Urinary leukotriene E4 excretion: a biomarker of inflammatory bowel disease activity.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders collectively referred to as inflammatory bowel diseases (IBD). Cysteinyl leukotrienes are proinflammatory 5-lipoxygenase-derived products that play a major role in the immune and inflammatory response. Consequently, they may be involved in the pathogenesis of IBD. The aim of this study was therefore to evaluate 1) the urinary excretion of leukotriene E(4) (LTE(4)) in IBD patients and healthy volunteers, and 2) the association between LTE(4) production and the activity (relapse/remission) of the disease. METHODS: IBD patients and healthy volunteers were prospectively recruited. CD and UC activity was determined on inclusion with the Crohn's Disease Activity Index and Clinical Activity Index, respectively. Urine was collected and the urinary excretion of LTE(4) was measured by liquid chromatography tandem mass spectrometry. RESULTS: 32 CD patients, 28 UC patients, and 30 controls were enrolled in the study. LTE(4) urinary excretion was significantly increased (P < 0.01) in CD [52.0 pg/mg creatinine (10th-90th percentiles: 26.2-148.0)] and UC [64.1 pg/mg creatinine (10th-90th percentiles: 26.7-178.0)] patients compared to controls [32.3 pg/mg creatinine (10th-90th percentiles: 21.8-58.8)]. LTE(4) levels were higher (P < 0.001) in patients with active disease than in patients in remission, for whom the levels of LTE(4) were similar to the levels of controls. CONCLUSIONS: Cysteinyl leukotriene pathway activation could contribute to the inflammation associated with IBD. The quantification of urinary LTE(4) could be an interesting noninvasive biomarker for the assessment of IBD activity.

[Steatosis, chronic hepatitis virus C infection and homocysteine]. / Rôle de l'homocystéine au cours de la stéatose hépatique et de l'hépatite chronique C.

Homocysteine, a sulfuric amino acid involved in methionine metabolism, belongs to the group of intracellular thiols. Hyperhomocysteinemia is frequent in the Caucasian population (more than 15%) and its role in vascular pathology has been clearly established. In hepatology, experimental data in transgenic mice deficient in homocysteine metabolism enzymes have shown the presence of severe liver steatosis with occasional steatohepatitis. In human beings, many studies have found a correlation between homocysteine and steatosis or even NASH. Some authors have suggested a discriminating threshold to differentiate simple steatosis from NASH. In chronic hepatitis C, preliminary data have shown that hyperhomocysteinemia is an independent risk factor for steatosis or even fibrosis. The physiopathological mechanism has now begun to be better understood. On one hand, there is a strong correlation between homocysteine and insulin resistance whatever its etiology. On the other hand, homocysteine has a direct effect on the liver, resulting in over expression of SREBP-1 and favouring steatosis. It stimulates proinflammatory cytokine secretion such as NF kappa B increasing the risk of NASH. Finally, homocysteine could increase the risk of fibrosis by stimulating TIMP 1. Moreover hepatitis C virus induces hypomethylation of STAT 1 and could decrease the antiviral activity of interferon. Results from in vitro studies have shown that the normalisation of STAT 1 methylation by bringing betaine and S Adenosyl Methionine (which belongs to homocysteine cycle) restores the antiviral activity of interferon. These data should be confirmed to evaluate the importance of homocysteine dosage in the diagnosis of NASH. Finally, treatment of hyperhomocysteinemia could have favourable consequences in steatopathies and HCV infection.

[Cytomegalovirus and cryptogenic inflammatory bowel disease]. / Le cytomégalovirus et les maladies inflammatoires cryptogénétiques de l'intestin.

CMV infection has been reported in association with some flares of IBD. Its prevalence varies with the method of diagnosis and the severity of IBD. Although the link between CMV and IBD is not clear, the immunomodulator properties of the virus may play a role in the evolution of IBD. Besides the necessity of immunosuppression to treat IBD, inflammation per se can maintain in situ viral replication. Antiviral treatment can be useful in some situations. New molecular methods will permit earlier and more sensitive diagnosis of CMV infection and a better evaluation of treatment efficacy.