Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease

Background & Aims: Plasma citrulline, a nonprotein amino acid produced by enterocytes, was suggested as a marker of remnant enterocyte mass in patients with short bowel. Our objective was to evaluate citrulline as a marker of severity and extent of villous atrophy in patients without intestinal resection. Methods: Forty-two patients with celiac disease and 10 patients with non-celiac villous atrophy disease were studied by plasma postabsorptive citrulline and biological dosages, biopsies of proximal (duodenojejunal) small bowel and distal ileum (n = 25), or measurement of vitamin B-12 absorption (n = 4). Nine patients were reevaluated after following a gluten-free diet for 1 year. Controls were 51 healthy subjects and 10 severely malnourished patients with anorexia nervosa with no intestinal mucosal abnormalities. Results: Plasma citrulline concentration was lower (P < 0.001) in patients with villous atrophy (24 13 μmol/L) than in healthy subjects (40 +/- 10 μmol/L) and patients with anorexia nervosa (39 +/- 9 μmol/L). Three thresholds were individualized: <10 mumol/L for patients with diffuse total villous atrophy (n = :10), 10-20 mumol/L for patients with proximal-only total villous atrophy (n = 12), and 20-30 mumol/L for patients with partial villous atrophy (n = 1.0). Plasma citrulline concentration was correlated to the severity and extent of villous atrophy (r = 0.81; P < 0.001) and to albuminemia (r = 0.47; P < 0.01). Receiver operating characteristic curves indicated that plasma citrulline concentration was the best biological variable to predict villous atrophy. Following a 1-year gluten-free diet, plasma citrulline concentration increased in histologically responsive (n = 6) but not in unresponsive (n = 3) patients. Conclusions: In patient villous atrophy diseases, plasma citrulline concentration may prove to be a simple and reliable marker of reduced enterocyte mass.