
embryotoxon on ophthalmologic examination.
Laboratory Evaluation
Cholestatic or obstructive
• Elevation of mainly
alkaline phosphatase
(AP), gamma glutamyl
transpeptidase (GGT),
and conjugated
bilirubin.
Liver cell injury
• Elevation of mainly
aminotransferases (ALT
and AST)
Liver function tests
• The term is NOT accurate… Why??
• Only two of the parameters commonly obtained
are true measures of hepatic function
– the prothrombin time (PT) and
– serum albumin level, both assess synthetic ability.
• All of the other parameters are essentially
indirect measures of liver function, and some of
these values are altered in settings other than
liver disease
Liver function tests
• Cholestasis is defined by conjugated
hyperbilirubinemia more than 20 % of total
serum bilirubin.
• Dark urine due to bilirubinuria
• The levels of alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) are the most
sensitive tests of hepatocyte necrosis.
• ALT is more specific of liver disease because it is
found only in low concentrations in other tissues .
Liver function tests
• An elevated serum AP level usually indicates
obstructive liver disease especially if the rise in
AP is associated with a rise in GGT… Why??
• A low serum albumin concentration is a late
finding in liver disease. When it is present, it
suggests chronic disease.
• Hyperammonemia and encephalopathy are
classic findings of liver failure, and there is a labile
correlation between the degree of
encephalopathy and serum ammonia levels.
Liver function tests
• The PT (prothrombin time) which measures
the time required for prothrombin (factor II)
to be converted into thrombin, will be
elevated in the presence of biliary obstruction.
• This is the basis for parenteral administration
(not oral) of vitamin K to patients who have
elevated PT values.
Liver function tests
• No matter what the cause, an elevated PT
value in patients who have liver disease is
serious. One of the first steps when
evaluating a newborn who has cholestasis is
to measure PT/PTT and administer vitamin K.
• Untreated hypoprothrombinemia may lead
to spontaneous bleeding and intracranial
hemorrhage.
Imaging and Histopathology
of the Liver and Biliary Tract
• Abdominal ultrasonography
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Liver size and texture
Choledochal cysts and stones (95% accuracy)
Space occupying lesions & dilated bile ducts.
Absence of gallbladder in case of biliary atresia.
• Radionuclide imaging (technetium-99)
– Detects liver uptake and excretory abilities.
– The appearance of the tracer within the intestinal
region by 24 hours virtually excludes biliary atresia, but
the converse is not true.
Percutaneous liver biopsy
• The cardinal method by which to arrive quickly at
a diagnosis of underlying liver disease.
• Shows the degree of fibrosis/cirrhosis and permits
the diagnosis of biliary atresia, neonatal hepatitis,
congenital hepatic fibrosis, and alpha 1-antitrypsin
deficiency.
• In neonatal hepatitis there is giant cell
transformation with inflammatory infiltrates of the
portal zones and an absence of bile ductule
proliferation.
Percutaneous liver biopsy
• In EHBA there is proliferation of the
interlobular bile ducts, periportal fibrosis, and
bile plugs in canaliculi and ductules.
Older children
• Wilson disease needs to be included in the
differential diagnosis of any child who
presents with liver disease, neurologic
abnormalities, behavioral changes, or KayserFleischer rings.
Management
Liver transplantation
• Survival rates approach 80% at 1 year and 70%
at 5 years.
• Biliary atresia is the most common indication
for transplant and may be the initial treatment
when detected late or may be used as a
salvage procedure for a failed Kasai.
• Used early in cases of tyrosinemia
Medical management of liver diseases
• Nutritional support
• Treatment of pruritus, choleretics and bile acidbinders
• Management of portal hypertension and its
consequences
Treatment
• Nutritional support
– Adequate calories and protein
– Supplement calories with medium chain
triglycerides
– Treatment and/or prophylaxis for fat-soluble
vitamin deficiencies (vitamins A, D, E, and K)
Treatment
• Nutritional support (cont.)
– Supplemental calcium and phosphate when bone
disease is present
– Prophylaxis for zinc deficiency
– Low-copper diet as poorly excreted
– Sodium restriction when ascites present
Treatment
• Treatment of pruritus
– Bile acid-binders: cholestyramine
– Ursodeoxycholic acid
– Phenobarbital as a choleretic
Treatment
• Management of portal hypertension and its
consequences
– Variceal bleeding
•
•
•
•
•
•
Fluid resuscitation
Blood products
Sclerotherapy
Balloon tamponade
Portovenous shunting
Propanolol
Treatment
• Management of portal hypertension and its
consequences (cont.)
– Ascites
•
•
•
•
Sodium restriction
Diuretics: spironolactone, furosemide
Albumin
Paracentesis
Conclusion
• Identifying the presence of serious liver
disease in a pediatric patient at the initial
presentation is of cardinal importance.
• Early recognition of babies who have biliary
atresia is critical for optimal medical or
surgical intervention.
Case Studies
A 15-year-old girl who is being evaluated for poor
school performance and acting-out behaviors is
noted to have a large, firm liver. Kayser- Fleischer
rings are apparent on ophthalmologic examination.
Determination of which of the following is most
likely to confirm the diagnosis in this patient?
.
A. Hepatic copper concentration.
B. Hepatic iron concentration.
C. Hepatitis B antibody titers.
D. Serum alpha 1-antitrypsin level.
E. Serum chloride level
A 3-year-old girl who has cholestasis and is
malnourished is suspected of having a
nutrient deficiency.
Which one of the following clinical findings
is most likely to be present in this child?
.
A. Megaloblastic anemia.
B. Neuritis.
C. Pellagra.
D. Photophobia.
E. Rachitic rosary
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