About cholestasis and jaundice
Cholestasis is one of the main reasons for admission to pediatric liver services , and it accounts for the vast majority (80%) of paediatric liver transplants.1
The liver is the second most commonly transplanted organ after the kidneys in paediatric patients in France.2
WHAT IS CHOLESTASIS?
Cholestasis refers to the impairment of bile formation or flow resulting in retention of biliary substances within the liver.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 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. 5,8
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 jaundice caused by non-cholestatic conditions (such as physiologic jaundice of the newborn) is critical because cholestatic jaundice is likely to be pathologic. Consequently, patients with cholestatic jaundice can benefit from prompt diagnosis and initiation of specific, effective therapy.3
Early recognition of neonatal cholestasis or cholestatic jaundice is essential in order to rapidly identify the cause 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.
Cholestasis occurs most often in the neonatal period and affects around 1 in 2,500 term neonates.1-3 Most primary health care providers are confronted with cholestatic jaundice from time to time.3 Cholestasis or cholestatic jaundice is always pathologic and suggests hepatobiliary dysfunction.3
The causes of cholestasis are very variable with many of them being associated with a poor prognosis.1
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.1
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 physiological jaundice in the first weeks of life and, interestingly, the condition is more common in breastfed babies than bottle-fed babies.7 For most babies, jaundice is not indicative of a serious underlying medical condition and this early jaundice (known as “physiological jaundice”) is usually harmless.7 However, about 10% of breastfed babies are still jaundiced at 1 month.
Infants who are still jaundiced after 2 weeks of age should be evaluated for cholestasis and referred to a paediatric gastroenterologist or hepatologist.3 Prolonged jaundice – jaundice lasting beyond the first 14 days – is more common in breastfed babies. Although prolonged jaundice is usually harmless, it should be investigated as it may be an indication of a more serious liver disorder.7
1. Gonzales E, Jacquemin E. Cholestases néonatales. Pédiatrie 2006:4-060-A-15.
2. Le rapport médical et scientifique du prélèvement et de la greffe en France: L’Agence de la biomédecine; 2016 [Available from: https://www.agence-biomedecine.fr/annexes/bilan2016/donnees/organes/09-pediatrie/synthese.htm.
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 Nutr2017;64(1):154-68. doi: 10.1097/MPG.0000000000001334
4. Feldman AG, Sokol RJ. Neonatal cholestasis. Neoreviews 2013;14(2):10.1542/neo.14-2-e63. doi: 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. doi: 10.1016/S2352-4642(18)30139-1 [published Online First: 2018/06/28]
7. Jaundice in newborn babies under 28 days. Updated October 2016 ed. London: NICE: National Institute for Health and Care Excellence, 2010.
8. Valla DC. Cholestase. Hépato Gastro 2013;20:618-27.