High‐dose cholecalciferol in critically ill patients with liver cirrhosis
Bibliographic record
Abstract
Vitamin D deficiency is extremely common in chronic liver disease (CLD), particularly in patients with cirrhosis 1. The interplay between vitamin D and liver function is complex; besides decreased vitamin D binding protein and albumin production in CLD, altered hepatic cytochrome P450 (CYP450) activity may influence 25-hydroxylation of nutritional or sunlight-derived vitamin D precursors. Besides substrate availability, hepatorenal function and parathyroid hormone levels have been identified as important determining factors for the regulation of these enzymes 2. Vitamin D is important for CLD patients for several reasons. In a recent meta-analysis in chronic hepatitis C, a poor vitamin D status was associated with advanced hepatic fibrosis and a lower chance for sustained virologic response following antiviral treatment 3. Furthermore, vitamin D sufficiency (25(OH)D > 25–30 ng mL−1) is a recommended treatment goal for the American Gastroenterological Association, especially with regard to bone health 4. From 2010 to 2012, we performed the VITdAL-ICU trial, a randomized, controlled, double blind intervention trial in a mixed population of 475 adult medical/surgical critically ill patients with vitamin D deficiency (25(OH)D > 20 ng mL−1). The patients received a loading dose of 540 000 IU vitamin D3 orally or via nasogastric feeding tube followed by monthly maintenance doses of 90 000 IU. The study did not find a difference in the primary end-point length of hospital stay, but found a 44% relative risk reduction for hospital mortality in the predefined subgroup with severe vitamin D deficiency (25(OH)D of 12 ng mL−1; or lower; hazard ratio 0.56, 95% CI 0.35–0.90). Detailed methods and results have been described previously 5. In this post hoc analysis, we identified patients with liver cirrhosis (n = 23, 11 placebo, 12 vitamin D3) and compared them to the rest of the cohort. Cirrhotic subjects (78% men) were significantly younger (57 ± 11 vs. 65 ± 15 years, P = 0.01) and had a lower BMI (25 ± 5 vs. 27 ± 5 kg m−2, P = 0.07). Simplified Acute Physiology Score 2, kidney function and the need for respiratory or circulatory support were similar. Admission diagnoses for cirrhotic participants mainly represented neurologic pathology (i.e. intracranial bleeding) and liver transplantation. The median Model of End-Stage Liver Disease (MELD) score was 13 (interquartile range 15) points. Outcome parameters including 6-month mortality (39% for both groups and length of stay (LOS) in the hospital (median 20 days in noncirrhotic vs. 18 in cirrhotic patients, P = 0.99)) were not different between groups. Overall, cirrhotic patients achieved significantly lower 25(OH)D, but not 1,25(OH)2D serum levels on days 3 and 7 (Fig. 1). To date, no randomized controlled trial has evaluated the effect of high-dose vitamin D3 in critically ill cirrhotic patients. In comparison with critically ill patients without cirrhosis, we show a blunted 25(OH)D response following high-dose cholecalciferol on day 3 and 7 in cirrhotic patients. Evaluation of clinically relevant outcomes did not identify differences between groups, although this could relate to small sample size. Further studies are needed to identify the ideal method of vitamin D status assessment (including other biomarkers such as free vitamin D) and best practice for the prevention of vitamin D deficiency in CLD. K. Amrein, H. Dobnig has received speaker honoraria from Fresenius Kabi. K. Amrein, H. Dobnig, T. Pieber were investigators in the VITdAL-ICU study which was supported by Fresenius Kabi with an unrestricted research grant.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.010 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.006 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".