Cirrhosis in children and adolescents: An overview

Table 1 Diseases potentially resulting in cirrhosis in children and adolescents

Biliary obstruction

Biliary atresia

Choledochal cysts

Gallstones

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

Galactosemia

Fructosemia

Tyrosinemia type 1

Wilson’s disease

Mitochondrial hepatopathies

Late cutaneous porphyria

Cystic fibrosis

Hemochromatosis

Wolman disease

Drugs and toxins

Total parenteral nutrition

Isoniazid

Methotrexate

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

Disease	Relevant clinical aspects	Laboratory findings	Chromosome
PFIC1	Early jaundice and increasing pruritus. Extrahepatic clinical manifestations: chronic diarrhea, pancreatitis, deafness. Early cirrhosis and liver transplantation in the first years of life	GGT: Normal ALP: high Cholesterol: ↑	18q21-q22
PFIC2	Early 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 life	GGT: Normal ALP: v. high Cholesterol: ↑	2q24
PFIC3	Variable phenotype and progression to cirrhosis in adolescence. Cholelithiasis. Liver transplantation in the first years of life. No extrahepatic symptoms	GGT: High ALP: v. high Cholesterol: normal	7q21

PFIC: Progressive familial intrahepatic cholestasis; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase.

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

Adapted from: McCormick[57], 2011; Högler et al[35], 2012; Hsu[31], 2014. TPN: Total parenteral nutrition.

Table 4 Investigation of chronic liver disease and cirrhosis in childhood and adolescence

Hematology

Hemoglobin, leukocyte and platelet count, prothrombin time (INR)

Coombs test, blood type, Rh factor

Biochemistry

Bilirubins

Transaminases

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

Immunology

Smooth muscle, mitochondrial, anti-nuclear, anti-LKM-1 antibodies

Hepatitis B antigen

Anti-HCV

α-fetoprotein

Immunoglobulins

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)

Other:

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)

Adapted from: McCormick[57], 2011; Högler et al[35], 2012. LKM-1: Liver/kidney microsomal; PFIC: Progressive familial intrahepatic cholestasis; MRI: Magnetic resonance imaging; INR: International normalized ratio; HIV: Human immunodeficiency virus.