Anders Kilander

Role of bile acids and bile acid binding agents in patients with collagenous colitis

BACKGROUND In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. AIMS To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. METHODS Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the 75Se-homocholic acid taurine (75SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the 75SeHCAT test. RESULTS Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The 75SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with 75SeHCAT values 0.5–9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal 75SeHCAT tests. CONCLUSION Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.

Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial

The proportion of proton pump inhibitor users on long‐term therapy who can discontinue proton pump inhibitor (PPI) medication without developing symptoms is unknown.

Comparison of the 1-Gram 14C-D-Xylose Breath Test and the 50-Gram Hydrogen Glucose Breath Test for Diagnosis of Small Intestinal Bacterial Overgrowth

Background/Aims: Culture of small bowel aspirate is the most direct method and the gold standard for diagnosing small intestinal bacterial overgrowth. However, cultures are cumbersome and fluoroscopy is required for obtaining aspirate. Therefore, different breath tests such as the xylose breath test and the hydrogen breath test have been developed. There is no general agreement as to which test is to be preferred. In the only previous direct comparison between these two tests an advantage for the 1-gram-14C-D-xylose breath test was found. The aim of the study was to compare the 50-gram glucose hydrogen breath test and the 1-gram 14C-D-xylose breath test in relation to results of cultures of small bowel aspirate. Methods: Forty-six consecutive patients, mean age 57 (range 27–87) years, 12 men and 34 women, were included because of suspicion of small intestinal bacterial overgrowth. After small bowel aspiration, all patients received a solution of 1 g xylose, labelled with 50 µg 14C-D-xylose, and 50 g glucose dissolved in 250 ml water. The concentration of breath hydrogen was analyzed every 15 min for 2 h and 14CO2 was analyzed every 30 min for 4 h. A positive hydrogen breath test was defined as a rise in hydrogen concentration of 15 ppm. A positive xylose test was defined as an accumulated dose 4.5% after 4 h. Two definitions for a positive culture were used, either growth of 105 colonic-type bacteria/ml or growth of 105 bacteria/ml of any type. Results: Twenty-four patients had growth of 105 bacteria, of whom 10 had growth of 105 colonic-type bacteria in small bowel aspirate. Twenty-two patients had no significant growth. The hydrogen breath test and the xylose breath test had a sensitivity for growth of 105 bacteria of 58 and 42%, respectively. For growth of 105 colonic-type bacteria the sensitivity was 90% for the hydrogen breath test and 70% for the xylose breath test. The specificity was similar for the two tests. Conclusion: Although no significant difference between the two tests was found, there was a tendency in favor of the 50-gram glucose hydrogen breath test. The simplicity in combination with high sensitivity makes the hydrogen breath test suitable as a screening method to select patients for further investigation.

Serum antibodies to gliadin in coeliac disease after gluten withdrawal.

Serum gliadin antibodies of the IgA and IgG classes were determined by the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in 10 adult patients with villous atrophy of the small-intestinal mucosa. After introduction of a gluten-free diet a gradual decrease in serum gliadin antibody levels occurred, reaching statistical significance at 3 months of treatment for the IgA class (p less than 0.01) and at 6 months for the IgG class (p less than 0.05). A decrease of serum gliadin antibody levels after gluten withdrawal was related to an improvement of the intestinal mucosa and should thus be indicative of whether the patient is following the dietary recommendations. However, determination of gliadin antibody levels cannot replace small-intestinal biopsy, as there are a few patients in whom the antibody levels are not related to the morphology of the gut mucosa.

Is smoking a risk factor for collagenous colitis

Abstract Objective. The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohns disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking in microscopic colitis of the collagenous type (CC) are lacking. The aim of this investigation was to study smoking habits in CC and to observe whether smoking had any impact on the course of the disease. Materials and methods. 116 patients (92 women) with median age of 62 years (interquartile range 55–73) answered questionnaires covering demographic data, smoking habits and disease activity. As control group we used data from the general population in Sweden retrieved from Statistics Sweden, the central bureau for national socioeconomic information. Results. Of the 116 CC patients, 37% were smokers compared with 17% of controls (p < 0.001, odds ratio (OR) 2.95). In the age group 16–44 years, 75% of CC patients were smokers compared with 15% of controls (p < 0.001, OR 16.54). All CC smoker patients started smoking before the onset of disease. Furthermore, smokers developed the disease earlier than non-smokers – at 42 years of age (median) compared with 56 years in non-smokers (p < 0.003). Although the proportion with active disease did not differ between smokers and non-smokers, there was a trend indicating that more smokers received active treatment (42% vs. 17%, p = 0.078). Conclusions. Smoking is a risk factor for CC. Smokers develop their disease more than 10 years earlier than non-smokers.

Diagnostic yield of colonoscopy based on symptoms.

Objective. There are only a few data on the diagnostic yield of colonoscopy in different symptoms. The aim of this study was to assess the outcome of colonoscopy in patients with various gastrointestinal symptoms and to estimate the relation between the findings and the presenting symptoms. Material and methods. 1121 consecutive colonoscopies were registered during 1 year. Asymptomatic subjects and patients with known inflammatory bowel disease (IBD) were excluded, leaving 767 eligible for the study. Symptoms, findings and clinical judgement about their relation were recorded. Results. In patients with bleeding symptoms (n=405), serious colonic pathology – cancers and adenomas >1 cm, IBD and angiodysplasia – was found in 54 (13.3%), 83 (20.5%) and 20 (4.9%) patients, respectively; 162 (40%) patients had findings that could be related to the symptom. In 173 subjects with non-bloody diarrhoea, the diagnostic yield was 31.2%, i.e. mostly IBD and microscopic colitis. In 189 subjects with other gastrointestinal symptoms, the diagnostic yield was 13.2%. Serious colonic pathology was found in 8 of 362 (2.2%) subjects examined because of non-bleeding symptoms. Conclusion. The diagnostic yield of colonoscopy is high in patients with bleeding symptoms or diarrhoea, while the prevalence of significant findings is equal to a screening population in patients with other symptoms.

Granulocyte, monocyte/macrophage apheresis for inflammatory bowel disease: The first 100 patients treated in Scandinavia

Objective. Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohns disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated. Material and methods. Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5–30). Results. The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohns disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohns disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7). Conclusions. Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low.

Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption

Introduction Bile acid malabsorption as reflected by an abnormal 75Se-labelled homocholic acid-taurine (75SeHCAT) test is associated with diarrhoea, but the mechanisms and cause-and-effect relations are unclear. Objectives Primarily, to determine whether there is a reduced active bile acid uptake in the terminal ileum in patients with bile acid malabsorption. Secondarily, to study the linkage between bile acid malabsorption and hepatic bile acid synthesis. Methods Ileal biopsies were taken from patients with diarrhoea and from controls with normal bowel habits. Maximal active bile acid uptake was assessed in ileal biopsies using a previously validated technique based on uptake of 14C-labelled taurocholate. To monitor the hepatic synthesis, 7&agr;-hydroxy-4-cholesten-3-one, a bile acid precursor, was assayed in blood. The 75SeHCAT-retention test was used to diagnose bile acid malabsorption. Results The taurocholate uptake in specimens from diarrhoea patients was higher compared with the controls [median, 7.7 (n=53) vs 6.1 μmol/g per min (n=17)] (P<0.01) but no difference was seen between those with bile acid malabsorption (n=18) versus diarrhoea with a normal 75SeHCAT test (n=23). The 75SeHCAT values and 7&agr;-hydroxy-4-cholesten-3-one were inversely correlated. Conclusions The data do not support bile acid malabsorption being due to a reduced active bile acid uptake capacity in the terminal ileum.

Severe Jaundice in Sweden in the New Millennium: Causes, Investigations, Treatment and Prognosis

Background: The aims of the study were to assess the causes of jaundice in Gothenburg, Sweden, to study the types of investigations applied in cholestatic and hepatocellular types of jaundice and treatment and to evaluate the prognosis of these patients up to a year from the diagnosis. Methods: Over a 3-month period, all adult patients with bilirubin >100 r 7 mol/l were identified by the clinical chemistry laboratory serving all three hospitals in Gothenburg. Relevant clinical information was obtained from medical records. Followup was performed 9-12 months later. Results: A total of 173 patients were identified; 40% were under surgical care while 38% were in the care of internists. The most common cause of jaundice was malignancy in 58 patients, liver metastases in 20, cholangiocarcinoma in 16, pancreatic cancer in 13, cancer of papilla Vateri in 2 and primary liver cancer in 7. Alcoholic liver disease was the second most common cause, found in 29 patients, followed by bile duct stones (28 patients). Only 3% had viral hepatitis. Ultrasound and/or CT were performed in 95% of those with cholestasis and ultrasound had been performed in 75% of those with hepatocellular type and CT in almost 50%. Thirty-two patients were operated on, 27 patients were treated endoscopically and 17 patients required liver transplantation. Total mortality was 51% and in malignancy 82%. Conclusion: Malignancy and alcoholic liver disease are the most common causes of severe jaundice, whereas viral hepatitis is a rare cause. Many patients are under surgical care, probably due to historical reasons as surgery is rarely indicated.

Budesonide treatment is associated with increased bile acid absorption in collagenous colitis

Background  Bile acid malabsorption is frequent in collagenous colitis and harmful bile acids may play a pathophysiological role. Glucocorticoids increase ileal bile acid transport. Budesonide have its main effect in the terminal ileum.