Yi-Ting Yeh1, Niang-Cheng Lin2, Yi-Chen Yeh3, Hsin-Lin Tsai4, Cheng-Yen Chen2, Chia-Pei Liu1, Chinsu Liu5. 1. Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan. 2. Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan. 3. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan. 4. Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan. 5. Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan. Electronic address: csliu@vghtpe.gov.tw.
Abstract
BACKGROUND: Antifibrosis therapy may prevent progressive liver fibrosis after successful Kasai portoenterostomy (KPE) in biliary atresia (BA) patients. The aim of this study is to evaluate the efficacy of antifibrosis therapy in a rat model of BA and KPE. METHODS: BA model was created on three-week-old Sprague-Dawley rats by intrabiliary alcohol injection as previously described, and KPE was performed at postoperative week (POW) 5 by cystoenterostomy. Liver biopsies were performed at the time of BA creation, during KPE, POW 9, and at sacrifice (POW 17). Prednisolone (0.1 mg/100 g/day, group 1, n = 20), Vitamin A (0.5 mg/100 g/day, group 2, n = 20), and ursodeoxycholic acid (UDCA, 1.5 mg/100 g/day, group 3, n = 20) were respectively given to three groups after KPE and continued daily until sacrifice. Histological evaluation of fibrosis and immunohistochemistry stains for 8 fibrosis markers were compared to the control group (without medication, n = 10). RESULTS: Among the four markers, namely ɑ-smooth muscle actin (ɑ-SMA), glial fibrillary acidic protein (GFAP), tumor growth factor β1 (TGFβ1) receptors 1 and 2, which showed persistently high expression after successful KPE in the examined 8 markers, only the expression of ɑ-SMA was significantly reduced in all treatment groups at POW17. However, the fibrosis grade at POW 17 was only significantly reduced in group 2 in comparison with the control group (Vitamin A vs. control group, Ishak score 3 vs. 1.8, p < 0.05). CONCLUSION: In our rat model of BA with KPE, Vitamin A was effective in reducing liver fibrosis, and the mechanisms deserve further study. LEVEL OF EVIDENCE: Basic science.
BACKGROUND: Antifibrosis therapy may prevent progressive liver fibrosis after successful Kasai portoenterostomy (KPE) in biliary atresia (BA) patients. The aim of this study is to evaluate the efficacy of antifibrosis therapy in a rat model of BA and KPE. METHODS: BA model was created on three-week-old Sprague-Dawley rats by intrabiliary alcohol injection as previously described, and KPE was performed at postoperative week (POW) 5 by cystoenterostomy. Liver biopsies were performed at the time of BA creation, during KPE, POW 9, and at sacrifice (POW 17). Prednisolone (0.1 mg/100 g/day, group 1, n = 20), Vitamin A (0.5 mg/100 g/day, group 2, n = 20), and ursodeoxycholic acid (UDCA, 1.5 mg/100 g/day, group 3, n = 20) were respectively given to three groups after KPE and continued daily until sacrifice. Histological evaluation of fibrosis and immunohistochemistry stains for 8 fibrosis markers were compared to the control group (without medication, n = 10). RESULTS: Among the four markers, namely ɑ-smooth muscle actin (ɑ-SMA), glial fibrillary acidic protein (GFAP), tumor growth factor β1 (TGFβ1) receptors 1 and 2, which showed persistently high expression after successful KPE in the examined 8 markers, only the expression of ɑ-SMA was significantly reduced in all treatment groups at POW17. However, the fibrosis grade at POW 17 was only significantly reduced in group 2 in comparison with the control group (Vitamin A vs. control group, Ishak score 3 vs. 1.8, p < 0.05). CONCLUSION: In our rat model of BA with KPE, Vitamin A was effective in reducing liver fibrosis, and the mechanisms deserve further study. LEVEL OF EVIDENCE: Basic science.