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

Background and Aim To synthesize data on circulating tumor necrosis factor (TNF)-alpha 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-alpha 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-alpha 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-alpha 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-alpha SMD was not associated with age, body mass index, and alanine aminotransferase in any pair of comparisons. Conclusions Circulating TNF-alpha levels were higher in patients with NAFLD compared with controls. Higher levels of circulating TNF-alpha were also associated with the severity of NAFLD.

Automated summary

The study synthesized data on circulating TNF-alpha levels in patients with NAFLD and controls. It found that TNF-alpha levels were higher in NAFLD patients than controls, and were also associated with the severity of NAFLD. Additionally, male ratio was positively associated with TNF-alpha levels in the comparison between NASH and NAFL patients.