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Exercise, Liver Cancer, and NAFLD Mortality

by Judith Gorski PhD, December 6, 2018 at 10:00 AM | Tags

Tumor-derived cell lines, organoids, PDX - complementary preclinical models for drug screeningand oncology research

graphic explaining the mechanisms of hepatocellular carcinoma development comorbid with obesityOur current understanding of the mechanisms linking obesity and liver cancer is poor. Preclinical research links regular exercise to lowered rates of comorbid hepatocellular carcinoma (HCC), as well as improvements in non-alcoholic fatty liver disease (NAFLD) mortality risk.

Metabolic Disease and Liver Cancer

According to the World Health Organization, most of the world's population lives in countries where conditions associated with obesity kill more people than those associated with being underweight. Since 1975, worldwide obesity levels have tripled.

The accompanying metabolic syndromes, and the development of NAFLD, leaves patients with major contributors to developing some of the most-deadly cancer types. This includes the third most common cause of cancer death, HCC, which represents 85-90% of primary liver cancers.

The incidence of HCC has nearly doubled in the US alone since the 1970s. In 2016, a Cancer Research article concluded that high body mass index (BMI) and a large waist circumference were associated with an increased liver cancer risk.

Uncovering Obesity and Liver Cancer Links

Despite the epidemiologic evidence linking obesity and hyper-nutrition to elevated liver cancer incidence and greater risk of HCC-related death, we don’t really understand the molecular reasons why. To date, mechanisms include:

  • Insulin resistance leading to increased levels of insulin and insulin-like growth factors.
  • Chronic inflammation.
  • Pro-inflammatory cytokine secretion.

While researchers continue to investigate underlying mechanisms, the incidence of liver cancer continues to rise in the US. This is in parallel with increasing trends for obesity and type 2 diabetes mellitus. With such poor prognosis, additional efforts are needed for primary prevention.

So, what can lower the risks? Start with physical exercise.

The Preclinical Benefit of Regular Exercise on HCC Development

Piguet et al used a preclinical NASH mouse model to show the beneficial effect of regular exercise on the development of HCC. This warrants clinical investigation in NAFLD patients to understand if the benefits translate to human patients.

In the study, the experimental NASH models were split into two groups. The first group were exercised on a treadmill, once a day for five days for 32 weeks. The other group remained inactive. After 32 weeks of regular exercise, only 71% of exercised mice developed nodules vs 100% of mice in the inactive group. The number of tumors per liver was also reduced by exercise, as well as the total tumor volume per liver, and tumor cell proliferation.

The exercise regime did not however affect steatosis and had no effect on the NAFLD Activity Score (NAS).

The Clinical Benefit of Regular Exercise on Mortality Risk in NAFLD

The clinical benefits of exercise have also recently been shown for NAFLD patients. Rutgers University was given honors as one of the Best of the Liver Meeting 2018 for their poster presentation, “Physical Activity and Risk of Mortality in Non-Alcoholic Fatty Liver Disease: A Population Based Study of United States Adults”.

The researchers investigated the associations between physical activity and the risks of mortality, related to all-causes, cardiovascular disease, and diabetes among U.S. adults with NAFLD. The team analyzed mortality-linked data for 2701 adults with NAFLD age 20 to 74 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III).

NAFLD patients with recommended levels of physical activity had significantly lower risks of mortality from all-causes, cardiovascular disease, and diabetes.

So: to help the fight against liver cancer, go for a walk. Start with just one day a week – grab a friend or your dog – get up and go!


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