Bo Wu1, Ying Zhou2, Xinbei Tian1, Wei Cai3,4,5,6, Yongtao Xiao7,8,9,10. 1. Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China. 2. Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China. 3. Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China. caiw204@sjtu.edu.cn. 4. Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China. caiw204@sjtu.edu.cn. 5. Shanghai Institute of Pediatric Research, Shanghai, China. caiw204@sjtu.edu.cn. 6. Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. caiw204@sjtu.edu.cn. 7. Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China. xiaoyongtao@xinhuamed.com.cn. 8. Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kong Jiang Road, Shanghai, China. xiaoyongtao@xinhuamed.com.cn. 9. Shanghai Institute of Pediatric Research, Shanghai, China. xiaoyongtao@xinhuamed.com.cn. 10. Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. xiaoyongtao@xinhuamed.com.cn.
Abstract
Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and liver fibrosis. The early diagnosis of BA is still challenging. This study aimed to evaluate the diagnostic values of matrix metalloprotease-7 (MMP-7), interleukin-8 (IL-8), and gamma-glutamyl transferase (GGT) in BA. Infants diagnosed with BA and non-BA between 2013 and 2018 were retrospectively analyzed. Plasma levels of MMP-7, IL-8, and GGT were measured in these infants. The receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to assess the diagnostic values of MMP-7, IL-8, and GGT. The expression of MMP-7 and IL-8 in the livers was detected by immunofluorescence staining. A total of 229 infants were enrolled in this study: 156 BA infants and 73 non-BA infants including 16 ones with infantile hepatitis syndrome. The plasma levels of MMP-7, IL-8, and GGT in BA infants had a median of 11.8 ng/mL (interquartile range, IQR: 5.3-57.5), 1.5 ng/mL (IQR: 1.0-2.8), and 381.0 U/L (IQR: 197.0-749.0), respectively, which were higher than non-BA subjects [MMP-7, 4.4 ng/mL (IQR: 3.3-6.1); IL-8, 0.7 ng/mL (IQR: 0.5-1.0); GGT, 59.0 U/L (IQR: 26.0-124.0)]. The AUC values of MMP-7, IL-8, and GGT for the diagnosis of BA were 0.8035, 0.8083, and 0.9126, respectively. The AUC values of MMP-7 + IL-8, MMP-7 + GGT, IL-8 + GGT, and MMP-7 + IL-8 + GGT for the diagnosis of BA were 0.8248, 0.9382, 0.9168, and 0.9392, respectively. The AUC values of MMP-7, IL-8, and GGT for differentiating BA infants with cholic stool from non-BA infants with cholic stool were 0.8006, 0.8258, and 0.9141, respectively. The expression of MMP-7 and IL-8 was increased in the cholangiocytes in BA livers. Conclusion: Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA and may be reliable biomarkers for BA. What is Known: • Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and progressive liver fibrosis. • Although early diagnosis of BA is crucial for good outcomes, it remains a clinical challenge. What is New: • Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA. • Plasma MMP-7, IL-8, and GGT have good accuracy for differentiating BA infants with cholic stool from non-BA infants with cholic stool.
Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and liver fibrosis. The early diagnosis of BA is still challenging. This study aimed to evaluate the diagnostic values of matrix metalloprotease-7 (MMP-7), interleukin-8 (IL-8), and gamma-glutamyl transferase (GGT) in BA. Infants diagnosed with BA and non-BA between 2013 and 2018 were retrospectively analyzed. Plasma levels of MMP-7, IL-8, and GGT were measured in these infants. The receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to assess the diagnostic values of MMP-7, IL-8, and GGT. The expression of MMP-7 and IL-8 in the livers was detected by immunofluorescence staining. A total of 229 infants were enrolled in this study: 156 BA infants and 73 non-BA infants including 16 ones with infantile hepatitis syndrome. The plasma levels of MMP-7, IL-8, and GGT in BA infants had a median of 11.8 ng/mL (interquartile range, IQR: 5.3-57.5), 1.5 ng/mL (IQR: 1.0-2.8), and 381.0 U/L (IQR: 197.0-749.0), respectively, which were higher than non-BA subjects [MMP-7, 4.4 ng/mL (IQR: 3.3-6.1); IL-8, 0.7 ng/mL (IQR: 0.5-1.0); GGT, 59.0 U/L (IQR: 26.0-124.0)]. The AUC values of MMP-7, IL-8, and GGT for the diagnosis of BA were 0.8035, 0.8083, and 0.9126, respectively. The AUC values of MMP-7 + IL-8, MMP-7 + GGT, IL-8 + GGT, and MMP-7 + IL-8 + GGT for the diagnosis of BA were 0.8248, 0.9382, 0.9168, and 0.9392, respectively. The AUC values of MMP-7, IL-8, and GGT for differentiating BA infants with cholic stool from non-BA infants with cholic stool were 0.8006, 0.8258, and 0.9141, respectively. The expression of MMP-7 and IL-8 was increased in the cholangiocytes in BA livers. Conclusion: Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA and may be reliable biomarkers for BA. What is Known: • Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and progressive liver fibrosis. • Although early diagnosis of BA is crucial for good outcomes, it remains a clinical challenge. What is New: • Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA. • Plasma MMP-7, IL-8, and GGT have good accuracy for differentiating BA infants with cholic stool from non-BA infants with cholic stool.
Authors: Chatmanee Lertudomphonwanit; Reena Mourya; Lin Fei; Yue Zhang; Sridevi Gutta; Li Yang; Kevin E Bove; Pranavkumar Shivakumar; Jorge A Bezerra Journal: Sci Transl Med Date: 2017-11-22 Impact factor: 17.956
Authors: Yuhuan Luo; Dania Brigham; Joseph Bednarek; Richard Torres; Dong Wang; Sara Ahmad; Cara L Mack Journal: Hepatology Date: 2021-04-27 Impact factor: 17.425
Authors: Anna Kerola; Hanna Lampela; Jouko Lohi; Päivi Heikkilä; Annika Mutanen; Jaana Hagström; Taina Tervahartiala; Timo Sorsa; Caj Haglund; Hannu Jalanko; Mikko P Pakarinen Journal: J Pathol Clin Res Date: 2016-05-12