Association of liver fibrosis markers and inflammation markers with the risk of gallstones in patients with metabolic dysfunction-associated fatty liver disease

Shuai ZHANG; Shoulu JIN; Wanqing LI; Xijing SHI; Hao LIANG; Hao DONG; Dailong LU; Ying ZHU; Xiaoxing XIANG; Jun LIU

doi:10.12449/JCH260312

Volume 42 Issue 3

Mar. 2026

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Article Navigation > Journal of Clinical Hepatology > 2026 > 42(3): 579-585

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Association of liver fibrosis markers and inflammation markers with the risk of gallstones in patients with metabolic dysfunction-associated fatty liver disease

DOI: 10.12449/JCH260312

1.
Department of Medicine，Yangzhou University，Yangzhou，Jiangsu 225009，China
2.
Department of Gastroenterology，Northern Jiangsu People’s Hospital of Jiangsu Province，Yangzhou，Jiangsu 225001，China

Research funding:

Jiangsu Provincial Basic Research Program （Natural Science Foundation）Youth Fund Project (BK20240498);

National Natural Science Foundation of China Youth Project (82400623)

More Information

Corresponding author: LIU Jun， sbyy_liujun@163.com （ORCID： 0000-0001-8738-6548）
Received Date: 2025-09-08
Accepted Date: 2025-12-02
Published Date: 2026-03-25

Abstract

Abstract

Objective To investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. Methods A total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. Results The prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. Conclusion NFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.
- Metabolic Dysfunction-Associated Fatty Liver Disease,
- Biomarkers,
- Gallstones

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References(32)

References

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Association of liver fibrosis markers and inflammation markers with the risk of gallstones in patients with metabolic dysfunction-associated fatty liver disease

DOI: 10.12449/JCH260312

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