No abstract

Fecal calprotectin and lactoferrin determination may be useful in predicting impending clinical relapse-especially during the following 3 months-in both CD and UC patients.

The mean prevalence of azathioprine (AZA) or 6-mercaptopurine (MP)-induced liver injury in patients with inflammatory bowel disease was approximately 3%, and the mean annual drug-induced liver disorder rate was only 1.4%. However, this low figure calculated from retrospective studies contrasts with a much higher incidence (>10%) reported by a prospective study. Thiopurine-induced hepatotoxicity can be grouped into three syndromes: hypersensitivity, idiosyncratic cholestatic reaction, and endothelial cell injury (with resultant raised portal pressures, veno-occlusive disease, or peliosis hepatis). A small percentage of patients present with a slight elevation of liver tests (LTs) that do not have clinical implications and LTs return to normal values during the follow-up, indicating that it is not always necessary to adjust the dose of the immunomodulator. However, when abnormalities in LTs are more marked, the dose of AZA/MP may be reduced 50%, with posterior clinical and analytical controls. With this strategy, LTs frequently normalize spontaneously, and the initial AZA/MP dose may be cautiously prescribed again. Thiopurines may induce an unusual severe cholestatic jaundice that may not regress but even progress despite thiopurine withdrawal. Therefore, these drugs should be completely withdrawn, and not only tapered, in those patients presenting clinically significant jaundice. Despite a lack of evidence that monitoring of LTs is necessary in patients receiving AZA/MP, routinely performed laboratory controls including LTs seem recommendable. However, the optimal monitoring schedule remains to be established. As long-term hepatotoxicity seems to be an unpredictable and potentially severe adverse drug reaction of 6-thioguanine, this drug should not be administered outside a clinical trial setting. (Am J Gastroenterol 2007;102:1518-527).

Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). There have been several case reports, including 46 patients, of renal disease associated with 5-ASA treatment in patients with IBD. 5-ASA treatment-related nephrotoxicity is reported most often within the first 12 months, but also delayed presentation after several years has been shown. The absence of a clear relationship between 5-ASA dose and the risk of nephrotoxicity suggests that this complication is idiosyncratic rather than dose-related. Most of the patients with renal disease associated with 5-ASA treatment suffered interstitial nephritis, with symptoms and signs being nonspecific, which may delay detection for many months. The nephrotoxicity potential of mesalazine and sulfasalazine seems to be similar. The risk with different oral preparations of 5-ASA is probably too small to influence the choice of agent. Mesalazine should be withdrawn when renal impairment manifests in a patient with IBD; if this does not result in a fall in serum creatinine, then renal biopsy should be considered. A trial of high-dose steroid may be recommended in patients whose renal function does not respond to drug withdrawal. The optimal monitoring schedule of serum creatinine in patients receiving 5-ASA treatment remains to be established, as there is no evidence to date that either the test, or the frequency of testing, improves patient outcomes.

We encourage you to use Adobe's editing tools (please see the next page for instructions). If this is not possible, please (i) reply to this message and send a list of corrections (in an email or attachment (Word doc or a scan)) listing each change in the following manner: line number, current text, change to be made, or (ii) print out the proof, mark your corrections clearly in black ink, and fax it to 144(0)1865355717. Please do not send corrections as track changed Word documents.Changes should be corrections of typographical errors only. Changes that contradict journal style will not be made.These proofs are for checking purposes only. They should not be considered as final publication format. The proof must not be used for any other purpose. In particular we request that you: do not post them on your personal/institutional web site, and do not print and distribute multiple copies (please use the attached offprint order form). Neither excerpts nor the article in its entirety should be included in other publications written or edited by yourself until the final version has been published and the full citation details are available. You will be sent these when the article is published.