Leisure-time physical activity (PA) can protect against advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction and alcohol-associated liver disease (MetALD), a new analysis suggested.

In contrast, while there was no clear evidence that work-related PA was harmful to the liver, the researchers did not see a protective effect of work PA after adjusting for socioeconomic and cardiometabolic factors.

“This protective signal was not confined to MASLD,” and MetALD, Juan Pablo Arab, MD, of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, Virginia, told Medscape Medical News. “We saw…a clear trend toward benefit in alcohol-associated liver disease, although the ALD group was smaller and confidence intervals were wider. That suggests that the liver ‘recognizes’ structured leisure exercise even in the context of alcohol-mediated injury,” he noted.

“We have seen a sharp rise in steatotic liver disease in parallel with the global epidemics of obesity, diabetes, and unhealthy alcohol use,” said Arab.

“At the same time, physical activity has emerged as one of the most powerful — and practical — tools we have to improve metabolic health. But most of the evidence in liver disease focused on MASLD and on ‘exercise’ in general, without separating work-related vs leisure-time activity,” he explained.

The study was published online in Hepatology Communications.

‘Occupational Activity Is Not Enough’

The National Health and Nutrition Examination Survey 2017-2020 gave Arab and colleagues an opportunity to examine the association between work PA or leisure-time PA and advanced fibrosis across the SLD spectrum of MASLD, MetALD, and ALD, said Arab, because the nationally representative sample provided transient elastography (to assess fibrosis), detailed alcohol use, and included a standardized PA questionnaire.

The researchers proceeded by categorizing the data based on alcohol use. A total of 2236 participants had MASLD; 1355 had MetALD; and 457 had ALD.

PA was quantified as metabolic equivalent (MET)-min/wk, and ≥ 600 MET-min/wk was used as the threshold for high activity (the World Health Organization minimum). Individuals who performed ≥ 600 vs < 600 METs/wk for both leisure-time PA and work-related PA were younger, men, with college or higher education, and with higher income. They also had fewer cardiometabolic risk factors (CMRFs).

A total of 1867 (47.7%) participants performed ≥ 600 METs of work-related PA. The proportion performing that amount of work activity was 41.6% in MASLD, 51.0% in MetALD, and 62.2% in ALD.

A total of 1176 (32.8%) subjects performed ≥ 600 METs of leisure-time PA. The proportion performing that amount of leisure activity was 26.5% in MASLD, 38.2% in MetALD, and 41.5% in ALD.

Overall, the prevalence of at-risk advanced fibrosis was lower among those performing ≥ 600 vs < 600 METs/wk work-related PA (19.6% vs 22.1%), with 14% reduced odds (odds ratio, 0.86) of advanced fibrosis.

However, after controlling for age, sex, race/ethnicity, education level, income-to-poverty ratio, SLD etiology, and the number of CMRFs, the odds for advanced fibrosis with ≥ 600 vs <600 METs/wk of work-related PA was similar (OR, 1.02).

In contrast, the prevalence of at-risk advanced fibrosis was lower among participants performing ≥ 600 vs < 600 METs/wk leisure-time PA (13.1% vs 24.7%), with 43% reduced odds of advanced fibrosis in adjusted analyses (OR, 0.57).

In subcategories, leisure-time PA was “strongly linked” to a lower risk for at-risk advanced fibrosis in MASLD (OR, 0.56), and in MetALD and ALD combined (OR, 0.55).

Work-related PA, however, was not associated with improved advanced fibrosis.

PA Paradox

“Our data fit with the broader ‘physical activity paradox,’” Arab said. “Leisure-time activity is clearly beneficial, whereas occupational activity — which often involves prolonged exertion without adequate recovery, higher stress, and sometimes adverse working conditions — does not seem to give the same health dividend.” 

“For liver fibrosis specifically,” he said, “our message is more ‘lack of benefit’ than ‘direct harm,’ but we absolutely would not tell patients that a physically demanding job is a substitute for structured exercise. Occupational activity is not enough. Clinicians should explicitly ask, ‘Do you do any exercise outside of work?’ A patient who is ‘on their feet all day’ may still be in the low-benefit group from a liver perspective.”

Furthermore, he said, “the risk is cumulative. Older age and a higher number of CMRFs (obesity, diabetes or prediabetes, dyslipidemia, hypertension) were consistently associated with higher odds of advanced fibrosis, regardless of activity type.”

‘Explicitly Prescribe Structured Leisure Activity’

“The protective association of leisure-time physical activity with reduced advanced fibrosis in MASLD is consistent with prior work, and it’s valuable to see this examined across the full SLD spectrum,” Jennifer C. Lai, MD, endowed professorship of Liver Health and Transplantation at the University of California San Francisco told Medscape Medical News.

“What’s notable is the magnitude of the effect,” said Lai, who was not involved in the study. “The lack of benefit from work-related physical activity, despite similar or even higher MET expenditure, reinforces that not all physical activity is metabolically equivalent.”

That said, Lai pointed to several study limitations. Cross-sectional data can’t establish causality, she said, and “it’s possible that patients with more advanced liver disease reduce their leisure activity because they feel unwell, rather than low activity causing fibrosis progression (reverse causation).”

In addition, “physical activity was self-reported, which introduces recall bias and doesn’t capture activity quality, intensity patterns, or recovery periods,” she said.

Furthermore, unmeasured confounders that independently affect liver health — for example, diet, sleep, stress — might affect the findings.

Nevertheless, she said, “these findings add to the growing evidence that we should be assessing and addressing physical activity as part of comprehensive liver disease management — much as we address weight, metabolic comorbidities, and alcohol use. Lifestyle counseling should be specific — we should explicitly prescribe structured leisure activity.”

The senior author of the study was supported by a National Institute on Alcohol Abuse and Alcoholism grant from National Institutes of Health and a US Department of Health and Human Services grant from Kentucky Medicaid. No other funding was reported. Arab and Lai reported no conflicts.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.