Liver Function Tests

Markers Of Hepatocellular Injury

Assess integrity of hepatocyte membrane.

Alt localizes predominantly in liver.
Ast localizes in liver, cardiac muscle, skeletal muscle, kidneys, brain, erythrocytes.
Elevation indicates hepatocyte inflammation or necrosis.
Normal creatinine phosphokinase confirms hepatic origin of elevated transaminases.
Magnitude of elevation offers diagnostic clues, though does not correlate with extent of necrosis.
Massive elevation (>1000 IU/L) suggests acute hepatocellular injury (ischemic hepatitis/shock liver, fulminant viral hepatitis, hepatotoxic drug injury).
Mild to moderate elevation indicates chronic liver disease.
Ast frequently exceeds Alt in Wilson disease; often accompanies low alkaline phosphatase and Coombs-negative hemolytic anemia.
Rapidly declining transaminases coupled with rising bilirubin and prolonged prothrombin time portends massive hepatic necrosis and poor prognosis.

Assess canalicular bile flow and biliary tree patency.

Identifies presence and etiology of jaundice.
Unconjugated (indirect) hyperbilirubinemia reflects increased production (hemolysis, hematoma) or defective conjugation (Gilbert syndrome, Crigler-Najjar syndrome).
Conjugated (direct) hyperbilirubinemia defines cholestasis; reflects defective hepatic excretion or biliary obstruction.
Conjugated hyperbilirubinemia defined as direct bilirubin >1 mg/dL if total <5 mg/dL, or direct >20% of total if total >5 mg/dL.
Conjugated bilirubin highly specific for liver pathology; always requires prompt investigation in neonates.

Alp found in liver, bone, placenta, intestine.
Normal Alp values inherently higher in growing children secondary to bone isoenzyme fraction.
Ggt highly specific for hepatobiliary origin.
Ggt values physiologically elevated in neonates; reach adult levels by 6-9 months age.
Concurrent elevation of Alp and Ggt confirms hepatobiliary pathology.
Disproportionate elevation of Alp/Ggt compared to transaminases indicates primary biliary pathology.

Ggt Level	Associated Conditions
Elevated (High-Ggt Cholestasis)	Biliary atresia, Alagille syndrome, choledochal cyst, progressive familial intrahepatic cholestasis (PFIC) type 3, neonatal sclerosing cholangitis.
Normal or Low (Low-Ggt Cholestasis)	PFIC types 1, 2, 4, 5, 6; inborn errors of bile acid synthesis; arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.

Assess functional liver mass and reserve. Crucial for determining disease severity.

Liver synthesizes factor V and vitamin K-dependent factors (II, VII, IX, X).
Pt/Inr serves as highly sensitive, dynamic marker of acute hepatic synthetic capability.
Factor VII has shortest half-life (4-6 hours); depletes first in acute liver failure, elevating Pt/Inr rapidly.
Prolongation of Pt >3 seconds above control considered abnormal.
Correction of coagulopathy following intravenous vitamin K administration confirms vitamin K malabsorption (cholestasis) rather than intrinsic hepatocellular synthetic failure.
Pt >15 seconds (Inr >1.5) with encephalopathy, or Pt >20 seconds (Inr >2.0) without encephalopathy defines acute liver failure in pediatrics.

Albumin half-life approximately 20 days; reliably marks chronic synthetic function.
Hypoalbuminemia reflects end-stage chronic liver disease, severe malnutrition, or significant protein-losing enteropathy.
Gamma globulins (IgG) markedly elevated in autoimmune hepatitis.
Reversal of albumin-to-globulin ratio indicates cirrhosis.

Cleared via hepatic urea cycle.
Elevated in acute liver failure, decompensated chronic liver disease, urea cycle defects, and severe mitochondrial hepatopathies.
Portosystemic shunts bypass hepatic clearance, causing profound hyperammonemia.
High levels associate with hepatic encephalopathy, though absolute value does not strictly correlate with encephalopathy grade.

Clinical Entity	Key Biochemical Findings
Acute Viral Hepatitis	Massive transaminase elevation (Alt > Ast); variable bilirubin; normal albumin initially; Pt/Inr normal unless progressing to acute liver failure.
Acute Liver Failure	Progressive coagulopathy (Inr >1.5-2.0) unresponsive to vitamin K; hypoglycemia; hyperammonemia; transaminases may paradoxically drop as liver mass undergoes massive necrosis.
Autoimmune Hepatitis	Elevated transaminases; hypergammaglobulinemia (elevated IgG); positive autoantibodies (ANA, SMA, LKM-1); interface hepatitis on biopsy.
Biliary Atresia	Conjugated hyperbilirubinemia; disproportionately elevated Ggt (>200 IU/L) and Alp; mildly elevated transaminases; normal synthetic function initially.
Wilson Disease	Elevated transaminases (Ast > Alt); low serum ceruloplasmin (<20 mg/dL); low alkaline phosphatase; elevated 24-hour urine copper (>40 mcg/d); Coombs-negative hemolytic anemia.
Alpha-1 Antitrypsin Deficiency	Conjugated hyperbilirubinemia; low serum alpha-1 antitrypsin levels; PiZZ phenotype; mildly elevated transaminases.