BackgroundInflammatory cytokines have been considered to be significant factors contributing to the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the role of inflammatory cytokines in NAFLD remains inconclusive.ObjectiveThis study aimed to evaluate the association between inflammatory cytokines and NAFLD.MethodsPubMed, Web of Science, the Cochrane Library, and EMBASE databases were searched until 31 December 2021 to identify eligible studies that reported the association of inflammatory cytokine with NAFLD and its subtypes. We pooled odds ratios (ORs) and hazard risk (HRs) with 95% confidence intervals (CIs) and conducted heterogeneity tests. Sensitivity analysis and analysis for publication bias were also carried out.ResultsThe search in the databases identified 51 relevant studies that investigated the association between 19 different inflammatory cytokines and NAFLD based on 36,074 patients and 47,052 controls. The results of the meta-analysis showed significant associations for C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) with NAFLD (ORs of 1.41, 1.08, 1.50, 1.15 and 2.17, respectively). In contrast, we observed non-significant associations for interferon-γ (IFN-γ), insulin-like growth factor (IGF-II), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), monocyte chemoattractant protein-1(MCP-1), and transforming growth factor-β (TGF-β) with NAFLD. Our results also showed that CRP, IL-1β, and TNF-α were significantly associated with non-alcoholic steatohepatitis (NASH) and hepatic fibrosis.ConclusionsOur results indicated that increased CRP, IL‐1β, IL-6, TNF‐α, and ICAM-1 concentrations were significantly associated with increased risks of NAFLD. These inflammatory mediators may serve as biomarkers for NAFLD subjects and expect to provide new insights into the aetiology of NAFLD as well as early diagnosis and intervention.

Objective Fetuin-A has been associated with the progression of metabolic syndrome, but previous studies found inconsistent results on the relationship between metabolic syndrome and the concentration of fetuin-A. The aim of this study was to perform a meta-analysis to summarize previous findings on this relationship. Method This study was registered with the International Prospective Register of Systematic Reviews PROSPERO (CRD42019129566). Studies examining the relationship between metabolic syndrome and the concentration of circulating fetuin-A were identified using a systematic search in the electronic databases of Embase, PubMed, Web of Science, and Cochrane Library before March 2019. A random effects model was used to summarize the effect size of the association in terms of the standardized mean difference (SMD). Results Fourteen eligible studies compared fetuin-A concentrations between 4,551 metabolic syndrome patients and 8,805 controls. The circulating fetuin-A concentration was significantly higher in the metabolic syndrome patients than in the controls (SMD = 0.65, 95% confidence interval (CI): 0.48 to 0.83, Z = 7.18, p<0.001). Besides, circulating fetuin-A was a risk factor for metabolic syndrome (odds ratio 1.23, 95% CI: 1.08 to 1.40). Conclusion These findings suggest that fetuin-A may be an important indicator for metabolic syndrome, in which case this may lead to new perspectives in early diagnosis, identification of novel biomarkers, and providing novel targets for pharmacological interventions.