Copyright ©2013 Baishideng Publishing Group Co.
World J Gastroenterol. May 14, 2013; 19(18): 2740-2751
Published online May 14, 2013. doi: 10.3748/wjg.v19.i18.2740
Table 1 Main causes of asymptomatic hypertransaminasemia in children
Hepatic originExtrahepatic origin
Obesity (non-alcoholic fatty liver disease)Duchenne/Becker muscular dystrophy (prevalence: 1:4700)
Viral infections (major and minor hepatotropic viruses)Other myopathies (e.g., caveolinopathies; prevalence: 1:14000 to 1:120000)
Autoimmune liver diseaseMyocardiopathies
(prevalence: 1:200000)
Celiac disease and inflammatory bowel diseaseNephropathies
Wilson’s disease (prevalence: 1:30000)Hemolytic disorders
Cystic fibrosis (prevalence: 1:2500) and Shwachman-Diamond syndrome (prevalence: 1:50000)Macro - AST (prevalence: 30% of children with isolated aspartate aminotransferasemia)
Alpha1 antitrypsin deficiency (prevalence: 1:7000)
Other genetic and metabolic diseases1
Toxic: Drugs and alcohol
Cryptogenic hypertransaminasemia
Table 2 Retesting panel; first, second, and third line investigations in children with asymptomatic mild hypertransaminasemia
Retesting panel1First line panel
Second and third line panels
Liver function testsEtiology tests
ALT AST CPK GGTConjugated 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-ASTViral 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 IgAUrinary 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)
Table 3 Fatty liver disease; possible causes in likely asymptomatic children and adolescents
General or systemicGenetic-metabolic causesDrugs/chemicals
ObesityCystic fibrosisEthanol
Metabolic syndromeShwachman syndromeEcstasy, cocaine, solvents
Obstructive sleep apneaWilson’s diseaseNifedipine
Polycystic ovary syndromeAlpha 1-antitrypsin deficiencyDiltiazem
Diabetes mellitus type 1FructosemiaEstrogens
Thyroid disordersCholesterol ester storage diseaseCorticosteroids
Hypothalamic-pituitary disordersGlycogen storage disease (type I, VI and IX)Methotrexate
Inflammatory bowel diseaseMitochondrial and peroxisomal defectsPrednisolone
Celiac diseaseα- and β-oxidation defectsValproate
Protein calorie malnutritionOrganic acidosisVitamin
Rapid weight lossAbeta or hypobetalipoproteinemiaZidovudine and HIV treatments
Anorexia nervosaPorphyria cutanea tardaSolvents
Small intestinal bacterial overgrowthHomocystinuriaPesticides
Hepatitis CFamilial hyperlipoproteinemias
Bile acids synthesis defects
Congenital disorders of glycosylation
Citrin deficiency
Turner syndrome
Table 4 Clinical and laboratory findings for orienting diagnosis of some genetic metabolic liver diseases
Clinical/laboratory findingsPossible genetic-metabolic causePrevalenceLiver involvement
Pancreatic failure, hematological disordersShwachman syndrome1:50000+++1
Asymptomatic, hemolysisWilson’s disease1:30000+++
Previous neonatal cholestasis, hepatomegalyAlpha 1 antitrypsin deficiency1:7000+++
Hypoglycemia, hepatomegalyGlycogen storage disease (type I, VI and IX)From 1:100000 to 1:1000000+++
Fructose refusal, hepatomegalyHereditary fructose intolerance1:20000+++
Lethargy, increased serum ammonia levelsUrea cycle defects1:30000 (all disorders)++
Lethargy, increased serum ammonia levelsUrea cycle defects1:30000 (all disorders)++
Chubby face, fatty liver, specific serum amino acids patternCitrin deficiency1:20000 in East Asia++
Failure to thrive, lactic acidosisMitochondrial diseases1:8500 (all disorders)+
Failure to thrive, ketoacidosis, hypoglycemiaOrganic acidosis1:1000 (all disorders)+
Mild coagulopathy, clinical phenotypeCongenital disorders of glycosylationFrom 1:10000 to 1:100000+
Short stature, female gender, karyotypeTurner syndrome1:2000+
Failure to thrive, positive sweat testCystic fibrosis1:2500+