Plasma Citrulline Concentration in Tropical Enteropathy

Plasma Citrulline as Quantitative Biomarker of HIV Associate Villous Atrophy in a Tropical Enteropathy Population

Citrulline is an amino acid produced in the intestine and in the liver, but the liver does not contribute significantly to circulating citrulline concentrations. The intestine is thus the only organ that normally releases significant amounts of citrulline into the blood stream. The investigators have designed a study looking at the value of measuring plasma citrulline concentration in patients with tropical enteropathy of mixed HIV status. The focus will be on the ability of the intestine to sustain the individual concerned from a nutritional standpoint. The investigators hypothesise that plasma citrulline concentration is a marker of small bowel absorptive integrity and an appropriate surrogate for HIV related enteropathy.

Preliminary studies reported that plasma citrulline concentrations may be a reliable biochemical marker for intestinal dysfunction and absorptive enterocyte mass. The relationship between citrulline concentration and intestinal function has been supported in other studies including those examining rejection in small bowel allografts. Concentrations of citrulline are dramatically reduced in cases of mucosal damage (e.g. moderate graft rejection or viral enteritis)and strongly correlate (inversely) with severity on biopsy. Plasma citrulline concentration is lower also in patients with villous atrophy (24±13µmol/L)than in healthy subjects (40±10µmol/L)and patients with anorexia nervosa (39±9µmol/L).Experimental studies have been carried out also in assessing the value of citrulline as a marker for severity of small bowel epithelial damage from radiation and viral infections. The plasma citrulline was shown to be a simple, non invasive and sensitive essay to monitor and quantify radiation and/or chemotherapy induced small bowel damage in mice and humans. Otherwise, the literature on citrulline as a potential marker of intestinal and nutritional integrity is young and consistent data for specific conditions as for HIV enteropathy are missing.We hypothesise that plasma citrulline concentration is a marker of small bowel absorptive integrity and an appropriate surrogate for HIV related enteropathy.

Inclusion Criteria: histologically ascertained Tropical enteropathy Mixed HIV status Body mass index within normal range Exclusion Criteria: Patients with surgical resection of stomach, duodenum or pancreas; or (UGI) bypass. Patients with other important disease, which may interfere with the study (especially diabetes and renal impairment). Alcoholism, drug abuse or any other circumstances, which may compromise the patient's ability to comply with the study requirements. Pregnancy Patients experiencing diarrhoea within one month since enrolment date Use of glucagon-like peptide 2 (GLP2), growth hormone (GH) or glutamine or triglycerides Coeliac Disease, Crohn's disease or infectious intestinal disease Patients on steroids or FANS Oral feeding>1.0-fold the estimated basal metabolic rate as assessed using Harris and Benedict equation