TY - JOUR
T1 - Elevated Serum Liver-Type Fatty Acid Binding Protein Levels in Non-acetaminophen Acute Liver Failure Patients with Organ Dysfunction
AU - For the US Acute Liver Failure Study Group
AU - Karvellas, Constantine J.
AU - Speiser, Jaime L.
AU - Tremblay, Mélanie
AU - Lee, William M.
AU - Rose, Christopher F.
N1 - Funding Information:
The study was sponsored by NIH Grant U-01 58369 (from NIDDK) and the CDTRP ATIF Research Innovation Grant jointly supported by the Alberta Ministry of Economic Development and Trade, the University Hospital Foundation, Astellas Pharma Canada, and the Canadian Donation and Transplant Research Program. Acknowledgment
Funding Information:
Members and institutions participating in the Acute Liver Failure Study Group 1998?2018 are as follows: W.M. Lee, M.D. (Principal Investigator); Anne M. Larson, M.D., Iris Liou, M.D., University of Washington, Seattle, WA; Oren Fix, M.D., Swedish Medical Center, Seattle, WA; Michael Schilsky, M.D., Yale University, New Haven, CT; Timothy McCashland, M.D., University of Nebraska, Omaha, NE; J. Eileen Hay, M.B.B.S., Mayo Clinic, Rochester, MN; Natalie Murray, M.D., Baylor University Medical Center, Dallas, TX; A. Obaid S. Shaikh, M.D., University of Pittsburgh, Pittsburgh, PA; Andres Blei, M.D., Northwestern University, Chicago, IL (deceased), Daniel Ganger, M.D., Northwestern University, Chicago, IL; Atif Zaman, M.D., University of Oregon, Portland, OR; Steven H.B. Han, M.D., University of California, Los Angeles, CA; Robert Fontana, M.D., University of Michigan, Ann Arbor, MI; Brendan McGuire, M.D., University of Alabama, Birmingham, AL; Raymond T. Chung, M.D., Massachusetts General Hospital, Boston, MA; Alastair Smith, M.B., Ch.B., Duke University Medical Center, Durham, NC; Robert Brown, M.D., Cornell/Columbia University, New York, NY; Jeffrey Crippin, M.D., Washington University, St Louis, MO; Edwin Harrison, Mayo Clinic, Scottsdale, AZ; Adrian Reuben, M.B.B.S., Medical University of South Carolina, Charleston, SC; Santiago Munoz, M.D., Albert Einstein Medical Center, Philadelphia, PA; Rajender Reddy, M.D., University of Pennsylvania, Philadelphia, PA; R. Todd Stravitz, M.D., Virginia Commonwealth University, Richmond, VA; Lorenzo Rossaro, M.D., University of California Davis, Sacramento, CA; Raj Satyanarayana, M.D., Mayo Clinic, Jacksonville, FL; and Tarek Hassanein, M.D., University of California, San Diego, CA; Constantine J. Karvellas MD, University of Alberta, Edmonton, AB; Jodi Olson MD, University of Kansas, Kansas City, KA; Ram Subramanian MD, Emory, Atlanta, GA; James Hanje MD, Ohio State University, Columbus, OH; Bilal Hameed MD, University of California San Francisco, CA. The University of Texas Southwestern Administrative Group included Grace Samuel, Ezmina Lalani, Carla Pezzia, and Corron Sanders, Ph.D., Nahid Attar, Linda S. Hynan, Ph.D., and the Medical University of South Carolina Data Coordination Unit included Valerie Durkalski, Ph.D., Wenle Zhao, Ph.D., Jaime Speiser, Catherine Dillon, Holly Battenhouse, and Michelle Gottfried. Special thanks to Dr. Elaine Leslie for study advice. Dr. Karvellas and Dr Rose are members of CDTRP Theme 3: Engineer and allocate a better graft.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/1
Y1 - 2021/1
N2 - Background: Liver-type fatty acid binding protein (FABP1) has previously been demonstrated to improve prognostic discrimination in acetaminophen (APAP)-induced ALF but has not been investigated in other etiologies of ALF. Aim: To determine whether FABP1 levels (early: admission or late: days 3–5) are associated with 21-day transplant-free survival in non-APAP ALF. Methods: FABP1 was measured in serum samples from 384 ALF patients (n = 88 transplant-free survivors (TFS), n = 296 died/LT–NTFS) using solid-phase enzyme-linked immunosorbent assay and analyzed with US ALFSG registry data. Results: Of 384 ALF patients (autoimmune hepatitis n = 125, drug-induced liver injury n = 141, Hepatitis B n = 118), 177 (46%) patients received LT. Early FABP1 levels were significantly higher in ALF patients requiring vasopressor support (203.4 vs. 76.3 ng/mL) and renal replacement therapy (203.4 vs. 78.8 ng/mL; p < 0.001 for both). Late FABP1 levels were significantly higher in patients requiring mechanical ventilation (77.5 vs. 53.3 ng/mL), vasopressor support (116.4 vs. 53.3 ng/mL) and in patients with grade 3/4 hepatic encephalopathy (71.4 vs. 51.4 ng/mL; p = 0.03 for all). Late FABP1 levels were significantly lower in TFS patients (TFS 54 vs. NTFS 66 ng/mL; p = 0.049) but not admission (TFS 96 vs. NTFS 87 ng/mL; p = 0.67). After adjusting for significant covariates, serum FABP1 did not discriminate significantly between TFS and patients who died/received LT at day 21 either on admission (p = 0.29) or late (days 3–5, p = 0.087) time points. Conclusion: In this first report of FABP1 in non-APAP ALF, FABP1 levels at late time points (days 3–5) were significantly lower in ALF patients who were alive without transplant at day 21 but not after adjusting for covariates reflecting severity of illness. Higher FABP1 levels were associated with the presence of increased organ failure.
AB - Background: Liver-type fatty acid binding protein (FABP1) has previously been demonstrated to improve prognostic discrimination in acetaminophen (APAP)-induced ALF but has not been investigated in other etiologies of ALF. Aim: To determine whether FABP1 levels (early: admission or late: days 3–5) are associated with 21-day transplant-free survival in non-APAP ALF. Methods: FABP1 was measured in serum samples from 384 ALF patients (n = 88 transplant-free survivors (TFS), n = 296 died/LT–NTFS) using solid-phase enzyme-linked immunosorbent assay and analyzed with US ALFSG registry data. Results: Of 384 ALF patients (autoimmune hepatitis n = 125, drug-induced liver injury n = 141, Hepatitis B n = 118), 177 (46%) patients received LT. Early FABP1 levels were significantly higher in ALF patients requiring vasopressor support (203.4 vs. 76.3 ng/mL) and renal replacement therapy (203.4 vs. 78.8 ng/mL; p < 0.001 for both). Late FABP1 levels were significantly higher in patients requiring mechanical ventilation (77.5 vs. 53.3 ng/mL), vasopressor support (116.4 vs. 53.3 ng/mL) and in patients with grade 3/4 hepatic encephalopathy (71.4 vs. 51.4 ng/mL; p = 0.03 for all). Late FABP1 levels were significantly lower in TFS patients (TFS 54 vs. NTFS 66 ng/mL; p = 0.049) but not admission (TFS 96 vs. NTFS 87 ng/mL; p = 0.67). After adjusting for significant covariates, serum FABP1 did not discriminate significantly between TFS and patients who died/received LT at day 21 either on admission (p = 0.29) or late (days 3–5, p = 0.087) time points. Conclusion: In this first report of FABP1 in non-APAP ALF, FABP1 levels at late time points (days 3–5) were significantly lower in ALF patients who were alive without transplant at day 21 but not after adjusting for covariates reflecting severity of illness. Higher FABP1 levels were associated with the presence of increased organ failure.
KW - ALFSG index
KW - Acute liver failure
KW - Liver-type fatty acid binding protein
KW - Multiorgan failure
KW - Prognosis
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U2 - 10.1007/s10620-020-06166-w
DO - 10.1007/s10620-020-06166-w
M3 - Article
C2 - 32125573
AN - SCOPUS:85080976057
SN - 0163-2116
VL - 66
SP - 273
EP - 283
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 1
ER -