Liver Mitochondrial Morphology and Gene Expression as Markers of Liver Reserve: Prognostic Implications for Native Liver Survival in Biliary Atresia

• Published in: Journal of pediatric surgery 2024-07, p.161648, Article 161648
• Main Authors: Fujimoto, Takashi, Goto, Hiroki, Hida, Masataka, Tsuboi, Koichi, Suzuki, Takamasa, Iida, Hisae, Fukada, Ayaka, Shimizu, Sakika, Ebata, Yu, Nikai, Koki, Ishii, Junya, Takeda, Masahiro, Ishiyama, Asuka, Shibuya, Soichi, Yazaki, Yuta, Nakazawa-Tanaka, Nana, Miyano, Go, Okazaki, Tadaharu, Yanai, Toshihiro, Urao, Masahiko, Suzuki, Mitsuyoshi, Koga, Hiroyuki, Lane, Geoffrey J., Yamataka, Atsuyuki, Suda, Kazuto
• Format: Article
• Language: English
• Subjects: Biliary atresia; Heat shock protein 60; Hepatocyte; Mitochondria; Native liver survivor
• ISSN: 0022-3468; 1531-5037; 1531-5037
• DOI: 10.1016/j.jpedsurg.2024.07.033

Hepatocyte mitochondrial morphology and gene expression were compared between biliary atresia (BA), infantile cholestasis (IC), and normal liver (NL) as prognostic indicators. Specimens of liver at portoenterostomy (PE) for BA, from intrahepatic bile duct paucity patients for IC, and from choledochal cyst or hepatoblastoma patients for NL were collected prospectively (P) beginning in 2021 (P-BA = 11, P-IC = 9, P-NL = 7) and retrospectively (R) from paraffin-embedded tissue going back to 1981 (R-BA = 25, R-IC = 9, R-NL = 4). The P-cohort had transmission electron microscopy (TEM) to image mitochondria, immunoblotting for heat shock protein 60 (HSP60), and quantitative PCR (qPCR) for HSP60 and mitochondrial functional genes. Both cohorts had immunofluorescence for HSP60 quantified as a ratio to albumin-positive hepatocytes (ALB) with HSP60/ALB