Page 90 - EASL POSTGRADUATE COURSE
P. 90
intake of red meat, processed meats and salt. Physical activity recommendations in these guidelines
mirror those for a healthy population, generally 30 minutes of moderate to vigorous exercise at least five
days per week.
While there have been no randomized controlled studies investigating the effect of lifestyle intervention
after curative therapy of HCC, there are a number on weight loss interventions among overweight
survivors of other cancers [26]. None have examined effects on cancer-related death or recurrence.
In general, the data from these studies suggest that physical activity interventions are safe and yield
improvements in fitness, strength and physical function; whereas diet interventions improve diet quality,
nutrition-related biomarkers and body weight. Lifestyle intervention may mitigate adverse changes
in body composition associated with cancer, such as decreased muscle mass in the setting of obesity
(sarcopenic obesity). Most patients with HCC will be cirrhotic and this has implications for dietary
manipulations with regards to calorie restriction, protein intake and malnutrition.
Lifestyle Intervention and HCC
Obesity, body composition and HCC risk. Obesity is associated with diabetes, steatosis, hepatic
inflammation and increased oxidative stress, all of which may increase the risk of advanced fibrosis and
cirrhosis. Although several studies have investigated a link between obesity and liver carcinogenesis,
there is a paucity of data on whether obesity (with or without cirrhosis) is a prognostic factor in patients
with NASH-related HCC who undergo curative therapy. A retrospective observational study from Japan
found that obese patients (defined in that population as BMI>25) were no different to non-obese in
relation to overall survival or recurrence-free survival from non-viral HCC [27].
The relationship between obesity and HCC survival is complex and more sophisticated assessment
of body composition is needed to fully elucidate a link between obesity and NASH-related HCC
recurrence. In addition to the proportion of overall adiposity and muscle mass, the presence or absence
of cirrhosis at the time of, and after curative therapy, may significantly impact metabolism. Both aerobic
and resistance exercise seems to be effective in protecting against muscle loss experienced during dieting
and should be included as part of any recommendations to reduce weight after HCC curative therapy.
There is also a suggestion that supplementing protein during calorie restriction may lead to reduced
fat mass with preservation of muscle tissue in those at risk of sarcopenia [28]. In the absence of studies
specifically targeting NASH-related HCC populations, a lifestyle intervention that combines dietary
calorie restriction with exercise in order to reduce adiposity is likely to improve NASH and associated
necro-inflammation. However, specific advice regarding the dose, frequency and type of exercise and
weight loss prescription to reduce HCC risk in NAFLD is unknown.
Dietary patterns and HCC risk. The Mediterranean dietary pattern has been inversely related to
cancer risk and the potential beneficial effects of this traditional cuisine on HCC risk is a field of growing
interest. A recent study that combined two large HCC case-control datasets from Italy and Greece
(HCC from all causes n=518; control n=772) demonstrated that adherence to the Mediterranean diet
(defined as MDS ≥5) was associated with a 50% reduction in HCC incidence compared with MDS
≤3 [29]. The presence of cirrhosis was not included in the modelling. No individual component of the
diet (such as vegetables, legumes, fish and seafood) was significantly associated with HCC risk. This
suggests biological interactions between various components of the Mediterranean dietary pattern may
be important. In a large dataset of 495,006 men and women participating in the NIH-AARP Diet
and Health Study, it was found that red meat and saturated fat (both typically low in a Mediterranean
dietary pattern) were associated with a statistically significant increased risk of HCC, while white meat
appeared protective [30].
To date, epidemiological studies have used incidence of HCC from all causes and have not controlled
for the influence of cirrhosis or viral hepatitis (which could account for up to 75% of cases) [29]. As
non-viral HCC cases are typically rare in epidemiological datasets, it can prevent reliable risk estimates
in this group.With increasing incidence of NASH-related HCC in the future, it is likely that this field of
investigation will become more robust as the statistical power grows.
90 Postgraduate Course Syllabus • Metabolic Liver Disease
mirror those for a healthy population, generally 30 minutes of moderate to vigorous exercise at least five
days per week.
While there have been no randomized controlled studies investigating the effect of lifestyle intervention
after curative therapy of HCC, there are a number on weight loss interventions among overweight
survivors of other cancers [26]. None have examined effects on cancer-related death or recurrence.
In general, the data from these studies suggest that physical activity interventions are safe and yield
improvements in fitness, strength and physical function; whereas diet interventions improve diet quality,
nutrition-related biomarkers and body weight. Lifestyle intervention may mitigate adverse changes
in body composition associated with cancer, such as decreased muscle mass in the setting of obesity
(sarcopenic obesity). Most patients with HCC will be cirrhotic and this has implications for dietary
manipulations with regards to calorie restriction, protein intake and malnutrition.
Lifestyle Intervention and HCC
Obesity, body composition and HCC risk. Obesity is associated with diabetes, steatosis, hepatic
inflammation and increased oxidative stress, all of which may increase the risk of advanced fibrosis and
cirrhosis. Although several studies have investigated a link between obesity and liver carcinogenesis,
there is a paucity of data on whether obesity (with or without cirrhosis) is a prognostic factor in patients
with NASH-related HCC who undergo curative therapy. A retrospective observational study from Japan
found that obese patients (defined in that population as BMI>25) were no different to non-obese in
relation to overall survival or recurrence-free survival from non-viral HCC [27].
The relationship between obesity and HCC survival is complex and more sophisticated assessment
of body composition is needed to fully elucidate a link between obesity and NASH-related HCC
recurrence. In addition to the proportion of overall adiposity and muscle mass, the presence or absence
of cirrhosis at the time of, and after curative therapy, may significantly impact metabolism. Both aerobic
and resistance exercise seems to be effective in protecting against muscle loss experienced during dieting
and should be included as part of any recommendations to reduce weight after HCC curative therapy.
There is also a suggestion that supplementing protein during calorie restriction may lead to reduced
fat mass with preservation of muscle tissue in those at risk of sarcopenia [28]. In the absence of studies
specifically targeting NASH-related HCC populations, a lifestyle intervention that combines dietary
calorie restriction with exercise in order to reduce adiposity is likely to improve NASH and associated
necro-inflammation. However, specific advice regarding the dose, frequency and type of exercise and
weight loss prescription to reduce HCC risk in NAFLD is unknown.
Dietary patterns and HCC risk. The Mediterranean dietary pattern has been inversely related to
cancer risk and the potential beneficial effects of this traditional cuisine on HCC risk is a field of growing
interest. A recent study that combined two large HCC case-control datasets from Italy and Greece
(HCC from all causes n=518; control n=772) demonstrated that adherence to the Mediterranean diet
(defined as MDS ≥5) was associated with a 50% reduction in HCC incidence compared with MDS
≤3 [29]. The presence of cirrhosis was not included in the modelling. No individual component of the
diet (such as vegetables, legumes, fish and seafood) was significantly associated with HCC risk. This
suggests biological interactions between various components of the Mediterranean dietary pattern may
be important. In a large dataset of 495,006 men and women participating in the NIH-AARP Diet
and Health Study, it was found that red meat and saturated fat (both typically low in a Mediterranean
dietary pattern) were associated with a statistically significant increased risk of HCC, while white meat
appeared protective [30].
To date, epidemiological studies have used incidence of HCC from all causes and have not controlled
for the influence of cirrhosis or viral hepatitis (which could account for up to 75% of cases) [29]. As
non-viral HCC cases are typically rare in epidemiological datasets, it can prevent reliable risk estimates
in this group.With increasing incidence of NASH-related HCC in the future, it is likely that this field of
investigation will become more robust as the statistical power grows.
90 Postgraduate Course Syllabus • Metabolic Liver Disease
