Circulating lipoprotein(a) in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Background and aim: Although nonalcoholic fatty liver disease (NAFLD) and lipoprotein(a) [Lp(a)] are associated with cardiovascular diseases, existing data on Lp(a) in NAFLD are conflicting. The aim of this systematic review and meta-analysis was to summarize and compare data on circulating Lp(a) between NAFLD patients and non-NAFLD controls.

Methods: A systematic literature search was performed in PubMed, Scopus, and Cochrane Library. This meta-analysis included 18 studies containing data on 74 691 individuals (20 220 patients with NAFLD and 54 471 controls).

Results: Circulating Lp(a) was similar between patients with NAFLD and controls (standardized mean difference [SMD] 0.09; 95% confidence interval [95% CI] -0.21, 0.38). The heterogeneity among studies was high (I² = 100%); no publication bias was detected (Egger's test P = 0.941). However, in subgroup analysis, Lp(a) was lower in NAFLD patients than controls, when Lp(a) was measured with nephelometry (SMD -0.26; 95% CI -0.46, -0.06), but not turbidimetry; this analysis also resulted in mild reduction of heterogeneity within the subgroup of nephelometry (I² = 87%). The sensitivity analyses, based on the exclusion of studies with Newcastle-Ottawa Scale score ≤6 (n = 5), studies in which liver biopsy was used for NAFLD diagnosis (n = 4) or studies that adopted the criteria of metabolic dysfunction-associated fatty liver disease (n = 2), and meta-regression analysis did not explain the high heterogeneity among studies.

Conclusions: Overall, circulating Lp(a) was similar between NAFLD patients and non-NAFLD controls; however, patients with NAFLD had lower circulating Lp(a) compared with controls, when Lp(a) was measured with nephelometry. These results should be cautiously interpreted, because of the high heterogeneity among studies.