WOFAPS 2025 8th World Congress of Pediatric Surgery

Shilpa Sharma, Javed Quadri, Prasenjit Das

All India Institute of Medical Sciences, New Delhi

PURPOSE: Biliary atresia is a progressive, fibro-obliterative disease of the extrahepatic bile ducts, leading to cholestasis and end-stage liver disease in infants. Although histopathological alterations in biliary atresia are well documented, ultrastructural changes in hepatocytes and other parenchymal cells remain incompletely characterized. This study aimed to delineate and describe the spectrum of ultrastructural hepatic alterations in biliary atresia to enhance understanding of disease pathogenesis and cellular injury.

METHODOLOGY: Following institutional ethical committee approval, liver biopsy specimens were collected from 20 patients of biliary atresia. Immediately after excision, the liver tissues were fixed in freshly prepared Karnovsky’s fixative solution to preserve ultrastructural integrity. Specimens were then post-fixed, dehydrated, and embedded for ultrathin sectioning. Sections were stained with uranyl acetate and lead citrate. Transmission electron microscopy was employed to systematically evaluate hepatocytes, sinusoidal lining cells, and bile duct epithelial cells for subcellular alterations, including mitochondrial morphology, nuclear architecture, endoplasmic reticulum integrity, and cytoplasmic ground substance preservation.

RESULTS: Examination revealed a consistent pattern of severe hepatocellular injury. Mitochondriopathy was observed in the majority of specimens, characterized by marked mitochondrial swelling, disruption of cristae architecture, and rarefaction of the matrix. Pronounced disintegration and discontinuity of the nuclear membranes were frequently noted, accompanied by pyknotic nuclei in affected hepatocytes. Endoplasmic reticulum showed dilatation, vesiculation, and fragmentation suggestive of endoplasmic reticulum stress. Hypervacuolation of the cytoplasm was a recurrent finding, often accompanied by lysis of cytoplasmic ground substances, further indicating advanced degenerative processes. Occasional bile duct epithelial cells also demonstrated cytoplasmic rarefaction and organellar loss. Occasional liver oval cells were also identified. The ultrastructural damage observed supports the concept that biliary obstruction induces profound metabolic and structural stress within hepatocytes early in disease progression.

CONCLUSION: This study provides comprehensive ultrastructural evidence of severe mitochondrial injury, nuclear disintegration, endoplasmic reticulum stress, and cytoplasmic degeneration in the livers of infants with biliary atresia. These findings highlight the critical role of subcellular organelle dysfunction in disease pathogenesis and may inform future strategies for early diagnosis, therapeutic intervention, and prognostic assessment in biliary atresia.