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

Victoria Potoupni; Maria Georgiadou; Eftychia Chatzigriva; Georgia Polychronidou; Erietta Markou; Christos Zapantis Gakis; Ioanna Filimidou; Myriam Karagianni; Dimitrios Anastasilakis; Kleo Evripidou; Argyro Ftergioti; Marianthi Togkaridou; Nikolaos Tsaftaridis; Apostolos Apostolopoulos; Stergios A Polyzos

doi:10.1111/jgh.15631

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

J Gastroenterol Hepatol. 2021 Nov;36(11):3002-3014. doi: 10.1111/jgh.15631. Epub 2021 Jul 30.

Authors

Victoria Potoupni¹, Maria Georgiadou¹, Eftychia Chatzigriva¹, Georgia Polychronidou¹, Erietta Markou¹, Christos Zapantis Gakis¹, Ioanna Filimidou¹, Myriam Karagianni¹, Dimitrios Anastasilakis¹, Kleo Evripidou¹, Argyro Ftergioti¹, Marianthi Togkaridou¹, Nikolaos Tsaftaridis¹, Apostolos Apostolopoulos¹, Stergios A Polyzos¹

Affiliation

¹ First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

PMID: 34289181
DOI: 10.1111/jgh.15631

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.

Keywords: cytokines; insulin resistance; metabolic syndrome; non-alcoholic fatty liver disease; tumor necrosis factor-alpha.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Adult
Body Mass Index
Female
Humans
Male
Non-alcoholic Fatty Liver Disease* / blood
Severity of Illness Index
Tumor Necrosis Factor-alpha* / blood

Substances

Tumor Necrosis Factor-alpha