Research ArticleEffect of exercise on the development of new fatty liver and the resolution of existing fatty liver
Graphical abstract
Introduction
It is now accepted that the clinical burden of non-alcoholic fatty liver disease (NAFLD) extends beyond liver-related morbidity and mortality, with the concept that NAFLD is a multisystem disease that also affects several extra-hepatic organs and regulatory pathways [1], [2]. Incidence rates for NAFLD are uncertain (because of difficulties with establishing a precise diagnosis during sequential follow-up) but current incidence rates are approximately 20/10,000 person-years, peaking in the sixth decade of life with NAFLD being more common in men [3]. NAFLD comprises a complex spectrum of disease that begins with liver fat accumulation (non-alcoholic fatty liver or NAFL) and progress with inflammation and fibrosis (non-alcoholic steatohepatitis or NASH). There is now a wealth of evidence that NAFLD increases risk of type 2 diabetes (T2DM) (summarised in [1], [4]) but there is limited evidence to date that treatment of NAFLD decreases risk of T2DM. We have shown previously that resolution of fatty liver (detected by ultrasound) over 5 years, was independently associated with marked attenuation of the risk of incident T2DM [5] and also incident hypertension [6], over five years of follow-up. Recently our findings for attenuation of the risk of T2DM has been verified in a Japanese population (that also confirmed the resolution of liver fat by ultrasonography) [7]. In contrast to previous notions that NAFL did not cause serious chronic liver disease, increasing evidence is now showing that NAFL is not harmless. Recently it has been shown that NAFL is an important risk factor for the development of clinically relevant liver fibrosis [8], [9], [10], [11] and consequently it is now being realized that it is important to understand what interventions and treatments are effective for decreasing liver fat [12] within the spectrum of liver disease in NAFLD.
In short duration studies, lifestyle changes that have focussed on diet and exercise modification have shown promise in decreasing liver fat as a manifestation of early disease in NAFLD [13], [14], [15], [16]. However, guidelines from specialist societies regarding recommendations for amounts and intensity of exercise/physical activity in NAFLD are variable. For example, the American Association for the Study of Liver Diseases guideline does not make a specific recommendation about the amount or the desired intensity of exercise in NAFLD and states that ‘exercise alone in adults (with NAFLD) may reduce hepatic steatosis, but its ability to improve other aspects of liver histology are unknown’ [17]. The European Association for the Study of the Liver (EASL) recommends that in NAFLD guidelines for patients with type 2 diabetes are followed and recommends 150 min per week of moderate intensity exercise [18] and this recommendation is largely in keeping with guidelines for the general population [19]. Thus, at present it is unclear how much exercise is needed or how intense that exercise should be to prevent development of new fatty liver or to resolve existing fatty liver. We have utilized a retrospective study design of an occupational cohort in which there were measurements of exercise/physical activity at baseline and at follow-up (as key exposures) with measurements of fatty liver assessed by ultrasonography at baseline and at follow-up (as the key outcomes) to assess relationships between exercise and change in fatty liver status over time. Although ultrasonography has limited sensitivity to detect liver fat in NAFLD, liver ultrasonography is a good technique to assess whether liver fat is present, providing liver fat accumulation is approximately 30% [20], [21]. Since it remains uncertain how much exercise is needed, or for how long that exercise is needed, (to treat liver fat and to decrease risk of developing new liver fat), we have studied relationships between numbers of weekly exercise sessions at baseline and change in numbers of weekly exercise sessions between baseline and follow-up, with both incident fatty liver at follow-up and resolution of baseline fatty liver at follow-up. Specifically, our aim was to determine the amount of baseline exercise that was associated with: a) decreased development of incident liver fat and b) resolution of baseline liver fat (as the outcomes of interest), at five-year follow-up. Additionally, we aimed to assess whether any increase in the number of exercise sessions between baseline and follow-up was associated with these fatty liver-related outcomes at five-year follow-up after adjusting for key confounders that also included change in body mass index (BMI) between baseline and follow-up.
Section snippets
Study population
The Kangbuk Samsung Health Study is a cohort study of South Korean men and women 18 years of age or older who underwent a comprehensive annual or biennial health examination at the clinics of the Kangbuk Samsung Hospital Total Healthcare Center in Seoul and Suwon, South Korea. More than 80% of participants were employees of various companies and local governmental organizations and their spouses. In South Korea, the Industrial Safety and Health law requires annual or biennial health screening
Results
233,676 men and women were studied between 2002 and 2014. 128,811 individuals were identified without fatty liver, and of these subjects, 97,797 remained free from fatty liver at follow-up, whereas 29,014 subjects (22.5%) developed incident fatty liver during follow-up. The baseline characteristics of the cohort according to the development of incident fatty liver at follow-up are shown in Table 1. All traditional cardiovascular and metabolic risk factors were adversely affected in individuals
Discussion
The novel results of our study are that any amount exercise is beneficial in either decreasing risk of development of new fatty liver, or in improving resolution of existing fatty liver, over 5 years of follow-up. Additionally, and importantly, our data shows that over this period of follow-up, any increase in the number of weekly exercise sessions was associated with both a decrease in risk of incident fatty liver and also in resolution of existing fatty liver. Given the accepted importance of
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Authors’ contributions
K.S contributed to the hypothesis, wrote methods and contributed to discussion. S.R analysed data, C.D.B. wrote introduction, results and discussion, J.K, S.H.W and J.L reviewed/edited the manuscript and contributed to discussion. K.S. is the guarantor for the article.
Acknowledgments
We acknowledge the efforts of the health screening group at Kangbuk Samsung Hospital, Korea. C.D.B. is supported in part by the Southampton National Institute for Health Research Biomedical Research Centre.
References (28)
- et al.
NAFLD: a multisystem disease
J Hepatol
(2015) - et al.
Non-alcoholic fatty liver disease and diabetes
Metabolism
(2016) - et al.
Development of new fatty liver, or resolution of existing fatty liver, over five years of follow-up, and risk of incident hypertension
J Hepatol
(2014) - et al.
A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver
J Hepatol
(2013) - et al.
Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management
J Hepatol
(2015) - et al.
Time to replace assessment of liver histology with MR-based imaging tests to assess efficacy of interventions for nonalcoholic fatty liver disease
Gastroenterology
(2016) - et al.
Exercise and diet in the management of nonalcoholic fatty liver disease
Metabolism
(2016) - et al.
Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis
J Hepatol
(2012) - et al.
The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology
Gastroenterology
(2012) - et al.
A position statement on NAFLD/NASH based on the EASL 2009 special conference
J Hepatol
(2010)
The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis
Dig Liver Dis
The utility of radiological imaging in nonalcoholic fatty liver disease
Gastroenterology
Effect of aerobic exercise training dose on liver fat and visceral adiposity
J Hepatol
Extrahepatic complications of nonalcoholic fatty liver disease
Hepatology
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