Copyright ©The Author(s) 2015.
World J Hepatol. Mar 27, 2015; 7(3): 392-405
Published online Mar 27, 2015. doi: 10.4254/wjh.v7.i3.392
Table 1 Diseases potentially resulting in cirrhosis in children and adolescents
Biliary obstruction
Biliary atresia
Choledochal cysts
Bile duct stenosis
Familial intrahepatic cholestasis
Alagille syndrome
FIC1 deficiency (ATP8B1)
BSEP deficiency (ABCB11)
MDR3 deficiency (ABCB4)
Defects of bile acid synthesis
Hepatotropic viral infections
Hepatitis B and D
Hepatitis C
Hepatitis E
Inherited genetic-metabolic diseases
α-1-antitrypsin deficiency
Glycogenosis type III and IV
Tyrosinemia type 1
Wilson’s disease
Mitochondrial hepatopathies
Late cutaneous porphyria
Cystic fibrosis
Wolman disease
Drugs and toxins
Total parenteral nutrition
Vitamin A intoxication
Autoimmune diseases
Autoimmune hepatitis
Primary sclerosing cholangitis
Vascular alterations
Budd-Chiari syndrome
Veno-occlusive disease
Congenital cardiopathy
Congestive heart failure
Constrictive pericarditis
Other: Fatty liver disease, Neonatal hepatitis, Zellweger disease
Table 2 Characteristics of progressive familial intrahepatic cholestasis
DiseaseRelevant clinical aspectsLaboratory findingsChromosome
PFIC1Early jaundice and increasing pruritus. Extrahepatic clinical manifestations: chronic diarrhea, pancreatitis, deafness. Early cirrhosis and liver transplantation in the first years of lifeGGT: Normal ALP: high Cholesterol: ↑18q21-q22
PFIC2Early jaundice. Progression to cirrhosis and ductopenia in the first years of life. Frequent cholelithiasis. Possible complications include liver and bile duct cancer. No extrahepatic symptoms. Liver transplantation in the first years of lifeGGT: Normal ALP: v. high Cholesterol: ↑2q24
PFIC3Variable phenotype and progression to cirrhosis in adolescence. Cholelithiasis. Liver transplantation in the first years of life. No extrahepatic symptomsGGT: High ALP: v. high Cholesterol: normal7q21
Table 3 Evaluation of children and adolescents with cirrhosis
Clinical history
Age, sex, ethnicity
Pregnancy and birth data: Adverse events during pregnancy, maternal serologies, birthweight, neonatal cholestasis, surgery, TPN
Signs and symptoms of systemic disease: anorexia, fatigue, muscle weakness, failure to thrive
Nausea, vomiting, abdominal pain, diarrhea, dyspepsia
Jaundice, pruritus, discoloration of urine and feces
Abdominal distension
Peripheral edema
Bleeding - nose, gums, skin, gastrointestinal tract
Bone pain, fractures
Adolescence: Menstrual history
Previous medical history: Jaundice, hepatitis, drug use, blood transfusions, inflammatory bowel disease
Social behaviors (adolescence): Use of alcohol or other drugs, tattoos, piercings
Family history: Consanguinity, liver disease, autoimmune disease
Physical examination:
General: Anthropometric data (malnutrition or obesity), fever
Skin and extremities: jaundice, flushing or pallor, spider nevi, telangiectasias, palmar erythema, clubbing of the nails, xanthoma, Terry’s nails
Abdomen: Distension, prominent blood vessels, liver and spleen alterations (reduced liver size, splenomegaly)
Neurological alterations: Academic performance, sleep, asterixis, positive Babinski sign, mental status changes
Miscellaneous: Pubertal delay, gynecomastia, testicular atrophy, feminization
Table 4 Investigation of chronic liver disease and cirrhosis in childhood and adolescence
Hemoglobin, leukocyte and platelet count, prothrombin time (INR)
Coombs test, blood type, Rh factor
Alkaline phosphatase
Gamma-glutamyl transferase
Albumin and globulin
25-OH vitamin D, parathyroid hormone, calcium, phosphorus, magnesium
Urea, creatinine
Lactic acid, fasting blood glucose, uric acid
Serum transferrin and ferritin saturation
Serum ceruloplasmin and copper, 24 h urinary copper (if age > 3 yr)
Alpha-1-antitrypsin phenotype
If ascites present
Paracentesis (in case of fever or sudden-onset ascites):
Cell count, albumin, total protein, neutrophil count
Amylase, cytology, PCR and mycobacterial culture (according to clinical suspicion)
Serum sodium, potassium, bicarbonate, chloride, urea and creatinine
Urinary sodium excretion
Smooth muscle, mitochondrial, anti-nuclear, anti-LKM-1 antibodies
Hepatitis B antigen
HIV serology
Genetic-metabolic diseases
Metabolic screen (urine and serum amino acids, urine organic acids)
Genetic tests (if alpha-1-antitrypsin deficiency, Alagille syndrome, etc., suspected)
Sweat electrolytes test
Urine and serum analysis for bile acid and acid precursors (if PFIC suspected)
Bone marrow examination and skin fibroblast culture (if glycogen storage disease suspected)
Endoscopy (if prophylactic treatment is considered)
Abdominal ultrasound (computed tomography or MRI in selected cases)
Needle liver biopsy (if blood coagulation permits)
EEG (if neuropsychiatric changes present)