Systematic Review and Meta-Analysis of the Use of Serum Leucine-Rich Alpha-2 Glycoprotein to Assess Crohn's Disease Activity

Background Although fecal calprotectin is the most widely used biomarker for assessing Crohn's disease activity, serum leucine-rich alpha-2 glycoprotein has recently attracted attention, especially in Japan. Here we performed a systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein to obtain evidence for its accuracy in assessing Crohn's disease activity. Methods On February 1, 2023, we performed searches of PubMed, Web of Science, and CENTRAL. The Prospero number is CRD42023396034. The primary outcomes were the sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein for assessing Crohn's disease activity. We used a bivariate generalized linear mixed model, assuming a binomial distribution at the test level and a bivariate normal distribution at the between-test level. Results We selected 9 studies involving 797 individuals in our systematic review. Regarding the primary outcomes, the synthesized sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein were 77.0% (95% confidence interval, 67.8% to 84.2%) and 81.1% (95% confidence interval, 72.6% to 87.4%), respectively. The area under the curve was 0.86, and the partial area under the curve was 0.78. Regarding between-study heterogeneity, both the I-2 value by Zhou and Dendukuri approach and the I-2 value by Holling sample size-adjusted approaches were 0%. Conclusions Our systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein demonstrated its accuracy in assessing Crohn's disease activity. Further studies are needed to demonstrate its clinical utility and clinical validity. Lay Summary We conducted the first systematic review and meta-analysis of the ability of serum leucine-rich alpha-2 glycoprotein (LRG) to assess Crohn's disease activity and found that the synthesized sensitivity and specificity were 77.0% and 81.1%, respectively.