About cholestasis and jaundice
WHAT IS CHOLESTASIS?
Cholestasis is defined as reduced bile formation or flow resulting in the retention of biliary substences within the liver normally excreted into bile and destined for elimination into intestinal lumen.3 It may be caused by intrahepatic or extrahepatic disorders.4
The presence of any of the following signs is highly suggestive of cholestasis:3-5
WHAT IS JAUNDICE?
Jaundice refers to the yellowish discolouration of the skin, sclera, and mucous membranes caused by hyperbilirubinaemia resulting from a metabolic imbalance favouring bilirubin production over hepatic-enteric bilirubin clearance.6
Jaundice can be caused by:5
Jaundice can be caused by unconjugated (indirect) hyperbilirubinaemia or conjugated (direct) hyperbilirubinaemia.5 Normally, bilirubin circulates in the plasma, mainly in unconjugated (indirect) form bound to albumin, with only a fraction (<5%) circulating in conjugated form. 5
Unconjugated hyperbilirubinaemia is never a sign of cholestasis while, conversely, conjugated hyperbilirubinaemia is theoretically synonymous with the condition. Certain rare medical conditions may be associated with conjugated hyperbilirubinaemia such as Rotor syndrome and Dubin-Johnson syndrome, but they are so rare that in practice, conjugated hyperbilirubinaemia should evoke cholestasis.5
Cholestatic jaundice VS physiological jaundice
Distinguishing jaundice caused by cholestasis from noncholestatic conditions (such as physiologic jaundice of the newborn) is critical because cholestatic jaundice is likely to be pathologic and therefore patients with cholestatic jaundice will benefit from prompt diagnosis and institution of specific therapy.3
Early recognition of neonatal cholestasis is essential to ensure timely treatment and optimal prognosis.4
Physiological jaundice results from physiological haemolysis and immaturity of the glucuronoconjugation process. An example of this is “mother’s milk jaundice”, which is observed in 2 to 3% of breastfed newborns or young infants. The precise cause is not known, but the condition is generally mild and transient and stool colouration is in the normal range.5
Cholestasis occurs most often in the neonatal period and affects around 1 in 2,500 term neonates.3
Cholestatic jaundice is always pathologic and suggests hepatobiliary dysfunction.3
The most common cause of cholestatic jaundice in the first months of life is biliary atresia, accounting for 25 to 40% of the cases of cholestatic jaundice at this age.3 It is essential that biliary atresia be diagnosed as early as possible because the prognosis depends very much on how soon surgery is performed.5
Physiological jaundice in newborns
Physiological jaundice is a ubiquitous and often benign condition in newborns manifesting in the first days of life.6
Approximately 60% of term and 80% of preterm babies develop jaundice in the first week of life and about 10% of breastfed babies are still jaundiced at 1 month.7 For most babies, jaundice is not an indication of an underlying disease, and this early jaundice (termed “physiological jaundice”) is usually harmless.7
Breastfed babies are more likely than bottle-fed babies to develop physiological jaundice within the first week of life.7
Prolonged jaundice – that is, jaundice persisting beyond the first 14 days – is also seen more commonly in breastfed babies. Prolonged jaundice is usually harmless, but can sometimes be an indication of serious liver disease.7
Infants who are still jaundiced after 2 weeks of age should be evaluated for cholestasis with measurement of total and direct sreum bilirubin, and that an elevated serum direct bilirubin level warrants timely consideration for evaluation and referral to a pediatric gastroenterologist or hepatologist.3
3. 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 PediatrGastroenterol Nutr 2017;64(1):154-68.
4. Feldman AG, Sokol RJ. Neonatal cholestasis. Neoreviews 2013;14(2):10.1542/neo.14-2-e63.
5. Protocole national de diagnostic et de soins : Déficits de synthèse des acides biliaires primaires. In: Génétiques CdRCdlAdVBedC, ed., 2019.
6. Olusanya BO, Kaplan M, Hansen TWR. Neonatal hyperbilirubinaemia: a global perspective. The Lancet 2018;2(8):610-20.
7. Jaundice in newborn babies under 28 days. Updated October 2016 ed. London: NICE: National Institute for Health and Care Excellence, 2010.