Cholestasis neonatal

Jacquemin E, de Vree JM, Cresteil D, Sokal EM, Sturm E, Dumont M et al. The wide spectrum of multidrug resistance 3 deficiency from neonatal cholestasis to cirrhosis of adulthood. Gastroenterology 2001 120(6) 1448-1458. 

Elevation of serum copper is found in cholestasis, obstructive jaundice, primary biliary cholangitis, malignant tumours, kwashiorkor, exocrine pancreatic insufficiency, during the last trimenon of pregnancy and after administration of oestrogens. A decrease in serum copper is typical of Wilson s disease. In some rare cases, it is caused by familial benign hypocupraemia and nutritional deficiency in neonates. 

Kimura, A., Ushijima, K., Kage, M., Mahara, R., Tohma, M., Inokuchi, T., Shibao, K., Tanaka, N., Fujisawa, T., Ono, E., YamasUta, F. Neonatal Dubin-Johnson syndrome with severe cholestasis effective pheno-barbital therapy. Acta Paediatr. Scand. 1991 80 381-385... 

Perinatal asphyxia In 8-10% of asphyxiated newborns, transient cholestasis was found. The actual condition was related to the severity of neonatal stress. (23)... 

This rare form, which is inherited via a recessive autosomal route, was described in 1968 as a variant of BRIC. (1, 2) The genetic defect is located on chromosome 15 q. A specific feature of this disease in neonates is giant-cell hepatitis with cholestasis, (s. p. 417) From about the 6 year of life until puberty, pathogenetic hypoplasia or ectasia of the lymphatic vessels with oedema are found in the lower extremities. It is not clear whether (suspected) congenital hyperplasia of lymphatic vessels in the liver is the prime cause of cholestasis. Pronounced fibrosis is often in evidence, whereas cirrhosis only occurs rarely. 

TypeC is characterized by a slow course with neurological symptoms and gradual mental deterioration. A rare event is the development of neonatal cholestasis (243) or an HCC (242). 

Yerusalem, B., Sokol, R.J., Narkewicz, M.R., Smith, D., Ashmead, J.W., Wenger, D.A. Niemann-Pick disease type C in neonatal cholestasis at a North American center. J. Pediatr. Gastroenterol. Nutrit. 2002 35 44-50... 

In a retrospective study of the incidence of cholestasis and liver failure in 42 patients with intestinal resection in the neonatal period who subsequently became dependent on parenteral nutrition support, the effect of various associated clinical factors on the incidence and severity of cholestasis was determined (103). Cholestasis developed in 28 while they were receiving parenteral nutrition. In 21 patients, the raised direct bilirubin concentration returned to normal while they continued to receive parenteral nutrition. Seven patients progressed to liver failure. Patients without cholestasis had been dependent on parenteral nutrition for longer than patients with cholestasis. It was clear from this study that cholestasis in neonates with intestinal resection is not simply a function of the duration of exposure to intravenous nutrition. 

Sondheimer JM, Asturias E, Cadnapaphornchai M. Infection and cholestasis in neonates with intestinal resection and long-term parenteral nutrition. J Pediatr Gastroenterol Nutr 1998 27(2) 131-7. 

Levine A, Maayan A, Shamir R, Dinari G, Sulkes J, Sirotta L. Parenteral nutrition-associated cholestasis in preterm neonates evaluation of ursodeoxycholic acid treatment. J Pediatr Endocrinol Metab 1999 12(4) 549-53. 

E222 Ou, C.-N., Buffone, G.J., Herr-Calomeni, P.J., Finegold, M.J. and Shirey, T.L. (1985). Unconjugated hyperbilirubinemia is overestimated in neonates with cholestasis. A more reliable method is proposed. Am. J. Clin. Pathol. 84, 752-756. 

Specific defects in bile acid synthesis Cerebrotendinous xanthomatosis Intrahepatic cholestasis familial neonatal hepatitis) 3-p-hydroxysteroid dehydrogenase/isomerase deficiency A -3-oxosteroid 5-P-reductase deficiency C24 steroid 7-a-hydroxylase deficiency Peroxisomal disorders... 

In addition to primary defects in bUe acid synthesis, secondary abnormalities have been noted in peroxisomal disorders, such as neonatal adrenoleukodystrophy and cerebrohepatorenal (ZeUweger s) syndrome—an autosomal recessive condition associated with severe cholestasis in which side chain oxidation is impaired. 

The liver has a limited number of ways of responding to injury. Acute injury to the liver may be asymptomatic, but often presents as jaundice. The two major acute liver diseases are acute hepatitis and cholestasis. Chronic liver injury generally takes the clinical form of chronic hepatitis its long-term complications include cirrhosis and HCC. The discussion of liver disease wiU focus mainly on these patterns, and a few diseases that differ from this general pattern. Because the types of disease seen in neonates differ significantly from this model, diseases of infancy are discussed separately in Chapter 31. 

Hydroxylation. The 2)8-hydroxylated derivative of cholic acid, 2, 3a,7a,12a-tetrahydroxy-5i8-cholanate, was characterized as a minor component of gastric contents of neonates with duodenal atresia [202], Identification was facilitated by the availability of the authentic compound, arapaimic acid, which was isolated from bile of Arapaima gigas (Chapter 10) and was synthesized [204], This tetrol is also a minor urinary metabolite of cholate in patients with intrahepatic cholestasis [123]. A polar bile acid formulated as a 2,3,6,7-tetrol obtained from urine of healthy newborn infants [199] apparently differs from an unidentified urinary tetrol from patients with cholestasis [164],... 

Hydroxylation. Urinary acids hydroxylated at position 6, especially 6a, include hyodeoxycholate, hyocholate, 3a,6 /, 12a-trihydroxy- and 3a,6a,7a,12 -tetrahy-droxy-5 -cholanates. Hyocholate, the major bile acid in urine, serum and duodenal fluid of a child with intrahepatic cholestasis [109], is a major urinary metabolite of chenodeoxycholate in patients with intrahepatic cholestasis, while 3a,6a,12a-trihy-droxy-5j3-cholanate is only a minor metabolite of deoxycholate [123]. The 3a,6a,7a,12a-tetrahydroxy acid, obtained from urine of patients with liver diseases [194] and from gastric contents of neonates with duodenal atresia [203] is another metabolite of cholic acid [123] several unidentified tetrols have yet to be char-... 

Barbiturates such as phenobarbital, amobarbital, and butabarbital induce glucuronyl transferase, an enzyme obligatory in bilirubin metabolism. Thus, they may be used in patients with chronic cholestasis. Phenobarbital is also used for lowering serum bilirubin in the neonate. 

Idiopathic neonatal hepatitis is an inflammation of the liver parenchyma responsible for most cases of intrahepatic cholestasis, and accounts for at least 25%-40% of patients with neonatal cholestasis. A multitude of etiologies can be the cause (Gubernick et al. 2000). 

Ichikawa T, Federle MP, Grazioli L et al (1999) Fibrolamellar hepatocellular carcinoma imaging and pathologic findings in 31 recent cases. Radiology 213 352-361 Jaw TS, Kuo YT, Liu GC et al (1999) MR cholangiography in the evaluation of neonatal cholestasis. Radiology 212 249-256... 

In contrast, in a retrospective analysis of 292 neonates who received parenteral nutrition with lipid emulsions containing omega-3 fatty acids for more than 1 day, 104 (36%) developed cholestasis after a mean of 22 days, with a conjugated bilirubin concentration over 34 pmol/l 31 had a serum conjugated bilirubin concentration over 100 pmoUl and 13 developed liver failure 4 underwent transplantation and 5 died of hepatic disease [385]. The authors suggested that in the absence of definitive evidence of efficacy, as well as increased costs, it is difficult to justify the routine use of lipid... 

The susceptibility factors for cholestasis associated with parenteral nutrition have been studied in 62 premature infants in a neonatal intensive care unit, of whom 11 (18%) developed cholestasis [72 ]. There were significant differences in terms of... 

Garzbn L, Ledo A, Cubells E, Sdenz P, Vento M. Cholestasis associated with prolonged parenteral nutrition in neonates the role of urso-deoxycholic acid. An Pediatr (Bare) 2009 70(6) 547-52. 

The observed increase in values for hepatic uptake of taurocholate at birth therefore implies a developmentally related decrease in efficiency of uptake for bile acid and may be relevant to the development of clinical neonatal cholestasis. 

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