Vitamin D May Modulate Immune Function in Chronic HBV Infection

Findings from a recent study are providing clinicians with an overview of the role of vitamin D deficiency in viral hepatitis, underscoring its significant immunomodulatory role in hepatitis B virus (HBV) but not hepatitis C virus (HCV) infection.¹

Study results were published in Nutrition and showed vitamin D affected CD8, CD4, HBV DNA, and CD19 in the natural progression of chronic HBV infection, further revealing a negative relationship between vitamin D and complement C3.¹

A vaccine-preventable liver infection, HBV is often a short-term illness but in some cases can become a long-term, chronic infection leading to serious health issues like liver disease or liver cancer. The risk for chronic infection varies based on age at infection and is greatest among young children.² Suppressing virus replication and restoring host immune response are both significant in HBV therapy strategies, and recent research has alluded to the potential role of vitamin D concentration in these processes.¹

“It is speculated that reduced hepatic vitamin D receptor expression diminishes the ability of vitamin D to support the immune defense system, consequently weakening its effect on inhibiting viral replication,” Osman Evliyaoglu, of the Institute for Clinical Chemistry at the University of Heidelberg and colleagues wrote.¹ “However, this cycle can be disrupted by effective antiviral therapy, leading to improved vitamin D levels.”

Investigators sought to study the relationship of vitamin D with innate and adaptive immune response parameters in patients with chronic HBV and HCV. To do so, they enrolled inpatients from University Hospital Mannheim registered in the hospital information system with vitamin D, complement, serological tests, or fluorescence-activated cell sorting parameters from January 2013 to April 2023. Investigators identified patients with chronic viral hepatitis based on ICD codes and extracted laboratory data for those with HBV (n = 302) and HCV (n = 32), additionally including health patients (n = 256) in a separate control group for comparison.¹

Results showed the percentage of CD4-positive T lymphocytes and the CD4-positive/CD8-positive ratio significantly decreased (P <.05) in patients with chronic HBV and HCV, but the percentage of CD8-positive increased (P <.05) compared to the control group. Of note, patients with HBV had significantly lower serum vitamin D concentration compared to the control group and this decrease became significant over time (P <.001), but the decreased level of vitamin D in patients with HCV was not significant. Additionally, vitamin D showed a moderate negative influence on the CD8 cell count in patients with HBV.¹

Investigators further stratified the study groups based on their vitamin D status, categorized as sufficient (≥31 ng/mL), insufficient (21–30 ng/mL), deficient (11–20 ng/mL), and severely deficient (1–10 ng/mL), regardless of viral infection. Upon analysis, the vitamin D deficient group showed significantly lower antibody production compared to the normal group and exhibited significantly decreased CD4 numbers and increased CD8 numbers (P <.05 and P <.001, respectively), while the CD4/CD8 ratio was also significantly decreased in the insufficiency group (P <.001). Investigators noted this imbalance of helper T cells (CD4-positive T cells) and cytotoxic T cells (CD8-positive T cells) indicates immune system dysfunction.¹

Investigators noted complement C3 levels were not associated with CD4 and CD8 but had an inverse relation with vitamin D, suggesting the complement system does not exert a direct influence on cellular immune regulation. However, they noted the association between vitamin D and the complement system shows the anti-inflammatory properties of vitamin D. Additionally, investigators observed a significant association between vitamin D levels and complement C3, CD8+, CD4+, CD19+ cells, and HBV DNA levels.¹

Investigators outlined several potential limitations to these findings, including their reliance on data mining, inability to account for comorbidities and certain parameters across HBV subgroups, and variability in the types of testing parameters included in the study.¹

“This study supports the theoretical basis of the relationship between Vitamin D and the immune system in a big cohort and provides a novel reference for further studies,” investigators concluded.¹

References:

1. ^{Gerhards C, Teufel A, Gerigk M, et al. Potential role of Vitamin D in immune response in patients with viral hepatitis. Nutrition. Published online March 30, 2024. doi:10.1016/j.nut.2024.112447}
2. ^{US Centers for Disease Control and Prevention. Hepatitis B Information. Viral Hepatitis. March 9, 2023. Accessed May 6, 2024. https://www.cdc.gov/hepatitis/hbv/index.htm}