Effect of nutritional intervention on interleukin-18 and alpha-2-macroglobulin in women with obesity and metabolic dysfunction-associated fatty liver disease: a prospective cohort study

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely linked to metabolic abnormalities, including central obesity, dyslipidaemia, hypertension, hyperglycaemia, and impaired liver function. Identifying effective lifestyle interventions and reliable noninvasive biomarkers remains a public health priority. OBJECTIVE: This study aimed to evaluate the effect of dietary modification on metabolic and hepatic parameters in women with MAFLD and to assess the potential role of interleukin-18 (IL-18) and alpha-2-macroglobulin (A2M) as noninvasive biomarkers. METHODS: A prospective interventional study was conducted on 54 women with obesity and at least one criterion of metabolic syndrome. Participants were categorized into mild MAFLD, moderate MAFLD, or healthy liver groups based on ultrasonographic findings. All participants followed a calorie-restricted, balanced diet (1000-1200 kcal/day) for eight weeks. Anthropometric measurements, 24-hour dietary recall, and biochemical parameters, including IL-18, A2M, and liver enzymes, were assessed at baseline and post-intervention. RESULTS: At baseline, women with moderate MAFLD exhibited significantly higher body mass index (BMI), minimal waist circumference (MWC), low-density lipoprotein cholesterol (LDL-C), and LDL/HDL ratio, along with lower high-density lipoprotein cholesterol (HDL-C), reflecting an adverse metabolic profile. They also reported higher macronutrient intake and lower dietary fiber consumption. A strong positive correlation between IL-18 and A2M (p ≤ 0.01) was observed across all groups and was associated with an unfavorable metabolic status. Following the intervention, significant improvements (p ≤ 0.05) were observed in weight, BMI, MWC, LDL-C, and gamma-glutamyl transferase (GGT), along with increased HDL-C levels. A highly significant reduction (p ≤ 0.01) in IL-18 was observed only among participants with MAFLD, while A2M levels decreased significantly (p ≤ 0.05-0.01) across all groups. CONCLUIONS: A calorie-restricted, balanced diet significantly improves metabolic and hepatic parameters in women with MAFLD. These findings highlight the beneficial impact of dietary intervention on liver enzymes and inflammatory markers, particularly GGT, IL-18, and A2M, and support the potential utility of A2M as a noninvasive biomarker and therapeutic target.