Background and Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is a common liver condition associated with increased cardiovascular disease (CVD) risk. Cytokeratin 18 (CK-18) is indicative of liver injury and used as surrogate biomarker covering NAFLD to cirrhosis phenotypes. Autoantibodies against apolipoprotein A-1 (AAA-1) are known CVD risk factors inducing NAFLD in vitro, but their role in modulating hepatic fibrosis is still elusive. We investigated AAA-1's contribution to systemic low-grade inflammation, liver steatosis, and fibrosis using a NAFLD mouse model and a validated passive immunization protocol (PIP).

Methods: Male C57BL/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) and immunized with AAA-1 or control antibodies for ten days. Priori sacrifice, plasma samples were collected, and CK-18 levels (M65 isoform), and proinflammatory cytokines were measured using the Mesoscale Discovery platform. Hematoxylin and Eosin and Sirius Fast Red staining were used to reveal liver steatosis and fibrosis, respectively.

Results: Compared to control IgG recipients, CDAHFD mice injected with AAA-1 exhibited significantly elevated levels of CK-18 (5.3 vs 2.1, p=0.031), IL-6 (13 vs 6.9, p=0.035), IL-10 (27.3 vs 9.8, p=0.007) and TNF-a (32.1 vs 24.2, p=0.032), and liver steatosis (93.4 vs 73.8, p=0.007). The amount of liver fibrosis was however unaffected.

Conclusions: Short AAA-1 PIP induced enhanced liver damage and steatosis accompanied by systemic inflammation in CDAHFD mice, suggesting that AAA-1 may induce transition from NAFLD to NASH. Knowing whether increased exposure time to AAA-1 could lead to cirrhosis, and if this could apply to humans as well warrant further investigations.