Abstract
Background
Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease involving chronic inflammation and fibrosis of intra- and extra-hepatic ducts. Vitamin D is a secosteroid implicated in anti-inflammatory and anti-fibrotic pathways, and its deficiency has been associated with worse outcomes in chronic liver disease. Vitamin D status may also influence the course of PSC but studies evaluating this link are scarce.
Aims
To determine the association of vitamin D deficiency with the development of cirrhosis, mortality, and need for liver transplantation in patients with PSC.
Methods
Ninety-four patients with the diagnosis of PSC were evaluated and followed by the autoimmune liver disease clinic at the University of Alberta, Edmonton, Canada. Clinical data were recovered from medical charts. Vitamin D status was defined by the serum concentration of 25-hydroxyvitamin D3. Patients with levels <50 nmol/L (10 ng/ml) were defined as deficient. Univariate and multivariate analyses were constructed using the Cox proportional hazards regression models. Event-free survival was defined as time from vitamin D assessment to the time of liver transplant or death.
Results
Mean age at PSC diagnosis was 32±14 years, with 67% of patients being male. The mean vitamin D level was 69±33 nmol/L (range, 4–163 nmol/L) and 26 patients (28%) had vitamin D deficiency (<50 nmol/L). Among 85 patients without cirrhosis at diagnosis, 43 patients (51%) developed cirrhosis. By univariate Cox analysis, serum ALP, albumin, bilirubin and vitamin D deficiency were predictors of cirrhosis development. Vitamin D deficiency was independently associated with higher risk of developing cirrhosis (HR 2.11, 95% CI 1.002–4.44, P=0.049) after adjusting for other predictors. Median time to develop cirrhosis was shorter in patients with vitamin D deficiency (6.8 years; 95% CI, 1.7–11.8) compared to those without (10.8 years; 95% CI, 9.2 -12.4; P=0.007). Over a median follow-up period of 5.6 years, adverse outcomes (liver transplant or death) were observed in 34 patients (36%). Serum levels of albumin, ALP, bilirubin, INR, platelet count, ascites, variceal bleeding and vitamin D deficiency were associated with adverse outcomes in univariate analysis. Vitamin D deficiency was independently associated with higher risk of adverse endpoints (HR 2.87, 95% CI, 1.16–7.12, P=0.02) after adjusting for confounding factors. Event-free survival was shorter in the patients with vitamin D deficiency compared to those without deficiency (7.1 years; 95% CI, 2.4–11.9 vs. 11.4 years; 95% CI, 8.9–13.9, P=0.03, Figure 1).
Conclusions
Vitamin D deficiency was frequent in patients with PSC and was associated with higher risk of progression to cirrhosis, as well as decreased time to death and liver transplantation. The possibility of improving outcomes in PSC by vitamin D supplementation awaits further investigation.
Funding Agencies
Food and Health Innovation Initiative (Vitamin Fund), University of Alberta
Novel Composite Endpoint for Assessing Outcome in Liver Transplantation:
Arterial and Biliary Complication‐Free Survival