Autoimmune liver diseases (AILDs) are uncommon, chronic hepatic disorders characterized by abnormal immune attack on hepatocytes or bile ducts, thereby leading to inflammation and, potentially, impaired liver function [1]. From an epidemiological standpoint, the prevalence and incidence of AILDs vary considerably across global populations. The incidence and prevalence of AILDs are reportedly increasing in Europe, North America and the Asia-Pacific region. Recent contemporary meta-analyses have revealed the following estimated incidence rate ranges of various AILDs per 100,000 people as follows: primary biliary cholangitis (PBC), 0.84 to 2.75; primary sclerosing cholangitis (PSC), 0.1 to 4.39; and autoimmune hepatitis (AIH), 0.4 to 2.39. In addition the corresponding prevalence rates ranged from 1.91 to 40.2 for PBC; from 0.78 to 31.7 for PSC; and from 4.8 to 42.9 [2] for AIH. The impact of AILD is substantial, as it not only affects the quality of life of individuals but also places considerable economic and healthcare burdens on societies. The etiopathogenesis of AILD is the subject of rigorous research, with several risk factors identified, encompassing genetic predispositions, environmental triggers, and associated comorbid conditions [3,4]. Understanding these risk factors is crucial for developing targeted preventative strategies and personalized management for those affected.

Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease in which the body's immune system aberrantly targets its own tissues, leading to a myriad of clinical manifestations [5]. Epidemiologically, the prevalence of SLE varies significantly across populations, with some ethnic groups demonstrating increased susceptibility globally [6]. This disease can involve one or more organs, but the liver is not often involved [5]. Lupus hepatitis, often marked by asymptomatic transaminasemia due to immune-complex deposition, necessitates differentiation from AILD [7]. Previous studies have reported that the coexistence of AILD with SLE is common, indicating a potential causal relationship between these two conditions [8,9]. However, no observational studies to date have elucidated the causal relationship between these diseases, which is vital for understanding their pathogenesis and developing improved therapies. Thus, the causal association between SLE and autoimmune hepatitis is still unclear.

Mendelian randomization (MR) represents a powerful methodological framework in the fields of epidemiology and genetics and is designed to infer causal relationships between exposure and outcome. This approach employs genetic variants as instrumental variables (IVs) to estimate the causal effect of exposure on the outcome, aiming to overcome some of the intrinsic limitations observed in traditional observational studies [10]. The principle of MR is rooted in the random assortment of alleles during gamete formation, as described by Mendel's laws of inheritance [11]. MR offers distinct advantages over conventional observational studies. This approach significantly mitigates confounding by leveraging genetic variants that are randomly allocated at conception, thereby making them independent of many potential confounders. This feature of MR enables a clearer assessment of causal relationships by minimizing the biases that typically arise from confounding variables in observational research. Moreover, MR facilitates temporal inference, establishing a clearer sequence of cause and effect since the genetic makeup predates the development of disease, thus addressing concerns of reverse causation. Therefore, MR has been aptly described as "nature's randomized controlled trial” [[12], [13], [14]]. In this study, we investigated the causal associations between SLE and various AILDs using two-sample MR analysis.