Serum 25-hydroxyvitamin D levels and mortality risk in patients with liver cirrhosis: a protocol for a systematic review and meta-analysis of observational studies

Background: Liver cirrhosis represents a substantial global burden in terms of morbidity and mortality. Observational studies have reported an increased risk of death with low circulating 25-hydroxyvitamin D concentrations in such patients. Because the occurrence of inadequate vitamin D status is very common in patients with liver cirrhosis, the aim of this study is to conduct a meta-analysis of observational studies in such patients to assess whether vitamin D deficiency increases their risk of mortality. Methods: We will search electronic databases (MEDLINE, Embase, Web of Science, CENTRAL and Google Scholar from time of inception until now), conference proceedings and conduct manual searches to identify studies eligible for inclusion. There will be no restrictions based on publication status or language, and the meta-analysis will be reported in accordance with the MOOSE guidelines. We will employ random-effects meta-analysis to assess the relationship between vitamin D deficiency and risk of mortality. Quality of studies will be judged using the Newcastle-Ottawa scale, and between-trial heterogeneity will be evaluated by means of subgroup and sensitivity analyses. Discussion: The study will assess the effects of serum 25-hydroxyvitamin D concentrations on mortality in patients with liver cirrhosis. The results will be published in a high-quality peer-reviewed journal. Systematic review registration: Prospero CRD42016052007