Circulating tumor necrosis factor‐α levels in non‐alcoholic fatty liver disease: A systematic review and a meta‐analysis

Abstract

Background and Aim To synthesize data on circulating tumor necrosis factor (TNF)‐α levels between patients with histologically confirmed non‐alcoholic fatty liver disease (NAFLD) (simple steatosis or non‐alcoholic fatty liver [NAFL] and/or non‐alcoholic steatohepatitis [NASH]) and controls. Methods We performed a systematic search in PubMed, Scopus, and Cochrane Library. Fifty‐six studies, published between 2003 and 2019, were finally included, reporting data from 5848 individuals (1634 controls and 4214 NAFLD patients). Results Higher circulating TNF‐α levels were observed in NAFLD patients than controls (standardized mean difference [SMD] 0.84; 95% confidence interval [95% CI] 0.59–1.09), NAFL patients than controls (SMD 0.56; 95% CI 0.27–0.85), NASH patients than controls (SMD 0.93; 95% CI 0.64–1.22), and NASH than NAFL patients (SMD 0.31; 95% CI 0.16–0.46). There were only minimal changes in the comparisons between groups after excluding studies with morbidly obese populations (n = 11), or pediatric/adolescent populations (n = 6), or other than enzyme‐linked immunosorbent assay method of TNF‐α measurement (n = 8). There was high heterogeneity among studies in all comparisons, which was not essentially affected after sensitivity analyses. The meta‐regression analysis revealed that the male ratio was positively associated with TNF‐α SMD in the comparison between patients with NASH and NAFL (beta = 0.809; 95% CI 0.052–1.566) and accounted for 36% (P = 0.037) of the heterogeneity in this pair of comparison. TNF‐α SMD was not associated with age, body mass index, and alanine aminotransferase in any pair of comparisons. Conclusions Circulating TNF‐α levels were higher in patients with NAFLD compared with controls. Higher levels of circulating TNF‐α were also associated with the severity of NAFLD.

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

“…Correspondingly, recent clinical data showed that patients with NAFLD had significantly compromised cardiac and autonomic function, and, in particular, the raised levels of TNF-α and CK-18 (as markers for liver injury) in NAFLD patients were independently connected with augmented sympathetic activity and reduced parasympathetic activity [179]. Moreover, NAFLD has been reported to be related to systemic inflammatory responses, characterized by elevated levels of cytokines IL-6 and TNF-α [180,181]. Proinflammatory cytokine, such as the mentioned H. pylori-related TNF-α and IL-6, have been revealed to regulate the expression of the mentioned RAAS components, especially angiotensinogen production in the liver and kidneys, further promoting systemic and local angiotensin II formation and angiotensin II-dependent hypertension [182].…”

Gene regulation modules in non-alcoholic fatty liver disease revealed by single-nucleus ATAC-seq

“…T cell [27]. In human biomarker studies, higher circulating TNFa level was 14 associated with NAFLD [28] and future NAFLD [29]. In NAFLD patients, soluble IL1R1 was higher (Ajmera et al, 2017).…”

“…A number of genes have been reported as NAFLD biomarkers in humans. For hepatocytes, we found Il1r1 [43], Il1r2 and Tnf [28]. For endothelial cells, there was Hgf [44–46].…”

“…CXCL12 (aka SDF1) induced migration of stellate cells (Sawitza et al, 2009), endothelial cells (Salcedo et al, 1999) and CD4 + T cell (Boujedidi et al, 2014). In human biomarker studies, higher circulating TNFα level was associated with NAFLD (Potoupni et al, 2021) and future NAFLD (Seo et al, 2013). In NAFLD patients, soluble IL1R1 was higher (Ajmera et al, 2017).…”

Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications

“…A key feature is the low‐grade inflammatory state, which characterizes NAFLD and extends beyond the liver 9 . In NAFLD, chronic production of proinflammatory cytokines (eg, tumour necrosis factor‐α [TNF‐α], interleukin [IL]‐1, IL‐6, IL‐17), 10 produced mainly by the inflammatory cells infiltrating hepatic and adipose tissue, and adipokines (leptin, resistin, retinol‐binding protein‐4, visfatin, chemerin), produced mainly by the adipocytes, create a milieu of a chronic systemic inflammatory process, known as “metabolic inflammation” 11,12 . This inflammatory cascade promotes the progression of NAFLD in the liver and links NAFLD to extrahepatic chronic diseases, possibly including osteoporosis.…”