Association between zinc and chronic hepatitis: A 2-sample Mendelian randomization study.

Micronutrients play a critical role in the development and progression of chronic hepatitis (CH). Variations in the levels of these essential nutrients can significantly influence disease outcomes in CH patients. This study investigates the causal relationships between 14 key micronutrients - copper, zinc, magnesium, vitamins A, C, D, B6, B12, folate, carotene, iron, selenium, calcium, and potassium - and the pathogenesis of CH. We utilized Mendelian randomization (MR) to explore causal relationships between 14 micronutrients and CH. Instrumental variables for micronutrient levels were derived from large-scale genome-wide association studies in European populations, with CH outcome data sourced from the FinnGen database. Our MR analysis employed 5 methodologies - inverse-variance weighting (primary approach), MR-Egger, weighted median, simple mode, and weighted mode - to identify micronutrients linked to CH. Sensitivity analyses assessed heterogeneity and pleiotropy, while a multivariable MR approach, supported by further sensitivity analyses, ensured the robustness of the findings. The inverse-variance weighting analysis revealed a significant causal association between zinc levels and CH, with a P-value of .022, an odds ratio of 0.806, and a 95% confidence interval of 0.670 to 0.970. Sensitivity analyses confirmed the robustness and reliability of this finding, with no evidence of heterogeneity or pleiotropy affecting the results. This study demonstrates a protective effect of zinc against CH, establishing a significant causal relationship. These findings provide foundational insights that advance our understanding of CH pathogenesis and support the development of targeted therapeutic interventions for its management.