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Head-to-head comparison between MEFIB, MAST, and FAST for detecting stage 2 fibrosis or higher among patients with NAFLD

  • Author Footnotes
    † These authors equally contributed to the study.
    Beom Kyung Kim
    Footnotes
    † These authors equally contributed to the study.
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States

    Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Author Footnotes
    † These authors equally contributed to the study.
    Nobuharu Tamaki
    Footnotes
    † These authors equally contributed to the study.
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States

    Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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  • Kento Imajo
    Affiliations
    Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan

    Department of Gastroenterology, Shin-yurigaoka General Hospital, Kanagawa, Japan
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  • Masato Yoneda
    Affiliations
    Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
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  • Nancy Sutter
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Jinho Jung
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Tuo Lin
    Affiliations
    Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, United States
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  • Xin M. Tu
    Affiliations
    Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, United States
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  • Jaclyn Bergstrom
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Khang Nguyen
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Leyna Nguyen
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Tracy Le
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Egbert Madamba
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Lisa Richards
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
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  • Mark A. Valasek
    Affiliations
    Department of Pathology, University of California San Diego, La Jolla, CA, United States
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  • Cynthia Behling
    Affiliations
    Sharp Medical Group, Department of Pathology, University of California San Diego, La Jolla, CA, United States
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  • Claude B. Sirlin
    Affiliations
    Liver Imaging Group, Department of Radiology, University of California San Diego, La Jolla, CA, United States
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  • Atsushi Nakajima
    Affiliations
    Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
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  • Rohit Loomba
    Correspondence
    Corresponding author. Address: ACTRI Building, 1W202, 9452 Medical Center Drive, La Jolla, CA 92037, United States; Tel.: 858-246-2201, fax: 858-246-2255.
    Affiliations
    NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States

    Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States
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  • Author Footnotes
    † These authors equally contributed to the study.
Published:August 13, 2022DOI:https://doi.org/10.1016/j.jhep.2022.07.020

      Highlights

      • Patients with NAFLD and significant fibrosis (fibrosis stage ≥2) are candidates for pharmacological trials.
      • We performed a head-to-head comparison of the diagnostic test characteristics of three non-invasive stiffness-based models.
      • To detect significant fibrosis, MEFIB outperformed both MAST and FAST (both p <0.001).
      • MEFIB demonstrated a robust PPV (95%) and NPV (90%), and should be used in a two-step strategy to identify significant fibrosis.

      Background & Aims

      Patients with non-alcoholic fatty liver disease (NAFLD) and significant fibrosis (fibrosis stage ≥2) are candidates for pharmacological trials. The aim of this study was to perform a head-to-head comparison of the diagnostic test characteristics of three non-invasive stiffness-based models including MEFIB (magnetic resonance elastography [MRE] plus FIB-4), MAST (magnetic resonance imaging [MRI]-aspartate aminotransferase [AST]), and FAST (FibroScan-AST) for detecting significant fibrosis.

      Methods

      This prospective study included 563 patients with biopsy-proven NAFLD undergoing contemporaneous MRE, MRI proton density fat fraction (MRI-PDFF) and FibroScan from two prospective cohorts derived from Southern California and Japan. Diagnostic performances of models were evaluated by area under the receiver-operating characteristic curve (AUC).

      Results

      The mean age of the cohort was 56.5 years (51% were women). Significant fibrosis was observed in 51.2%. To detect significant fibrosis, MEFIB outperformed both MAST and FAST (both p <0.001); AUCs for MEFIB, MAST, and FAST were 0.901 (95% CI 0.875–0.928), 0.770 (95% CI 0.730–0.810), and 0.725 (95% CI 0.683–0.767), respectively. Using rule-in criteria, the positive predictive value of MEFIB (95.3%) was significantly higher than that of FAST (83.5%, p = 0.001) and numerically but not statistically greater than that of MAST (90.0%, p = 0.056). Notably, MEFIB’s rule-in criteria covered more of the study population than MAST (34.1% vs. 26.6%; p = 0.006). Using rule-out criteria, the negative predictive value of MEFIB (90.1%) was significantly higher than that of either MAST (69.6%) or FAST (71.8%) (both p <0.001). Furthermore, to diagnose “at risk” non-alcoholic steatohepatitis defined as NAFLD activity score ≥4 and fibrosis stage ≥2, MEFIB outperformed both MAST and FAST (both p <0.05); AUCs for MEFIB, MAST, and FAST were 0.768 (95% CI 0.728–0.808), 0.719 (95% CI 0.671–0.766), and 0.687 (95% CI 0.640–0.733), respectively.

      Conclusions

      MEFIB was better than MAST and FAST for detection of significant fibrosis as well as “at risk” NASH. All three models provide utility for the risk stratification of NAFLD.

      Lay summary

      Non-alcoholic fatty liver disease (NAFLD) affects over 25% of the general population worldwide and is one of the main causes of chronic liver disease. Because so many individuals have NAFLD, it is not practical to perform liver biopsies to identify those with more severe disease who may require pharmacological interventions. Therefore, accurate non-invasive tests are crucial. Herein, we compared three such tests and found that a test called MEFIB was the best at detecting patients who might require treatment.

      Graphical abstract

      Keywords

      Linked Article

      • MEFIB vs MAST and FAST: Not a competition but useful tools
        Journal of Hepatology
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          We read with interest the article by Kim et al.1 which as its primary objective, compared MEFIB to MAST and FAST for the identification of significant fibrosis (≥F2). The secondary objective compared the diagnostic accuracies of these tests for the identification of at-risk NASH. The latter objective is a welcome effort to determine if MEFIB can assess at-risk NASH. Nevertheless, we believe that the primary objective compares “apples to oranges,” as MAST and FAST were not created to assess ≥ F2.
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