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OxNASH Score Correlates with Histologic Features and Severity of Nonalcoholic Fatty Liver Disease

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Abstract

Background and Aim

Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). By employing a highly sensitive liquid chromatography–tandem mass spectrometry (LC/MS/MS) approach we recently were able to define the circulating profile of bioactive lipid peroxidation products characteristic of patients with nonalcoholic steatohepatitis (NASH) and developed the OxNASH score for NASH diagnosis. The aims of this study were to assess the utility of OxNASH as a predictor of NASH and study the association between OxNASH and specific histologic features of NAFLD.

Methods

Our cohort consisted of 122 patients undergoing liver biopsy for clinical suspicion of NAFLD. The NAFLD activity score (NAS) was calculated for each patient. Levels of fatty acid oxidation products were quantified using stable isotope dilution LC/MS/MS, and OxNASH was calculated.

Results

The mean age of our patients was 49.3 (±11.6) years, and the mean body mass index was 31.5 (±4.8) kg/m2. The majority of patients were Caucasian (82 %) and 48 % were female. OxNASH correlated with NAS and with the individual histologic features of NAFLD, namely, steatosis, inflammation, and ballooning (P < 0.05), with the strongest association being with inflammation [rho (ρ) 0.40, 95 % confidence interval 0.23, 0.57, P < 0.001]. There was also a correlation between the stage of fibrosis and OxNASH (P = 0.001). These associations remained statistically significant after adjustment for multiple confounders.

Conclusions

Based on our results, in adult patients with NAFLD, OxNASH correlates with histologic features of NASH and appears to be a promising noninvasive marker.

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Acknowledgments

This work was supported by National Institutes of Health Grants P01 HL076491, 1P20HL113452, P01HL098055, DK076852, AA017748, and P01 HL087018-020001, Stanley L. Hazen is also supported by a gift from the Leonard Krieger Fund. Studies were supported by National Institutes of Health Grants P01 HL076491 and P20HL113452-01. Stanley L. Hazen reports partial support from a gift from the Krieger Foundation. Mass Spectrometry studies were performed on instrumentation housed in the Cleveland Clinic Mass Spectrometry facility, which is partially supported by a Center of Innovation Award by ABI SCIEX.

Conflict of interest

Dr. Hazen is listed as co-inventor on pending and issued patents held by the Cleveland Clinic relating to diagnostics. He has received payments as a consultant or speaker for Abbott, Cleveland Heart Lab, Esperion, Lilly, Liposcience Inc., Merck & Co., Inc., and Pfizer Inc. and received research funds from Abbott, Cleveland Heart Lab, Liposcience Inc., and Pfizer Inc. Dr. Hazen reports having the right to receive royalty payments for inventions or discoveries related to diagnostics or therapeutics from the companies. All of the other authors report no conflict of interest.

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Author notes

  1. Ariel E. Feldstein

    Present address: Department of Pediatric Gastroenterology, Rady Children’s Hospital, University of California, San Diego, San Diego, CA, USA

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Naim Alkhouri

  2. Department of Cell Biology, Lerner Research Institute, College of Medicine of Case Western Reserve University, Cleveland, OH, USA

    Michael Berk, Yoon-Mi Chung, Renliang Zhang, Thomas M. McIntyre, Ariel E. Feldstein & Stanley L. Hazen

  3. Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH, USA

    Naim Alkhouri, Yoon-Mi Chung, Renliang Zhang, Thomas M. McIntyre & Stanley L. Hazen

  4. Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA

    Lisa Yerian

  5. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    Rocio Lopez

  6. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA

    Stanley L. Hazen

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  1. Naim Alkhouri
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  2. Michael Berk
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  9. Stanley L. Hazen
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Corresponding author

Correspondence to Naim Alkhouri.

Additional information

Stanley L. Hazen and Ariel E. Feldstein are senior authors for this article.

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Alkhouri, N., Berk, M., Yerian, L. et al. OxNASH Score Correlates with Histologic Features and Severity of Nonalcoholic Fatty Liver Disease. Dig Dis Sci 59, 1617–1624 (2014). https://doi.org/10.1007/s10620-014-3031-8

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  • DOI: https://doi.org/10.1007/s10620-014-3031-8

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