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

Tracey G. Simon, Mi Na Kim, Xiao Luo, Wanshui Yang, Yanan Ma, Dawn Q. Chong, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kathleen E. Corey, Raymond T. Chung, Meir Stampfer, Xuehong Zhang, Edward L. Giovannucci, Andrew T. Chan

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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 (ptrend<0.0001) and with weight gain during early adulthood (ptrend <0.0001). The risk of liver-related mortality also declined progressively, with increasing physical activity (ptrend = 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.

Original languageEnglish
Pages (from-to)1062-1069
Number of pages8
JournalJournal of Hepatology
Issue number6
StatePublished - Jun 2020
Externally publishedYes


  • Cirrhosis
  • Lifestyle
  • Modifiable risk factor
  • Prevention


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