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Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults

BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5367 (Published 08 October 2019) Cite this as: BMJ 2019;367:l5367

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Re: Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults

To the Editor:

Sir,

Almost 25 years ago, I was probably first in alerting physicians that NAFLD could possibly carry an inherent excess of cardiovascular risk (1). Based on subsequently accumulated evidence, this notion is now universally accepted (2-6). Therefore, the EASL guidelines state that, based on A1 evidence, "cardiovascular complications frequently dictate the outcome of NAFLD and screening of the cardiovascular system is mandatory in all persons, at least by detailed risk factor assement " (7)

With this background, the paper by Alexander et al. reaches conflicting and disappointing results (8). In order to understand the reasons accounting for these unexpected results I recommend that everyone should be willing to read the correspondence among Reviewers and Authors which is available on the BMJ site. This correspondence clearly pinpointed the multiple, substantial, methodological problems of this study which fully account for the conclusions which are, in my opinion, completely wrong. Probably the most important mistake in the study design was the inability to correctly discriminate those who had NAFLD from those who did not. In addition, it is also clear that most of the criticisms correctly raised by Reviewers seem to have been eluded by the Authors. On these grounds, in my opinion, the study (8) should never have been published. Never in BMJ !

References
1. Lonardo A, Bellini M, Tondelli E, Frazzoni M, Grisendi A, Pulvirenti M, Della Casa G. Nonalcoholic steatohepatitis and the "bright liver syndrome": should a recently expanded clinical entity be further expanded? Am J Gastroenterol. 1995;90:2072-4.
2. Mahfood Haddad T, Hamdeh S, Kanmanthareddy A, Alla VM. Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: A systematic review and meta-analysis. Diabetes Metab Syndr. 2017;11 Suppl 1:S209-S216.
3. Wu S, Wu F, Ding Y, Hou J, Bi J, Zhang Z. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis. Sci Rep. 2016 Sep 16;6:33386.
4. Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. J Hepatol. 2016;65:425-43.
5. Kovalic AJ, Satapathy SK. The Role of Nonalcoholic Fatty Liver Disease on Cardiovascular Manifestations and Outcomes. Clin Liver Dis. 2018;22:141-174.
6. Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016;65:589-600.
7. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-402.
8. Alexander M, Loomis AK, van der Lei J, Duarte-Salles T, Prieto-Alhambra D, Ansell D, Pasqua A, Lapi F, Rijnbeek P, Mosseveld M, Avillach P, Egger P, Dhalwani NN, Kendrick S, Celis-Morales C, Waterworth DM, Alazawi W, Sattar N. Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ. 2019 Oct 8;367:l5367.

Competing interests: No competing interests

15 October 2019
Amedeo Lonardo
Hospital Consultant
AOU, Modena, Italy