The role of the advanced lung cancer inflammation index (ALI) in the risk of liver fibrosis and mortality among US adult MAFLD patients: a cross-sectional study of NHANES 1999-2018

Abstract

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease globally, with inflammation and nutrition playing key roles in its progression. The Advanced Lung Cancer Inflammation Index (ALI) is a novel biomarker reflecting nutritional and inflammatory status. This study aims to explore the association between ALI and the risk of liver fibrosis and prognosis in MAFLD patients.

Methods: This cross-sectional study analyzed NHANES data from the 1999-2018 on adult participants in the US. Weighted logistic regression assessed the association between ALI and liver fibrosis risk. Mortality outcomes, including all-cause, cardiovascular disease (CVD), and cancer mortality, analyzed using weighted Kaplan-Meier and Cox proportional hazards models. Restricted cubic splines (RCS) and threshold effect analyses were uesd to explore non-linear relationships. Receiver operating characteristic (ROC) curve evaluated the prognostic value of ALI, and stratified analyses examined subgroup differences.

Results: A total of 6,858 MAFLD patients (mean age 51.38 ± 17.22 years, 54% male) were included. A non-linear relationship was found between ALI and liver fibrosis risk, with a threshold at 5.68, beyond which the risk increased significantly (OR = 2.35, 95% CI: 1.89-2.95). Stronger associations were observed in subgroups with central obesity and prediabetes (P for interaction < 0.05). ALI was inversely associated with all-cause mortality (HR = 0.64, 95% CI: 0.56-0.72) and CVD mortality (HR = 0.57, 95% CI: 0.46-0.65), but not cancer mortality. RCS analysis showed an L-shaped non-linear relationship with all-cause mortality (threshold at 5.36) and a linear relationship with CVD mortality. Low HDL cholesterol and excessive alcohol consumption influenced the association between ALI and all-cause mortality (P for interaction < 0.05). ALI demonstrated the highest predictive accuracy for CVD mortality.

Conclusion: ALI is associated with an increased risk of liver fibrosis and reduced all-cause and CVD mortality, highlighting its potential value in assessing MAFLD prognosis, particularly CVD-related mortality.

Keywords: Advanced lung Cancer inflammation index (ALI); All-cause mortality; Cardiovascular disease (CVD) mortality; Cross-sectional study; Metabolic dysfunction-associated fatty liver disease (MAFLD); National health and nutrition examination survey (NHANES).

Fig. 1

Restrictive cubic spline fitting of the association between ALI and liver fibrosis. Model 1: No covariates were adjusted; Model 2: Adjusted age, sex and race/ethnicity; Model 3: Adjusted age, sex, race/ethnicity, PIR, education, marital status, BMI, smoking, alcohol, diabetes, hypertension, sedentary behaviour, energy intake, and TC; ALI: Advanced lung cancer inflammation index; OR (95% CI): Odd ratio (95% confidence interval); Liver fibrosis risk assessment using MAF-5, low risk vs. medium to high risk

Fig. 2

Kaplan-Meier survival curves of ALI impact mortality in patients with NAFLD. (A): All-cause; (B): CVD; (C): Malignant neoplasms; ALI: Advanced lung cancer inflammation index; Q1: < 53.2; Q2: [53.2, 72.6); Q3: [72.6, 98.2); Q4: >= 98.2

Fig. 3

Restrictive cubic spline fitting of the association between ALI and mortality in patients with NAFLD. (A): All-cause; (B): CVD; Model 1: No covariates were adjusted; Model 2: Adjusted age, sex and race/ethnicity; Model 3: Adjusted age, sex, race/ethnicity, PIR, education, marital status, BMI, smoking, alcohol, diabetes, hypertension, sedentary, behaviour, energy intake, and TC