High‐dose cholecalciferol in critically ill patients with liver cirrhosis
Notice bibliographique
Résumé
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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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,010 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,006 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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