**1. Introduction**

Autoimmune liver diseases, such as primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH), have complex etiologies and are characterized by the progressive destruction of liver structures through autoimmunity mechanisms [1,2]. The vast majority of patients with PBC (80%–90%) are women [3]. The reaction between antimitochondrial antibodies (AMA) and pyruvate dehydrogenase complex-E2 (PDC-E2), located in the inner mitochondrial membrane, underlies the pathogenesis of PBC [4]. The most common clinical symptoms are persistent pruritus and chronic fatigue; however, a substantial percentage of patients may experience no symptoms of liver disease [1]. In biochemistry, elevated alkaline phosphatase and gamma-glutamyltranspeptidase activity, hypercholesterolemia, and often an increase in IgM level are observed. Histologically, the disease is characterized by bile-duct damage leading to chronic cholestasis, progressive fibrosis, and liver cirrhosis [3].

AIH is a disease that affects women more often than men regardless of age or ethnicity [5]. Biochemically, it is characterized by elevated transaminases and hypergammaglobulinemia. It can be

divided into two types depending on autoantibodies; Type 1 is the most common and confirmed by the presence of an antinuclear antibody (ANA) or anti-smooth muscle antibody (ASMA). Histologically, AIH is marked by interface hepatitis, emperipolesis, and hepatocyte rosettes [6].

A substantial impairment of health-related quality of life (HRQoL) was reported in both PBC and AIH, with chronic fatigue and depression occurring in a significant proportion of patients with both diseases and pruritus affecting patients with PBC [7,8].

Vitamin D3 inhibits parathyroid-hormone secretion, cell proliferation, and adaptive immunity [9]. The activity of autoimmune diseases is influenced by vitamin-D3 deficiency [10], and this nonclassical effect of vitamin D is associated with the presence of the vitamin-D receptor (VDR) on numerous cells in the immune system. It was demonstrated that vitamin D has an impact on the Th1 lymphocytes responsible for the production of interleukin 2, tumor necrosis factor-alpha (TNA-α), and interferon gamma (IFNγ) [11]. The secretion of these cytokines can inhibit calcitriol (1.25(OH)2D3—the active metabolite of vitamin D), which translates into the alleviation of the inflammatory reaction. This substance also has a promoting effect on T regulatory cells that are also responsible for turning off the immune-system response, which may be crucial in the treatment of autoimmune diseases associated with excessive responses by the immune system [12]. Furthermore, the presence of VDR was observed on Th2 cells that, after activation, produce interleukins 4 and 10 [13]. Vitamin D enhances the diversification of macrophages and their bactericidal effect; it also inhibits the maturation of dendritic cells, which is essential in autoimmune diseases [14]. Consequently, attempts were made to use vitamin D3 as a biopreparate capable of treating humans through the immunomodulation of the immune system [15].

Recent studies showed that vitamin D is also involved in neurotransmission and neuroprotection, and its receptor (VDR) is present in brain tissue, like glial cells, hippocampus, thalamus, or neurons [16]. In turn, the polymorphism of the *VDR* gene modulates *VDR* expression that can affect the vitamin D3 signaling cascade [17,18]. A combination of these factors may suggest the impact of polymorphisms of the *VDR* gene on cognitive dysfunction, thus reducing the quality of life of patients with PBC and AIH.

Therefore, bearing in mind the results of our own study regarding the reduced expression of *VDR* in patients with PBC [19], the clinical symptoms of patients with PBC and AIH (including chronic fatigue and insomnia) [20,21], and reports on the protective effect of vitamin D on vessels and nerves, the aims of this study were characterizing the relationship between *VDR* gene polymorphisms (*BsmI and ApaI*, located in an intron between exons 8 and 9, and *TaqI* C > T located in exon 9) and the HRQoL in patients with a clinical diagnosis of PBC and AIH using validated scale tools and clinical-data forms.
