Abstract
Observational studies have suggested an association between vitamin D (Vit D) and chronic hepatitis (CH). However, the nature of this relationship remains uncertain. Therefore, the aim of this study is to investigate the potential causal links and specific directions between Vit D deficiency and CH. Gaining insights into the potential cause-and-effect association between Vit D deficiency and CH is crucial for understanding the disease progression and developing innovative strategies for the prevention and management of CH, as well as its associated complications. We employed a bidirectional 2-sample Mendelian randomization design to investigate the causal relationship between Vit D and CH, specifically chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The exposure variables of interest were Vit D and its metabolite 25-hydroxyvitamin D (25-OHD), while the outcome variables were CHB and CHC. To identify suitable instrumental variables, we utilized genome-wide association study datasets to select potential candidate single-nucleotide polymorphisms. The primary statistical approach utilized in this study was the inverse variance weighted (IVW) method. Additionally, we conducted a range of sensitivity analyses to assess the robustness of our findings, including evaluations of heterogeneity and pleiotropy, aiming to ensure the reliability of the results. The findings of our research indicated that the genetically estimated serum 25-OHD, which acts as a mediator in the metabolism of Vit D, had a causal impact on CHC (IVW odds ratio = 1.28, 95% CI: 1.08-1.51, P = .004). However, no significant correlation was observed between genetically estimated 25-OHD and CHB (IVW odds ratio = 1.01, 95% CI: 0.70-1.46, P = .954). In IVW, circulating Vit D levels had no causal effect on CHB and CHC (P = .265; P = .308). No causal relationship was found between CHB or CHC and Vit D or 25-OHD in the reverse Mendelian randomization analysis, with a P-value > .05. In this research, we carried out an extensive inquiry to explore the cause-and-effect connection between Vit D and CH. Our findings provide evidence that serum 25-OHD significantly increases the vulnerability to CHC. The results of this study enhance our comprehension of the causes of CH and carry significant consequences for the medical treatment of individuals suffering from CH.