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 29 June 2016

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News

Non-invasive marker of small intestinal health in celiac disease

This month's issue of the American Journal of Gastroenterology investigates CYP3A4-catalyzed simvastatin metabolism as a non-invasive marker of small intestinal health in celiac disease.

News image

Histological examination of duodenal biopsies is the gold standard for assessing intestinal damage in celiac disease.

A noninvasive marker of disease status is necessary, because obtaining duodenal biopsies is invasive and not suitable for routine monitoring of celiac disease patients.

As the small intestine is a major site of cytochrome P450 3A4 activity, and also the location of the celiac lesion, Dr Belén Morón and colleagues investigated whether patients with active celiac disease display abnormal pharmacokinetics of an orally administered CYP3A4 substrate, simvastatin, which could potentially be used for noninvasive assessment of their small intestinal health.

Preclinical experiments were performed in CYP3A4-humanized mice to examine the feasibility of the test.

Subsequently, a clinical trial was undertaken with 11 healthy volunteers, 18 newly diagnosed patients with celiac disease, and 25 celiac patients who had followed a gluten-free diet for more than 1 year.

The team measured the maximum concentration of orally administered simvastatin plus its major non-CYP3A4-derived metabolite simvastatin acid, and compared with clinical, histological, and serological parameters.

The calculated pooled gastric cancer incidence-rate was about 0.3% per person-years
American Journal of Gastroenterology

In CYP3A4-humanized mice, the researchers observed a marked decrease in simvastatin metabolism was observed in response to enteropathy.

The doctors found that in the clinical setting, untreated celiac patients displayed a significantly higher SVeq Cmax compared with treated patients or healthy subjects.

SVeq Cmax correctly predicted the diagnosis in 16/18 untreated celiac patients, and also the recovery status of all follow-up patients that exhibited normal or near-normal biopsies.

All patients with abnormal SVeq Cmax showed a reduction in the value after 1 year of following a gluten-free diet.

The docters comments:

"Simvastatineq Cmax is a promising noninvasive marker for assessment of small intestinal health."

"Further studies are warranted to establish its clinical utility for assessing gut status of patients with celiac disease."

Am J of Gastroenterol 2013: 108: 1344-1351
23 August 2013

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