Granulocyte-colony stimulating factor GCSF mobilizes hematopoietic stem cells in Kasai patients with biliary atresia in a phase 1 study and improves short term outcome

Holterman, Ai Xuan; Nguyen, Hoang-Nam; Nadler, Evan P.; Vu, Giap H.; Mohan, Parvathi; Vu, Megan; Trinh, Thuy; Bui, Huong Thuy Thi; Nguyen, Binh Thanh; Tran, Quynh Anh; Pham, Hien

doi:10.1016/j.jpedsurg.2021.03.038

Cited by 14 publications

(8 citation statements)

References 33 publications

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“…The surgical effect of biliary atresia depends on the age of the child, the severity of liver fibrosis, and postoperative complications, and progressive liver fibrosis is an important factor affecting the surgical effect [ 19 ]. Studying the mechanism of liver fibrosis and preventing liver fibrosis is a major topic for domestic and foreign scholars [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Serum TGF-β1 and VEGF Levels Reflect the Liver Hardness and Function in Children with Biliary Atresia

Chang

Zhou

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. This study further explored the wind direction correlation analysis between serum levels of TGF-β1 and VEGF and liver function assessment in children with biliary atresia. Methods. A total of 62 children with biliary atresia (BA) who received surgical treatment in our hospital from October 2020 to October 2021 were selected as the research objects (BA group), and 50 normal healthy children who received routine physical examination in our hospital during the same period were selected as blank control group. Outcome measures included postoperative total bilirubin levels and conjugality of enrolled patients. Bilirubin level, unbound bilirubin level, serum transforming growth factor-beta-1 (TGF-β1), vascular endothelial growth factor (VEGF), liver function indicators albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other observation indicators were included. All data in this study were collected and analyzed by SPSS 23.0 software, and t -test was performed. Results. The serum levels of TGF-β1, VEGF, ALT, AST, GGT, and liver hardness were significantly higher in children with jaundice than those without jaundice, and the serum ALB level was significantly lower than that in children without jaundice ( P < 0.05 ). The levels of TGF-β1 and VEGF in BA group were positively correlated with the levels of ALT, AST, GGT, and liver hardness ( P < 0.05 ) but negatively correlated with the level of ALB ( P < 0.05 ). Conclusion. The levels of serum TGF-β1 and VEGF in children with biliary atresia have a certain risk correlation with liver function damage, which will become a research focus on the mechanism of liver fibrosis in the diagnosis and treatment of biliary atresia in children.

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Section: Discussionmentioning

confidence: 99%

Serum TGF-β1 and VEGF Levels Reflect the Liver Hardness and Function in Children with Biliary Atresia

Chang

Zhou

et al. 2022

Computational and Mathematical Methods in Medicine

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“…In infants with BA after Kasai portoenterostomy, the effect of administering three consecutive days of granulocyte-colony-stimulating-factor (G-CSF) on liver inflammation was examined in a phase 1 trial showing that peripheral neutrophils and HSPCs initially increased before decreasing to baseline levels after two weeks. Notably, G-CSF treatment was associated with reduced cholestasis at one month after treatment began but reverted to control levels after three months [18]. A phase 2 randomized controlled trial is currently underway to determine the efficacy of G-CSF in patients with BA (NCT04373941).…”

Section: Discussionmentioning

confidence: 99%

Neonatal hepatic myeloid progenitors expand and propagate liver inflammation in mice

Alkhani

Korsholm

Mohamedaly

et al. 2022

Preprint

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Background and Aims: Biliary atresia is a rapidly progressive pediatric inflammatory disease of the liver that leads to cirrhosis and necessitates liver transplantation. The rapid progression from liver injury to fulminant liver failure in children with biliary atresia suggests that factors specific to the perinatal hepatic environment are important for disease propagation. Hematopoietic stem and progenitor cells (HSPCs) serve as central hubs of inflammation and rely on inflammatory signals for their emigration from the liver to the bone marrow in neonatal mice. We hypothesized that HSPCs are critical for the propagation of perinatal liver inflammation (PLI). Methods: Newborn BALB/c mice were injected intraperitoneally with 1.5x106 focus forming units of Rhesus Rotavirus (RRV) to induce PLI or with PBS as control. Livers from RRV and PBS-injected mice were compared using histology and flow cytometry. To determine the effects of HSPCs on perinatal inflammation, RRV-infected neonatal mice were injected with anti-CD47 and anti-CD117 to deplete HSPCs. Results: RRV-induced PLI led to a significant increase in the number of common myeloid progenitors (Flt3+ CMPs: PBS=4426+247.2 vs RRV=9856+2009, p=0.0316; Flt3- CMPs: PBS=3063+254.9 vs RRV=9743+1539, p=0.0012). We corroborated these findings by observing a significant increase in CD34+ hematopoietic progenitors/cm2 in histological sections of RRV-infected livers (PBS=4.977+2.573 vs RRV=27.09+12.49, p=0.0075). Elimination of progenitors through antibody-mediated myeloablation rescued animals from PLI and significantly increased survival (RRV+isotype control 55.56% vs RRV+myeloablation 94.12%, Chi test=0.01). Conclusions: These data demonstrate that RRV causes expansion of HSPCs and propagates PLI. Targeting of HSPCs may be useful in preventing and treating neonatal inflammatory diseases of the liver like biliary atresia.

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“…In the last 5 years, we extended our building capacity activities to basic science research ( 23 ) and applied research such as a multi-center randomized clinical trial for Biliary Atresia at the National CH in Hanoi and CH1, using a repurposed medication ( 28 ). We assisted the pediatric surgical faculty at UMP in reforming pediatric surgical training to standardize and update its curriculum and define training goals for HCMC pediatric surgeons.…”

Section: Ipsac-vn’s Global Health Activitiesmentioning

confidence: 99%

“…We conducted regular teleconferences for mentoring and case-based learning to enhance clinical decision-making. Some of the measurable impact of the academic efforts include engaging pediatric surgeons in cross-disciplinary research collaborations (hepatology, critical care, hematology, radiology, and pathology support for the clinical trial) and clinical trial funding for the local principal investigators ( 28 ); private industry support for translational basic science projects at the University of Science, and Vietnam Education Foundation Grant from the US Government for the pilot project in the PASS Pediatric Acute Surgical Support course.…”

Section: Ipsac-vn’s Global Health Activitiesmentioning

confidence: 99%

Academic Pediatric Surgery Capacity Building in Vietnam Through PASS, a Pediatric Acute Surgical Support Course

Nguyen

Holterman

et al. 2022

Front. Surg.

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Neonatal and pediatric surgical emergencies in Low and Low Middle Income countries remain a significant challenge in combatting the burden and inequities of global health. IPSAC-Vietnam is a small Non-Governmental Organization that has been engaged in a 12-year multi-pronged partnership with several children’s hospitals in Vietnam VN to enhance pediatric surgery capacity. We describe the health care, medical training and emergency system in VN as the background for IPSAC activities and development of Pediatric Acute Surgical Support (PASS) course. The course goal is to prepare health care personnel in the immediate management of neonatal/pediatric life-threatening surgical conditions and road injuries at their first point of entry into Vietnam hospitals. PASS is a horizontal outreach initiative that adopts an interprofessional, multidisciplinary, team-training, train-the-trainers, and outcome-based training approach. PASS can be used as a tool for sustainable horizontal capacity-building by champion leaders at the teaching children’s hospitals and medical universities in developing countries, to strengthen training for pediatric surgical emergencies, to integrate pediatric and pediatric surgical care and to advocate for a comprehensive approach to emergency care of the critically ill child.

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Granulocyte-colony stimulating factor GCSF mobilizes hematopoietic stem cells in Kasai patients with biliary atresia in a phase 1 study and improves short term outcome

Cited by 14 publications

References 33 publications

Serum TGF-β1 and VEGF Levels Reflect the Liver Hardness and Function in Children with Biliary Atresia

Serum TGF-β1 and VEGF Levels Reflect the Liver Hardness and Function in Children with Biliary Atresia

Neonatal hepatic myeloid progenitors expand and propagate liver inflammation in mice

Academic Pediatric Surgery Capacity Building in Vietnam Through PASS, a Pediatric Acute Surgical Support Course

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