Overview
Definition:
Liver function tests (LFTs) are a panel of blood tests that provide information about the state of a patient's liver
In pediatrics, interpretation of these tests requires careful consideration of age-specific reference ranges and physiological variations.
Epidemiology:
Abnormal LFTs are common in pediatric practice, with etiologies ranging from benign transient elevations to severe congenital or acquired liver diseases
Prevalence varies significantly with age and underlying causes like neonatal cholestasis, viral hepatitis, metabolic disorders, and drug-induced liver injury.
Clinical Significance:
Accurate interpretation of pediatric LFTs is crucial for early diagnosis, monitoring disease progression, assessing treatment response, and predicting outcomes in a wide spectrum of pediatric hepatobiliary disorders
Deviations from age-appropriate norms can signal significant pathology requiring timely intervention, vital for patient care and success in DNB/NEET SS exams.
Age Considerations
Neonates And Infants:
Newborns and infants have immature hepatic enzyme systems and distinct metabolic pathways
Reference ranges for enzymes like ALT, AST, and alkaline phosphatase differ significantly
Neonatal cholestasis, often presenting with conjugated hyperbilirubinemia, is a critical concern requiring prompt evaluation for causes like biliary atresia, neonatal hepatitis, and genetic disorders.
Children:
In this age group, LFTs generally approach adult ranges
However, specific conditions like viral hepatitis (Hepatitis A, B, E), autoimmune hepatitis, and Wilson's disease need to be considered
Drug-induced liver injury is also a significant cause of abnormal LFTs.
Adolescents:
LFTs are closer to adult norms
Common etiologies include viral hepatitis, autoimmune conditions, fatty liver disease (NAFLD/NASH), and drug-induced liver injury
Puberty can influence some enzyme levels
Considerations for sexually transmitted infections (Hepatitis B, C) and substance abuse are also relevant.
Key Liver Enzymes And Markers
Alanine Aminotransferase Alt And Aspartate Aminotransferase Ast:
These transaminases are released when liver cells are damaged
Neonates typically have lower baseline levels than older children and adults
Transient elevations can be seen after birth
Persistent elevations in infants and children warrant investigation for viral hepatitis, metabolic diseases, autoimmune hepatitis, and biliary obstruction.
Alkaline Phosphatase Alp:
ALP is produced by the liver, bone, intestines, and placenta
Pediatric reference ranges are significantly higher in infancy and childhood due to active bone growth, peaking in early adolescence
Elevated ALP in the context of elevated GGT suggests a hepatobiliary source.
Gamma Glutamyl Transferase Ggt:
GGT is a sensitive marker of hepatobiliary disease, particularly cholestasis
It is often elevated in neonatal cholestasis and is a good indicator of biliary tract obstruction or damage
GGT levels are generally lower in neonates and infants compared to older children.
Bilirubin Total And Direct:
Neonatal jaundice is common, but persistent or severe hyperbilirubinemia, especially conjugated hyperbilirubinemia, is pathological
In conjugated hyperbilirubinemia, direct bilirubin >20% of total bilirubin suggests a hepatobiliary issue like biliary atresia or intrahepatic cholestasis.
Albumin:
Albumin is synthesized by the liver and reflects synthetic function
Its half-life is long (approx
20 days), so it changes gradually
Low albumin levels usually indicate chronic liver disease or severe malnutrition, rarely seen in acute pediatric liver conditions unless there is significant protein loss or poor intake.
Prothrombin Time Pt And International Normalized Ratio Inr:
PT/INR reflects the synthetic function of the liver, specifically the production of vitamin K-dependent clotting factors
A prolonged PT/INR indicates impaired hepatic synthetic function and is a sensitive indicator of acute liver failure or severe chronic liver disease.
Diagnostic Approach
History Taking:
Detailed history including birth history (gestational age, mode of delivery), feeding patterns, jaundice duration and progression, stool and urine color changes, family history of liver disease or genetic disorders, recent infections, medications, and exposure to toxins
Red flags include persistent jaundice > 2 weeks, acholic stools, dark urine, poor weight gain, lethargy, and hepatomegaly.
Physical Examination:
Assess for jaundice (icterus), hepatomegaly, splenomegaly, ascites, signs of chronic liver disease (e.g., palmar erythema, spider angiomata, though rare in children), edema, and signs of underlying conditions (e.g., dysmorphic features for genetic syndromes).
Laboratory Investigations:
Initial LFT panel
Depending on findings, further tests include complete blood count, coagulation profile, viral serologies (HAV, HBV, HCV, HEV), autoimmune markers (ANA, ASMA, anti-LKM), metabolic screens (serum ceruloplasmin for Wilson's disease, alpha-1 antitrypsin level), urine analysis for reducing substances, and blood gas analysis.
Imaging Modalities:
Abdominal ultrasound is the initial imaging of choice to assess liver size, echotexture, presence of masses, biliary tree dilation, and gallbladder
Magnetic Resonance Cholangiopancreatography (MRCP) is useful for detailed biliary anatomy and detecting blockages
Transient elastography (FibroScan) can assess liver stiffness non-invasively.
Differential Diagnosis:
In neonates: biliary atresia, neonatal hepatitis, alpha-1 antitrypsin deficiency, galactosemia, tyrosinemia, sepsis
In older children: viral hepatitis, autoimmune hepatitis, Wilson's disease, NASH, drug-induced liver injury, alpha-1 antitrypsin deficiency, Budd-Chiari syndrome.
Management And Monitoring
Age Specific Treatment Considerations:
Treatment strategies are tailored to the underlying etiology and the child's age and weight
Neonates with biliary atresia require early surgical intervention (Kasai procedure)
Metabolic disorders may require dietary modifications or specific enzyme replacement therapy
Autoimmune hepatitis is managed with immunosuppressants.
Nutritional Support:
Adequate caloric and protein intake is vital for growth and hepatic regeneration
Fat-soluble vitamin supplementation (A, D, E, K) may be necessary in cholestatic liver disease
Medium-chain triglycerides (MCTs) can be used as an alternative fat source in malabsorption.
Pharmacological Management:
Specific medications include ursodeoxycholic acid for cholestatic conditions, steroids and azathioprine for autoimmune hepatitis, penicillamine or trientine for Wilson's disease
Antivirals for chronic viral hepatitis
Doses are carefully calculated based on weight and age.
Monitoring Frequency:
The frequency of LFT monitoring depends on the clinical condition and treatment
Critically ill neonates or those with acute liver failure may require daily monitoring
Stable chronic liver disease patients might be monitored monthly to quarterly
Post-transplant patients require lifelong monitoring.
Key Points
Exam Focus:
Remember age-specific reference ranges for LFTs, especially for ALT, AST, ALP, and bilirubin
Understand the significance of conjugated hyperbilirubinemia in neonates (biliary atresia)
Differentiate causes of elevated LFTs in different pediatric age groups
Recall key management principles for common pediatric liver diseases.
Clinical Pearls:
Always correlate LFT findings with the clinical presentation and other laboratory/imaging results
A single abnormal LFT value may not be significant
serial monitoring is often essential
Consider non-hepatic causes of elevated enzymes (e.g., hemolysis for AST/ALT, bone disease for ALP).
Common Mistakes:
Using adult reference ranges for pediatric patients
Delaying investigation of neonatal cholestasis
Misinterpreting elevated ALP in children without considering bone growth
Overlooking drug-induced liver injury as a cause of abnormal LFTs
Failing to consider genetic/metabolic causes in unexplained chronic liver disease.