Vitamin D supplementation for chronic liver diseases in adults.

Systematic review and meta-analysis of randomized trials in adults with chronic liver diseases, including chronic hepatitis C, cirrhosis, nonalcoholic fatty liver disease, and liver transplant recipients. Studies were conducted across multiple countries in inpatient and outpatient settings.

Oral vitamin D supplementation was tested in multiple formulations, mainly vitamin D3, but also calcitriol and vitamin D2. Doses ranged from 1,000 IU/day to 50,000 IU every 14 days or 2 to 3 times weekly, with treatment durations from 4 weeks to 1 year, versus placebo or usual care; some trials used it alongside standard liver-disease therapy.

Vitamin D supplementation increased vitamin D status but did not show clear benefit on clinically important liver outcomes or survival. All-cause mortality was uncertain (Peto OR 0.70, 95% CI 0.09 to 5.38; 15 trials; 1034 participants), and liver-related mortality remained very imprecise (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants). Vitamin D status improved (MD 17.24 ng/mL, 95% CI 12.5 to 22.0; 6 trials; 424 participants), but there was no consistent evidence of improvement in liver-related morbidity, health-related quality of life, or adverse events. The overall evidence was very low certainty.

Only a small number of trials and participants were available, with high risk of bias, substantial between-trial heterogeneity, and wide confidence intervals. Trial Sequential Analysis showed the mortality information size was far below the required 6396 participants, so the evidence is insufficient for firm conclusions.