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Elevated Serum Liver-Type Fatty Acid Binding Protein Levels in Non-acetaminophen Acute Liver Failure Patients with Organ Dysfunction

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Abstract

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.

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Abbreviations

ALF:

Acute liver failure

ALFSG:

Acute Liver Failure Study Group

APAP:

Acetaminophen

FABP1:

Liver-type fatty acid binding protein

HE:

Hepatic encephalopathy

ICU:

Intensive Care Unit

INR:

International normalized ratio

IQR:

Interquartile range

KCC:

King’s College Criteria

LT:

Liver transplantation

MAP:

Mean arterial pressure (mm Hg)

MELD:

Model for end-stage liver disease score

MV:

Mechanical ventilation

OR:

Odds ratio

RRT:

Renal replacement therapy

TFS:

Transplant-free survivor at day 21

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Acknowledgment

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.

Funding

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.

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Authors and Affiliations

  1. Divisions of Hepatology and Critical Care Medicine, University of Alberta, Edmonton, Canada

    Constantine J. Karvellas

  2. Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston Salem, NC, USA

    Jaime L. Speiser

  3. Hepato-neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada

    Mélanie Tremblay & Christopher F. Rose

  4. Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    William M. Lee

  5. Canadian Donation and Transplant Research Program, Edmonton, Canada

    Constantine J. Karvellas & Christopher F. Rose

  6. Division of Gastroenterology (Liver Unit), Division of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, AB, T6G-2X8, Canada

    Constantine J. Karvellas

Authors
  1. Constantine J. Karvellas
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  2. Jaime L. Speiser
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  3. Mélanie Tremblay
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  4. William M. Lee
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  5. Christopher F. Rose
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For the US Acute Liver Failure Study Group

Contributions

CJK conceived the study concept and design, performed analysis and interpretation of the data, and drafted the final manuscript. JLS performed statistical analysis and interpretation of data and critically revised the final manuscript. MT performed laboratory analysis and revised the final manuscript. WML, supervisor of entire US Acute Liver Failure Study Group (U-01 Grant), critically revised the manuscript for important intellectual content. CFR conceived the idea of the study, assisted in developing study design and interpretation of data, and critically revised the final manuscript for important intellectual content.

Corresponding author

Correspondence to Constantine J. Karvellas.

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Karvellas, C.J., Speiser, J.L., Tremblay, M. et al. Elevated Serum Liver-Type Fatty Acid Binding Protein Levels in Non-acetaminophen Acute Liver Failure Patients with Organ Dysfunction. Dig Dis Sci 66, 273–283 (2021). https://doi.org/10.1007/s10620-020-06166-w

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  • DOI: https://doi.org/10.1007/s10620-020-06166-w

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