- This analysis of two large prospective nationwide cohorts of men and women examined how physical activity and body mass index (BMI) affect the risk of death from hepatocellular carcinoma and other complications of cirrhosis
- The risk of liver-related mortality was significantly elevated with obesity
- Increased physical activity predicted significantly lower risk of liver-related mortality, regardless of BMI
- The excess risk conferred by obesity was substantially reduced among adults who engaged in at least nine metabolic equivalent task hours of physical activity per week, the equivalent of walking an average of three hours/week or more
Obesity is a risk factor for cirrhosis, hepatocellular carcinoma (HCC) and liver-related death. Exercise interventions have been shown to reduce liver fat, inflammation and fibrosis in the short term, but whether those changes translate to reductions in mortality was unknown.
Tracey G. Simon, MD, MPH, hepatologist in the Division of Gastroenterology at Massachusetts General Hospital, Andrew T. Chan, MD, MPH, director for Cancer Epidemiology in the Mass General Cancer Center, chief of the Clinical and Translational Epidemiology Unit (CTEU) in the Department of Medicine and vice chief for clinical research in the Division of Gastroenterology, and colleagues conducted the first prospective study that simultaneously evaluated the long-term influence of physical activity and adiposity on liver-related mortality. In the Journal of Hepatology, they report that obesity predicted significantly increased risk of liver-related mortality, whereas physical activity predicted significantly lower risk.
The researchers used data from two prospective, nationwide epidemiologic studies:
- The Nurses' Health Study, which enrolled 121,700 female registered nurses, ages 30–55, in 1976
- The Health Professionals Follow-up Study, which enrolled 51,529 male health professionals, ages 40–75, in 1986
125,264 participants were analyzed who did not report liver disease or cancer at baseline. Over 1,856,226 person-years of follow-up there were 295 deaths from HCC or another complication of cirrhosis.
Each one-unit increase in cumulative average body mass index (BMI) predicted a 5.1% higher risk of liver-related mortality (P for trend < 0.0001).
This strong gradient of risk was:
- Similar to men and women
- Consistent across prespecified risk factors (age, race/ethnicity, diabetes, alcohol use, smoking and diet)
- Similar to HCC-specific and cirrhosis-specific mortality
Physical Activity and Joint Associations
Overall, every three metabolic equivalent task (MET)–hours/week of exercise was associated with a 3.5% reduction in risk of liver-related mortality.
At all levels of BMI, increasing levels of physical activity predicted significantly reduced risk of liver-related mortality. Physical activity appeared to reduce the excess risk associated with obesity.
Compared with lean/active adults (BMI <25; ≥18 MET-hours/week):
- Obese/active adults (BMI ≥ 30; ≥18 MET-hours/week)—adjusted HR for mortality, 1.04
- Obese/moderately active adults (BMI ≥30; 9 to <18 MET-hours/week)—multivariable-adjusted hazard ratio (aHR), 1.13
However, being lean did not fully reduce the excess risk associated with sedentary behavior. The aHR for lean/sedentary adults compared with lean/active adults was 2.08.
The Guidelines Gap
No national guidelines discuss how to prevent major adverse hepatic events, including death from cirrhosis or HCC. An important takeaway from this study is that in patients with chronic liver disease, the excess risk associated with obesity was substantially reduced by exercising for at least nine MET-hours/week, the equivalent of walking at an average pace for just three hours a week.
Even at that low level, exercising could have prevented 25% of liver-related deaths.
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