NAFLD Linked to Increased Risk of Metabolic Syndrome in Patients Without MAFLD


Among individuals without metabolic-associated fatty liver disease (MAFLD), those with nonalcoholic fatty liver disease (NAFLD) had a higher risk of developing metabolic syndrome.

Patients with nonalcoholic fatty liver disease (NAFLD) but without metabolic-associated fatty liver disease (MAFLD) have a higher risk of developing metabolic syndrome compared with patients who do not have either condition, according to a study published in Clinical Gastroenterology and Hepatology.

To come to this finding, the authors conducted a retrospective cohort study of 12,197 adult patients without metabolic dysfunction, defined by MAFLD criteria. These patients also did not have heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or a malignancy that would impact their risk of incident metabolic syndrome.

The study sample was mostly female, with 9043 women and 3154 men included, and the mean (SD) age was 47.3 (7.4) years.

By design, no participants had MAFLD at baseline. NAFLD prevalence at baseline among participants without metabolic dysfunction or significant alcohol intake who met MAFLD criteria was 7.6%.

All patients had at least 2 comprehensive health check-up examinations with an abdominal ultrasound at the Samsung Medical Center in Seoul, Republic of Korea, between January 1st, 2004, and December 31st, 2020.

Based on standard criteria—which included parenchymal brightness, liver-to-kidney contrast, deep beam attenuation, and bright vessel walls—fatty liver was diagnosed.

Some exclusion criteria at baseline included excessive alcohol use, defined as at least 30 grams/day for men and at least 20 grams/day for women, and other identifiable causes of fatty liver. Because of this, the authors considered fatty liver as NAFLD.

Participants with NAFLD were more likely to be male or smokers and more likely to have metabolic abnormalities compared with participants without NAFLD.

Study participants were followed up with between baseline and the health examination during which they developed metabolic syndrome, or until the last available examination for those who did not develop metabolic syndrome.

The number of follow-up visits was similar between the group with NAFLD without MAFLD and the group without either condition (5.7 vs 5.6; P = .34).

MAFLD diagnosis was based on the presence of NAFLD plus metabolic dysfunction, determined using The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III) criteria, which defines metabolic syndrome as the presence of at least 3 of the following 5 risk determinants:

  • high waist circumference (≥90 cm in men or ≥80 cm in women)
  • high triglycerides (≥150 mg/dL)
  • low HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women)
  • elevated blood pressure (≥130/≥85 mm Hg)
  • impaired fasting glucose (≥110 mg/dl)

During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome.

The overall metabolic syndrome incidence rate was 29 cases per 1000 person-years. Additionally, the incidence rate of metabolic syndrome was 27 per 1000 person-years in participants without NAFLD, and 69 per 1000 person-years in participants with NAFLD.

Additionally, the incidence rates of MAFLD in participants without and with NAFLD were 17 and 134 per 1000 person-years, respectively.

The study showed participants with NAFLD without MAFLD were at a higher risk of developing metabolic syndrome compared with participants without NAFLD and without MAFLD (adjusted HR, 1.61; 95% CI, 1.42-1.83).

This association between NAFLD and metabolic syndrome was consistent in all analyzed subgroups. Further, the link was stronger in individuals with increased waist circumference compared with those with normal waist circumference, and stronger in individuals without elevated triglycerides compared with those with elevated triglycerides.

According to the authors, the findings of this cohort study indicate NAFLD without MAFLD is not a benign condition.

“Using MAFLD criteria instead of NAFLD may underestimate the prognostic value of hepatic steatosis itself, and may exclude NAFLD without MAFLD subjects from earlier lifestyle interventions,” they said. “The newly proposed MAFLD definition should not overlook a group of NAFLD patients who also need medical attention.”


Sinn DH, Kang D, Choi SC, et al. Non-alcoholic fatty liver disease without metabolic associated fatty liver disease and the risk of metabolic syndrome. Clin Gastroenterol Hepatol. 2022;S1542-3565(22)00912-0. doi:10.1016/j.cgh.2022.09.014

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