Junfeng Wang1,2, Jiayin Xu3, Mingyang Xia2, Yifan Yang1,2, Zhen Shen1,2, Gong Chen1,2, Rui Dong1,2, Shan Zheng1,2. 1. Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China. 2. Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China. 3. Clinical Laboratory, Children's Hospital of Fudan University, Shanghai, China.
Abstract
AIM: To assess the level of hepatic oxidative damage and its correlation with clinical severity in biliary atresia (BA), and to understand BA mitochondrial gene sequencing. METHODS: Forty-eight BA patients and 28 control subjects (20 hepatoblastoma and 8 cholestasis patients) were enrolled. Hepatic oxidative damage was assessed by the expression of oxidation and antioxidant genes, and the correlation between oxidative damage and BA incidence, liver inflammation, and fibrosis was evaluated. Moreover, 8-hydroxyguanine (8-OHdG), mitochondrial DNA (mtDNA) copy number, and mitochondrial gene sequences were determined to evaluate oxidative mtDNA damage in BA. RESULTS: The expression of oxidation gene cytochrome b-245 beta chain (CYBB) in BA was significantly increased and patients with a higher CYBB expression had the higher risk of BA incidence, liver inflammation, and cirrhosis. However, the expression of antioxidant genes was significantly decreased, and glutathione S-transferase alpha 1 (GSTA1) negatively correlated with BA incidence and cirrhosis. When GSTA1 mRNA expression was <0.5487, the sensitivity was 80.85% and the specificity was 80% for BA diagnosis. Moreover, 8-OHdG was increased, whereas mtDNA copy number was significantly decreased in BA. Using mitochondrial gene sequencing, 10 mutation sites were identified, and one family showed a maternal inheritance in genetic loci 15 326. CONCLUSIONS: In BA, oxidative damage positively correlated with BA incidence, liver inflammation, and cirrhosis. GSTA1 could be a novel diagnostic indicator. Genetic loci 15 326 could be a maternal genetic mutation site. Taken together, antioxidation therapy after Kasai surgery might have great potential in relieving liver inflammation and fibrosis in BA patients.
AIM: To assess the level of hepatic oxidative damage and its correlation with clinical severity in biliary atresia (BA), and to understand BA mitochondrial gene sequencing. METHODS: Forty-eight BA patients and 28 control subjects (20 hepatoblastoma and 8 cholestasispatients) were enrolled. Hepatic oxidative damage was assessed by the expression of oxidation and antioxidant genes, and the correlation between oxidative damage and BA incidence, liver inflammation, and fibrosis was evaluated. Moreover, 8-hydroxyguanine (8-OHdG), mitochondrial DNA (mtDNA) copy number, and mitochondrial gene sequences were determined to evaluate oxidative mtDNA damage in BA. RESULTS: The expression of oxidation gene cytochrome b-245 beta chain (CYBB) in BA was significantly increased and patients with a higher CYBB expression had the higher risk of BA incidence, liver inflammation, and cirrhosis. However, the expression of antioxidant genes was significantly decreased, and glutathione S-transferase alpha 1 (GSTA1) negatively correlated with BA incidence and cirrhosis. When GSTA1 mRNA expression was <0.5487, the sensitivity was 80.85% and the specificity was 80% for BA diagnosis. Moreover, 8-OHdG was increased, whereas mtDNA copy number was significantly decreased in BA. Using mitochondrial gene sequencing, 10 mutation sites were identified, and one family showed a maternal inheritance in genetic loci 15 326. CONCLUSIONS: In BA, oxidative damage positively correlated with BA incidence, liver inflammation, and cirrhosis. GSTA1 could be a novel diagnostic indicator. Genetic loci 15 326 could be a maternal genetic mutation site. Taken together, antioxidation therapy after Kasai surgery might have great potential in relieving liver inflammation and fibrosis in BA patients.