W. Petritsch

Effect of oral tacrolimus (FK 506) on steroid‐refractory moderate/severe ulcerative colitis

Background : Steroid refractory ulcerative colitis is most commonly treated with intravenous ciclosporin to avoid colectomy. In search for an alternative drug that can be administered orally we investigated oral tacrolimus (FK 506) for this indication.

Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia.

OBJECTIVE:Inflammatory bowel disease (IBD)-associated anemia responds to i.v. iron therapy. However, because of concurrent chronic inflammation, some patients do not respond adequately. Erythropoietin therapy has been shown to be effective in the latter cohort. Our goal was to find parameters that can predict the effectiveness of iron sucrose in IBD-associated anemia.METHODS:One hundred three patients with severe IBD-associated anemia (Hb ≤ 10.5 g/dl) were treated prospectively for 4 wk with iron sucrose (total iron dose = 1.2 g) in an open label, multicenter trial. Treatment response was defined as an increase in Hb of ≥2.0 g/dl. A logistic regression analysis was performed with treatment response as the dependent variable and the following independent variables: serum erythropoietin, mean corpuscular Hb, transferrin, ferritin, soluble transferrin receptor (sTfR), C-reactive protein, interleukin 6 (IL-6), and disease activity.RESULTS:Sixty-seven of 103 patients (65%) responded to iron sucrose. From the variables under investigation, erythropoietin, sTfR, transferrin, and IL-6 were significantly associated with treatment response. The R2 values showed that erythropoietin (8.0%), sTfR (11.4%), and transferrin (10.4%), but not IL-6 (1.3%), contribute a relevant amount of information to the model. An estimated 80% probability of treatment response was found at erythropoietin levels of >166 U/L, sTfR levels of >75 nmol/L, or transferrin levels of >3.83 g/L.CONCLUSIONS:Serum erythropoietin, sTfR, and transferrin concentrations have the potential to predict the response to iron sucrose therapy in IBD-associated anemia. These parameters may help to identify individuals who benefit the most from additional erythropoietin treatment.

Mycophenolate mofetil in patients with Crohn's disease.

Objective:Intolerance to azathioprine is a rare but important problem in treating chronically active Crohns disease. We performed this study to evaluate mycophenolate mofetil as an alternative immunosuppressive therapy for patients with Crohns disease who did not tolerate azathioprine.Methods:Four patients with highly active perianal Crohns disease and two patients with chronically active, steroid-dependent Crohns disease were included. All patients consumed 2 g/day of mycophenolate mofetil for a median of 8 months (range, 6–12 months). Disease activity was measured by the Perianal Crohns Disease Activity Index in patients with perianal disease and by the Crohns Disease Activity Index in patients with chronically active Crohns disease.Results:Azathioprine-induced side effects disappeared after the drug was discontinued. All patients improved during treatment with mycophenolate mofetil, as shown by a remarkable reduction in the respective clinical scores. Five patients showed no side effects during treatment with mycophenolate mofetil. After 4 months’ treatment one patient developed diarrhea that was probably not due to mycophenolate mofetil.Conclusions:Mycophenolate mofetil could be an alternative therapy to azathioprine in patients with Crohns disease.

Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: Results in three patients

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.

Acute Budd-Chiari syndrome with fulminant hepatic failure in a pregnant woman with factor V Leiden mutation

Budd-Chiari syndrome during pregnancy has rarely been reported. This report presents a case of acute hepatic failure in a 20-year-old pregnant woman attributable to Budd-Chiari syndrome with underlying resistance to activated protein C caused by factor V Leiden mutation. The patient delivered a healthy girl by cesarean section in the 31st week of pregnancy. Acute hepatic failure in the 6th week postpartum was successfully treated by emergency liver transplantation, and the patient and her child were doing well at 8-month follow-up. Liver transplantation was lifesaving; normal factor V production by the transplant corrected the underlying coagulopathy. In this patient, latent thrombophilia attributable to activated protein C resistance was apparently aggravated by the hypercoagulable state of pregnancy leading to acute Budd-Chiari syndrome. Activated protein C resistance should be sought as an etiologic factor in patients with Budd-Chiari syndrome.

Mycophenolate mofetil for Crohn's disease: short-term efficacy and long-term outcome

Aim : To assess the long‐term efficacy of the antimetabolite agent mycophenolate mofetil in patients with Crohns disease.

Diagnose und Behandlung von Eisenmangel und Anämie bei chronisch entzündlichen Darmerkrankungen. Konsensus der österreichischen Arbeitsgruppe für CED

Iron deficiency with and without anaemia is a common burden of patients with inflammatory bowel diseases (IBD) and has considerable impact on their quality of life and the ability to perform. The IBD working group of the Austrian Society of Gastroenterology and Hepatology developed five consensus statements on the following topics: (i) diagnosis of iron deficiency and (ii) anaemia, (iii) screening of iron deficiency, (iv) treatment of iron deficiency and (v) therapeutic goals. The clinical importance of intravenous iron replacement therapy in IBD with regard to effectiveness and compliance was discussed.

[Adalimumab for the treatment of Crohn's disease - consensus paper of the Working Group "chronic inflammatory bowel diseases" of the Austrian Society for Gastroenterology and Hepatology].

The advent of anti-TNF alpha antibodies has clearly improved the outcome of patients with Crohns disease. With adalimumab, the first fully human, monoclonal anti-TNF alpha antibody, which can be administered subcutaneously by means of a pen, became available in 2007. In Europe adalimumab is approved for the treatment of severe, active Crohns disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. Adalimumab is clinically efficacious both in patients with Crohns disease naïve to previous exposure to anti-TNF alpha antibodies and in those previously exposed with a rapid onset of action and a confirmed maintenance performance over 3 years. A reduction in the rate of hospitalisation and an improvement of health-related quality of life are associated with this treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to low immunogenicity, allergic reactions are rare. A careful screening of patients before and during treatment with adalimumab is of key importance. The presented therapy guidelines based on existing evidence are aimed to assist in the efficient and safe use of adalimumab in the treatment of Crohns disease.

Effects of acute respiratory acidosis on water and electrolyte transport in the human ileum

Abstract. Animal experiments have shown that acute respiratory acidosis stimulates water, Na and C1 absorption and HCO3 secretion in the ileum. The aim of this study was to investigate whether the human ileum also responds to changes in systemic acid‐base balance. Seven healthy volunteers (mean age 24, range 21–29 years) underwent segmental ilea perfusion using a multi‐lumen tube assembly with a proximal occluding balloon. A 30 cm test segment was perfused under steady state conditions with a plasma‐like electrolyte solution containing PEG as a non‐absorb‐able volume marker. After a control period, respiratory acidosis (blood pCO2 56.2 mmHg, pH 7.29 and [HCO3] 26.4 mmol 1‐1) was induced by CO2‐breathing over a period of 50 min. Acute respiratory acidosis stimulated net HCO3 secretion in patients secreting HCO3 and reduced absorption in patients exhibiting net HCO3 absorption. These changes were immediate and appeared to be at least partly reversible. Net water, Na, K and CI movement were not affected. The data suggest that HCO3 transport in the human ileum responds to acute respiratory acidosis.

[Adalimumab for the treatment of ulcerative colitis--a consensus report by the working group inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology].

TNF alpha antibodies have clearly improved the outcome of moderately to severely active ulcerative colitis. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which is administered subcutaneously. Since April 2012 adalimumab is approved for the treatment of moderately to severely active ulcerative colitis in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Adalimumab can induce and maintain clinical remission and mucosal healing compared to placebo in moderately to severely active ulcerative colitis, can reduce the rate of ulcerative colitis related hospitalisations and improve health-related quality of life. The response can be observed after two weeks of treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Studies on the treatment of ulcerative colitis with adalimumab did not reveal new safety aspects. The present consensus report by the Working Group Inflammatory Bowel Diseases of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence of adalimumab for the treatment of ulcerative colitis and is aimed to assist as code of its practice.