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Evaluation of plasma microRNA-122, high-mobility group box 1 and keratin-18 concentrations to stratify acute gallstone disease: a pilot observational cohort study in an emergency general surgery unit
  1. Francesca Th’ng1,
  2. Bastiaan Vliegenthart2,
  3. Jonathan D Lea3,
  4. Daniel J Antoine3,
  5. James W Dear2,
  6. Damian J Mole1,4,5
  7. Edinburgh Emergency Surgery Study Group, Royal Infirmary of Edinburgh, NHS Lothian
    1. 1 Clinical Surgery, School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh, UK
    2. 2 BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
    3. 3 MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
    4. 4 MRC Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
    5. 5 General Surgery, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK
    1. Correspondence to Miss Francesca Th’ng; fcsthng1{at}


    Objective To obtain pilot data to evaluate the discriminatory power of biomarkers microRNA-122 (miR-122), high-mobility group box 1 (HMGB1), full-length keratin-18 (flk-18) and caspase-cleaved keratin-18 (cck-18) in plasma to identify potential biliary complications that may require acute intervention.

    Design An observational biomarker cohort pilot study.

    Setting In a Scottish University teaching hospital for 12 months beginning on 3 September 2014.

    Participants Blood samples were collected from adults (≥16 years old) referred with acute biliary-type symptoms who have presented to hospital within 24 hours prior were recruited. Patients unable or refused to give informed consent or were transferred from a hospital outside the National Health Service regional trust were excluded.

    Primary outcome measures To evaluate whether circulating miR-122, HMGB1, flk-18 and cck-18 can discriminate between people with and without gallstone disease and uncomplicated from complicated gallstone disease during the first 24 hours of hospital admission.

    Results 300 patients were screened of which 285 patients were included. Plasma miR-122, cck-18 and flk-18 concentrations were increased in patients with gallstones compared with those without (miR-122: median: 2.89×104 copies/mL vs 0.90×104 copies/mL (p<0.001); cck-18: 121.2 U/L vs 103.5 U/L (p=0.031); flk-18: 252.4 U/L vs 145.1 U/L (p<0.001)). Uncomplicated gallstone disease was associated with higher miR-122 and cck-18 concentrations than complicated disease (miR-122: 5.72×104 copies/mL vs 2.26×104 copies/mL (p=0.023); cck-18: 139.7 U/L vs 113.6 U/L (p=0.047)). There was no significant difference in HMGB1 concentration between patients with and without gallstones (p=0.559). Separation between groups for all biomarkers was modest.

    Conclusion miR-122 and keratin-18 plasma concentrations are elevated in patients with gallstones. However, this result is confounded by the association between biomarker concentrations, age and gender. In this pilot study, miR-122 and keratin-18 were not sufficiently discriminatory to be progressed as clinically useful biomarkers in this context.

    • biochemistry
    • gallstone disease
    • microrna-122
    • HMGB-1
    • Keratin-18

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    • Contributors FT: designed study; acquired, analysed and interpreted data; drafted and revised paper including the final version to be published; agreed to be accountable for all aspects of the work. BV, JDL and DJA: analysed and interpreted data; revised paper including the final version to be published; agreed to be accountable for all aspects of the work. JWD and DJM: designed study; analysed and interpreted data; revised paper including the final version to be published; agreed to be accountable for all aspects of the work.

    • Funding This work was supported by the Edinburgh and Lothians Health Foundation. BV was supported by an NC3Rs PhD Studentship (NC/K001485/1).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval This study was assessed by South East Scotland Research Ethics Service of National Health Service (NHS) Lothian and was given ethical approval under the terms of the Governance Arrangements for Research Ethics Committees (Harmonised Edition). Lothian R&D project number 2014/0224; REC number 14/EM/0211.

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

    • Data sharing statement There are no additional unpublished data from the study.

    • Collaborators Edinburgh Emergency Surgery Study Group, Royal Infirmary of Edinburgh, NHS Lothian: Graeme Couper, Christopher Deans, Gavin G P Browning, Anna M Paisley, Bruce Tulloh, Richard J E Skipworth, Simon Paterson-Brown, Rajan Ravindran, Andrew de Beaux, Ijeoma Azodo.

    • Presented at International Surgical Congress of the Association of Surgeons of Great Britain and Ireland (ASGBI) 2016, Belfast, Ireland. Oral presentation as Short Paper. Basic and Applied Clinical Science session, on 11 May 2016. Presentation number 370. Abstract published in British Journal of Surgery: ‘The role of microRNA biomarkers to predict complications of gallstones’ (Aug 2016. Vol. 103, Issue S6, Page 17).

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