Diagnostic algorithm for cholestasis in INFANTS​/CHILDREN1-2

NORMAL

NORMAL

ABNORMAL

INCREASED

MONITORING

CHOLANGIO-
GRAM

CHOLANGIO-
GRAM

SERUM GGT

Cholestasis
and / or
cholestatic jaundice

abdominal
ultrasound :
bile ducts
dilated ?

biliary
obstruction
on liver
biopsy

Pruritus

Increased
serum total
bile acids

and

YES

YES

YES

NO

NO

NO

Biliary lithiasis

Other extrahepatic
causes

Choledochal cysts

Primary bile acid
synthesis disorders
(3β-HSD and Δ4–3-oxoR
deficiencies)

PFIC 3

Autoimmune cholangitis

Biliary atresia

Primary sclerosing
cholangitis

Check for :

Check for :

Extrahepatic causes :

Check for :

Check for :

PFIC1

PFIC2

BRIC1

BRIC2

TJP2 deficiency (PFIC4)

NR1H4 deficiency (PFIC5)

Myosin 5B deficiency

UNC45A deficiency 

ARC syndrome

Hepatitis A

Alagille syndrome

Alpha-1-antitrypsin deficiency

Cystic fibrosis

Drug toxicity

Cortisol deficiency

NORMAL

NORMAL

ABNORMAL

INCREASED

MONITORING

Prurits

SERUM GGT

Cholestasis
AND / OR
cholestatic jaundice

abdominal
ultrasound :
bile ducts
dilated ?

biliary
obstruction
on liver
biopsy

YES

YES

YES

NO

NO

NO

CHOLANGIO-
GRAM

CHOLANGIO-
GRAM

Increased
serum total
bile acids

and

Biliary lithiasis

Other extrahepatic
causes

Choledochal cysts

Extrahepatic causes :

Check for :

Alagille syndrome

Alpha-1-antitrypsin
deficiency

Cystic fibrosis

Drug toxicity

PFIC1

PFIC2

BRIC1

BRIC2

 TJP2 deficiency (PFIC4)

NR1H4 deficiency (PFIC5)

Myosin 5B deficiency

UNC45A
deficiency 

ARC syndrome

Hepatitis A

PFIC 3

Autoimmune cholangitis

Check for :

Biliary atresia

Primary sclerosing
cholangitis

Check for :

Primary bile acid
synthesis disorders
(3β-HSD and Δ4–3-oxoR
deficiencies)

Cortisol deficiency

1. Adapted from, Protocole national de diagnostic et de soins : Déficits de synthèse des acides biliaires primaires. In: Génétiques CdRCdlAdVBedC, ed., 2019

2. Fawaz R, Baumann U, Ekong U, et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2017;64(1):154-68. doi: 10.1097/MPG.0000000000001334