Pediatric Hepatology Flashcards
Define biliary atresia. What is the pathogenesis? What are 5 clinical manifestations? When and how do they present? What are some lab findings? How do you diagnose it?
Progressive, idiopathic, fibro-obliterative
disease of the extrahepatic biliary tree that
presents with biliary obstruction exclusively in
the neonatal period.
BA is a mult-ifactorial disease that is
uniformly characterized by inflammation and
subsequent fibrosis of the biliary tree.
Jaundice, Acholic Stool, Dark Urine, Growth Failure
Hepatosplenomegaly
Classic presentation is of a previously healthy term infant who around 4 weeks of age develops those symptoms.
LAB FINDINGS •Conjugated hyperbilirubinemia > 2 mg/dl or >20% of total bilirubin level •Mild to moderate increases in serum aminotransferases •Disproportionately increased GGTP •Elevated Alkaline phosphatase •Initially, normal albumin and PT
How is the diagnosis of biliary atresia made?
DIAGNOSIS
Abdominal Ultrasound: to rule out other anatomic causes of cholestasis
Hepatobiliary Scintigraphy (HIDA Scan): Diagnostic technique in which a 2-D picture of internal body tissue is produced through the detection of radiation emitted by a radioactive substance administered into the body •Infants with biliary atresia usually have normal uptake of thE isotope but absent excretion into the bile and intestine •Neonatal hepatitis have delayed uptake but appropriate excretion
Liver biopsy is recommended in all infants with
suspected biliary atresia
•To identify changes suggestive of biliary atresia
that would warrant surgical management
Proliferation of bile ducts
•To rule out other cases of intrahepatic
cholestasis that would not need surgical
management
Alagille syndrome (paucity of bile ducts)
Alpha-1-antitrypsin deficiency
Intraoperative Cholangiogram
Gold standard
Determines patency proximally into the liver and distally into the bowel
How is biliary atresia treated? Treatment outcomes?
TREATMENT
If the IOC demonstrates biliary obstruction (i.e., if
the contrast does not fill the biliary tree or reach
the intestine), the surgeon should perform a
hepatoportoenterostomy (Kasai HPE) at that time
Treatment outcomes
1/3 fail immediately and go on to liver
transplant.
1/3 fail in a few years and go to transplant
1/3 do well for many years with variable
degrees of liver disease and complications
Describe alagille syndrome? Inheritance? Principle feature? 4 possible related features? How is the diagnosis made? Treatment?
An autosomal dominant condition, with variable
penetrance and multiple genes involved
•The principal feature is of chronic cholestasis
due to paucity of intrahepatic bile ducts and
associated features:
Cardiac anomalies, most commonly peripheral pulmonic stenosis (>80 percent)
Butterfly vertebrae (>80 percent)
Posterior embryotoxon of the eye (>80% percent)
Dysmorphic facies, consisting of broad nasal bridge,
triangular facies, and deep set eyes (>90 percent)
DIAGNOSIS
The diagnosis of AGS is made by identifying
the constellation of clinical features, with
the characteristic histology of paucity of the
intralobular bile ducts and confirmed by
molecular DNA
TREATMENT
Therapy is generally symptomatic, liver failure is
uncommon.
•Cholestasis
Ursodeoxycholic acid (Ursodiol) may improve the biochemical cholestasis, but the effects on actual outcomes is questionable.
•Pruritus
Typically more severe than in other causes of cholestasis
and may be difficult to control.
•Efficacy of antipruritic medication varies with each patient
•If no response to medication, partial external biliary
diversion may be performed, although results are variable.
•
What is the inheritance of A1AT deficiency? Pathophys? How do the liver symptoms present? How are they treated?
Autosomal recessive disease in which individuals homozygous for the “Z” mutation are at risk for liver disease as children or adults, and early onset adult pulmonary emphysema.
•Many mutations in the gene have been described,
but the “Z” and “S” mutations are by far the most
commonly associated with disease.
•ZZ homozygotes are found in 1/2000 – 1/5000
births in US and European populations.
•About 2% of the US population are heterozygous
“carriers”
•The mutant Z protein accumulates within
hepatocytes, rather than being secreted, causing
hepatocellular damage.
- Most common inherited cause of neonatal cholestasis
- The A1AT gene directs the synthesis of a protein in the liver which is secreted into serum in high quantities (second only to albumin).
- The normal function of A1AT protein is inhibition of neutrophil proteases (especially elastase) to protect “self” tissues from inflammation-induced damage while fighting infection.
- This is especially important in the lung.
The serum is “deficient” in A1AT, leaving the lung
vulnerable to proteolytic attack.
•
Lung injury is greatly potentiated by smoking.
•
Risk of life-threatening liver disease in childhood is 3-5%,
but 15-50% lifetime risk of any liver damage.
•
The presentation is often neonatal cholestasis and hepatitis
•
“Silent” cirrhosis in older adults is common.
•
The condition is widely underappreciated and often
misdiagnosed as alcoholic disease.
•
No specific treatment
•Manage complications of liver disease as they develop
Liver transplantation if needed.
Describe the symptom set for any perinatal/neonatal liver injury.
The perinatal/neonatal liver has a unique, and
often common set of responses to any injury.
Hepatocellular injury; increased AST, ALT
Cholestasis; elevated conjugated bilirubin
Hepatomegaly
Hepatocytes forming giant cells, along with inflammation and cholestasis on biopsy.
These findings are not specific to any particular
neonatal cholestasis syndrome, but may be seen
in all neonatal liver injury
•
What is idiopathic neonatal hepatitis?
NH is defined as prolonged conjugated hyperbilirubinemia without an obvious etiology after a complete evaluation has excluded identifiable infectious and
With identification of specific disorders (such
as A1AT) that had been previously included
in this category, the incidence of idiopathic
neonatal hepatitis has declined.
•
When is pediatric liver transplantation indicated?
Liver transplantation (LTx) in pediatrics has become
an accepted modality of treatment in end-stage liver
disease and irreversible acute liver failure (ALF).
Cholestatic conditions
•Biliary Atresia (50%). Most require transplant within first 2 years of life. Alagille Syndrome Familial Cholestasis (PFIC) TPN (short gut)
Metabolic liver disease:
A1AT deficiency Wilson’s Disease, CF Tyrosinemia Neonatal hemochromatosis
Fulminant Liver Failure
Autoimmune hepatitis
Malignancy
Hepatoblastoma
Hepatocellular carcinoma
What is the PELD score? How is it used? What does it take into account? What else is used in organ allocation?
Pediatric End Stage Liver Disease [PELD] score is used to support
organ allocation.
•PELD and MELD (adults) are used to allocate organs for patients with chronic liver disease; they were not designed for use in Acute Liver Failure (ALF).
Albumin (g/dl)
Bilirubin (mg/dl)
INR
Growth failure (base on gender, height, and weight)
Age at listing
Patients with ALF and in need of liver transplantation are given priority over those listed with a PELD/MELD score and are listed as Status 1A, the category with the highest priority status.
What might lead to poor outcomes with pediatric liver transplant?
Excellent outcomes after liver transplant (>80%, 5
year) when compliance is assured.
•
Adherence to the prescribed medical regimen is essential for good graft function.
•Poor compliance with medications is a leading cause of late morbidity in children and adolescents who have received LTx.
Viral infections with cytomegalovirus (CMV) and Epstein Barr virus (EBV) are an important cause of morbidity and mortality after LTx in pediatrics.
•The occurrence of primary EBV infection may be associated with post-transplant lymphoproferative disorder (PTLD), a type of lymphoma, after LTx in children.
•Incidence of PTLD can be minimized by regular surveillance of EBV by PCR or appropriate reduction of immunosuppression with or without antiviral therapy.
