Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free course
Abstract Background and Aim Alagille syndrome (ALGS) is a multisystem disorder with variable clinical courses. This study investigated the clinical and genetic features of ALGS patients with different outcomes and analyzed the liver pathology at liver transplantation (LT) compared with that in bilia...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | JGH Open |
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| Online Access: | https://doi.org/10.1002/jgh3.12830 |
| _version_ | 1811185698593570816 |
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| author | Che‐Ming Chiang Yung‐Ming Jeng Ming‐Chih Ho Ming‐Wei Lai Huei‐Ying Li Pei‐Lung Chen Ni‐Chung Lee Jia‐Feng Wu Yu‐Chun Chiu Bang‐Yu Liou Yen‐Hsuan Ni Hong‐Yuan Hsu Mei‐Hwei Chang Huey‐Ling Chen |
| author_facet | Che‐Ming Chiang Yung‐Ming Jeng Ming‐Chih Ho Ming‐Wei Lai Huei‐Ying Li Pei‐Lung Chen Ni‐Chung Lee Jia‐Feng Wu Yu‐Chun Chiu Bang‐Yu Liou Yen‐Hsuan Ni Hong‐Yuan Hsu Mei‐Hwei Chang Huey‐Ling Chen |
| author_sort | Che‐Ming Chiang |
| collection | DOAJ |
| description | Abstract Background and Aim Alagille syndrome (ALGS) is a multisystem disorder with variable clinical courses. This study investigated the clinical and genetic features of ALGS patients with different outcomes and analyzed the liver pathology at liver transplantation (LT) compared with that in biliary atresia (BA). Methods We report the clinical characteristics, outcomes, and genetic mutations of 25 children with ALGS followed for a median of 7.3 years. Patients were classified into (i) jaundice‐free (JF) group (resolving jaundice after 2 years of age); (ii) progressive disease (PD) group (persistent jaundice or progressive cholestasis). In addition, we analyzed the explant liver in 10 ALGS patients compared with 20 age‐matched BA patients at the time of LT. Results Nine patients (36%) in the JF group had a favorable outcome, with longer native liver survival than patients with PD (n = 16, P < 0.001). Fourteen of the PD group patients received LT or died. We identified 18 different JAG1 mutations in 22 patients. Three unrelated probands in the JF group had the same de novo mutation in JAG1, c.2122‐2125delCAGT. Compared with BA children, ALGS patients had lower METAVIR scores in liver pathology, higher serum albumin levels, and lower weight‐for‐age z‐scores when receiving LT. Conclusion One‐third of ALGS patients had JF and a favorable course. Children with ALGS presenting with persistent jaundice beyond 2 years of age should be cautioned for poor prognosis. ALGS patients tend to have a lesser extent of cirrhosis, and more growth problems than BA patients at the time of LT. |
| first_indexed | 2024-04-11T13:33:37Z |
| format | Article |
| id | doaj.art-c4fe4b8c39664be18f32bf07e6276ac7 |
| institution | Directory Open Access Journal |
| issn | 2397-9070 |
| language | English |
| last_indexed | 2024-04-11T13:33:37Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | JGH Open |
| spelling | doaj.art-c4fe4b8c39664be18f32bf07e6276ac72022-12-22T04:21:40ZengWileyJGH Open2397-90702022-12-0161283984510.1002/jgh3.12830Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free courseChe‐Ming Chiang0Yung‐Ming Jeng1Ming‐Chih Ho2Ming‐Wei Lai3Huei‐Ying Li4Pei‐Lung Chen5Ni‐Chung Lee6Jia‐Feng Wu7Yu‐Chun Chiu8Bang‐Yu Liou9Yen‐Hsuan Ni10Hong‐Yuan Hsu11Mei‐Hwei Chang12Huey‐Ling Chen13Department of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pathology National Taiwan University Hospital Taipei TaiwanDepartment of Surgery National Taiwan University Hospital Hsin‐Chu Branch Hsinchu TaiwanDivision of Pediatric Gastroenterology, Department of Pediatrics, Liver Research Center, Chang Gung Memorial Hospital Linkou, Chang Gung University College of Medicine Taoyuan TaiwanMedical Microbiome Center National Taiwan University College of Medicine Taipei TaiwanDepartment of Medical Genetics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanDepartment of Pediatrics National Taiwan University Hospital Taipei TaiwanAbstract Background and Aim Alagille syndrome (ALGS) is a multisystem disorder with variable clinical courses. This study investigated the clinical and genetic features of ALGS patients with different outcomes and analyzed the liver pathology at liver transplantation (LT) compared with that in biliary atresia (BA). Methods We report the clinical characteristics, outcomes, and genetic mutations of 25 children with ALGS followed for a median of 7.3 years. Patients were classified into (i) jaundice‐free (JF) group (resolving jaundice after 2 years of age); (ii) progressive disease (PD) group (persistent jaundice or progressive cholestasis). In addition, we analyzed the explant liver in 10 ALGS patients compared with 20 age‐matched BA patients at the time of LT. Results Nine patients (36%) in the JF group had a favorable outcome, with longer native liver survival than patients with PD (n = 16, P < 0.001). Fourteen of the PD group patients received LT or died. We identified 18 different JAG1 mutations in 22 patients. Three unrelated probands in the JF group had the same de novo mutation in JAG1, c.2122‐2125delCAGT. Compared with BA children, ALGS patients had lower METAVIR scores in liver pathology, higher serum albumin levels, and lower weight‐for‐age z‐scores when receiving LT. Conclusion One‐third of ALGS patients had JF and a favorable course. Children with ALGS presenting with persistent jaundice beyond 2 years of age should be cautioned for poor prognosis. ALGS patients tend to have a lesser extent of cirrhosis, and more growth problems than BA patients at the time of LT.https://doi.org/10.1002/jgh3.12830Alagille syndromebiliary atresiaJAG1 genejaundice freeliver transplantation |
| spellingShingle | Che‐Ming Chiang Yung‐Ming Jeng Ming‐Chih Ho Ming‐Wei Lai Huei‐Ying Li Pei‐Lung Chen Ni‐Chung Lee Jia‐Feng Wu Yu‐Chun Chiu Bang‐Yu Liou Yen‐Hsuan Ni Hong‐Yuan Hsu Mei‐Hwei Chang Huey‐Ling Chen Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free course JGH Open Alagille syndrome biliary atresia JAG1 gene jaundice free liver transplantation |
| title | Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free course |
| title_full | Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free course |
| title_fullStr | Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free course |
| title_full_unstemmed | Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free course |
| title_short | Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice‐free course |
| title_sort | different clinical and genetic features of alagille patients with progressive disease versus a jaundice free course |
| topic | Alagille syndrome biliary atresia JAG1 gene jaundice free liver transplantation |
| url | https://doi.org/10.1002/jgh3.12830 |
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