Mini review
Cholestasis in the newborn and infant

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Summary

Neonatal cholestasis occurs in approximately 1 in 2500 term infants, the most common underlying disease being biliary atresia, viral infections and α1-antitrypsin deficiency. The incidence of cholestasis is much higher in extremely premature newborns. The etiology of biliary atresia remains unclear, which in turn makes the search for additional treatments to surgery challenging. Reliable non-invasive tools to differentiate biliary atresia from other forms of neonatal cholestasis need to be further investigated. Despite important findings in the last decades, the pathogenesis of cholestatic liver disease in α1-antitrypsin deficiency remains to be clarified. Any such explanation would also need to explain why only a minority of individuals with PiZZ phenotype develop liver disease. For other genetic diseases causing neonatal cholestasis, such as Alagille's syndrome and progressive familial intrahepatic cholestasis the breakthrough within the field of molecular biology has definitely deepened our understanding of both etiology and pathogenesis. However, the correlation between genotype and phenotype is rarely obvious and for several patients with the seemingly correct phenotype no known genetic mutation is detected. A stepwise approach to the management of cholestasis in the newborn and infant is suggested, where percutaneous liver biopsy is of value to select patients with suspected biliary atresia for laparotomy.

Introduction

Decreased or obstructed bile flow at any level from the hepatocyte to the junction of the extrahepatic biliary tree and the duodenum is referred to as cholestasis. Generally, jaundice and pale stools are regarded as the main clinical signs of cholestasis. However, other phenomena such as dark urine, pruritus, unexplained profuse bleedings and steatorrhea could be cholestatic manifestations, as well. Biochemically, a conjugated hyperbilirubinemia and/or increased levels of gamma-glutamyl transpeptidase (G-GT), alkaline phosphatase (ALP) and fasting bile acids are noted.

Section snippets

Clinical presentation

Early after birth there is an immaturity in the enterohepatic circulation of bile acids, resulting in a state of physiologic cholestatis [1]. This may last for at least the first half year of life, and during this period there is an increased vulnerability to cholestatic agents. Neonatal cholestasis will most often present as prolonged jaundice, defined as visible icterus beyond 2 weeks of age. Such babies should always be investigated for conjugated hyperbilirubinemia and if this is detected

Causes

A large number of causes for neonatal cholestasis have been identified [3]. Somewhat simplified they are often classified as either extrahepatic or intrahepatic in origin. In the first group biliary atresia (BA) is by far the most common. The second group, which includes a long list of different diseases, can be referred to as intrahepatic neonatal cholestasis. The term neonatal hepatitis is often used for the latter group. However, while this could be an adequate term considering the

Incidence

The incidence of neonatal cholestasis is difficult to establish, since mostly referred patients are reported and this would underestimate the number of mild cases. However, the generally accepted figure is between 1 in 2500–5000 term infants [4]. For extremely premature babies this figure is much higher, due to the combination of several risk factors such as immaturity, lack of enteral feedings, long-term use of total parenteral nutrition, and frequent episodes of septicemia. In the subset of

Management

Once cholestasis is established in a neonate, there is a need for a relatively rapid series of investigations. The reason for this “semiacute” management is to define certain situations where early treatment is life saving, such as septicemia, galactosemia or hypocortisolism, as well as to ensure timely surgical management in the subset of patients where BA is highly probable. The most important factor for a successful outcome after portoenterostomy for BA is indeed the yearly caseload of the

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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