Relationships Between Histopathological Findings in the Liver and Prognosis in Patients With Biliary Atresia

Abstract

Background: Biliary atresia (BA) is a progressive obstructive hepatic disease that requires early diagnosis and the prompt initiation of treatment. Although portoenterostomy (PES) is usually performed as the initial surgical procedure, the liver damage may subsequently progress, such that liver transplantation (LTx) may be required. In this study, we comprehensively evaluated the histopathology of liver samples collected during PES and retrospectively evaluated its relationship with prognosis.

Methods: Forty-seven patients with BA who underwent PES between 2002 and 2021 were included. Their biopsy samples were semi-quantitatively graded according to the severity of liver fibrosis, bile duct proliferation, cholestasis, ductal plate malformation, and inflammatory cell infiltration; and the expression of cluster of differentiation (CD)3, CD20, human leukocyte antigen II-DR, and α-smooth muscle actin (α-SMA). The relationships of each with the prevalence of survival with native liver (SNL) were evaluated to identify prognostic markers.

Results: The median postoperative duration of follow-up was 11.8 years (maximum, 18.0 years; minimum, 3.5 years). There were no deaths during this period, but LTx was performed in 31 patients and the final prevalence of SNL was 34.0% (16/47). There were negative correlations of liver fibrosis and α-SMA with SNL, and a positive correlation between CD20 and SNL. Multivariate analysis using a proportional hazards regression model showed that only CD20 expression was significant.

Conclusions: Comprehensive histopathological analysis of liver biopsy samples obtained at the time of PES showed a positive correlation between CD20 expression and SNL, suggesting that this may represent a useful prognostic marker.

Level of evidence: III.

Keywords: Biliary atresia; cluster of differentiation 20; graft versus host disease; histopathology; prognosis; survival with native liver.

Figure 1.

(A) Fibrosis grade 3, with fibrotic extension of the portal area and the formation of nodules (pseudo-lobules) (Masson’s trichrome, ×40). (B) Cholestasis grade 3, with severe cholestasis in the hepatocyte and in the small bile ducts at the margins of the portal area (hematoxylin and Eosin, ×200). (C) BDP Grade 3, with marked hyperplasia of the bile ducts at the margins of the portal area, forming multiple structures of 3 or more layers (anti-cytokeratin 7, ×100). (D) DPM present, with concentrically-arranged bile ducts in the portal area (anti-cytokeratin 7, ×100).

Figure 2.

(A) CD3 grade 3. Positive cells are present in the portal regions and hepatic lobules (×200). (B) CD20 grade 3. Positive cells are present throughout the portal regions, with some clustering (×200). (C) HLA II-DR grade 3. Positive cells are present throughout the portal regions and in the lobules (×200). (D) α-SMA grade 3, with multiple layers of positive areas at the margins of the portal areas and positive areas within (×200).

Figure 3.

(A) Survival curve for fibrosis. (B) Survival curve for CD20 expression. (C) Survival curve for α-SMA expression. Survival curves for the 3 parameters that showed significant correlations in the log rank tests of the relationships between each histopathological and immunohistochemical parameter and the prevalence of SNL. Liver fibrosis and α-SMA expression showed negative correlations with SNL, whereas CD20 showed a positive correlation. There were no significant relationships of other parameters with SNL.