Proton pump inhibitors reduce phlebotomy burden in patients with HFE-related hemochromatosis: A systematic review and meta-analysis

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) may reduce iron absorption and serum ferritin levels in patients with homeostatic iron regulator (HFE)-related hemochromatosis, reducing the need for frequent phlebotomies. Our study aimed to perform for the first time a meta-analysis of existing observational and randomized controlled studies to ascertain the overall effect of PPI use in patients with HFE-related hemochromatosis.

METHODS: Studies in adults reporting the outcomes of PPIs use in hereditary hemochromatosis patients from Medline, Embase, Scopus and Google Scholar databases from inception to December 2019 were systematically searched. The study outcomes were the serum ferritin levels and annual requirement for phlebotomies. Pooled mean difference, and 95% confidence intervals (CIs) were obtained by the random-effects model. Forrest plots were constructed to show the summary pooled estimate. Heterogeneity was assessed by using I2 measure of inconsistency.

RESULTS: Following an initial search of 202 manuscripts, a total of three studies involving 68 patients with hemochromatosis (34 in the PPIs group and 34 in the placebo or non-PPI group) were included. A minimum duration of PPI use was 1 year. Patients who received PPIs therapy did not have a statistically significant lower serum ferritin levels (mean difference: -18.86, 95% CI: -60.44, 22.72, P = 0.37, I2 = 88%) but required significantly less sessions of phlebotomies annually (mean difference: -3.10, 95% CI: -4.46, -3.08, P < 0.00001, I2 = 93%). No publication bias was found on Egger (P = 0.94) or Begg (P = 0.98) tests.

CONCLUSION: PPIs can be used as an adjuvant therapy to reduce phlebotomy burden in patients with HFE-related hemochromatosis.