Vitamin D deficiency has been associated with several adverse health consequences that include autoimmune diseases, cardiovascular diseases and infections[16
]. 1,25-dihydroxyvitamin D3 acts as an immunomodulator targeting various immune cells, including monocytes, macrophages and dendritic cells, as well as T-lymphocytes and B-lymphocytes, hence modulating both innate and adaptive immune responses[18
]. Prospective studies in the involvement of vitamin D in autoimmune disorders are conceptually limited but most cross-sectional studies have shown an inverse relationship between vitamin D levels and disease activity[19
]. A study performed on patients with rheumatoid arthritis concluded that the serum concentrations of vitamin D were inversely related to disease activity[19
]. An in vitro
study concluded that when vitamin D was added, many immunological abnormal characteristics of SLE were resolved, thus suggesting that vitamin D deficiency shifts the immunological response towards the loss of tolerance[20
]. Our study supports this possible link between normal vitamin D levels and the likelihood of a positive clinical and serological response. To the best of our knowledge, this is the first study that has investigated the association between vitamin D levels and spontaneous HBsAg seroclearance. Our findings suggest a link between normal vitamin D levels and the occurrence of spontaneous HBsAg seroclearance. Normal levels of vitamin D had a statistically significant association with spontaneous HBsAg seroclearance. The mechanisms that link vitamin D normal levels with spontaneous HBsAg seroclearance are unknown. HBV infection has also been associated with a variety of immunological manifestations, including non-organ-specific autoantibodies, membranous and membranous proliferative glomerulonephritis, mixed cryoglobulinemia and polyarteritis nodosa[6
]. Moreover, about one third of patients with polyarteritis nodosa are infected by HBV, the vasculitic lesions usually appear during primary HBV infection and are related to the presence of HBeAg. Anti-HBe seroconversion, either spontaneous or induced by antiviral treatment, may lead to a resolution of the vasculitic process[21
]. Another finding of our study was the importance of host and virological factors in spontaneous HBsAg seroclearance, similar to previously published data that indicate that older age, male gender, low viral load and HBeAg-seronegativity are associated with spontaneous HBsAg seroclearance[3
]. Our data supported these findings.
Our study contains some limitations. The link between vitamin D levels and HBsAg seroclearance was not shown to be causal but associative. The retrospective pattern of this study was unable to determine the cause effect of vitamin D levels to HBsAg seroclearance. More studies with a larger number of patients and with a prospective and controlled design are needed to confirm this hypothesis. Furthermore, this study did show that a very high percentage of spontaneous converters do have high levels of vitamin D but this percentage was not compared to a similar group of patients with hepatitis B without a spontaneous seroclearance. Other limitations are that the study had a small number of participants and did not exclude obese or overweight patients. These patients may have low levels of vitamin D. Patients with hepatic steatosis were also included in our study, although it is known that steatosis is an important predictor host factor for spontaneous HBsAg seroclearance.
In summary, we found a strong correlation between normal vitamin D levels and spontaneous HBsAg seroclearance. Vitamin D deficiency may be a significant risk factor for the lack of HBsAg seroconversion.