Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis

Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC.

Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded.

In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5 years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively.

Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.