11 - Pediatric Diseases of the Liver Flashcards
Cholestasis
Impairment in bile flow From: Defects in intrahepatic production Transmembrane transport Mechanical obstruction
Cholestasis - Manifestations
Retention of bile components Elevated serum bile acids - Pruritis Hyperbilirubinemia - Jaundice Hypercholesterolemia - Xanthomas Impaired copper excretion - fibrosis Neonatal cholestasis > 2 weeks affects 1 in 2500 births
Cholestasis Consequences - Impaired Bile Salt Excretion
Fat Malabsorption - Nutritional Impairment
Fat Soluble Vitamin Deficiency
Cholestasis Consequences - Hepatocellular Injury
Progressive fibrosis, evolving to cirrhosis
Portal hypertension
Loss of hepatic synthetic function
Most common cause of neonatal cholestasis, but least understood
Idiopathic Neonatal Hepatitis
Idiopathic Neonatal Hepatitis
30 - 40% of neonatal cholestasis Jaundice in the first week of life 33% FTT or fulminant course Hepatomegaly +/- Splenomegaly Acholic stool possible
Two forms of Idiopathic Neonatal Hepatitis
Sporadic (60 - 70% full recovery)
Familial (20 - 30% recovery, 10 - 15% cirrhosis)
Idiopathic Neonatal Hepatitis - Pathology
Severe diffuse hepatocellular disease
Marked infiltration by inflammatory cells
Focal hepatocellular necrosis
GIANT CELL HEPATITIS
Not present:
Bile ductular proliferation
Bile duct paucity
Biliary Atresia
Uncommon
No familiar pattern
Icteric by first week
Acholic stools
Biliary Atresia - Associated abnormalities
Polysplenia
Heterotaxia
Intra-abdominal vascular abnormalities
Biliary Atresia - Cause
Unknown
Can be induced via infectious agents (Reovirus III, CMV)
Biliary Atresia - Investigations
Abdominal ultrasound (to rule out biliary obstruction like a choledochal cyst)
HIDA scan with phenobarb x 5D (good for ruling out)
Liver biopsy
Intra-op cholangiogram
If you give phenobarb to a pediatric patient, what are the two ways they can go about bile absorption?
Bile acid dependent (main/only pathway in adults)
Bile acid independent (about 10% of the pathway in kids, can induce this pathway with phenobarb)
Biliary Atresia - Pathology
Infantile obstructive cholangiopathy Bile ductular proliferation Portal expansion with edema +/- fibrosis Bile plugs Intact lobular architecture Giant cells may be present
Biliary Atresia - Treatment
Kasai hepatic porto-enterostomy
Performed in the first few months of life (
Alagille Syndrome
Autosomal Dominant Arteriohepatic dysplasia Variable penetrance JAG 1 (notch ligand) mutation (>90%) Chromosome 20p12 Intrahepatic interlobular bile duct paucity
Alagille syndrome - Abnormalities
Face - Broad forehead, underdeveloped mandible, straight nose (95%)
Ocular - Posterior embryotoxon - finding in the eye, doesn’t change vision(88%)
Cardiovascular - Peripheral Pulmonic Stenosis or Tetralogy of Fallot (85%)
Vertebral - Butterfly vertebrae (87%)
Minor abnormalities - Renal disease, short stature, pancreatic insufficiency
Alagille’s Syndrome - Prognosis
Prolonged survival good (80% without OLT)
Pruritus
Xanthoma - Lipoprotein X
Neurologic complications (Vitamin E deficiency)
Defective spermatogenesis
Growth retardation
CNS anyeurisms
Progressive Familial Intrahepatic Cholestasis (PFIC)
Byler’s-like syndrome
Autosomal Recessive
PFIC-1 defect in P-type ATPase gene (ATP8B1)
FIC-1 gene localized to chromosome 18q21
Defect in biliary canalicular membrane phospholipid transport
PFIC-2 - defective bile salt export pump (BSEP) - You can stain for this on biopsy now!!
Normal GGTP (it’s a transport defect!)
Post transplant sometimes you end up with bile salty diarrhea
Choledocal Cyst
Congenital biliary dilatation
Common bile duct affected
Cyst wall - fibrous tissue lacking epithelium
Malignant potential - Merits resection
Early
Choledocal Cyst - Type 1
50 - 80%
Diffuse fusiform dilatation of the common bile duct
Choledocal Cyst - Type 2
Diverticulum of common bile duct
Choledocal Cyst - Type 3
Within the duodenal wall
Choledocal Cyst - Type 4
Type 1 (diffuse fusiform dilatation) with intrahepatic duct cyst
Choledocal Cyst - Diagnosis
Abdominal ultrasound
Caroli’s Disease
Cystic dilatation of intrahepatic ducts
Not familial
75% male
Usually present in childhood or early adult life
Abdominal pain, hepatomegaly, gram (-) sepsis
Caroli’s Disease - Diagnosis
Ultrasound, CT scan, ERCP, PTC
Common bile duct normal, multiple saccular dilatations of intrahepatic ducts, can be unilateral
Cholangiocarcinoma risk - 7% of patients
Caroli’s Disease - Treatment
Stenting, suppressive antibiotics, pain meidcation
Gestational Alloimmune Liver Disease
Formerly known as neonatal hemochromatosis
Hepatic failure (at birth!) and iron deposition
Onset is intrauterine
Anti-human C5B-9 complex - Transplacental IgG
Activates fetal complement cascade
Target protein not identified
Gestational Alloimmune Liver Disease - Treatment
IVIG and exchange transfusion
Liver transplant if medical treatment fails
Subsequent pregnancies treated with IVIG beginning at 18 weeks gestation (90% recurrence)
Infectious Hepatitis - Pathogens
Toxoplasmosis Rubella CMV Herpes Syphillis Coxsackie Echovirus (11, 14, 19) Adenovirus Parvovirus B19 EBV (unusual)
Alpha-1 Antitrypsin Deficiency
AAT serine protease inhibitor (PI)
Accumulation of abnormal protein in ER
PI phenotyping - defined by isoelectric focusing of plasma
Gene on chromosome 14 with over 100 known mutations
Most common allele causing liver disease is Z
Transplant for severe liver disease / cirrhosis - 65%
Risk of COPD with panlobular emphysema
Alpha-1 Antitrypsin Deficiency - Path
PAS+ Globules that resist diastase treatment
Parenteral Nutrition-Associated Liver Disease
Formerly TPN Cholestasis
Range from mildly elevated LFTs and Fatty Liver to Frank Cirrhosis
Cholestasis - Worse with time and lack of enteral stimulation
Etiology unknown - Toxic bile acid metabolites, bacterial toxins, glucose concentration, free oxygen radicals from peroxidation of lipids
Parenteral Nutrition-Associated Liver Disease - Treatment
Feed, Cycle or stop TPN Reduce lipids Bowel in circuit STEP Ursodiol Bowel decontamination
Parenteral Nutrition-Associated Liver Disease - Biopsy
Indistinguishable from Biliary Atresia
Bile plugs
Ductular abnormalities
Tyrosinemia
Autosomal Recessive
Lack fumaryl acetoacetate hydrolase (FAH)
Metabolites toxic to liver and kidney (RTA)
Neurologic impairment can occur
Painful crises, mimicking porphyria
HCC occur in >40% of cases
Tyrosinemia - Diagnosis
Elevated urinary succinyl acetone
Tyrosinemia - Treatment
NTBC/Orfadin
Specific inhibitor of tyrosine metabolism
Tyronsinemia - Cure
Transplant
Galactosemia
Autosomal recessive
Lacking galactose-1-phosphate-uridyl transferase
Diffuse hepatocellular fatty change
Galactosemia - Infant signs
Feeding problems, cataracts, vomiting, jaundice, diarrhea, ascites, HM, sepsis
Galactosemia - Diagnosis
+ Urine reducing substance, G1PUT levels
Galactosemia - Treatment
Withdrawal of dietary milk and milk products
Cholestasis - Overall management
Nutritional support (vitamin supplementation)
Alleviate pruritus (Choleretic agents)
Monitor growth, clinical and biochemical parameters
Optimize psychosocial development
Assess quality of live
Gauge success, search for complications
Disease specific therapy - diet, surgical palliation, medications
Liver transplant
