3.1 Prevalence and characteristics of MAFLD, NAFLD, and their subgroups
The demographics, anthropometrics, and laboratory test characteristics of 6718 subjects are presented in Table 1. The median age of the participants was 57 years (range, 50-65 years), and 34.7% of the participants were men. MAFLD was diagnosed in 2330 participants, and its prevalence was 34.7%. Compared with those without MAFLD, participants with MAFLD were more likely to be older, unemployed or farmers, and suffered from T2DM and hypertension. Compared with the non-MAFLD group, the MAFLD group had dramatically higher levels of WC, BMI, SBP, DBP, ALT, AST, TG, FBG, and 2h-PG and significantly lower HDL-c levels.
The prevalence of NAFLD was 32.4%. Participants with NAFLD tended to be older, women, unemployed or farmers, smokers, and had T2DM or hypertension. The NAFLD group had dramatically higher levels of WC, BMI, SBP, DBP, ALT, TG, FBG, and 2h-PG and significantly lower HDL-c levels compared with the non-NAFLD group.
The entire population was regrouped into non-FLD, overlap-FLD, MAFLD-only, and NAFLD-only groups. Participants who met the criteria for both MAFLD and NAFLD were categorized in the overlap-FLD group. The overlapping population included 2132 subjects, with an overlapping rate of 89.7%. Participants who met the inclusion criteria for MAFLD but not NAFLD were classified as MAFLD-only, and those who met the criteria for NAFLD but not MAFLD were classified as NAFLD-only. The prevalence of MAFLD-only and NAFLD-only was 8.3%, and 1.9%, respectively.
3.2 SI levels of MAFLD, NAFLD, and their subgroups
The 15 SI indicators are shown in Table 2. Except for MPV, d_NLR, and SII, other indicators dramatically differed between MAFLD and non-MAFLD groups, and the MAFLD group had higher levels of SI. Similarly, compared with the non-NAFLD group, NAFLD participants had higher levels of all the indicators, except for MPV, SII, and SIRI.
Compared among non-FLD, overlap-FLD, MAFLD-only, and NAFLD-only groups, the MAFLD-only group had the highest levels of CRP, WBC, LYMPH, NEUT, MONO, ALB, NLR, and SIRI, whereas the NAFLD-only group had the highest levels of PLR and the overlap-FLD group had the highest levels of LMR and ALI. The non-FLD group had the lowest levels of all 15 SI indicators (Table 3).
3.3 Inflammatory status of MAFLD with/without CRP
Considering that CRP was an item in the MAFLD definition, we removed CRP and re-defined MAFLD. Only 10 participants were excluded from the fully defined MAFLD group. No differences in SI indicators were observed after excluding the 10 participants. The Mann-Whitney U test was used to explore the relationship between SI indicators and MAFLD, and no significant differences in SI indicators were found between the re-defined and fully defined MAFLD (Table 4).
3.4 Relationship between SI indicators and MAFLD/NAFLD
Logistic regression analyses were used to explore the relationship between SI indicators and MAFLD, and the results are shown in Table 5. Except for MPV and SII, the ORs of other SI indicators were statistically significant in crude models. After adjusting for age, sex, BMI, smoking history, alcohol drinking history, education, and occupation, CRP, WBC, LYMPH, NEUT, MONO, ALB, PLR, SIRI, LMR, ALI, and CA were positively associated with MAFLD prevalence, and PLR had an inverse association. RCS analysis showed that a linear relationship existed between MPV, ALB, NLR, d_NLR, and PLR and MAFLD, whereas CRP, WBC, LYMPH, NEUT, MONO, SII, SIRI, LMR, ALI, and CA exhibited a non-linear relationship with MAFLD (Supplementary Figure 1).
The results for the relationship between SI indicators and NAFLD are shown in Table 6. The ORs of CRP, WBC, LYMPH, NEUT, MONO, ALB, PLR, LMR, ALI, and CA were greater than 1.0, and the OR of PLR was less than 1.0 in multivariable-adjusted logistic regression analysis. RCS analysis showed that there was a linear relationship between MPV, ALB, NLR, d_NLR, PLR, SIRI, and LMR and NAFLD, whereas CRP, WBC, LYMPH, NEUT, MONO, SII, ALI, and CA showed a non-linear relationship with NAFLD (Supplementary Figure 2).
3.5 ROC analysis of SI indicators in MAFLD and NAFLD
The AUC, sensitivity, specificity, and positive predictive values of SI indicators for MAFLD and NAFLD are depicted in Table 7. The AUC values of all SI indicators were lower than 0.7 in both MAFLD and NAFLD. The AUC values of LYMPH and ALI were higher than those of other indicators for both MAFLD (0.63 and 0.63, respectively) and NAFLD (0.62 and 0.62, respectively), and the AUCs of MPV and SII were lower than those of other indicators for both MAFLD (0.51 and 0.51, respectively) and NAFLD (0.50 and 0.51, respectively). The sensitivity, specificity, and positive predictive values of LYMPH, ALI, and MPV in MAFLD were 0.69, 0.50, and 0.42, 0.65, 0.55, and 0.43, and 0.15, 0.82, and 0.31, respectively. The sensitivity, specificity, and positive predictive values of LYMPH, ALI, and MPV in NAFLD were 0.69, 0.49, and 0.38, 0.71, 0.47, and 0.38, and 0.86, 0.16, and 0.32, respectively.