Our study showed that vitamin D insufficiency [serum level of 25 (OH) vitamin D<30 ng/ml] was prevalent in 50% of the patients in the patient group. A significantly lower serum level of 25-hydroxy vitamin D was found in the patient group compared with the controls, whereas a significant inverse association was found between 25-hydroxyl vitamin D and stages of liver fibrosis. Moreover, those HCV patients with insufficient vitamin D levels were more at risk of developing severe fibrosis compared with those with adequate vitamin D levels.
The prevalence of vitamin D deficiency in the general population affects all age groups and ranges from 20 to 100% in terms of serum 25(OH) vitamin D concentrations less than 20 ng/ml 27. Arteh et al. 10 found vitamin D less than 32 ng/ml (i.e. 80 nmol/l) in 92% of 118 patients with CLD (HCV with cirrhosis, n=43; HCV without cirrhosis, n=57; non-HCV-related cirrhosis, n=18). Similarly, Fisher and Fisher 28 found inadequate 25(OH) vitamin D levels (<32 ng/ml) in 91% of patients with noncholestatic CLD, and the majority (68%) were vitamin D deficient (<20 ng/ml). Both studies showed a higher prevalence than in our study and that may be because of the differences in the age groups of the patients; our study included children whereas their study included adults.
Previously, vitamin D deficiency was considered to be found predominantly in cholestatic liver disorders because of impaired intestinal absorption commonly observed in such patients 29. Accumulating evidence, however, supports its widespread presence in CLD, irrespective of etiology. Putz-Bankuti et al. 30 reported an inverse association (r=−0.21, P=0.08) between serum 25(OH) vitamin D levels and the severity of liver disease in a cohort of 75 patients with cirrhosis. This study is in agreement with the current study, which showed a significant inverse association between serum 25(OH) vitamin D and stages of liver fibrosis (r=−0.381, P=0.003). A low vitamin D status is also evident in patients with other CLDs, particularly in the presence of cirrhosis. For instance, 50 patients with nonalcoholic steatohepatitis and 10 patients with simple steatosis were observed by Targher et al. 31 to have lower 25(OH) vitamin D concentrations compared with 60 controls matched for age, sex, and BMI. Overall, this Italian-based study found lower vitamin D status in patients with nonalcoholic fatty liver disease (NAFLD), which was also associated with histopathological NAFLD features. These findings were corroborated recently by the same group 32 in a larger study (n=262), in which low 25(OH) vitamin D levels were associated independently with NAFLD (n=162) and serum 25(OH) vitamin D was significantly (P<0.001) lower than that in patients who were free from NAFLD and other liver diseases (15±9 vs. 21±9 ng/ml). It is noteworthy that when compared with the lowest quartile, patients in the highest quartile of serum 25(OH) vitamin D levels showed an OR of 4.7 (95% CI, 2.2–10.3, P<0.001) for NAFLD.
The current study has several important limitations. First, it is a cross sectional case–control study capturing the relationship between vitamin D and liver disease at only a single point in time and therefore could not assess changes in vitamin D temporally with the progression of liver disease. Second, the number of patients was limited to only 60. In addition, we evaluated only patients with hepatitis C-induced liver disease and did not study the role of vitamin D in other forms of CLD. Although clear evidence of an association between vitamin D and liver disease exists in our study, it remains unknown whether vitamin D deficiency confers an increased risk of liver disease or whether liver disease causes vitamin D deficiency.
Vitamin D deficiency is highly prevalent in young patients with chronic HCV infection and is directly associated with disease severity. Chronic HCV patients with insufficient vitamin D levels have significantly increased ORs for severe fibrosis compared with patients with adequate vitamin D levels. Vitamin D deficiency and CLD may represent cause or effect as multiple endogenous and environmental factors affect vitamin D metabolism. Benefits of normalized vitamin D status are emerging in patients with CLD. We recommend the inclusion of vitamin D assessment and replacement in the management of chronic HCV patients. We also recommend the use of serum 25-hydroxy vitamin D as a reliable noninvasive biomarker of liver fibrosis in those patients. However, further studies in children are needed to evaluate the role of vitamin D and its supplementation in patients with chronic HCV infection.
There are no conflicts of interest.
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