Page 88 - EASL POSTGRADUATE COURSE
P. 88
The metabolic benefit of exercise alone in NASH may not be equivalent across all insulin sensitive
organs. After a 6 month intervention of moderate intensity circuit exercise training (without weight
loss) there were improvements in hepatic and adipose tissue IS but no effect on muscle IR [5]. Most
participants were profoundly insulin resistant in their muscles at baseline, remaining one third that of
healthy controls after the intervention. On the other hand, hepatic IR seems to particularly benefit from
exercise irrespective of obesity, steatosis or weight change. This can occur after high intensity exercise
without changes in peripheral IS [6].
The type and intensity of exercise prescription in the absence of weight loss still requires further
refinement to determine which prescription will best target the severe IR associated with NASH. Given
that muscle IR is likely the primary driver of progression to T2DM in this group [7], further research
into the independent and combined effect of lifestyle factors on muscle metabolism is of great clinical
importance.
Effect of lifestyle intervention on liver injury in NASH
Weight loss through combined diet and exercise. A randomized controlled study of a combined diet
and exercise weight loss intervention demonstrated that weight reduction was positively correlated with
improvement in disease severity as assessed histologically by the NAS, with improvements in steatosis
seen with minimal decreases in weight. However, substantial improvements in necro-inflammation
and hepatocyte ballooning was only seen in those with >7% weight loss. Of note, this histological
improvement occurred without an apparent improvement in overall IR (measured indirectly by HOMA
score) [8].
Exercise alone. In the first study to assess the histological effects of exercise alone on NASH, moderate
intensity circuit exercise x3/week for 6 months was inadequate to improve steatosis, lobular inflammation
or hepatocyte ballooning in NASH [5]. Furthermore, four months of moderate physical activity in line
with general physical activity guidelines did not benefit hepatic lipoprotein kinetics in obese people
with NAFLD [9]. These data contrast with other studies of exercise without weight loss that have used
magnetic resonance spectroscopy to measure hepatic fat content. A number of studies have shown
short term low to moderate intensity aerobic or resistance training without weight loss can result in
measurable decreases in visceral adiposity and intrahepatic triglyceride content [10, 11]. The long term
histological effect of these real, albeit, small changes in steatosis is of great interest.
Exercise intensity may be another important variable, with cross-sectional data suggesting an apparent
protective effect of vigorous activity on the development of NASH [12]. The effects of high intensity
exercise on established NASH are unknown.
The Mediterranean diet. Traditional/indigenous eating patterns may benefit obesity-related chronic
diseases irrespective of changes in BMI and there has been considerable interest in the beneficial role
of the Mediterranean diet on the development and progression of NASH. There is no single defined
prescription of the Mediterranean diet, but rather it is a recommended eating pattern inspired by the
traditional cuisines of Greece, Crete, southern France and parts of Italy. The emphasis is on plant
foods such as fruits, vegetables, nuts, beans, legumes, seeds and grains, and olive oil, with moderate
consumption of fish, low to moderate consumption of dairy products, predominantly as cheese and
yoghurt, moderate consumption of wine (1-2 glasses per day) and low consumption of red meat and
meat products.
The Mediterranean diet score (MDS) is commonly used to assess adherence to this pattern of eating
and is based on the 9 dietary components typical of the traditional Mediterranean diet [13].While there
are a number of variations to the scoring system that have been developed, briefly, each study subject is
assigned a score of 0 (low consumption) or 1 (high consumption) for each of the eight dietary components
(excluding alcohol) relative to a study-specific and sex-specific median cut-off calculated from controls.
For the alcohol component, a score of 1 is typically assigned for moderate alcohol consumption (defined
88 Postgraduate Course Syllabus • Metabolic Liver Disease
organs. After a 6 month intervention of moderate intensity circuit exercise training (without weight
loss) there were improvements in hepatic and adipose tissue IS but no effect on muscle IR [5]. Most
participants were profoundly insulin resistant in their muscles at baseline, remaining one third that of
healthy controls after the intervention. On the other hand, hepatic IR seems to particularly benefit from
exercise irrespective of obesity, steatosis or weight change. This can occur after high intensity exercise
without changes in peripheral IS [6].
The type and intensity of exercise prescription in the absence of weight loss still requires further
refinement to determine which prescription will best target the severe IR associated with NASH. Given
that muscle IR is likely the primary driver of progression to T2DM in this group [7], further research
into the independent and combined effect of lifestyle factors on muscle metabolism is of great clinical
importance.
Effect of lifestyle intervention on liver injury in NASH
Weight loss through combined diet and exercise. A randomized controlled study of a combined diet
and exercise weight loss intervention demonstrated that weight reduction was positively correlated with
improvement in disease severity as assessed histologically by the NAS, with improvements in steatosis
seen with minimal decreases in weight. However, substantial improvements in necro-inflammation
and hepatocyte ballooning was only seen in those with >7% weight loss. Of note, this histological
improvement occurred without an apparent improvement in overall IR (measured indirectly by HOMA
score) [8].
Exercise alone. In the first study to assess the histological effects of exercise alone on NASH, moderate
intensity circuit exercise x3/week for 6 months was inadequate to improve steatosis, lobular inflammation
or hepatocyte ballooning in NASH [5]. Furthermore, four months of moderate physical activity in line
with general physical activity guidelines did not benefit hepatic lipoprotein kinetics in obese people
with NAFLD [9]. These data contrast with other studies of exercise without weight loss that have used
magnetic resonance spectroscopy to measure hepatic fat content. A number of studies have shown
short term low to moderate intensity aerobic or resistance training without weight loss can result in
measurable decreases in visceral adiposity and intrahepatic triglyceride content [10, 11]. The long term
histological effect of these real, albeit, small changes in steatosis is of great interest.
Exercise intensity may be another important variable, with cross-sectional data suggesting an apparent
protective effect of vigorous activity on the development of NASH [12]. The effects of high intensity
exercise on established NASH are unknown.
The Mediterranean diet. Traditional/indigenous eating patterns may benefit obesity-related chronic
diseases irrespective of changes in BMI and there has been considerable interest in the beneficial role
of the Mediterranean diet on the development and progression of NASH. There is no single defined
prescription of the Mediterranean diet, but rather it is a recommended eating pattern inspired by the
traditional cuisines of Greece, Crete, southern France and parts of Italy. The emphasis is on plant
foods such as fruits, vegetables, nuts, beans, legumes, seeds and grains, and olive oil, with moderate
consumption of fish, low to moderate consumption of dairy products, predominantly as cheese and
yoghurt, moderate consumption of wine (1-2 glasses per day) and low consumption of red meat and
meat products.
The Mediterranean diet score (MDS) is commonly used to assess adherence to this pattern of eating
and is based on the 9 dietary components typical of the traditional Mediterranean diet [13].While there
are a number of variations to the scoring system that have been developed, briefly, each study subject is
assigned a score of 0 (low consumption) or 1 (high consumption) for each of the eight dietary components
(excluding alcohol) relative to a study-specific and sex-specific median cut-off calculated from controls.
For the alcohol component, a score of 1 is typically assigned for moderate alcohol consumption (defined
88 Postgraduate Course Syllabus • Metabolic Liver Disease
