Plasma citrulline as a quantitative biomarker of HIV-associated villous atrophy in a tropical enteropathy population

Background & aims: Studies have shown that the circulating citrulline concentration is decreased in patients with proximal small bowel villous atrophy from coeliac disease and more so in patients with extensive damage to the intestinal mucosa, but there have been few data on HIV enteritis and tropical enteropathy (TE). Our primary aim was to correlate serum citrulline with the degree of reduction of the enterocyte mass in HIV-infected patients with TE. Methods: Postabsorptive fasting serum citrulline was measured in 150 TE pts, 44 of whom had HIV infection, using reverse phase, high performance liquid chromatography. Absorptive capacity and permeability were measured after intrajejunal instillation of 4 sugars (5 g lactulose, 1 g l-rhamnose, 0.5 g d-xylose, 0.2 g 3-O methyl Dglucose) with assay by thin-layer chromatography. Morphometric analysis was carried out on jejunal biopsies. Results: In HIV positive patients, the median serum citrulline was significantly lower (median 19, interquartile range (IQR) 17-24 μmol/L) than in HIV negative patients (median 27, IQR 23-33 μmol/L; p < 0.001). There were statistically significant correlations (p < 0.005) between citrulline and: crypt depth; villous height/crypt depth ratio; Shenk-Klipstein score; and xylose absoption, only in the HIV positive. Conclusions: Serum citrulline concentration appears to be a quantitative biomarker of small bowel mass integrity in HIV positive enteropathy and desrves assessment as a surrogate for monitoring anti-retroviral therapy.