Histopathological diagnosis of intra- and extrahepatic neonatal cholestasis

Abstract

The histopathology of the liver is fundamental for the differential diagnosis between intra-and extrahepatic causes of neonatal cholestasis. However, histopathological findings may overlap and there is disagreement among authors concerning those which could discriminate between intra-and extrahepatic cholestasis. Forty-six liver biopsies (35 wedge biopsies and 11 percutaneous biopsies) and one specimen from a postmortem examination, all from patients hospitalized for neonatal cholestasis in the Pediatrics Service of Hospital de Clínicas de Porto Alegre, were prospectively studied using a specially designed histopathological protocol. At least 4 of 5 different stains were used, and 46 hepatic histopathological variables related to the differential diagnosis of neonatal cholestasis were studied. The findings were scored for severity on a scale from 0 to 4. Sections which showed less than 3 portal spaces were excluded from the study. Sections were examined by a pathologist who was unaware of the final diagnosis of each case. Bile tract permeability was defined by scintigraphy of the bile ducts and operative cholangiography. The F test and discriminant analysis were used as statistical methods for the study of the hepatic histopathological variables. The chi-square method with Yates correction was used to relate the age of the patients on the date of the histopathological study to the discriminatory variables between intraand extrahepatic cholestasis selected by the discriminant function test. The most valuable hepatic histopathological variables for the discrimination between intra-and extrahepatic cholestasis, in decreasing order of importance, were periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules, foci of myeloid metaplasia, and portal-portal bridges. The only variable which pointed to the diagnosis of intrahepatic cholestasis was myeloid metaplasia. Due to the small number of patients who were younger than 60 days on the date of the histopathological study (N = 6), no variable discriminated between intra-and extrahepatic cholestasis before the age of 2 months and all of them, except for the portal expansion, were discriminatory after this age. In infants with cholestasis, foci of myeloid metaplasia, whenever present in the liver biopsy, suggested intrahepatic cholestasis. Periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules, portal cholestasis and portal-portal bridges suggested extrahepatic obstructive cholestasis.

Usefulness of a scoring system in the interpretation ofhistology in neonatal cholestasis

“…A review of the literature on the histological interpretation of neonatal cholestasis was performed [2,[9][10][11][16][17][18][19] . The histological features indicative of BA are bile ductular proliferation, porto-portal bridging, and the presence of bile plugs in the portal ductules [3,[10][11][12]16] .…”

“…The histological features indicative of BA are bile ductular proliferation, porto-portal bridging, and the presence of bile plugs in the portal ductules [3,[10][11][12]16] . Histological features more indicative of neonatal hepatitis are portal lymphocytic infiltration, neutrophilic infiltration, multinucleated giant cells, and hepatocellular swelling [2,7,16] .…”

“…Other authors have also attempted to devise a histological scoring system [10,11] . The scoring system reported by Zerbini et al [11] involved a series of initial complex statistical analyses using a logistic regression method.…”

“…The histological features of neonatal hepatitis, on the other hand, are more heterogeneous [8,9] , with giant-cell hepatitis a prominent feature, but others such as diffuse hepatocyte degeneration, minimal degree of bile ductular proliferation, and portal infiltration of lymphocytes, eosinophils and neutrophils less specific [8,9] . Other authors noted that the only consistent hepatic histological feature of neonatal hepatitis was extramedullary haemopoiesis [10] . Recently, a mathematical approach have been devised to identify the most useful histological feature differentiating BA from other causes of neonatal cholestasis [11] .…”

Advances in biliary atresia: from patient care to research

“…Although the liver histopathology of biliary atresia varies, expanded portal tracts with edema and bile duct proliferation with bile plugs in neoductules are the most frequent findings at diagnosis (1,2). Different levels of fibrosis and inflammation may be related to staging of the disease or to predominant biological processes producing the atresia phenotype (3,4).…”