Vitamin D deficiency has higher prevalence in
patients with chronic liver disease than in general population with range
between 64% and 92%
(12). This high prevalence in those patients occurs regardless of liver disease etiology (13). In the current study 27 (60%) of cirrhotic patients with infection had
insufficient vitamin D levels, and 13 (28.9%) had vitamin D deficiency (p
value <0.001).While its level was insufficient only in 12 patients (28.6%) in those without infection. Low vitamin D level in patients with chronic liver disease is caused by several mechanisms such as malnutrition, low sunlight exposure, low intestinal absorption of vitamin D caused by intestinal oedema complicating portal hypertension, or cholestasis-induced bile salt disruption. In addition low levels of vitamin D binding proteins (DBP) and albumin, which transfer vitamin D to the liver and kidney for subsequent activation could be a contributing factor. Moreover, hepatic hydroxylation of vitamin D is impaired leading to low production of the active vitamin, whereas the catabolism of the vitamin is increased (14). Lymphocytes T and B cells, macrophages and dendritic cells express CYP27B1 enzymes which metabolize 25(OH)vitamin D to calcitriol. Calcitriol binds to its receptor in the nucleus of innate immune cells, particularly in antigen-presenting cells, acting as a transcription factor for the antimicrobial peptides cathelicidin and beta defensins. This process leads to enhanced phagocytic, chemotactic, and antimicrobial activity (15,16). Thus vitamin D has a direct effect on the immune system which could contribute to immune regulation with a protective role against infections. It has been also reported that, vitamin D deficiency increases as the liver disease progresses. In the present study, the mean vitamin D level was significantly lower among infected patients with Child class C when compared with Child class B (p value = 0.037). This was in agreement with the study of Fisher et al, who found more vitamin D deficiency in cirrhotic patients with Child-Pugh class C than in patients in with Child-Pugh class A (17). The present study showed that spontaneous bacterial peritonitis (SBP) was the commonest cause of infection among cirrhotic Group with infection (62.2%) followed by respiratory tract infection, skin & soft tissue infection, and urinary tract infection. Low vitamin D level could be a risk factor for spontaneous bacterial peritonitis which requires supplementation in this group of patients and could be used as a prophylaxis also. Trepo et al. (2013) reported a tendency to increase incidence of spontaneous bacterial peritonitis (15.7 vs. 6.9%, P=0.056) in cirrhotic patients with (n=142) and without (n=112) a severe deficit in 25-OH vitamin D (18). The antimicrobial peptide cathelicidin (LL-37) which is involved in the protection of the epithelial barrier against infection is secreted in the bloodstream by immune cells and its activation is mediated by vitamin D intracellular signaling via vitamin D receptor (VDR) (19). Zhang et al. evaluated the role of the vitamin D/LL-37 pathway in the pathogenesis and treatment of spontaneous bacterial peritonitis (SBP) and concluded that supplementation with vitamin D could enhance peritoneal macrophage VDR and LL-37 expressions to fight against SBP in patients with decompensated cirrhosis (20). However, in a recent study urinary tract infections were the most common infections, followed by lower respiratory tract infections, spontaneous bacterial peritonitis and sepsis and concluded that vitamin D deficiency was one of the risk factors for infections in patients affected by HCV-related liver cirrhosis (21). On multivariate regression analysis of risk factors for infection, vitamin D deficiency was a risk factor for infection in cirrhotic patients in the current study (p value = 0.000). In the present study, the optimum vitamin D cut-off level in cirrhotic patient with infection was 21 ng/ ml with a sensitivity and specificity of 84.44% and 88.10% respectively. However, Anty et al. (2014) studied 88 subjects and found that patients with cirrhosis and severe vitamin D deficiency (<10 ng/mL) had more bacterial infections versus patients with vitamin D levels ?10 ng/mL (54% versus 29%, p= 0.02) (9). According to the Institute of Medicine (IOM) of the National Academies in the United States, vitamin D level of 20 ng/mL is adequate (22). However, the Endocrine Society (Maryland, USA) recommends levels of at least 30 ng/mL (i.e. 75 nmol/L) as adequate and levels between 40 and 60 ng/mL (i.e. 100-150 nmol/L) as optimal (23). There is still no definition regarding the optimal vitamin D levels for patients with chronic liver diseases (24). The efficacy of vitamin D supplementation in liver cirrhosis to decrease the risk of infection with determination of the optimal dose, route of administration and duration needs to be further evaluated and validated in large prospective studies and randomized trials. The present study has some limitations as the small sample size and lack of cultures for the causative organisms of infection which may have a relation with the level of vitamin D in these patients. In conclusion, vitamin D deficiency is a risk factor for infection in patients with liver cirrhosis. Vitamin D level correlates with severity of liver disease. Supplementation of vitamin D in these patients could have a protective role against risk of infection and could improve their prognosis.
Vitamin D deficiency has higher prevalence in