Neonatal cholestatic jaundice is defined by the persistence of jaundice of variable intensity, choluria and hypocholic or acholic stools for more than 10 days, occurring during the first months of life (1). Its reported frequency is variable. In Australia, the prevalence was of 1:5000 liveborn infants (2) and in Norway, Henriksen et al. (3) reported 1 case of neonatal cholestasis per 9000 liveborn infants. In the Pediatric Gastroenterology sector of Hospital de Clínicas de Porto Alegre, about 25% of the outpatient visits are related to neonatal cholestasis (4). Neonatal cholestasis is caused by two large groups of diseases, i.e., extrahepatic (EHC) and intrahepatic (IHC) conditions. This division based on the presence or absence of extrahepatic obstruction to bile flow is useful with respect to the intervention strategy to be used, since in terms of management, the patient belonging to the first group needs to undergo surgery, whereas those belonging to the second group are subjected to nonsurgical treatment. Although there is a large number of possible causes, the relative frequency of idiopathic neonatal hepatitis (INH) and of biliary atresia (BA) far exceeds that of any other etiology. In the United States, these two disorders account for 70 to 80% of all cases of neonatal cholestasis (5). In Brazil, Silveira (4), in a study of 287 neonatal cholestasis cases, found a higher frequency of intrahepatic than extrahepatic causes of neonatal cholestasis. Taken together, INH and BA accounted for about 54% of all cases. INH is an inflammation of the neonatal liver of unknown etiology which was histopathologically defined by Craig and Landing in 1952 (6). Balistreri (7) estimated its frequency at 1.25 cases per 10,000 livebirths. BA is a disease occurring only in childhood whose cause is still unknown and which consists of total obliteration of part or all of the extrahepatic bile ducts. Its frequency is 1:8,000 to 1:15,000 livebirths and, according to Balistreri (8), one-third of neonatal cholestasis cases are due to BA. After 1968, with the spread of the Kasai technique (portoenterostomy) in the Western world, many cases which were classified as" noncorrectable BA" became surgically correctable with good results (9-13). Other authors agree that it is of fundamental importance to perform the surgery before eight weeks of life in order for it to be effective and that the results of surgeries performed after this period are poor. Thus, the differential diagnosis between obstructive extrahepatic causes, particularly BA, and intrahepatic causes, especially INH, is of great importance. Among the tests used for this purpose, the liver biopsy is of great importance.
The differential histopathological study of neonatal cholestasis is performed by determining the presence or absence of variables which characterize either group of diseases - IHC or EHC. The histopathological characterization of INH by Craig and Landing (6) introduced the perspective of morphological differentiation between INH and BA. At large centers, the histopathological study is the method of choice, among others such as scintigraphy of the bile ducts, duodenal intubation, ultrasonic echography and cholangiography. Correction rates of about 90% after this differential diagnosis through a liver biopsy have been reported in the literature (14-17). Previous experience of the pathologist with this group of diseases is essential, since there are more similarities than differences between IHC and EHC from an anatomopathological point of view. The difficulties for a correct differential diagnosis, according to Dahms (18), include: a) a specimen with few portal triads, b) the overestimation of the mild bile duct hyperplasia in INH, c) the nonrecognition that infants younger than 4 weeks with BA may not yet show portal duct proliferation, and d) the nonrecognition that this proliferation is not exclusive of BA.
In 1985, Zerbini (19) assessed 49 hepatic histopathological variables in 100 biopsies from 78 infants with neonatal cholestasis in terms of their discriminant value in the differential diagnosis between IHC and EHC. She divided the variables into two classes," indicating variables" and "guiding variables" of the diagnosis of EHC. The former, with a higher discrimination power (P£0.0001), includes portal ductal proliferation, distribution of the portal proliferation in the portal spaces, overall degree of cholestasis, cholestasis in the portal neoductules, cholestasis in the bile capillaries, and portal fibrosis. The second class, with lower discriminatory power (Pbetween 0.0001 and 0.05), includes myeloid metaplasia, portal-portal bridges, periductal fibrosis, neutrophils in the general inflammatory infiltrate, swelling of hepatocytes and giant cells.
The aim of the present study was to define the discriminant value of the hepatic histopathological variables in the differential diagnosis of neonatal cholestasis in patients with this disorder seen at the sector of Pediatric Gastroenterology of the Pediatrics Service of Hospital de Clínicas de Porto Alegre, and to identify the hepatic histopathological variables which discriminated between IHC and EHC before and after the age of two months.
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