Vigorous Physical Activity Provides Protection Against All-Cause Deaths Among Adults Patients With Nonalcoholic Fatty Liver Disease (NAFLD)

Austin Henry; James M. Paik; Patrick Austin; Katherine Elizabeth Eberly; Pegah Golabi; Issah Younossi; Linda Henry; Lynn Gerber; Zobair M. Younossi


Aliment Pharmacol Ther. 2023;57(6):709-722. 

In This Article

Abstract and Introduction


Background: Mortality benefits of vigorous leisure time physical activity (LTPA) among adults with NAFLD is not known.

Aim: To investigate association between LTPA and reduction in all-cause mortality among adults with NAFLD.

Methods: We used NHANES (1999–2006) self-reported PA data for adults (≥40 years) with mortality follow-up through December 31, 2015. US-Fatty Liver Index in absence of secondary causes identified NAFLD. Moderate and vigorous LTPA were calculated by the 2018 PA Guidelines for Americans.

Results: NAFLD prevalence among 5211 adults (46.2% male; 75.8% white; mean age 53.2 years) was 32.7%. Adults with NAFLD were less likely to report the recommended minimal PA (≥ 150 min/week, 55.5% vs 64.8%) or highly active PA (≥300 min/week, 39.2% vs 48.5%) compared to adults without NAFLD. Over a median follow-up of 12.3 years, 355 deaths among adults with NAFLD and 510 deaths among adults without NAFLD were registered. In the metabolic comorbidities-adjusted model, adults with NAFLD who reported ≥50% of their total PA as vigorous activity had a 56% reduction in all-cause mortality risk (HR:0.44, 95%CI: 0.25–0.76) and cancer-specific mortality risk (HR: 0.21, 0.06–0.66) but not cardiac-specific mortality (p > 0.05) compared to adults with NAFLD who did not report any LTPA. This association remained significant even among adults with NAFLD who met the recommended minimal PA, among adults with NAFLD who reported any LTPA, and among adults with NAFLD who had metabolic abnormalities and in sensitivity analysis.

Conclusions: Engaging in vigorous activity is beneficial for adults with NAFLD - especially those with metabolic abnormalities.


Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, impacting about 30% of individuals worldwide.[1,2] NAFLD is closely associated with metabolic syndrome and its associated components of hypertension, type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and obesity.[1] Some patients with NAFLD can experience progressive disease leading to cirrhosis, hepatocellular carcinoma, liver transplantation and death. In fact, the progressive type of NAFLD or nonalcoholic steatohepatitis (NASH) is rapidly becoming the leading indication for liver transplantation in the United States.[3] NAFLD is often asymptomatic leading to an incidental finding or a delayed diagnosis when advanced liver disease is present.[1,4,5] Given NAFLD's close association with metabolic comorbidities, patients with NAFLD are also at high risk for cardiovascular disease (CVD) which is currently one of the top causes of death among those with NAFLD.[6]

Diet and exercise remain the most effective treatments for individuals with NAFLD. With weight loss of 5% through lifestyle modifications, individuals with NAFLD may experience a reversal of the underlying hepatic steatosis, while a 10% reduction may result in a reversal of hepatic fibrosis.[7] Physical activity (PA) and regular exercise may reverse the accumulation of intrahepatic triglycerides that contribute to NAFLD, independent of dietary changes.[8,9] Regular exercise is also independently associated with reductions in many adverse outcomes associated with NAFLD, including CVD, cancer, respiratory, metabolic and all-cause mortality.[10–12] The exact mechanisms of these benefits are not fully understood and are gradually being elucidated. For example, recent evidence suggests that higher PA volume may limit the expression of PNPLA3 rs738409, the most well-known genetic risk factor for progressive NAFLD.[13] There is increasing evidence that PA affects mortality. A recent study which objectively measured PA by accelerometer showed that PA reduces all-cause and cause-specific mortality among adults with NAFLD.[14,15] Nevertheless, it is important to remember that PA is a multidimensional construct, consisting of multiple criteria including frequency, intensity, duration and volume.[16,17] As such, it is important to consider the various components of PA and their unique benefits among adults with NAFLD. In particular, the intensity of PA has been shown to promote numerous health benefits where vigorous activity has more benefits than those obtained when only participating in moderate PA. These benefits include improvement in lipid profiles, CVD risk factors, CVD mortality, improvement in mental health and all-cause mortality.[18–27]

However, to our knowledge, the specific impact of vigorous PA among adults with NAFLD has not been measured, nor has specific guidance on activity intensity relative to total volume been proposed. Therefore, we investigated the association of the proportion of vigorous activity with all-cause mortality among adults with NAFLD using a nationally representative sample of the U.S. population.