Adverse Outcome Risk Increased in Metabolically Unhealthy Metabolic-Associated Fatty Liver Disease

Individuals who are metabolically unhealthy with metabolic-associated fatty liver disease are at increased risk for cardiovascular-related complications.

Metabolically unhealthy individuals with metabolic associated fatty liver disease (MU-MAFLD) have an increased risk for major adverse cardiovascular events (MACE) and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality compared with non-MAFLD individuals, according to a study in Clinical Gastroenterology and Hepatology.

Researchers sought to determine the prevalence, clinical characteristics, and differences in outcomes of overweight and obese metabolically healthy (MH)-MAFLD patients from the US National Health and Nutrition Examination Survey between 1999 and 2018.

A total of 32,683 individuals were included. MH-MAFLD was defined as being overweight or obese with fatty liver. MU-MAFLD was defined as having fatty liver and concomitant type 2 diabetes (DM) and/or at least 2 metabolic risk abnormalities.

In the overweight and obese group, participants were identified as non-MAFLD (n=11,884; 36.36%; 95% CI, 35.84%-36.88%), MH-MAFLD (n=14,701; 44.98%; 95% CI, 44.44%-45.52%), or MU-MAFLD (n=6098; 18.66%; 95% CI, 18.24%-19.08%). Among patients with MAFLD, 70.68% (95% CI, 70.06%-71.30%) were MH-MAFLD, and 29.32% (95% CI, 28.70%-29.94%) were MU-MAFLD.

MH-MAFLD patients were not at a significantly increased risk of MACE and all-cause, CVD, and cancer-related mortality compared with non-MAFLD individuals…

MU-MAFLD status was significantly associated with increased odds of MACE compared with non-MAFLD status (odds ratio [OR], 2.02; 95% CI, 1.73-2.36; P <.01), according to multivariate logistic regression analysis. No significant difference was found regarding the odds of MACE in MH-MAFLD individuals (OR, 1.03; 95% CI, 0.92-1.16; P =.58) compared with non-MAFLD individuals.

A significantly higher risk for all-cause mortality was observed for MU-MAFLD individuals (hazard ratio [HR], 1.51; 95% CI, 1.25-1.81; P <.01) vs non-MAFLD individuals. Mortality risk related to CVD (sub-distribution hazard ratio [SHR], 1.44; 95% CI, 1.16-1.79; P <.01) and cancer (SHR, 1.38; 95% CI, 1.17-1.63; P <.01) was only significantly higher in individuals categorized as MU-MAFLD or non-MAFLD. The mortality risks related to CVD (SHR, 1.03; 95% CI, 0.79-1.34; P =.85) and cancer (SHR, 1.13; 95% CI, 0.90-1.44; P =.29) were not significantly different between the MH-MAFLD and non-MAFLD groups.

MAFLD status with a concomitant DM diagnosis was associated with a significantly higher risk for all cancer events (OR, 1.19; 95% CI, 1.02-1.40; P =.03) and CVD mortality (SHR, 1.59; 95% CI, 1.39-1.82; P <.01) compared with non-MAFLD status.

Among several study limitations, lean patients with MAFLD were excluded to reduce heterogeneity from the variation in weight, and MAFLD was diagnosed using fatty liver index. In addition, the study was unable to account for variations in metabolically healthy status during the longitudinal follow-up, including the effects of postmenopausal metabolic health in women.

“Unsurprisingly in our analysis, MH-MAFLD patients were not at a significantly increased risk of MACE and all-cause, CVD, and cancer-related mortality compared with non-MAFLD individuals, while MU-MAFLD individuals were at an increased risk of these adverse outcomes relative to non-MAFLD individuals,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Gastroenterology Advisor


Chan KE, Ng CH, Fu CE, et al. The spectrum and impact of metabolic dysfunction in MAFLD. A longitudinal cohort analysis of 32,683 overweight and obese individuals. Clin Gastroenterol Hepatol. Published online October 2, 2022. doi:10.1016/j.cgh.2022.09.028