Keywords
NAFLD
NHANES
Inflammation
Mortality
Categories
How to Cite
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent global health concern, with systemic inflammation significantly contributing to disease progression and related cardiovascular complications. The systemic inflammatory response index (SIRI), which combines neutrophil, monocyte, and lymphocyte counts, has been associated with negative outcomes in various diseases. Nevertheless, the connection between the SIRI and mortality in NAFLD patients has yet to be thoroughly investigated.
Objective: This study aimed to examine the associations between the SIRI and all-cause and cardiovascular disease (CVD) mortality in a large cohort of NAFLD patients.
Methods: Data were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, including 5,179 individuals diagnosed with NAFLD. Kaplan-Meier (KM) survival curves, restricted cubic spline (RCS) analysis and Cox proportional hazard models were used to assess the relationship between the SIRI and mortality. Receiver operating characteristic (ROC) curves were used to explore the prognostic value of SIRI. Sensitivity analysis was performed to enhance the robustness of the results.
Results: Over a median follow-up of 109 months, 898 participants died, 310 of whom died from CVD. Participants who experienced mortality had higher levels of SIRI in the baseline. KM survival analysis revealed that participants in the highest SIRI quartile (Q4) had significantly worse survival outcomes than those in Q1 (log-rank test, P < 0.001). The multivariable-adjusted Cox regression models demonstrated that higher SIRI levels were independently associated with increased risks of all-cause mortality (HR per unit increase = 1.20; 95% CI: 1.09-1.32) and CVD mortality (HR per unit increase = 1.17; 95% CI: 1.02-1.35). Compared with those SIRI levels in Q1, participants in Q4 had a 57% higher risk of all-cause mortality (HR = 1.57; 95% CI: 1.17-2.10) and an 81% greater risk of CVD mortality (HR = 1.81; 95% CI: 1.07-3.07) compared to those in Q1. ROC curve analysis yielded an area under the curve (AUC) of 0.622 for predicting all-cause mortality and 0.625 for predicting CVD mortality.
Conclusion: The SIRI is a robust and independent predictor of all-cause and CVD mortality in NAFLD patients. These findings underscore the importance of systemic inflammation in NAFLD progression.
References
[1] Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397(10290):2212-2224.
[2] Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11-20.
[3] Riazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7(9):851-861.
[4] Younossi ZM, Golabi P, Paik JM, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335-1347.
[5] Pouwels S, Sakran N, Graham Y, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord. 2022;22(1):63.
[6] Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002;123(1):134-140.
[7] Zou J, Song Q, Shaw PC, et al. Tangerine Peel-Derived Exosome-Like Nanovesicles Alleviate Hepatic Steatosis Induced by Type 2 Diabetes: Evidenced by Regulating Lipid Metabolism and Intestinal Microflora. Int J Nanomedicine. 2024;19:10023-10043.
[8] Park CH, Lim H, Kim YN, et al. Non-alcoholic Fatty Liver Disease (NAFLD) and its association with kidney and cardiovascular outcomes in moderate to advanced chronic kidney disease. Am J Nephrol. 2024;1-23.
[9] Gong H, He Q, Zhu L, et al. Associations between systemic inflammation indicators and nonalcoholic fatty liver disease: evidence from a prospective study. Front Immunol. 2024;15:1389967.
[10] Tilg H, Adolph TE, Dudek M, et al. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab. 2021;3(12):1596-1607.
[11] Wong VW, Ekstedt M, Wong GL, et al. Changing epidemiology, global trends and implications for outcomes of NAFLD. J Hepatol. 2023;79(3):842-852.
[12] Kivrak A, Yildirim A. Relationship between systemic inflammation indices and time of symptom onset in cardiac remodeling after first ST-segment elevation myocardial infarction. Kardiol Pol. 2023;81(9):886-894.
[13] Gu X, Han X, Shen Y, et al. Prognostic value of systemic inflammation response index in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors. J Immunother Cancer. 2024;12(8):e008802.
[14] Liu Z, Ding Y, Liu J, et al. Predictive effect of the systemic inflammation response index (SIRI) on the efficacy and prognosis of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. BMC Surg. 2024;24:89.
[15] Dong W, Gong Y, Zhao J, et al. A combined analysis of TyG index, SII index, and SIRI index: positive association with CHD risk and coronary atherosclerosis severity in patients with NAFLD. Front Endocrinol (Lausanne). 2024;14:1281839.
[16] Sun W, Fang Y, Zhou B, et al. The association of systemic inflammatory biomarkers with non-alcoholic fatty liver disease: a large population-based cross-sectional study. Prev Med Rep. 2024;37:102536.
[17] Dong W, Gong Y, Zhao J, et al. A combined analysis of TyG index, SII index, and SIRI index: positive association with CHD risk and coronary atherosclerosis severity in patients with NAFLD. Front Endocrinol (Lausanne). 2023;14:1281839.
[18] Ruhl CE, Everhart JE. Fatty liver indices in the multiethnic United States National Health and Nutrition Examination Survey. Aliment Pharmacol Ther. 2015;41(1):65-76.
[19] Ebrahimi R, Yano EM, Alvarez CA, et al. Trends in Cardiovascular Disease Mortality in US Women Veterans vs Civilians. JAMA Netw Open. 2023;6(10):e2340242.
[20] Pan J, Zhou Y, Pang N, et al. Dietary Niacin Intake and Mortality Among Individuals With Nonalcoholic Fatty Liver Disease. JAMA Netw Open. 2024;7(2):e2354277.
[21] Qi Q, Zhuang L, Shen Y, et al. A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy. Cancer. 2016;122(14):2158-2167.
[22] Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822-1832.
[23] Moore KJ. Targeting inflammation in CVD: advances and challenges. Nat Rev Cardiol. 2019;16(2):74-75.
[24] Zhao S, Dong S, Qin Y, et al. Inflammation index SIRI is associated with increased all-cause and cardiovascular mortality among patients with hypertension. Front Cardiovasc Med. 2022;9:1066219.
[25] Liu Z, Zheng L. Associations between SII, SIRI, and cardiovascular disease in obese individuals: a nationwide cross-sectional analysis. Front Cardiovasc Med. 2024;11:1361088.
[26] Jin Z, Wu Q, Chen S, et al. The Associations of Two Novel Inflammation Indexes, SII and SIRI with the Risks for Cardiovascular Diseases and All-Cause Mortality: A Ten-Year Follow-Up Study in 85,154 Individuals. J Inflamm Res. 2021;14:131-140.
[27] Schuster S, Cabrera D, Arrese M, et al. Triggering and resolution of inflammation in NASH. Nat Rev Gastroenterol Hepatol. 2018;15(6):349-364.
[28] Ismaiel A, Dumitrascu DL. How to Reduce Cardiovascular Risk in Nonalcoholic Fatty Liver Disease. Am J Ther. 2023;30(3):e242-e256.
[29] Targher G, Byrne CD, Tilg H. MASLD: a systemic metabolic disorder with cardiovascular and malignant complications. J Hepatol. 2024;73(4):809-824.
[30] Gong M, Wen S, Nguyen T, et al. Converging Relationships of Obesity and Nonalcoholic Fatty Liver Disease With Incident Cardiovascular Disease and Mortality. J Am Heart Assoc. 2024;13(15):e036241.
[31] Zachou M, Flevari P, Nasiri-Ansari N, et al. The role of anti-diabetic drugs in NAFLD. Have we found the Holy Grail? A narrative review. Eur J Clin Pharmacol. 2024;80(1):127-150.
[32] Ong Lopez AMC, Pajimna JAT. Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: an updated systematic review and meta-analysis. Sci Rep. 2024;14(1):2122.
[33] Luo C, Lin Y, Zhou W, et al. Survival advantage associated with metformin usage in hepatocellular carcinoma patients with diabetes mellitus receiving radical resection: a propensity score matching analysis. Eur J Gastroenterol Hepatol. 2020;32(8):1030-1035.
[34] Xu F, Li Z, Zheng X, et al. SIRT1 mediates the effect of GLP-1 receptor agonist exenatide on ameliorating hepatic steatosis. Diabetes. 2014;63(11):3637-3646.
[35] Hu Y, Yang Y, Gao Y, et al. The impact of chronic diseases on the health-related quality of life of middle-aged and older adults: the role of physical activity and degree of digitization. BMC Public Health. 2024;24(1):2335.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 Frontiers in Preventive Medicine