Hepatic steatosis, an accumulation of fat in the liver that is usually linked to obesity, can proceed to fibrosis, cirrhosis, and nonalcoholic fatty liver disease (NAFLD) (1). The etiology and accompanying conditions, such as inflammation and fibrosis, which can cause cirrhosis and liver failure, affect the natural course of hepatic steatosis (2). Given the rising incidence of obesity globally, the deleterious effects hepatic steatosis are becoming a growing challenge for public health. The deleterious effects of hepatic steatosis are becoming a growing challenge for public health due to the rising incidence of obesity globally (3). NAFLD is now the most common type of hepatic steatosis, affecting 30%-40% of male and 15%-20% of female in the general population. It is regarded as a hepatic manifestation of metabolic syndrome and is connected to insulin resistance, hypertension, atherosclerosis, obesity, dyslipidemia. Nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, is caused by lipid buildup in hepatocytes, which causes oxidative stress and an inflammatory response. As a result, hepatic steatosis should be given special clinical attention.

Hu et al. created the systemic immune-inflammation index (SII) in 2014 to reflect local immune response and systemic inflammation across the human body (4). Studies have discovered that in malignant tumors patients, SII can objectively represent the balance between the inflammatory reaction and immunological response (5, 6). SII is currently utilized as a prognostic indicator in the research of carcinoma (7–9). However, research on SII in disorders like steatosis that affect the chronic liver is scarce.

Numerous investigations have demonstrated that inflammation is a crucial factor in hepatic steatosis (3, 10). Hepatic steatosis may proceed to hepatocyte damage, the development of inflammation, and the activation of immune cells, or it may remain benign. Infiltrating macrophages, T lymphocytes, neutrophils, and DCs are examples of the inflammatory cells in the liver that cause inflammation (11). However, it is not yet clear how the inflammatory level biomarker SII and hepatic steatosis are related.

Therefore, to ascertain the relationship between SII levels and hepatic steatosis among participants in the US National Health and Nutrition Examination Survey (NHANES), we carried out a population-based investigation.

By reviewing the literature, this is the first study that identify the direct relationship between SII and hepatic steatosis. In our cross-sectional study, which included 10505 participants, we discovered that participants with hepatic steatosis had significantly higher SII levels, besides participants with hepatic steatosis underwent bariatric surgery had significantly lower SII than did those without bariatric surgery. Our findings revealed that elevated SII levels were an independently risk factor for hepatic steatosis.

Previous studies using various epidemiological methods and target groups have demonstrated the correlation between SII and liver disorders. An Indonesian population-based cohort of 196 patients with hepatocellular carcinoma (HCC) demonstrated that SII was a better accurate predictor of 1-year survival in patients with advanced HCC who did not receive treatment than neutrophil-lymphocyte ratio (NLR) (15). Elevated pre-treatment SII was correlated to lower overall survival (HR:1.54, P < 0.001) and earlier time to recurrence (HR:1.77, P < 0.001), according to a meta-analysis of ten published retrospective studies including 2796 HCC patients (16). For disorders of the metabolism, this is especially true. Among individuals from the 2011–2016 NHANES, a cross-sectional study discovered a statistically significant correlation between SII and higher BMI (17). Other NHANES studies suggested that higher SII could increase the risk of peripheral arterial disease, isolated coronary artery ectasia, and Diabetic depression (18–20). Likewise, similar to all this, our subgroup analysis indicated that participants with hepatic steatosis had a higher risk of high SII than participants without hepatic steatosis, suggesting that people with hepatic steatosis should be given more attention, especially in individuals with NAFLD.

The precise mechanism underlying the relationship between inflammation and hepatic steatosis is yet uncertain. According to previous research, in rats, visceral fat accumulation and hepatic inflammation are the important factors that promote the progression of steatosis (21). Patients with hepatic steatosis may proceed to hepatic fibrosis because of increased production of the proinflammatory cytokine tumor necrosis factor-alpha in the Kupffer cells, which enhances oxidative stress. Furthermore, TNF-a may cause hepatic cellular damage by increasing glomerular mononuclear cell infiltration, hence hastening the course of liver failure (22). Susanne et al. proposed that the causes of liver inflammation may originate outside the liver (for instance, in adipose tissue or the digestive tract) together with inside the organ (for example, lipotoxicity, innate immune responses, cell death pathways, mitochondrial dysfunction, and endoplasmic reticulum stress), which may be one of the potential mechanisms (23). In similarity to the majority of previous investigations, our research discovered that a higher SII was individually correlated with a higher risk of hepatic steatosis, indicating that SII may have an independently significant detrimental effect on hepatic steatosis.

Additionally, our results indicate that SII could be used as a straightforward, non-invasive indicator to determine high-risk patients in hepatic steatosis. However, there are various classical inflammatory markers with widespread therapeutic uses in clinical practice, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Canan et al. hypothesized that the rise in SII and NLR supports the increase in inflammation brought on by the rise of fat in children with obesity. In addition, SII and NLR imply that there might be inflammatory markers that can be employed in follow-up study for obesity comorbidities (24). Jin et al. found that higher NLR levels were negatively correlated with progressed inflammatory activity and substantial fibrosis in Chinese patients with NAFLD (25).

Currently, bariatric surgery is considered effective in reducing hepatic steatosis (26, 27). According to a prospective 5-year follow-up of obesity patients with NASH by Lassailly et al, the positive effects of bariatric surgery on the resolution of NASH were long-lasting and resulted in a sustained decrease in fibrosis (28). In our cross-sectional study, the decrease of SII supports the decrease of inflammation due to bariatric surgery in hepatic steatosis participants. This indirectly indicates that there is a strong association between SII and hepatic steatosis. Bariatric surgery, which leads to weight loss, is generally believed to be the main reason for the ameliorate of hepatic steatosis and inflammation (29). Unexpectedly, bariatric surgery reduced SII even after PSM corrected for differences of BMI and HSI. It suggests that bariatric surgery may reduce inflammation through other pathways without resorting to weight loss and hepatic steatosis, such as gut microbiota and modification of ghrelin (30, 31). In addition, the effect of bariatric surgery on the expression of immune-related genes and the abundance of inflammatory cell infiltration may also be one of the potential mechanisms (3, 32). To the best of our knowledge, this is the first study to evaluate the relationship among SII, bariatric surgery, and hepatic steatosis. Our study showed that SII may be an effective marker for assessing the efficacy of bariatric surgery.

Many studies have demonstrated that SII has remarkable predictive ability. Simultaneously, SII was a widely available method with a non-intrusive methodology, simple accessibility, and low cost. The potential for therapeutic use is indeed positive. Our research has its own advantages. First, the sample size is sufficient, and the sample selection is representative. Second, to get more trustworthy results, we adjusted for confounding variables. However, the study’s shortcomings call for cautious interpretation of the findings. First, the cross-sectional study design precluded us from establishing a causal association. Therefore, future research with a larger number of participants is still necessary to define the causal relationship. Furthermore, despite the fact that we made adjustments for several relevant confounders, we were incapable of totally rule out the impact of additional potential confounding variables.

In summary, our study found that SII and hepatic steatosis were associated, and that bariatric surgery can decrease both SII and inflammation. To validate our findings, further expanded prospective investigations at scale are required.

Publicly available datasets were analyzed in this study. This data can be found here: https://www.cdc.gov/nchs/nhanes.

The studies involving human participants were reviewed and approved by the Research Ethics Review Board of the NCHS. The patients/participants provided their written informed consent to participate in this study.

YS & YL put forward the conception and design of the study. YS & WG collected and analyzed the data. ZPL, DG and ZL made the tables and figures. all the authors drafted and revised the paper. All authors contributed to the article and approved the submitted version.

Thanks to Zhang Jing (shanghai Tongren Hospital) for his work on the NHANES database. His outstanding work, nhanesR package and webpage, makes it easier for us to explore NHANES database.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.