Biomarkers of liver fibrosis: prospective comparison of multimodal magnetic resonance, serum algorithms and transient elastography

Mikael F. Forsgren, Patrik Nasr, Markus Karlsson, Nils Dahlström, Bengt Norén, Simone Ignatova, Ralph Sinkus, Gunnar Cedersund, Olof Dahlqvist Leinhard, Mattias Ekstedt, Stergios Kechagias, Peter Lundberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background and aims: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available. Methods: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King’s Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score). Results: The diagnostic performance (AUROC) for identification of significant fibrosis (F2–4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3–4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively. Conclusion: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summary Excessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalScandinavian Journal of Gastroenterology
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • P-MR spectroscopy
  • Elastography
  • Gadoxetate-enhanced MRI
  • liver fibrosis
  • MRE
  • serum fibrosis algorithms

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