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Liver Fibrosis and Perihematomal Edema Growth in Primary Intracerebral Hemorrhage

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Abstract

Background

Liver disease is associated with altered serum osmolality, increased thrombin generation, and systemic inflammation, all of which may contribute to perihematomal edema (PHE) after intracerebral hemorrhage (ICH). We evaluated the association between a validated liver fibrosis index and PHE growth in a cohort of patients with primary ICH.

Methods

We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive-ICH. We included adult patients with primary ICH presenting within 6 h of symptom onset. The exposure of interest was the Fibrosis-4 (FIB-4) score, a validated liver fibrosis index; this was modeled as a continuous variable. The primary outcome was absolute PHE growth over 96 h. Secondary outcomes were absolute admission and 96-h PHE volumes. We used multiple linear regression models adjusted for established determinants of PHE. In a secondary analysis, the FIB-4 score was modeled as a categorical variable to compare patients with versus without liver fibrosis.

Results

Among 354 patients with ICH, 8% had evidence of liver fibrosis based on a validated cutoff. The FIB-4 score was not associated with PHE growth in unadjusted (β, 0.03; 95% CI, − 0.01 to 0.12) or adjusted models (β, 0.04; 95% CI, − 0.03 to 0.13). In a secondary analysis treating FIB-4 as a categorical variable, patients with liver fibrosis did not have greater PHE growth than those without liver fibrosis. FIB-4 score was also not associated with absolute admission or 96-h PHE volumes.

Conclusions

In a multicenter cohort of patients with primary intracerebral hemorrhage, a liver fibrosis score was not associated with PHE volume or growth.

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Acknowledgements

VISTA-ICH Steering Committee

VISTA-ICH Steering Committee Collaborators: D.F. Hanley (Chair), K. Butcher, S. Davis, B. Gregson, K.R. Lees, P. Lyden, S. Mayer, K. Muir, and T. Steiner.

Funding

Dr. Parikh was supported by the Leon Levy Foundation, the New York State Department of Health Empire Clinical Research Investigator Program, and the Florence Gould Foundation. Dr. Jesudian has funding from the Society of Interventional Radiology Foundation. Dr. Kamel is supported by NINDS Grants R01NS097443 and U01NS095869 and the Michael Goldberg Research Fund. Dr. Hanley is supported by the NIH (1U01NS080824, U24TR001609). Dr. Ziai is supported by NIH 1U01NS080824. Dr. Murthy is funded by NINDS Grant K23NS105948 and the Leon Levy Foundation.

Author information

Authors and Affiliations

  1. Clinical and Translational Neuroscience Unit, Department of Neurology, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine/New York Presbyterian Hospital, 420 E 70th St, 4th Floor, New York, NY, 10021, USA

    Neal S. Parikh, Hooman Kamel & Santosh B. Murthy

  2. Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA

    Arun Jesudian

  3. Brain Injury Outcomes Division, Johns Hopkins University School of Medicine, Baltimore, USA

    Daniel F. Hanley

  4. Department of Neurology, Neurosurgery and Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, USA

    Wendy C. Ziai

Authors
  1. Neal S. Parikh
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  2. Arun Jesudian
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  3. Hooman Kamel
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  4. Daniel F. Hanley
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  5. Wendy C. Ziai
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  6. Santosh B. Murthy
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Consortia

the VISTA-ICH Collaboration

  • D. F. Hanley
  • , K. Butcher
  • , S. Davis
  • , B. Gregson
  • , K. R. Lees
  • , P. Lyden
  • , S. Mayer
  • , K. Muir
  •  & T. Steiner

Contributions

This study was conceptualized by NSP, HK, and SBM. Acquisition of data was done by SBM, and SBM was responsible for the analysis. NSP, AJ, HK, DFH, WCZ, and SBM interpreted the data. NSP and SBM were responsible for drafting the article, and AJ, HK, DFH, and WCZ were responsible for critical revision for important intellecutal content. All authors approved the final version of this manuscript for publication.

Corresponding author

Correspondence to Neal S. Parikh.

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Conflicts of interest

Dr. Parikh, Dr. Jesudian, Dr. Murthy: none. Hooman Kamel serves as the co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as a steering committee member of Medtronic’s Stroke AF trial (uncompensated), serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer Ingelheim, and has served on an advisory board for Roivant Sciences related to Factor XI inhibition. Dr. Hanley reports personal fees from Op2Lysis, personal fees from BrainScope, personal fees from Neurotrope, and non-financial support from Genentech outside the submitted work. Dr, Ziai receives consulting fees from C.R. Bard, Inc., and Portola Pharmaceuticals, Inc., outside of the area of work commented on here.

Ethical Approval

Trials included in the VISTA-ICH cohort were performed with institutional review board and/or regulatory approval, and our analysis was approved by the Weill Cornell Medicine Institutional Review Board.

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Parikh, N.S., Jesudian, A., Kamel, H. et al. Liver Fibrosis and Perihematomal Edema Growth in Primary Intracerebral Hemorrhage. Neurocrit Care 34, 983–989 (2021). https://doi.org/10.1007/s12028-020-01081-4

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  • DOI: https://doi.org/10.1007/s12028-020-01081-4

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