A healthy lifestyle is prospectively associated with lower onset of metabolic dysfunction-associated steatotic liver disease

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an unhealthy lifestyle. However, there is limited prospective evidence regarding the association between combined lifestyle factors and MASLD. This study aims to test the association of a combination of lifestyle components, expressed as a healthy lifestyle index (HLI), and unhealthful eating behavior habits with MASLD, insulin resistance (IR), liver fibrosis, and metabolic dysfunction-associated steatohepatitis.

Methods: A prospective cohort study was conducted among participants of metabolic and hepatic screening surveys. MASLD was evaluated by ultrasonography or controlled attenuation parameter at 2 time points to assess new-onset, persistence, or remission, and IR was estimated by homeostasis model assessment. Presumed liver fibrosis and metabolic dysfunction-associated steatohepatitis were evaluated using FibroMax biomarkers. The HLI was calculated as the sum of 4 lifestyle components: nonsmoking, healthy weight, healthy diet, and physical activity.

Results: The final cohort included 315 subjects with 6.7 years of follow-up, 40-70 years old. In multivariable analyses, a favorable lifestyle (≥3 components) was independently associated with lower odds of new-onset MASLD (OR = 0.42; 95% CI: 0.19-0.90). Similarly, a favorable lifestyle was associated with lower odds of new-onset/persistent (vs. never/remission) MASLD and IR, respectively (OR = 0.49; 95% CI: 0.30-0.80; OR = 0.40; 95% CI: 0.24-0.66). There was a dose-response association between HLI and new-onset/persistent MASLD and IR. A favorable lifestyle was associated with lower odds of new-onset metabolic dysfunction-associated steatohepatitis (OR = 0.50; 95% CI: 0.27-0.95). Adjusting for HLI, unhealthful eating behavior habits were associated with higher odds of MASLD prevalence (OR = 1.81; 95% CI: 1.07-3.06).

Conclusions: Adherence to a healthy lifestyle is prospectively associated with lower odds of MASLD, markers of liver damage, and IR. A holistic approach that considers overall lifestyle and eating behavior may be useful for preventing MASLD.

Graphical abstract

FIGURE 1

Flowchart of the study population. Three subjects in the first time point and 5 in the final prospective analysis did not have an insulin test. Abbreviations: AUS, abdominal ultrasound; CAP, controlled attenuation parameter; HLI, healthy lifestyle index; IR, insulin resistance; MASLD, metabolic dysfunction–associated steatotic liver disease.

FIGURE 2

Dose-response association between HLI at baseline and new-onset or persistent metabolic dysfunction–associated steatotic liver disease or insulin resistance. Bars represent the percentage of new-onset or persistent MASLD (A) and new-onset or persistent IR (B) cases; red points are the fitted values based on univariable logistic regression with the associated p value. ORs and their 95% CIs (with respect to HLI = 0), based on multivariable logistic regression of new-onset or persistent MASLD (C) and new-onset or persistent IR (D), adjusted for baseline age, sex, and energy intake. N cases/n total in each category (0, 1, 2, 3, and 4): 10/14, 30/68, 34/96, 25/94, and 10/43 for new-onset or persistent MASLD and 7/14, 31/67, 36/95, 24/92, and 6/42 for new-onset or persistent IR. N cases/n total for total MASLD sample 109/315 and IR sample 104/310 (310 subjects had complete data for HOMA-IR). Abbreviations: HLI, healthy lifestyle index; HOMA-IR, homeostasis model assessment of insulin resistance; IR, insulin resistance; MASLD, metabolic dysfunction–associated steatotic liver disease.

FIGURE 3

Multivariable analysis for the cross-sectional association between healthy lifestyle index, unhealthful eating behavior habits, and liver-related outcomes. ORs and their 95% CIs, based on multivariable logistic regression, adjusted for follow-up age (years), sex, follow-up energy intake (kcal/d), and for the other exposure variable; HLI or eating behavior habits accordingly (both evaluated at the follow-up survey). N cases/n total for each outcome: 109/314 for MASLD, 104/310 for IR, 51/303 for liver fibrosis, and 117/303 for MASH. HLI categories were defined as low HLI (unfavorable lifestyle) versus high HLI (favorable lifestyle); adherence to 0–2 versus 3–4 healthy lifestyle components, respectively. Eating behavior habits categories were defined as unhealthful (higher score reflects less appropriate eating behavior habits) versus healthful eating behavior habits; ≥14 (sample median score) versus <14, respectively. *Insulin resistance was defined as the upper quartile (≥Q4) of the study population’s HOMA levels (corresponding to a value ≥3.46 at follow-up) or diabetes with no insulin resistance according to the upper quartile of HOMA levels at follow-up. ^†Significant liver fibrosis and MASH were evaluated noninvasively using Fibromax. Abbreviations: HLI, healthy lifestyle index; HOMA, homeostasis model assessment; IR, insulin resistance; MASH, metabolic dysfunction–associated steatohepatitis; MASLD, metabolic dysfunction–associated steatotic liver disease.