Yang Mengying, Liu Jing, Liu Xiaoman, Li Qianqian, Liu Jun, Wang Baogui
Department of Infectious Disease, Fuyang People's Hospital, Fuyang, Anhui, People's Republic of China.
Physical Examination Center, Fuyang People's Hospital, Fuyang, Anhui, People's Republic of China.
J Inflamm Res. 2025 Apr 24;18:5555-5572. doi: 10.2147/JIR.S520257. eCollection 2025.
Bilirubin, as a potent endogenous antioxidant, has demonstrated protective effects in various metabolic and inflammatory diseases. However, the precise role and underlying mechanisms of bilirubin in metabolic-associated fatty liver disease (MAFLD) remain unclear.
This study involved 3000 participants, categorized into non-MAFLD and MAFLD groups. Using weighted multiple linear regression and mediation effect analysis, this study examined the protective impact of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) on MAFLD risk. Additionally, potential mediators-inflammation and insulin resistance (IR) through which bilirubin exerts its protective effects were explored.
TBIL and DBIL levels in the MAFLD group were significantly lower than those in the non-MAFLD group. Multiple linear regression analysis, adjusted for confounding variables, revealed that compared to the lowest tertile group (TBIL < 14.6), the odds ratios (ORs) for the middle tertile (TBIL 14.6-19.2) and the highest tertile (TBIL ≥ 19.3) groups were 0.735 and 0.615. Similarly, compared to the lowest tertile group (DBIL < 3.4), the ORs for the middle tertile (DBIL 3.4-4.4) and the highest tertile (DBIL ≥ 4.5) groups were 0.613 and 0.367. Mediation analysis revealed significant indirect effects of SIRI, PIV, TyG, TyGBMI, METS-IR, and AIP on the relationship between TBIL, DBIL, and MAFLD risk. Specifically, SIRI mediated 4.07% and 1.55% of the TBIL-MAFLD and DBIL-MAFLD associations, respectively; PIV mediated 9.56% and 4.22%; TyG mediated 69.27% and 81.91%; TyGBMI mediated 100% and 78.34%; METS-IR mediated 100% and 81.41%; and AIP mediated 100% for both TBIL-MAFLD and DBIL-MAFLD associations.
Our findings suggest that increased serum levels of TBIL and DBIL are significantly inversely correlated with MAFLD risk, with both serving as independent protective factors against MAFLD occurrence. Further mediation analysis indicates that this protective effect is likely mediated by improvements in IR and the alleviation of systemic chronic inflammation.
胆红素作为一种强大的内源性抗氧化剂，已在多种代谢性和炎症性疾病中显示出保护作用。然而，胆红素在代谢相关脂肪性肝病（MAFLD）中的具体作用及潜在机制仍不清楚。
本研究纳入3000名参与者，分为非MAFLD组和MAFLD组。采用加权多元线性回归和中介效应分析，研究总胆红素（TBIL）、直接胆红素（DBIL）和间接胆红素（IBIL）对MAFLD风险的保护作用。此外，还探讨了胆红素发挥保护作用的潜在中介因素——炎症和胰岛素抵抗（IR）。
MAFLD组的TBIL和DBIL水平显著低于非MAFLD组。在对混杂变量进行调整后的多元线性回归分析显示，与最低三分位数组（TBIL < 14.6）相比，中间三分位数组（TBIL 14.6 - 19.2）和最高三分位数组（TBIL≥19.3）的比值比（OR）分别为0.735和0.615。同样，与最低三分位数组（DBIL < 3.4）相比，中间三分位数组（DBIL 3.4 - 4.4）和最高三分位数组（DBIL≥4.5）的OR分别为0.613和0.367。中介分析显示，SIRI、PIV、TyG、TyGBMI、METS - IR和AIP在TBIL、DBIL与MAFLD风险之间的关系中存在显著的间接效应。具体而言，SIRI分别介导了TBIL - MAFLD和DBIL - MAFLD关联的4.07%和1.55%；PIV介导了9.56%和4.22%；TyG介导了69.27%和81.91%；TyGBMI介导了100%和78.34%；METS - IR介导了100%和81.41%；AIP对TBIL - MAFLD和DBIL - MAFLD关联均介导了100%。
我们的研究结果表明，血清TBIL和DBIL水平升高与MAFLD风险显著负相关，二者均为预防MAFLD发生的独立保护因素。进一步的中介分析表明，这种保护作用可能是通过改善IR和减轻全身慢性炎症介导的。
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