The systemic immune-inflammation index was non-linear associated with all-cause mortality in individuals with nonalcoholic fatty liver disease

OBJECTIVE: Systemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD. METHODS: Data was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan–Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines. RESULTS: A total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log(2)-SII group (quartile 1) and the highest log(2)-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47–2.37; p < 0.0001). After controlling for confounders, an increase in log(2)-SII was associated with an increased all-cause mortality risk of 41% for every unit raised (aHR = 1.41; 95% CI: 1.26–1.57; p < 0.0001). After adjusting for multiple potential confounders, the association between log(2)-SII and all-cause mortality was nonlinear, and the threshold value was 8.8. There was no association between an increase of one unit in log(2)-SII and all-cause mortality below the threshold (aHR = 0.90, 95% CI: 0.71–1.15, p = 0.419). However, a higher log(2)-SII was associated with a higher risk of death from any cause when it exceeded the threshold (aHR = 1. 73, 95% CI: 1.49–2.02, p < 0.001). CONCLUSION: Based on a study of US NAFLD patients, it was found that the baseline log(2)-SII is associated with all-cause mortality. Elevated SII is associated with poor survival among NAFLD patients. KEY MESSAGES: 1. Using a large nationally representative survey of individuals among US adults, the study demonstrated that log(2)-SII was J-shaped and associated with all-cause death among individuals with NAFLD. 2. Spline analyses demonstrated that the association between log(2)-SII and all-cause mortality was non-linear after adjusting for multiple potential confounders, and the threshold value was 8.8. 3. Higher log(2)-SII associated with poor survival in NAFLD.