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Original research
MRE combined with FIB-4 (MEFIB) index in detection of candidates for pharmacological treatment of NASH-related fibrosis
  1. Jinho Jung1,
  2. Rohan R Loomba1,2,
  3. Kento Imajo3,
  4. Egbert Madamba1,
  5. Sanil Gandhi1,
  6. Ricki Bettencourt1,
  7. Seema Singh1,
  8. Carolyn Hernandez1,
  9. Mark A Valasek4,
  10. Cynthia Behling5,
  11. Lisa Richards1,
  12. Katie Fowler6,
  13. Claude B Sirlin6,
  14. Atsushi Nakajima3,
  15. Rohit Loomba1,7
  1. 1 NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, La Jolla, California, USA
  2. 2 Cathedral Catholic High School, San Diego, California, USA
  3. 3 Department of Gastroenterology, Yokohama City University, Yokohama, Kanagawa, Japan
  4. 4 Department of Pathology, University of California San Diego, San Diego, California, USA
  5. 5 Department of Pathology, Sharp Medical Group, San Diego, California, USA
  6. 6 Liver Imaging Group, Department of Radiology, UCSD, La Jolla, California, USA
  7. 7 Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA
  1. Correspondence to Professor Rohit Loomba, NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA; roloomba{at}ucsd.edu

Abstract

Objective Patients with non-alcoholic fatty liver disease (NAFLD) with ≥stage 2 fibrosis are at increased risk for liver-related mortality and are candidates for pharmacological therapies for treatment of NAFLD. The aim of this prospective cohort study is to examine the diagnostic accuracy of MR elastography (MRE) combined with fibrosis-4 (FIB-4) in diagnosing ≥stage 2 fibrosis (candidates for pharmacological therapies).

Design This is a cross-sectional analysis of a prospective cohort (University of California at San Diego (UCSD)-NAFLD) including 238 consecutive patients with contemporaneous MRE and biopsy-proven NAFLD. Non-alcoholic steatohepatitis-Clinical Research Network-Histologic Scoring System was used to assess histology. The radiologist and pathologist were blinded to clinical, pathological and imaging data, respectively. Receiver operating characteristics (ROCs) were determined to examine the diagnostic accuracy of MRE and FIB-4 for diagnosis of ≥stage 2 fibrosis in NAFLD. We then validated these findings in an independent validation cohort derived from Yokohama City University in Japan (Japan-NAFLD Cohort; N=222 patients).

Results In the UCSD-NAFLD (training) Cohort, MRE demonstrated a clinically significant diagnostic accuracy for the detection of ≥stage 2 fibrosis with an area under the ROC curve (AUROC) of 0.93 (95% CI 0.90 to 0.97) vs FIB-4 with an AUROC of 0.78 (95% CI 0.71 to 0.85), which was both clinically and statistically significant (p<0.0001). We then combined MRE with FIB-4 (MRE ≥3.3 kPa and FIB-4 ≥1.6) to develop a clinical prediction rule to rule in ≥stage 2 fibrosis patients which had positive predictive value (PPV) of 97.1% (p<0.02) in the UCSD-NAFLD cohort (AUROC of 0.90 (95% CI 0.85 to 0.95)) which remained significant at PPV of 91.0% (p<0.003) in the Japan-NAFLD Cohort (AUROC of 0.84 (95% CI 0.78 to 0.89)).

Conclusion MRE combined with FIB-4 (MEFIB) index may be used for non-invasive identification of candidates for (≥stage 2 fibrosis) pharmacological therapy among patients with NAFLD with a high PPV.

  • fatty liver
  • liver imaging
  • liver function test
  • hepatic fibrosis

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. Data details can be provided upon request to credible investigators on verification for patient confidentiality.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. Data details can be provided upon request to credible investigators on verification for patient confidentiality.

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Footnotes

  • Contributors JJ: analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript, approved final submission. RRL: analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript, approved final submission. KI: data analysis, critical revision of the manuscript, approved final submission. EM: patient visits, critical revision of the manuscript, approved final submission. SG: data collection, critical revision of the manuscript, approved final submission. RB: data analysis, critical revision of the manuscript, approved final submission. SS: data collection, critical revision of the manuscript, approved final submission. CH: patient visits, critical revision of the manuscript, approved final submission. MAV: data analysis, critical revision of the manuscript, approved final submission. CB: data analysis, critical revision of the manuscript, approved final submission. LR: patient visits, critical revision of the manuscript, approved final submission. KF: data analysis, critical revision of the manuscript, approved final submission. CBS: data analysis, critical revision of the manuscript, approved final submission. AN: data analysis, critical revision of the manuscript, approved final submission. RL: study concept and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript, obtained funding, study supervision, approved final submission

  • Funding RL receives funding support from NIEHS (5P42ES010337), NCATS (5UL1TR001442), NIDDK (U01DK061734, R01DK106419, P30DK120515, R01DK121378, R01DK124318), NHLBI (P01HL147835) and DOD PRCRP (W81XWH-18-2-0026).

  • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

  • Competing interests RL serves as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myer Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse bio, GNI, GRI Bio, Intercept, Ionis, Janssen, Merck, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens. He is also cofounder of Liponexus.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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