Peroxisome Proliferator-Activated Receptor Gamma Agonist Attenuates Liver Fibrosis by Several Fibrogenic Pathways in an Animal Model of Cholestatic Fibrosis

Fatima Safira Alatas,Toshiharu Matsuura,Antonius Hocky Pudjiadi,Stephanie Wijaya,Tomoaki Taguchi 대한소아소화기영양학회 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.4

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

Modified Puestow Procedure for Chronic Pancreatitis in a Child Due to Annular Pancreas and Duodenal Duplication: A Case Report

Fatima Safira Alatas,Kouji Masumoto,Toshiharu Matsuura,Antonius Hocky Pudjiadi,Tomoaki Taguchi 대한소아소화기영양학회 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.3

An 18-year-old woman with annular pancreas and duodenal duplication presented with recurrent acute pancreatitis and underwent a resection of duodenal duplication. However, the patient experienced recurrent abdominal pain after resection. Abdominal computed tomography and magnetic resonance imaging showed a dilatation of the peripheral pancreatic duct and stenosis and malformation of both the Wirsung's and Santorini's duct due to multiple stones. The modified puestow procedure was performed. The main pancreatic ducts in the body and tail were opened, and the intrapancreatic common bile duct was preserved. A Roux-en-Y pancreatico-jejunostomy was performed for reconstructing the pancreaticobiliary system after removing the ductal protein plug. The patient experienced no abdominal pain, no significant elevation of the serum amylase and lipase levels, and no stone formation during the 2 years of follow-up. This procedure is considered to be beneficial for pediatric patients with chronic pancreatitis due to annular pancreas and duodenal duplication.

Association Between Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire Score, Endoscopy and Biopsy in Children with Clinical Gastroesophageal Reflux Disease: A Prospective Study

Fatima Safira Alatas,Dian Wulandaru Sukmaning Pertiwi,Muzal Kadim,Pramita Dwipoerwantoro,Hanifah Oswari,Badriul Hegar,Yvan Vandenplas 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.4

Purpose: Gastro esophageal reflux disease (GERD) is a burdensome disease affecting many children. A clinical examination is reported to be unreliable to diagnose GERD in children. This study aimed to investigate the relationship between the Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) and endoscopic and histopathological findings in children with symptoms suggesting GERD. Changes in the PGSQ score in children with esophagitis as response to one month therapy were recorded as secondary outcome. Methods: This is a prospective cohort study in the pediatric outpatient clinic in an Indonesian tertiary hospital. Children aged 2–17 years old with clinical symptoms suspected of GERD are included in the study. Blinded endoscopic and histopathological examination was performed in all patients before one month proton pump inhibitors (PPI) therapy. The PGSQ information was collected at inclusion and after one month PPI treatment. Results: Fifty-eight subjects were included. Esophagitis was found in 60.9% of subjects according to endoscopy and 58.6% according to histology. There was no significant relationship between the PGSQ score and endoscopic (p=0.781) nor biopsy (p=0.740) examinations. The PGSQ showed a low diagnostic value compared to endoscopy and biopsy (area under the curve [AUC] 0.477, p=0.477, 95% confidence interval [CI] 0.326–0.629 and AUC 0.474, p=0.740 (95% CI 0.321–0.627 respectively). The PGSQ improved significantly post one month of PPI treatment. Conclusion: The PGSQ cannot be used to diagnose esophagitis in children with clinical symptoms suggesting GERD. However, the PGSQ can be used to monitor the treatment response in children with esophagitis.

Modified Puestow Procedure for Chronic Pancreatitis in a Child Due to Annular Pancreas and Duodenal Duplication: A Case Report

Alatas, Fatima Safira,Masumoto, Kouji,Matsuura, Toshiharu,Pudjiadi, Antonius Hocky,Taguchi, Tomoaki The Korean Society of Pediatric Gastroenterology 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.3

An 18-year-old woman with annular pancreas and duodenal duplication presented with recurrent acute pancreatitis and underwent a resection of duodenal duplication. However, the patient experienced recurrent abdominal pain after resection. Abdominal computed tomography and magnetic resonance imaging showed a dilatation of the peripheral pancreatic duct and stenosis and malformation of both the Wirsung's and Santorini's duct due to multiple stones. The modified puestow procedure was performed. The main pancreatic ducts in the body and tail were opened, and the intrapancreatic common bile duct was preserved. A Roux-en-Y pancreatico-jejunostomy was performed for reconstructing the pancreaticobiliary system after removing the ductal protein plug. The patient experienced no abdominal pain, no significant elevation of the serum amylase and lipase levels, and no stone formation during the 2 years of follow-up. This procedure is considered to be beneficial for pediatric patients with chronic pancreatitis due to annular pancreas and duodenal duplication.

Peroxisome Proliferator-Activated Receptor Gamma Agonist Attenuates Liver Fibrosis by Several Fibrogenic Pathways in an Animal Model of Cholestatic Fibrosis

Alatas, Fatima Safira,Matsuura, Toshiharu,Pudjiadi, Antonius Hocky,Wijaya, Stephanie,Taguchi, Tomoaki The Korean Society of Pediatric Gastroenterology 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.4

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

Endoscopic Primary Prophylaxis to Prevent Bleeding in Children with Esophageal Varices: A Systematic Review and Meta-Analysis

Fatima Safira Alatas,Ervin Monica,Lukito Ongko,Muzal Kadim 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.5

Purpose: This systematic review and meta-analysis aimed to compare endoscopy as primary versus secondary prophylaxis to prevent future bleeding in children with esophageal varices. Methods: A systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was conducted using the Scopus, PubMed, and Cochrane databases for relevant studies on the outcome of rebleeding events after endoscopy in primary prophylaxis compared to that in secondary prophylaxis. The following keywords were used: esophageal varices, children, endoscopy, primary prophylaxis and bleeding. The quality of eligible articles was assessed using the Newcastle–Ottawa Scale and statistically analyzed using RevMan 5.4 software. Results: A total of 174 children were included from four eligible articles. All four studies were considered of high-quality based on the Newcastle-Ottawa Quality Assessment Scale. Patients who received primary prophylaxis had 79% lower odds of bleeding than those who received secondary prophylaxis (odds ratio, 0.21; 95% confidence interval [CI], 0.07–0.66; I2=0%, p=0.008). Patients in the primary prophylaxis group underwent fewer endoscopic procedures to eradicate varices than those in the secondary prophylaxis group, with a mean difference of 1.73 (95% CI, 0.91–2.56; I2=62%, p<0.0001). Conclusion: Children with high-risk varices who underwent primary prophylaxis were less likely to experience future bleeding episodes and required fewer endoscopic procedures to eradicate the varices than children who underwent secondary prophylaxis.

Echovirus-7 Infection in Children with Unusual Severe Manifestation: A Case Report

Pudjiadi Antonius Hocky,Antonjaya Ungke,Myint Khin Saw,Alatas Fatima Safira 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.1

We report a rare laboratory-confirmed, clinical case of Echovirus-7 infection in an immuno-competent child with central nervous system and systemic manifestation. Echovirus infection is usually mild, however in this case we identified echovirus-7 infection with 91% homology with the Echovirus-7 strain previously isolated in neighbouring country with severe manifestation.