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National Guideline Centre (UK). Non-Alcoholic Fatty Liver Disease: Assessment and Management. London: National Institute for Health and Care Excellence (NICE); 2016 Jul. (NICE Guideline, No. 49.)
12.1. Introduction
Exercise or exercise-related behaviours forms a part of the current treatment offered for NAFLD, especially in the absence of approved pharmaceutical agents. However, the field of evidence around exercise and NAFLD is relatively new in comparison to more established conditions, such as type 2 diabetes or heart disease.
The aim of this review is to define objectively the individual effect of exercise on liver fat and biomarkers of liver health in adults, young people and children with NAFLD.
12.2. Review question: What is the clinical and cost-effectiveness of exercise programmes for adults, young people and children with NAFLD compared with standard care?
For full details see review protocol in Appendix A.
Table 56
PICO characteristics of review question.
12.3. Clinical evidence
Six RCTs were identified (Table 57) in adults (4 studies were reported across multiple papers).41,59-61,148,182,183,193,194,234,236 Three compared aerobic exercise to standard care or no treatment, 41,148,182,183 2 compared resistance exercise with standard care or a stretching control,59-61,234,236 and 1 compared high intensity exercise with usual care. 193,194 No studies were identified in young people and children aged less than 12 years. The study diagnosis of NAFLD for the inclusion of participants varied and is detailed in Table 58. Similarly, the study selection flow chart can be found in Appendix E, study evidence tables in Appendix H, forest plots in Appendix K, GRADE tables in Appendix J and excluded studies list in Appendix M.
Table 57
Summary of studies included in the review.
Table 58
Clinical evidence summary: exercise versus control.
12.4. Economic evidence
No relevant economic evaluations were identified.
See also the economic article selection flow chart in Appendix F.
12.5. Evidence statements
12.5.1. Clinical
NAFLD progression
- Very low quality evidence from 4 RCTs (n=74) demonstrated an overall clinical benefit of exercise on NAFLD progression, as determined by MRS intrahepatic lipids, when compared to usual care and no treatment in adults at equal to or greater than 3 to less than 12 months. Very low quality evidence from a single RCT (n=20) demonstrated no clinically important benefit of exercise on NAFLD progression, as determined by the NAFLD activity score, when compared to usual care in adults at equal to or greater than 3 to less than 12 months, although the direction of effect favoured exercise.
Liver function tests (ALT and AST levels)
- Very low quality evidence from 6 RCTs (n=155) demonstrated no overall clinical benefit of exercise on ALT levels when compared to usual care, home stretching and no treatment in adults at equal to or greater than 3 to less than 12 months, although the direction of effect favoured exercise. Similarly, very low quality evidence from 3 RCTs (n=54) demonstrated no overall clinical benefit of exercise on AST levels when compared to usual care in adults at equal to or greater than 3 to less than 12 months, although the direction of effect favoured exercise.
Weight
- An overall clinical benefit of resistance exercise was seen on weight loss in adults when compared to usual care and home stretching from 2 RCTs (n=83) at equal to or greater than 3 to less than 12 months (low quality evidence). Very low quality evidence from 2 RCTs (n=29) comparing aerobic exercise to usual care and no treatment and a single RCT (n=23) comparing high intensity exercise to usual care showed no clinically important benefit on weight loss in adults at equal to or greater than 3 to less than 12 months, although the direction of effect favoured exercise.
12.5.2. Economic
- No relevant economic evaluations were identified.
12.6. Recommendations and link to evidence
| Recommendation |
|
|---|---|
| Relative values of different outcomes | The GDG agreed that the outcomes that were critical to decision-making were progression of NAFLD, quality of life and occurrence of serious adverse events. Of these, progression of NAFLD (as measured by liver biopsy) was the most important outcome. The GDG agreed that other outcomes described within the identified evidence could also be considered to be of clinical relevance. In particular, improvements in MRS intrahepatic lipid or triglyceride and reduction in liver enzyme values were all agreed to be appropriate potential surrogate markers for improvement in NAFLD and therefore considered as important outcomes. The GDG noted that the degree of improvement of such surrogate markers that could be defined as clinically important would depend upon the baseline values rather than purely the absolute reduction in those receiving an intervention. |
| Trade-off between clinical benefits and harms | The identified studies employed a variety of different exercise interventions (aerobic exercise, resistance exercise and high intensity exercise) and used a range of different outcome measures, as already described. The GDG agreed that physical activity and exercise produced moderate effects on the liver independent of weight change in children, young people and adults with NAFLD. However, studies were short term and in small numbers of participants. The GDG agreed that advice regarding increasing levels of physical activity and exercise generated health benefits beyond NAFLD and should be supported. It was noted that exercise in isolation of dietary modification does not result in weight loss. Furthermore, none of the included studies reported dietary habits of the participants and therefore it was considered unsurprising that a clinically important difference in weight loss was not demonstrated in this review. |
| Trade-off between net clinical effects and costs | No economic evidence was identified relevant to exercise interventions alone. Referring people with NAFLD to exercise programmes involving supervision by healthcare or exercise professionals would lead to costs to the NHS. However, the GDG is not recommending the use of any interventions involving a supervised exercise programme alone. The cost-effectiveness of exercise interventions when adopted as part of a broader lifestyle intervention is considered in the review of lifestyle interventions (Chapter 13). |
| Quality of evidence | The GDG noted that only a relatively small number of relevant studies were identified (with no appropriate studies including children or young people) and the number of people recruited into the studies tended to be low. The majority of the evidence was of very low quality as assessed by GRADE criteria. This was due to the lack of blinding, presence of selection bias and incomplete outcome reporting due to the high number of drop outs in some of the included studies, resulting in a high or very high risk of bias rating. Additionally, the imprecise nature of the results extracted and analysed in this review further downgraded the GRADE quality rating. The GDG observed that the exercise interventions were provided for a relatively short time (typically 12 weeks, with a maximum of 6 months) and also commented that very few of the studies described the actions taken to ensure that study participants were compliant with an exercise intervention. |
| Other considerations | The GDG noted the short duration of exercise interventions used in the identified studies; however, the GDG recommended exercise as a lifelong behavioural change, as the health benefits of exercise extend far beyond the short term. The GDG noted that there are studies that examine exercise in combination with other lifestyle interventions, which is more reflective of current practice. These are assessed in Chapter 13. The GDG agreed it was important to not discourage people from exercise. There is existing guidance published by NICE regarding exercise in overweight and obese children, young people and adults (including PH47, PH53 and CG189). The GDG agreed that the recommendations in these guidelines are relevant and applicable to overweight and obese children, young people and adults with NAFLD and that there was no reason why people with NAFLD should follow different advice. The GDG particularly emphasised the point described in CG189 (recommendation 1.6.1) that exercise provides health benefits even without weight loss, including reduced risks of type 2 diabetes mellitus and of cardiovascular disease. |
- Exercise interventions - Non-Alcoholic Fatty Liver DiseaseExercise interventions - Non-Alcoholic Fatty Liver Disease
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