The prevalence of vitamin D deficiency is
higher in patients with chronic liver disease than in general population
ranging between 64%
and 92% . This high prevalence of vitamin D deficiency in those patients occurs regardless
of liver disease etiology . 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.
In
chronic liver diseases, low vitamin D level is caused by several mechanisms
such as malnutrition,
low sunlight exposure, low intestinal absorption of vitamin D due to intestinal
oedema which complicates portal hypertension, or cholestasis-induced bile salt
disruption and low levels of vitamin D binding proteins (DBP) and albumin, which
transfer vitamin D to the liver and kidney for subsequent activation. In addition, hepatic
hydroxylation of vitamin D is impaired leading to low production of the active vitamin,
whereas the catabolism of the vitamin is increased .
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 .
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 .
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 .
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) .
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 . 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.
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) .
According
to the Institute of Medicine (IOM) of the National Academies in the United
States, vitamin D level of 20 ng/mL is adequate . 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 . There is still no
definition regarding the optimal vitamin D levels for patients with chronic
liver diseases .
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.