Advertisement

Reply to: “Associations of muscle mass and grip strength with severe NAFLD: A prospective study of 333,295 UK Biobank participants”

  • Fanny Petermann-Rocha
    Affiliations
    Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK

    Centro de Investigación Biomédica, Facultad de Medicina, Universidad Diego Portales, Santiago, Chile

    British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
    Search for articles by this author
  • Frederick K. Ho
    Affiliations
    Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
    Search for articles by this author
  • Jill P. Pell
    Correspondence
    Corresponding author. Address: Institute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8RZ United Kingdom; Tel.: 0141 330.
    Affiliations
    Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
    Search for articles by this author
Published:August 16, 2022DOI:https://doi.org/10.1016/j.jhep.2022.07.023

      Linked Article

      To the Editor:
      At the beginning of 2022, we identified that lower muscle mass and grip strength were associated with a higher risk of severe non-alcoholic fatty liver disease (NAFLD) incidence independent of major confounders in a UK Biobank cohort study of 333,295 participants.
      • Petermann-Rocha F.
      • Gray S.R.
      • Forrest E.
      • Welsh P.
      • Sattar N.
      • Celis-Morales C.
      • et al.
      Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants.
      We are grateful for the interest that our manuscript has generated. Especially, we appreciate the interesting arguments reported by Chen et al.,
      • Chen L.
      • Fan Z.
      • Lv G.
      Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants.
      which investigated the association between the exposures and NAFLD using Mendelian randomisation.
      In their study, Chen et al. identified non-significant causal associations of muscle mass (defined as appendicular lean mass) and grip strength with NAFLD.
      • Chen L.
      • Fan Z.
      • Lv G.
      Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants.
      Despite the non-significance, we found that the Mendelian randomisation effect estimates were not incompatible with ours (Fig. 1 in Chen et al.
      • Chen L.
      • Fan Z.
      • Lv G.
      Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants.
      ). Without additional information on the strength of the genetic instrument or explicit power analysis, we cannot infer whether the non-significance is due to insufficient statistical power (which is not uncommon in Mendelian randomisation studies) or a genuine lack of causal relationship.
      Apart from the statistical power, several methodological differences may explain the difference in conclusions. Firstly, to our knowledge, Chen et al. used a broader definition of NAFLD in their study, while we used the latest Expert Panel Consensus Statement for NAFLD.
      • Hagström H.
      • Adams L.A.
      • Allen A.M.
      • Byrne C.D.
      • Chang Y.
      • Grønbaek H.
      • et al.
      Administrative coding in electronic health care record-based research of NAFLD: an expert panel consensus statement.
      Since ascertaining NAFLD using routine data is tricky, the use of a broader NAFLD definition could have resulted in a regression dilution bias.
      • Hutcheon J.A.
      • Chiolero A.
      • Hanley J.A.
      Random measurement error and regression dilution bias.
      Moreover, our study has focused on severe NAFLD cases that resulted in hospitalisation,
      • Petermann-Rocha F.
      • Gray S.R.
      • Forrest E.
      • Welsh P.
      • Sattar N.
      • Celis-Morales C.
      • et al.
      Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants.
      which means that the findings in our original study could indicate the association of muscle mass and strength with the deterioration of NAFLD rather than the onset of it.
      Lastly, we would like to re-emphasise that even if grip strength and muscle mass may not be causal for NAFLD, they might be risk markers for severe NAFLD. Recent clinical trials and Mendelian randomisation studies have consistently refuted the causal effect of high-density lipoprotein cholesterol on cardiovascular disease. However, this emerging evidence did not change the fact that high-density lipoprotein cholesterol is useful in stratifying individuals based on their cardiovascular risk.
      • Xiang A.S.
      • Kingwell B.A.
      Rethinking good cholesterol: a clinicians' guide to understanding HDL.
      Similarly, while we are exploring the causal role of muscle mass and strength on NAFLD, we should not dismiss the prognostic potential of these easily measurable markers.

      Financial support

      UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation.

      Authors’ contributions

      F.P-R performed the literature search and draft the first version with the support of F.K.H and J.P.P. All authors critically reviewed this and previous drafts. All authors approved the final draft for submission, with final responsibility for publication. J.P.P is the guarantor.

      Conflict of interest

      The authors declare no conflicts of interest that pertain to this work.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following are the supplementary data to this article:

      References

        • Petermann-Rocha F.
        • Gray S.R.
        • Forrest E.
        • Welsh P.
        • Sattar N.
        • Celis-Morales C.
        • et al.
        Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants.
        J Hepatol. 2022; 76: 1021-1029
        • Chen L.
        • Fan Z.
        • Lv G.
        Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants.
        J Hepatol. 2022; 77: 1453-1454
        • Hagström H.
        • Adams L.A.
        • Allen A.M.
        • Byrne C.D.
        • Chang Y.
        • Grønbaek H.
        • et al.
        Administrative coding in electronic health care record-based research of NAFLD: an expert panel consensus statement.
        Hepatology. 2021; 74: 474-482
        • Hutcheon J.A.
        • Chiolero A.
        • Hanley J.A.
        Random measurement error and regression dilution bias.
        BMJ. 2010; 340: c2289
        • Xiang A.S.
        • Kingwell B.A.
        Rethinking good cholesterol: a clinicians' guide to understanding HDL.
        Lancet Diabetes Endocrinol. 2019; 7: 575-582