Physical activity compared to adiposity and risk of liver-related mortality: results from two prospective, nationwide cohorts

Abstract

Background & aims Obesity in adulthood has been associated with increased risk of liver-related mortality. Whether higher levels of physical activity counteract the excess risk conferred by obesity remains unknown. We simultaneously evaluated the long-term impact of physical activity and adiposity on liver-related mortality, within 2 nationwide populations.Methods We conducted a prospective cohort study of 77,238 women and 48,026 men, with detailed, validated assessments of weekly physical activity (metabolic equivalent task [MET]-hours]), adiposity (body mass index [BMI], waist circumference), and diet, alcohol use and clinical comorbidities, biennially from 1986 through 2012. Using Cox proportional hazards regression models, we calculated multivariable-adjusted hazard ratios (aHRs) and 95% CIs for liver-related mortality, including death from hepatocellular carcinoma (HCC) and other complications of cirrhosis.Results Over 1,856,226 person-years, we recorded 295 liver-related deaths (108 HCC; 187 cirrhosis). Risk of liver-related mortality increased monotonically with higher BMI during adulthood (p trend<0.0001) and with weight gain during early adulthood (p trend <0.0001). The risk of liver-related mortality also declined progressively, with increasing physical activity (p trend = 0.0003); the aHRs across increasing physical activity quintiles were: 1.0, 0.70 (95% CI 0.51-0.96), 0.59 (95% CI 0.42-0.84), 0.52 (95% CI 0.36-0.74) and 0.46 (95% CI 0.31-0.66). Compared to lean-active adults (BMI <25; ≥18 MET-hours/week), the aHRs for obese-active, lean-sedentary, and obese-sedentary adults were: 1.04 (95% CI 0.73-1.37), 2.08 (95% CI 1.21-3.33) and 3.40 (95% CI 2.06-5.56), respectively. Findings were similar for HCC-specific and cirrhosis-specific mortality. Overall, engaging in average-pace walking for >3 hours/week could have prevented 25% of liver-related deaths (95% CI 0.12-0.38).Conclusions In 2 prospective, nationwide cohorts, both excess adiposity and reduced physical activity were significant predictors of liver-related mortality. Achieving higher physical activity levels counteracted the excess liver-related risks associated with obesity.Lay summary This is the first large, prospective cohort study to simultaneously evaluate the impact of obesity and physical activity on the long-term risk of liver-related mortality in 2 nationwide populations of American men and women. The study demonstrated that obesity predicted significantly increased risk of liver-related mortality, while physical activity predicted significantly lower risk of liver-related mortality. Importantly, the excess risk of liver-related mortality observed with obesity was no longer statistically significant among adults who engaged in the equivalent of average-pace walking for 3 hours or more, per week.