Fernando Fernández-Bañares

Incidence of collagenous and lymphocytic colitis: a 5-year population-based study.

Objective:The incidence of collagenous and lymphocytic colitis is not well known. We sought to assess the incidence of collagenous and lymphocytic colitis in a well-defined population during a 5-yr study period.Methods:From January 1, 1993, to December 31, 1997, all new patients diagnosed with collagenous or lymphocytic colitis living in the catchment area of the Hospital Mútua de Terrassa (Barcelona, Spain) were identified. Since 1993 all patients with chronic diarrhea were referred for a diagnostic colonoscopy. Multiple biopsy sampling of the entire colon was performed when appearance of the colonic mucosa was grossly normal.Results:Twenty-three cases of collagenous colitis and 37 of lymphocytic colitis were diagnosed. The female:male ratios were 4.75:1 and 2.7:1 for collagenous and lymphocytic colitis, respectively. The mean age at onset of symptoms was 53.4 ± 3.2 (range, 29–82) yr for collagenous colitis, and 64.3 ± 2.7 (range, 28–87) yr for lymphocytic colitis (p= 0.012). The mean annual incidence per 100,000 inhabitants based on the year of onset of symptoms was 1.1 (95% confidence interval [CI], 0.4–1.7) for collagenous colitis, and 3.1 (95% CI, 2.0–4.2) for lymphocytic colitis. A peak incidence was observed in older women in both diseases. A rate of microscopic colitis of 9.5 per 100 normal-looking colonoscopies performed in patients with chronic watery diarrhea was observed. Normal rectal biopsies were found in 43% and 8% of patients with collagenous and lymphocytic colitis, respectively.Conclusions:The incidence of lymphocytic colitis is three times higher than that of collagenous colitis. Microscopic colitis should be considered as a major possibility in the work-up of chronic diarrhea in older women.

How Effective Is Enteral Nutrition in Inducing Clinical Remission in Active Crohn's Disease? A Meta-Analysis of the Randomized Clinical Trials

BACKGROUND The purpose of the study was to evaluate, using meta-analysis techniques, whether enteral nutrition is effective in inducing clinical remission in active Crohns disease. METHODS Randomized trials either comparing enteral nutrition with steroids or comparing elemental (amino acid-based) with nonelemental diets were selected using MEDLINE (1984 to 1994), reference lists from published articles, reviews, and abstracts from major gastrointestinal meetings. Sixteen studies fulfilled the inclusion criteria (four published as abstracts). Crude rates for induction of remission were collected on an intention-to-treat basis by three independent observers. Each study was given a quality score, based on predetermined criteria. RESULTS The pooled odds ratio (OR) for all type of enteral diets compared with steroid therapy was 0.35 (95% CI, 0.23 to 0.53). This result was similar for the best studies (by quality score) combined, for trials using tube feeding combined, and when noncompliant patients were withdrawn. Further subgroup analyses were conducted on the basis of the type of diet administered. Peptide-based diets were significantly inferior to steroids (pooled OR, 0.32; CI, 0.20 to 0.52). There was a trend to lower remission rate after elemental diets than after steroids (pooled OR, 0.44; CI 0.17 to 1.12). On the other hand, pooled OR for whole protein-based diets compared with elemental diets was 1.28 (CI, 0.40 to 4.02). CONCLUSIONS Data available to date show that steroids are better than enteral nutrition to induce remission in active Crohns disease. These results are more evident when peptide-based diets are administered, but they are not conclusive when either elemental or whole protein-based diets are used.

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU).

Objective:Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate, the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis.Methods:An open label, parallel-group, multicenter, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 mg t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months.Results:Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p= 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Coxs proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p= 0.018) was observed after Plantago ovata seed administration.Conclusions:Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis.

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis

Drug consumption and the risk of microscopic colitis.

BACKGROUND:Microscopic colitis is a rare disease of unknown etiology. It has been described that some drugs could cause or worsen the disease; however, the scientific evidence is limited.AIM:To investigate the possible association of chronic drug consumption with microscopic colitis.METHODS:This was a case–control study in which groups of cases were Group 1–39 patients with collagenous colitis; Group 2–39 patients with lymphocytic colitis; and Group 3–52 patients with chronic watery diarrhea of functional characteristics. 103 subjects formed the control group. At diagnosis, a drug consumption history of at least 2-wk duration was registered. An age- and sex-adjusted logistic regression analysis was used, and the odds ratio (OR, 95% CI) was calculated.RESULTS:Drug consumption was more frequent in lymphocytic colitis than in the control group (92.3% vs 76.3%, P < 0.05). The mean daily number of drugs by person was also higher in lymphocytic colitis (3.79 ± 0.44 vs 2.13 ± 0.22, P = 0.04). The following associations as compared with the control group were observed: Group 1—Consumption of NSAIDs (46.2% vs 23%, OR 2.9, 1.3–6.4), selective serotonin reuptake inhibitors (SSRIs) (18% vs 1%, OR 21, 2.5–177), specifically, sertraline (15.4% vs 0%, P < 0.0005); Group 2—SSRIs (28% vs 1%, OR 37.7, 4.7–304), beta-blockers (13 vs 3%, OR 4.79, 1.04–20), statins (13% vs 3%, OR 4.6, 1.04–20), biphosphonates (8% vs 0%, P = 0.022); Group 3—SSRIs (15% vs 1%, OR 16.2, 2–135), statins (11.5% vs 3%, OR 5.4, 1.2–24). As compared with the chronic diarrhea group, a significant association with the usage of sertraline in LC (P = 0.005) and a trend for NSAIDs in CC (P = 0.057) were found.CONCLUSIONSDrug consumption increases the risk of microscopic colitis. Some drugs might be trigger factors of colonic inflammation in predisposed hosts, and others might only worsen self-evolving microscopic colitis.

Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn's disease: results of a double blind randomised multicentre European trial

Background: Dietary fat has been suggested to determine the therapeutic effect of enteral diets in Crohns disease. Aim: To assess the efficacy of two whole protein based diets with different fat compositions (n6 polyunsaturated fatty acids v monounsaturated fatty acids) in inducing clinical remission in active Crohns disease compared with steroids. Methods: Sixty two patients with active Crohns disease were randomised to receive, for not more than 4 weeks: (a) a polymeric enteral diet containing 35 g of lipids per 1000 kcal, high in oleate (79%) and low in linoleate (6.5%) (PEN1), (b) an identical enteral diet except for the type of fat which was high in linoleate (45%) and low in oleate (28%) (PEN2), or (c) oral prednisone (1 mg/kg/day). Diets were double blindly administered. The steroid group received a conventional ward diet. Treatment failure was considered when remission was not achieved at week 4. Clinical activity and biological and nutritional parameters were monitored. Independent predictors of remission were identified by stepwise logistic regression analysis. Results: Overall remission rates (by intention to treat) were 20% (4/20) for PEN1, 52% (12/23) for PEN2, and 79% (15/19) for steroids (overall p=0.001; p<0.0005 steroids v PEN1, and p=0.056 PEN2 v PEN1). After excluding those patients who were non-compliant during the first week (per protocol analysis), remission rates were 27%, 63%, and 79%, respectively (p=0.008, steroids and PEN2 v PEN1). After adjusting for confounding variables, PEN1 remained significantly associated with a poor response. Conclusion: The type of dietary fat may be of importance for the primary therapeutic effect of enteral nutrition in active Crohns disease.

Collagenous and Lymphocytic Colitis: Evaluation of Clinical and Histological Features, Response to Treatment, and Long-Term Follow-Up

OBJECTIVE:Data on collagenous colitis (CC) and lymphocytic colitis (LC) have been based on retrospective studies of registries of patients from multiple hospitals. Such studies may induce a selection of patients with severe forms of the disease, and conclusions about the clinical spectrum of the disease and treatment efficacy are difficult to be drawn. The aim of this study was to compare the clinical features, response to treatment, and long-term follow-up of CC and LC in a large group of patients prospectively diagnosed in a single center.METHODS:A specific program was undertaken to prospectively diagnose all patients with microscopic colitis from those referred for a full colonoscopy because of recurrent or chronic diarrhea. Detailed clinical and histological features, response to treatment, and long-term follow-up were compared in patients with confirmed CC and LC.RESULTS:Thirty-seven patients with CC and 44 with LC were included. Patients with CC were significantly younger and had a significantly longer duration of diarrhea before diagnosis than those with LC. Otherwise, clinical presentation was similar. Drug-induced disease was suspected for ticlopidine, flutamide, gold salts, and bentazepam in LC. Complete resolution of diarrhea was achieved in all patients, spontaneously occurring in nearly 20% of them. Response to salicylates (mainly, mesalazine) was significantly better in LC than in CC (86% vs 42%, p = 0.005). Cholestyramine was highly effective in patients of both groups with concomitant bile acid malabsorption. Patients with CC required prednisone more often than those with LC (30% vs 4.5%, p = 0.005). Both prednisone and budesonide controlled ileal release were highly effective in patients with CC (82% and 89% efficacy). After cessation of diarrhea, 25% of patients with LC and 30% of those with CC relapsed after a mean follow-up of around 3 yr.CONCLUSIONS:CC and LC share a similar clinical picture and have a benign course with long-term cessation of diarrhea in more than 70% of patients. Mesalazine and budesonide seem to be good options as first-line treatment in LC and CC, respectively. Cholestyramine may be a good alternative in patients with concomitant bile acid malabsorption.

Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E2 synthesis

BACKGROUND Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated. AIMS To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E2 formation in male Sprague-Dawley rats with azoxymethane induced colon cancer. METHODS Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE2 were assessed at week 12, and tumour formation at week 19. RESULTS Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE2 formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets. CONCLUSIONS Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE2synthesis.

Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy

Background There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus (HCV). Aim To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD. Methods Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome. Results 162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV-infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with ≥2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg. Conclusion Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression.

Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea.

Bile acid malabsorption (BAM) has been described in patients with collagenous colitis. There are no similar studies in lymphocytic colitis. The possibility that BAM might not necessarily be part of the microscopic colitis process and that both entities could simply be concomitant has not been evaluated. Our aim was to assess the frequency and severity of BAM in patients with microscopic colitis as well as in patients with previously unexplained functional chronic diarrhea. Likewise, we wanted to investigate the effect of cholestyramine on the induction and maintenance of remission of these conditions. A [75Se]HCAT abdominal retention test was performed in 26 patients with collagenous colitis, 25 with lymphocytic colitis, and 32 with previously unexplained functional chronic diarrhea. Patients with microscopic colitis who had BAM as well as a subgroup of eight collagenous colitis patients without BAM received treatment with cholestyramine. All patients with previously unexplained chronic diarrhea who had BAM were treated with cholestyramine. Twenty-two (43.1%) patients with microscopic colitis and 24 (75%) patients with previously unexplained functional chronic diarrhea presented with BAM. The frequency of BAM was higher in lymphocytic colitis than in collagenous colitis (60% vs 27%; P = 0.025). Cholestyramine induced clinical remission in 19 of 22 patients with microscopic colitis and BAM, none of eight patients with collagenous colitis without BAM, and all patients with previously unexplained chronic diarrhea and BAM. In conclusion, BAM seems to be common in patients with microscopic colitis—mainly in lymphocytic colitis—and in those with previously unexplained functional chronic diarrhea, suggesting that idiopathic BAM and microscopic colitis are often concomitant conditions. In this setting, cholestyramine seems to be highly effective in stopping diarrhea.