Citation: Ismaiel, A.; Ciobanu, O.S.; Ismaiel, M.; Leucuta, D.-C.; Popa, S.-L.; David, L.; Ensar, D.; Al Srouji, N.; Dumitrascu, D.L. Atherogenic Index of Plasma in Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. Biomedicines 2022, 10, 2101. https://doi.org/10.3390/ biomedicines10092101 Academic Editors: François R. Jornayvaz and Karim Gariani Received: 11 August 2022 Accepted: 25 August 2022 Published: 27 August 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biomedicines Systematic Review Atherogenic Index of Plasma in Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis Abdulrahman Ismaiel 1 , Oana Sabina Ciobanu 2 , Mohamed Ismaiel 3 , Daniel-Corneliu Leucuta 4, * , Stefan-Lucian Popa 1 , Liliana David 1 , Dilara Ensar 5 , Nahlah Al Srouji 1 and Dan L. Dumitrascu 1 1 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania 2 Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania 3 Department of Surgery, St Michael’s Hospital, A96 D628 Dublin, Ireland 4 Department of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania 5 Department of Medicine, Tallaght University Hospital, D24 NR0A Dublin, Ireland * Correspondence: dleucuta@umfcluj.ro; Tel.: +40-26-459-7256 (ext. 2502) Abstract: (1) Background: Approximately a billion people worldwide are affected by NAFLD, which places a high clinical burden and financial cost on society. Liver biopsy is the gold standard for diagnosing NAFLD, but its invasivity limits the early diagnosis of NAFLD. Hence, it is important to look for alternate techniques in detecting and diagnosing NAFLD. NAFLD is associated with atherosclerosis. The purpose of this study was to assess the effectiveness of the atherogenic index of plasma (AIP) as a non-invasive modality for predicting NAFLD. (2) Methods: A search using electronic databases PubMed, EMBASE, and Scopus was carried out to find observational studies, looking at research that had been published up until the date of 11 May 2022. The included studies’ quality, risk of bias, and internal validity were evaluated using the QUADAS-2 quality assessment tool. The key summary outcomes were the mean difference (MD) and area under the curve (AUC). (3) Results: A total of eight studies (81,178 participants) were included in our review, while 17% of the included participants had NAFLD. A sex distribution of 57.8% men and 42.2% women was observed. The AIP between NAFLD and the controls was not significant (MD 0.212 [95% CI 0.231–0.655]). A significant MD in AIP between the males and females with NAFLD was observed (MD 0.246 [95% CI 0.098–0.395]). The AIP predicted NAFLD with an AUC of 0.764 as well as in males (AUC 0.761) and females (AUC 0.733). (4) Conclusions: There was a substantial MD in the AIP between both sexes, but there was no significant difference in the AIP values between patients with NAFLD and the controls. The AIP is a reliable biomarker for the diagnosis of NAFLD since its ability to predict the development of NAFLD was comparable to that of the other biomarkers. Keywords: non-alcoholic fatty liver disease (NAFLD); metabolic-dysfunction-associated fatty liver disease (MAFLD); hepatic steatosis; liver fibrosis; biomarkers; scores; non-invasive diagnosis 1. Introduction Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by the presence of excessive fat build up within hepatocytes, in the absence of other conditions that result in hepatic steatosis and with little to no alcohol consumption [1,2]. It refers to a broad range of conditions including steatosis, non-alcoholic steatohepatitis (NASH), and cirrhosis [3]. In addition, it is a significant public health problem, prevalent in both devel- oping and developed countries [4]. Approximately a billion people worldwide are affected by NAFLD, resulting in a substantial economic and medical burden on societies [5,6]. NAFLD diagnosis involves the exclusion of secondary causes resulting in hepato- cellular fat aggregation and the presence of imagistic or histopathological evidence of hepatic steatosis [7]. Histopathological evaluation using liver biopsy is the gold standard Biomedicines 2022, 10, 2101. https://doi.org/10.3390/biomedicines10092101 https://www.mdpi.com/journal/biomedicines