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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

In a large, population based cohort study, Alexander and colleagues report that a diagnosis of non-alcoholic fatty liver disease (NAFLD) does not confer an increased risk of ischemic heart disease or stroke.[1] In order to translate these findings into clinical practice, an appreciation the spectrum NAFLD severity must be made, especially as patients with advanced fibrosis have an increased risk of mortality.[2]

The severity of NAFLD ranges from simple steatosis to the inflammatory non-alcoholic steatohepatitis (NASH), progressive liver fibrosis, cirrhosis and primary liver cancer. Each of these disease stages have vastly different clinical outcomes. Moreover, at a pathophysiological level, the progression of NAFLD is mirrored by increasing activation of hepatic and systemic inflammatory cascades, processes which are closely associated with a heightened risk of cardiovascular disease.[3,4] Although dyslipidemia represents an independent risk factor for the development of ischemic heart disease and stroke, abnormal lipid ratios are seen at higher rates in patients with NAFLD with more histological inflammation.[4] Furthermore, insulin resistance and alterations in lipid metabolism associated with NAFLD may precede the development of type 2 diabetes and dyslipidemia which are controlled in this study.[5] As such controlling for these conditions may blunt the effect of NASH or more established fibrosis.

By not stratifying patients according to the disease severity, a clear limitation of this paper is the heterogeneous nature of the cohort studied, restricting the conclusions that can be made. Instead, the use of readily available non-invasive risk scores to determine disease severity can overcome the need for liver biopsy to stage NAFLD;[6] and may be useful in truly quantifying the risk of non-hepatic complications of this highly prevalent disease.

Yours sincerely

References:

1 Alexander M, Loomis AK, van der Lei J, et al. 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:l5367
2 Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease‐specific mortality in NAFLD after up to 33 years of follow‐up. Hepatology. 2015:61(5):1547-54.
3 Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. New England Journal of Medicine. 2010;363(14):1341-50.
4 Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. Journal of hepatology. 2016 Aug 1;65(2):425-43.
5 Alkhouri N, Tamimi TA, Yerian L, et al. The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk. Digestive diseases and sciences. 2010;55(9):2644-50.
5 Lonardo A, Ballestri S, Marchesini G, et al. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Digestive and Liver Disease. 2015 Mar 1;47(3):181-90.
6 Yoneda M, Fujita K, Inamori M, et al. Transient elastography in patients with non-alcoholic fatty liver disease (NAFLD). Gut. 2007:56(9):1330-1.
7 Chin JL, Pavlides M, Moolla A, Ryan JD. Non-invasive markers of liver fibrosis: adjuncts or alternatives to liver biopsy? Frontiers in pharmacology. 2016 Jun 20;7:159.

Competing interests: No competing interests

18 October 2019
Matthew T McKenna-Barry
Registrar
John D Ryan
Hepatology Unit, Beaumont Hospital/Royal College of Surgeons in Ireland, Dublin
Hepatology Unit, Beaumont Hospital, Dublin