Alcoholic liver disease and vitamin D deficiency

1. The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P < 0.005 and P < 0.05, respectively) but no difference was seen in controls. 2. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. 3. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P < 0.02) but concentrations in the two groups were not different. 4. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1, P < 0.05). 5. Urinary excretion over days 0–3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3(P < 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). 6. The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. 7. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.

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A21 VITAMIN D DEFICIENCY AND ITS ASSOCIATION WITH CLINICAL OUTCOMES IN PRIMARY SCLEROSING CHOLANGITIS

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.020 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 24-26

Author(s):

S Wang ◽

A J Montano-Loza ◽

M Ebadi

Keyword(s):

Vitamin D ◽

Liver Transplantation ◽

Liver Disease ◽

Vitamin D Deficiency ◽

Sclerosing Cholangitis ◽

Adverse Outcomes ◽

Vitamin D Status ◽

Event Free Survival ◽

Free Survival ◽

University Of Alberta

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

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