Abstract
Pediatric acute liver failure (PALF) is a potentially devastating condition that occurs in previously healthy children of all ages and frequently leads to a rapid clinical deterioration. An identified cause for liver injury is lacking in approximately 30% of cases. Children with undetermined diagnosis have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. A single-day workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases brought together clinicians and basic scientists to integrate aligned research findings and develop a foundation for new mechanistic studies and future treatment trials. The clinical phenotype of indeterminate PALF shares important similarities to the hyperinflammatory state characteristic of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). A failure of cytotoxic T cells to limit or contract inflammatory responses may propagate injury and lead to a local and systemic milieu that does not support normal hepatic regeneration. Evidence was presented that bone marrow (BM)-derived Sinusoidal endothelial cell PROgenitor Cells (sprocs) play a vital role in hepatic regeneration. Overwhelming systemic inflammatory responses may suppress mobilization of BM sprocs and dampen hepatic recovery. Conclusion: Experience gained through treatment trials of HLH and MAS in childhood may inform study design for therapy of PALF. Successful approaches to limiting neuroinflammation through reduction of systemic inflammation and standardized neuroprotection protocols that limit glial injury could significantly improve intact survival. Finally, given that PALF is a rare disease, investigative efforts must include broad multicenter collaboration and careful stewardship of biorepository specimens. (Hepatology 2017;65:1026-1037).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1026-1037 |
| Number of pages | 12 |
| Journal | Hepatology |
| Volume | 65 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2017 |
Funding
Speakers whose lectures contributed to the content of this meeting summary were as follows: Estella M. Alonso, M.D., Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL; Edward Behrens, M.D., Children's Hospital of Philadelphia and Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA; Charles Chiu, M.D., Ph.D., University of California San Francisco, San Francisco, CA; Laurie DeLeve, M.D., Ph.D., F.A.A.S.L.D., Keck School of Medicine of University of Southern California, Los Angeles, CA; Alexie A. Gromm, M.D., Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Simon Horslen, M.D., Ch.B., F.R.C.P.C.H., Seattle Children's Hospital and University of Washington School of Medicine, Seattle, WA; Hartmut Jaeschke, Ph.D., University of Kansas Medical Center, Kansas City, KS; David Kleiner, M.D., Ph.D., National Cancer Institute, Bethesda, MD; David Rudnick, M.D., Ph.D., Washington University School of Medicine, St. Louis, MO; R. Todd Stravitz, M.D., Virginia Commonwealth University, Richmond, VA; Yoram Vodovotz, Ph.D., University of Pittsburgh, Pittsburgh, PA; Mark Wainwright, M.D., Ph.D., Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL; Mark Yandell, Ph.D., University of Utah, Salt Lake City, UT. We also acknowledge Katie Neighbors-Benson, M.P.H., Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL for support for final review and formatting of the manuscript.
ASJC Scopus subject areas
- Hepatology
