Persistent hypertransaminasemia in asymptomatic children: A stepwise approach

Table 2 Retesting panel; first, second, and third line investigations in children with asymptomatic mild hypertransaminasemia

Retesting panel1	First line panel		Second and third line panels
	Liver function tests	Etiology tests
ALT AST CPK GGT	Conjugated and unconjugated bilirubin Protein electrophoresis Serum albumin Prothrombin time and partial thromboplastin time Blood cell count Hepatic ultrasonography If only AST elevation is confirmed: PEG test and electrophoresis for macro-AST	Viral markers (HAV, HBV, HCV) Minor hepatotropic viruses serology (e.g., EBV, CMV) Ceruloplasmin, serum copper ANA, SMA, LKM, LC1, anti-SLA, total IgG Serum α1 antitrypsin EMA, tTgasi IgA, deamidated AGA IgA (< 2 yr), total IgA	Urinary copper, molecular ATP B7 analysis HCV RNA, HBV DNA Genetic and metabolic enlarged screening2 (“non-alcoholic fatty liver disease bin”) Sweat test Fecal elastase, steatocrit Other hepatic imaging techniques (MRI, ERCP, CT, etc.) Liver biopsy3 Jejunal biopsy (after celiac disease serology)

¹After at least one week off from exercise;

²Genetic and metabolic enlarged screening: blood gases, lactic acid, serum ammonium concentrations, blood and urinary amino acids, urinary reducing substances, urinary organic acids, transferrin isoforms, screening test for congenital disorders of glycosylation, α1 anti-trypsin phenotype;

³Modified from the reference of 28. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; PEG: Polyethylene glycol; CPK: Creatine kinase; GGT: Gamma-glutamyl transferase; HAV: Hepatitis A virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; EBV: Epstein-Barr virus; CMV: Cytomegalovirus; ANA: Antinuclear antibodies; SMA: Smooth muscle antibodies; LKM: Anti-microsomal antibodies; LC1: Anti-liver cytosol antibodies type 1; SLA: Soluble liver antigen; IgG: Immunoglobulin G; EMA: Anti-endomysial antibodies; tTgasi: Anti-tissue transglutaminase antibodies; AGA: Anti-gliadin antibodies; IgA: Immunoglobulin A; ATP B7: ATP binding protein 7; MRI: Magnetic resonance imaging; ERCP: Endoscopic retrograde cholangiopancreatography; CT: Computed tomography.