Apolipoproteins Levels in Fatty Liver Disease: A Systematic Review and Meta-analysis

Background & Aims: Fatty liver disease (FLD) is a prevalent condition linked to metabolic disorders and can progress to severe liver diseases. Alterations in apolipoprotein (Apo) levels may provide valuable insights for diagnosing and managing FLD. This systematic review and meta-analysis evaluates these changes across different FLD phenotypes to evaluate their potential as diagnostic biomarkers. Methods: We evaluated studies from PubMed, EMBASE, and Scopus using a predefined search string. Predefined inclusion and exclusion criteria were applied, and the risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The main summary outcome was the mean difference (MD) in Apo levels. Results: Out of 773 initial articles, 55 studies involving 432,328 individuals were included. In NAFLD patients vs. controls, ApoA levels showed a MD of-0.029 (95% CI:-0.133, 0.075), ApoA-I had a MD of-0.064 (95%CI:-0.107,-0.021), and ApoB levels had a MD of 0.098 (95%CI: 0.076, 0.120), while ApoB100 had an MD of 0.042 (95% CI: 0.008, 0.076). For NASH vs. controls, ApoA-I levels had a MD of-0.108 (95% CI:-0.125,-0.091) and ApoB levels had a MD of 0.123 (95% CI: 0.054, 0.193), while ApoB100 had a MD of 0.042 (95% CI:-0.051,0.136). In MAFLD vs. controls, ApoA-I levels had a MD of-0.068 (95% CI:-0.124,-0.012) and ApoB a MD of 0.099 (95% CI: 0.091, 0.107). For diabetic NAFLD vs. T2DM (type 2 diabetes mellitus) without NAFLD, ApoA levels had an MD of 0.028 (95% CI:-0.147, 0.204) and ApoB levels an MD of 0.081 (95% CI: 0.040, 0.122). Conclusions: In NAFLD patients, ApoA-I levels were lower and ApoB and ApoB100 levels were higher compared to controls, with similar patterns seen in NASH patients, who also had higher ApoB levels than those with simple steatosis. MAFLD patients had elevated ApoB and ApoE levels, while overweight/obese NAFLD patients had higher ApoB levels than controls.