Fatty liver disease is rapidly increasing globally and is estimated to affect approximately one-quarter of the world’s population. Non-alcoholic fatty liver disease (NAFLD) is characterized by an increased tendency to develop cardiovascular disease as the leading cause of mortality, and extrahepatic malignancies.
In the recent scientific statement from the American Heart Association (AHA), NAFLD has been identified as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Similar epidemiological research also proved the connection of NAFLD with significant indicators of cardiovascular disease (CVD) as mortality and incidence rates.
Since 2020, there has been a global shift toward diagnosing metabolic dysfunction-associated fatty liver disease (MAFLD) instead of NAFLD. MAFLD provides simplified diagnostic criteria, improves risk stratification, enhances the identification of at-risk individuals, raises public awareness, and reduced stigma.
Due to diagnostic overlap, NAFLD and MAFLD are diagnosed in 70-90% of the general population and they indicate similar risks of CVD. More than 12 million participants were enrolled, and 17 observational studies occurred in the large-scale meta-analysis where MAFLD was associated with a greater risk of total mortality, CVD mortality, nonfatal CVD events, and stroke compared to NAFLD, hazard ratio (HR) 1.24, 95% confidence Interval (CI) 1.13-1.34,1.28, 95 % CI 1.03-1.53, 1.49, 95 % CI 1.34-1.64 and 1.55, 95 % CI 1.37-1.73 respectively. Therefore, 35% of NAFLD patients had raised CHD further evidenced by elevated carotid intima thickness, and had a significant odds ratio (OR) of 3.2-fold increase of having carotid atherosclerosis (CAS). NAFLD was also associated with a 5.04% prevalence of stroke, and with OR 1.88. Ischemic stroke is associated with carotid atherosclerosis which is characterized by plaques and stenosis. The estimated annual incidence of stroke in Asia varies from 116-483 cases per 100,000 individuals.
The data for the study was collected with the Health Management Center of Taichung Veterans General Hospital in Taiwan. Health exams under the self-pay system might be available for those adults who are over twenty years old, in the health management center. The study used data from participants who completed both abdominal ultrasonography and carotid artery ultrasonography during the last 14 years of data collection from January 2009 to December 2022. The participants with human immunodeficiency virus were excluded from the study.
The collected data included the participants’ sex, age, height, weight, personal medical history, biomedical marker data from carotid ultrasonography and liver ultrasonography, metabolic indicators, liver function, kidney function, serum uric acid levels, index for liver fibrosis (FIB-4), and NAFLD fibrosis scores. The current study was conducted after receiving permission from the institutional review board of Taichung Veterans General Hospital.
The cohort consisted of 17,747 participants; and after applying the exclusion criteria, the final participants was reduced to 11,194 patients. Out of the total participants with fatty liver, 5,589 individuals were identified as having NAFLD, making up 87.5% of the group. Similarly, 5,358 participants were diagnosed with MAFLD, representing 83.9% of the fatty liver cases. In the present study, 2% of the patients with fatty liver diseases were excluded from both MAFLD and NAFLD classifications and were classified as Group 1.
There were perceived differences between the intergroups. Group 1 (non-MAFLD-non-NAFLD) participants are younger than those in other groups; their body mass index (BMI) and waist circumference were worse; and they have fewer cases of diabetes and hypertension than other groups. Group 2 (NAFLD only) contained mostly young females with lower BMI and better metabolic parameters than either Group 3 (NAFLD-MAFLD) or Group 4 (MAFLD only). When comparing Group 2 with Group 3, no statistical variation was observed in the mean value of FIB-4. Group 4 included significantly more males, older participants, smokers, and higher liver-related indices, total cholesterol, triglycerides, and FIB-4 scores than Group 3. It also presented more individuals with FIB-4 > 1.3, and NAFLD fibrosis scores > −1.455. The odds ratios for concomitant carotid atherosclerosis compared to Group 1 were 1.07 for Group 2, 2.38 for Group 3, and 2.29 for Group 4.
The differences were statistically significant only in Group 3 and Group 4. In patients with NAFLD, 63.1% had concomitant carotid arteriosclerosis, and the odds ratio was 1.89 compared with non-NAFLD patients. Among MAFLD patients, 65.5% had concurrent carotid arteriosclerosis, with an odds ratio of 2.35 compared with non-MAFLD patients.
The results of the multivariable analysis revealed statistical significance in smoking, waist-to-hip ratio, age, and male sex. The relevance of diabetes, FIB-4, FIB-4> 1.3, and NAFLD fibrosis score > −1.455 in defining MAFLD risk was underscored by the following tests, all of which displayed odds ratios > 2 for MAFLD.
This study emphasizes the significance of metabolic and liver function biomarkers in the progression of fatty liver disease and cardiovascular risk. MAFLD was more closely associated with carotid atherosclerosis than NAFLD. Patients with MAFLD had a higher prevalence of coexisting carotid atherosclerosis, especially in the context of diabetes, FIB-4, and NFS values above the threshold.
Healthcare providers should pay more attention to patients with MAFLD and carotid atherosclerosis. The study emphasizes the need for accurate carotid sonography screening for cardiovascular risks in MAFLD patients.
Reference: Chung NT, Hsu CY, Shih NC, Wu JJ. Elevated concurrent carotid atherosclerosis rates in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) compared to non-alcoholic fatty liver disease (NAFLD): A cross-sectional observational study. Nutr Metab Cardiovasc Dis. 2025;35(1):103767. doi: 10.1016/j.numecd.2024.10.006
