open access publication

Article, 2024

Review: Opportunities and barriers for omics-based biomarker discovery in steatotic liver diseases

Journal of Hepatology, ISSN 1600-0641, 0168-8278, 10.1016/j.jhep.2024.03.035

Contributors

Thiele, Maja Sofie 0000-0003-1854-1924 [1] [2] Villesen, Ida Falk 0000-0001-7921-9707 [1] [2] Niu, Lili 0000-0003-4571-4368 [3] [4] Johansen, Stine 0000-0002-5031-2294 [1] Sulek, Karolina [5] Nishijima, Suguru 0000-0002-8444-9272 [6] Van Espen, Lore 0000-0002-3870-4551 [7] [8] Keller, Marisa Isabell 0000-0002-1485-415X [6] Israelsen, Mads Egerod 0000-0001-9443-5846 [1] [2] Suvitaival, Tommi 0000-0002-2583-4912 [5] De Zawadzki, Andressa 0000-0002-7442-3474 [5] Juel, Helene Baek 0000-0002-5763-8545 [3] Brol, Maximilian Joseph 0000-0003-2879-7560 [9] Stinson, Sara Elisabeth [3] Huang, Yun [3] Silva, Maria Camilla Alvarez [3] Kuhn, Michael 0000-0002-2841-872X [6] Anastasiadou, Ema [10] Leeming, Diana Julie [11] Karsdal, Morten Asser 0000-0002-4764-5100 [11] Matthijnssens, Jelle 0000-0003-1188-9733 [7] [8] Arumugam, Manimozhiyan [3] Dalgaard, Louise Torp 0000-0002-3598-2775 [12] Legido-Quigley, Cristina 0000-0002-4018-214X [5] Mann, Matthias [3] [4] Trebicka, Jonel [9] Bork, Peer 0000-0002-2627-833X [6] [13] [14] Jensen, Lars Juhl 0000-0001-7885-715X [3] Hansen, Torben [3] Krag, Aleksander Ahm 0000-0002-9598-4932 (Corresponding author) [1] [2] consortia, the MicrobLiver and GALAXY [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Consortium, Galaxy [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Krag, Aleksander Bork, Peer Hansen, Torben Arumugam, Manimozhiyan Trebicka, Jonel Karsdal, Morten Anastasiadou, Ema Israelsen, Hans Melberg, Hans Olav 0000-0002-2349-5902 Legido-Quigley, Cristina Thiele, Maja Consortium, Microbliver [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Mann, Matthias Matthijnssens, Jelle

Affiliations

  1. [1] Odense University Hospital
    2. [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  2. [2] University of Southern Denmark
    3. [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD];
  3. [3] University of Copenhagen
    4. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  4. [4] Max Planck Institute of Biochemistry
    5. [NORA names: Germany; Europe, EU; OECD];
  5. [5] Steno Diabetes Center
    6. [NORA names: Steno Diabetes Centers; Hospital; Denmark; Europe, EU; Nordic; OECD];

Abstract

The rising prevalence of liver diseases related to obesity and excessive use of alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis of steatohepatitis and significant fibrosis, monitoring, prognostication and prediction of treatment efficacy. Breakthroughs in omics methodologies and the power of bioinformatics have created an excellent opportunity to apply technological advances to clinical needs, for instance in the development of precision biomarkers for personalised medicine. Via omics technologies, biological processes from the genes to circulating protein, as well as the microbiome - including bacteria, viruses and fungi, can be investigated on an axis. However, there are important barriers to omics-based biomarker discovery and validation, including the use of semi-quantitative measurements from untargeted platforms, which may exhibit high analytical, inter- and intra-individual variance. Standardising methods and the need to validate them across diverse populations presents a challenge, partly due to disease complexity and the dynamic nature of biomarker expression at different disease stages. Lack of validity causes lost opportunities when studies fail to provide the knowledge needed for regulatory approvals, all of which contributes to a delayed translation of these discoveries into clinical practice. While no omics-based biomarkers have matured to clinical implementation, the extent of data generated has enabled the hypothesis-free discovery of a plethora of candidate biomarkers that warrant further validation. To explore the many opportunities of omics technologies, hepatologists need detailed knowledge of commonalities and differences between the various omics layers, and both the barriers to and advantages of these approaches.

Keywords

accurate biomarkers, alcohol, approach, approval, axis, bacteria, barriers, bioinformatics, biological processes, biomarker discovery, biomarker expression, biomarkers, breakthrough, circulating proteins, clinical implementation, clinical need, clinical practice, commonalities, community, community screening, complex, data, delayed translation, demand, development, diagnosis, diagnosis of steatohepatitis, differences, discovery, disease, disease complex, disease stage, diverse populations, dynamic nature, efficacy, excellent opportunity, excessive use, excessive use of alcohol, expression, fibrosis, fungi, genes, hepatologists, implementation, increasing demand, inter-, intra-individual variance, knowledge, knowledge of commonalities, lack, lack of validation, layer, liver disease, measurements, medicine, method, methodology, microbiome, monitoring, nature, needs, obesity, omics, omics layers, omics methodologies, omics technologies, omics-based biomarkers, opportunities, personalised medicine, platform, population, power, power of bioinformatics, practice, precision biomarkers, prediction, prediction of treatment efficacy, prevalence, prevalence of liver disease, process, prognostication, protein, regulatory approval, screening, semi-quantitative measurement, stage, standardisation, standardised methods, steatohepatitis, steatotic liver disease, study, technology, translation, treatment efficacy, untargeted platform, use of alcohol, validity, variance, virus

Funders

  • Deutsche Forschungsgemeinschaft
  • Siemens (Germany)
  • Research Foundation - Flanders
  • Novo Nordisk Foundation
  • European Commission

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