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Models for acute on chronic liver failure development and mortality in a veterans affairs cohort

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Abstract

Background and purpose

The diagnosis of acute on chronic liver failure (ACLF) carries a high short-term mortality, making early identification of at-risk patients crucial. To date, there are no models that predict which patients with compensated cirrhosis will develop ACLF, and limited models exist to predict ACLF mortality. We sought to create novel risk prediction models using a large North American cohort.

Methods

We performed a retrospective study of 75,922 patients with compensated cirrhosis from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) dataset. Using 70% derivation/30% validation sets, we identified ACLF patients using the Asian Pacific Association of Liver (APASL) definition. Multivariable logistic regression was used to derive prediction models (called VOCAL-Penn) for developing ACLF at 3, 6, and 12 months. We then created prediction models for ACLF mortality at 28 and 90 days.

Results

The VOCAL-Penn models for ACLF development had very good discrimination [concordance (C) statistics of 0.93, 0.92, and 0.89 at 3, 6, and 12 months, respectively] and calibration. The mortality models also had good discrimination at 28 and 90 days (C statistics 0.89 and 0.88, respectively), outperforming the Model for End-stage Liver Disease (MELD), MELD-sodium, and the APASL ACLF Research Consortium ACLF scores.

Conclusion

We have developed novel tools for predicting development of ACLF in compensated cirrhosis patients, as well as for ACLF mortality. These tools may be used to proactively guide patient follow-up, prognostication, escalation of care, and transplant evaluation.

Graphic abstract

Receiver operating characteristic (ROC) curves for predicting development of APASL ACLF at 3 months (a), 6 months (b), and 1 year (c)

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Acknowledgements

This work was supported by resources and facilities available through the Philadelphia Veterans Affairs Healthcare System and central data repositories maintained by the Veterans Affairs Information Resource Center. The views expressed herein do not reflect position or policy of the Department of Veterans Affairs or the United States government.

Funding

Nadim Mahmud is supported by a National Institutes of Health T32 Grant (2-T32-DK007740-21A1).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, 100 Centrex, Philadelphia, PA, 19104, USA

    Karen Y. Xiao

  2. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 604 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104, USA

    Rebecca A. Hubbard

  3. Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, PCAM 7S GI, 4th Floor, South Pavilion, Philadelphia, PA, 19104, USA

    David E. Kaplan & Nadim Mahmud

  4. Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA

    David E. Kaplan

  5. Division of Digestive Diseases, Yale University School of Medicine, Digestive Diseases, 333 Cedar Street, PO Box 208019, New Haven, CT, 06520, USA

    Tamar H. Taddei

  6. VA Connecticut Healthcare System, West Haven, CT, USA

    Tamar H. Taddei

  7. Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, 1120 NW 14th St, Suite 1112 (D49), Miami, FL, 33136, USA

    David S. Goldberg

  8. Leonard David Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA

    Nadim Mahmud

Authors
  1. Karen Y. Xiao
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  2. Rebecca A. Hubbard
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  3. David E. Kaplan
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  4. Tamar H. Taddei
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  6. Nadim Mahmud
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Corresponding author

Correspondence to Nadim Mahmud.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors. Institutional review board approval for this study was obtained from the Hospital of the University of Pennsylvania and the Philadelphia Veterans Affairs Hospital.

Compliance with ethical requirements

Karen Xiao, David Kaplan, Tamar Taddei, and Nadim Mahmud declare that they have no conflict of interest. Rebecca Hubbard has received research grants from Humana and Pfizer. David Goldberg has received research grants from Merck, AbbVie, and Gilead.

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Xiao, K.Y., Hubbard, R.A., Kaplan, D.E. et al. Models for acute on chronic liver failure development and mortality in a veterans affairs cohort. Hepatol Int 14, 587–596 (2020). https://doi.org/10.1007/s12072-020-10060-y

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  • DOI: https://doi.org/10.1007/s12072-020-10060-y

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