Chronic Hepatitis B and Related Liver Diseases Are Associated with Reduced 25-Hydroxy-Vitamin D Levels: A Systematic Review and Meta-Analysis.

Hepatitis B infection is a major public health problem globally leading to chronic liver disease and death, which are influenced by various environmental and host factors including serum 25-hydroxy-vitamin D levels. There is no comprehensive systematic review reporting the association of serum 25-hydroxy-vitamin D levels and different stages of chronic hepatitis B. This study aimed to analyze the association of 25-hydroxy-vitamin D levels in chronic hepatitis B with various determinants and outcomes. A bibliographic search in PubMed, Google Scholar, and Scopus was conducted using the search terms "Vitamin D", "cholecalciferol", "calcitriol", "Hepatitis B", and "HBV", which were published until September 2022. Meta-analysis using the "metafor" package in R was conducted with a random effect model. This analysis included 33 studies with 6360 chronic hepatitis B patients. The pooled estimates of serum 25-hydroxy-vitamin D level among CHB cases was 21.05 ng/mL and was significantly lower compared to healthy controls. ( p < 0.005). Reduced serum 25-hydroxy-vitamin D level was significantly associated with the severity of liver fibrosis as well as HBe positivity. This analysis suggests that serum 25-hydroxy-vitamin D levels are associated with disease activity and pathobiology, although the exact nature of the cause-effect relationship cannot be discerned from this study.