Lars Karlsen

Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy

Background: This study examined whether fecal calprotectin can be used in daily practice as a marker to monitor patients with ulcerative colitis (UC) receiving infliximab maintenance therapy. Methods: This prospective multicenter study enrolled adult patients with UC in clinical remission under infliximab maintenance therapy. Fecal calprotectin levels were measured every 4 weeks. Sigmoidoscopies were performed at inclusion and at study end. Relapse was defined as a clinical need for change in treatment or an endoscopic Mayo subscore of ≥2 at week 52. Sustained deep remission was defined as a partial Mayo score <3 at all points and an endoscopic Mayo score 0 at week 52. Results: Full analysis was possible for 87 of 113 included patients with UC (77%). Of these patients, 30 (34.4%) were considered to be in sustained deep remission and 13 (14.9%) to have relapsed. Calprotectin levels in patients with sustained deep remission remained very low (median < 40 mg/kg at all time points). Patients who flared had significantly higher calprotectin levels (median > 300 mg/kg) already 3 months before the flare. Further receiver operator curve analysis suggested that a calprotectin level >300 mg/kg had a reasonable sensitivity (58.3%) and specificity (93.3%) to model flare. Two consecutive calprotectin measurements of >300 mg/kg with 1-month interval were identified as the best predictor of flare (61.5% sensitivity and 100% specificity). Conclusions: Fecal calprotectin can be used in daily practice to monitor patients with UC receiving infliximab maintenance therapy. Two consecutive measurements >300 mg/kg is more specific than a single measurement for predicting relapse.

Hepatitis C reinfection after sustained virological response

BACKGROUND & AIMS On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier. METHODS In 2004-2006 we conducted a multicentre treatment trial comprising HCV genotype 2 or 3 patients in Sweden, Norway and Denmark (NORTH-C). Six months of abstinence from injecting drug use (IDU) was required before treatment. All Norwegian patients who had obtained SVR (n=161) were eligible for participation in this long-term follow-up study assessing virological and behavioural characteristics. RESULTS Follow-up data were available in 138 of 161 (86%) individuals. Persistent reinfection was identified in 10 of 94 (11%) individuals with a history of IDU prior to treatment (incidence rate 1.7/100 person-years (PY); 95% CI 0.8-3.1) and in 10 of 37 (27%) individuals who had relapsed to IDU after treatment (incidence rate 4.9/100 PY; 95% CI 2.3-8.9). Although relapse to IDU perfectly predicted reinfection, no baseline factor was associated with reinfection. Relapse to IDU was associated with age <30 years (vs. ⩾40 years) at treatment (adjusted odds ratio [aOR] 7.03; 95% CI 1.78-27.8) and low education level (aOR 3.64; 95% CI 1.44-9.18). CONCLUSIONS Over time, persistent HCV reinfection was common among individuals who had relapsed to IDU after treatment. Reinfection should be systematically addressed and prevented when providing HCV care for PWID.

Fatigue in Newly Diagnosed Inflammatory Bowel Disease

BACKGROUND AND AIMS The present study investigated the prevalence and severity of fatigue in patients with newly diagnosed and untreated ulcerative colitis (UC) and Crohns disease (CD) and examined relevant disease variables that may influence the severity of fatigue. METHODS Eighty-one patients with inflammatory bowel disease (IBD) (60 with UC and 21 with CD) were assessed for fatigue using two fatigue instruments: the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (fVAS). Cut-off for fatigue was defined as ≥4 for FSS and ≥50 for fVAS. Results were compared with fatigue scores from age-and gender-matched healthy individuals. Disease activity was assessed by symptom scores using the Mayo score in UC patients and the Harvey-Bradshaw index for CD patients, as well as C-reactive protein (CRP) and faecal calprotectin. RESULTS The prevalence of fatigue based on FSS and fVAS was 47 and 42%, respectively, in UC and 62 and 48% in CD. In multivariate regression models, disease activity markers were not associated with fatigue, while a significant relationship was found with age and depression for both fatigue measures. CONCLUSIONS Close to 50% of patients with IBD reported fatigue at the time of diagnosis. In newly diagnosed patients with active disease, the severity of fatigue was not associated with measures of disease activity.

Polyethylene glycol vs sodium picosulfate/magnesium citrate for colonoscopy preparation

Background and study aims: Polyethylene glycol-based electrolyte solutions (PEG-ELS) and the combination of sodium picosulfate/magnesium citrate (SPMC) are commonly used bowel preparation agents. The aim of the present study was to compare the two agents with regard to cleansing efficacy and tolerance among individuals scheduled for outpatient colonoscopy. Materials and methods: The 368 colonoscopy outpatients at three Norwegian hospitals were randomized to bowel lavage with either PEG-ELS or SPMC. Compliance and patient tolerance were evaluated using a patient questionnaire. Bowel cleansing was evaluated using the Ottawa Bowel Preparation Quality Scale (OBPS), a validated scoring system with scores between 0 (best) and 14. Results: There was no difference in the cleansing quality between the PEG-ELS and SPMC groups (median OBPS 5.0 in both groups). The group that received SPMC reported better overall patient tolerance than the PEG-ELS group (72.6 % vs 59.0 % reporting no or slight discomfort, P < 0.01). Compliance with the recommended total fluid intake (4 L) was better in the SPMC group than in the PEG-ELS group (94.2 % vs 81.2 % respectively, P < 0.01); moreover, the polyp detection rate was superior (34.3 % vs 23.3 %, P = 0.02). Conclusion: PEG-ELS and SPMC are equally effective in cleansing efficacy, but SPMC was better tolerated by patients and resulted in superior patient compliance and polyp detection rate. Clinical trial registration: NCT01624454

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections: A Scandinavian real-life study

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12–24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12–16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24–79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

Conventional treatment regimens for ulcerative colitis alleviate fatigue – an observational cohort study

Abstract Objective: The aim of the study was to investigate the course of fatigue in a conventional inflammatory bowel disease treatment setting. Materials and methods: Eighty-two patients with newly diagnosed ulcerative colitis were included in an observational cohort study and received conventional non-biological drug treatment for 3 months. Colonoscopy was performed at diagnosis and after 3 months, disease activity was assessed by Mayo score and measurements of serum C-reactive protein (CRP) and fecal calprotectin levels. Fatigue was evaluated using the fatigue visual analog scale (fVAS). Mood was assessed with the hospital anxiety and depression scale (HADS). Associations between fVAS scores and time; age; CRP, fecal calprotectin, hemoglobin, and ferritin levels; and Mayo scores, Mayo endoscopic scores, and HADS depression subscale (HADS-D) scores were explored. Results: Median fVAS scores decreased, as did Mayo scores and CRP and fecal calprotectin concentrations. HADS-D scores remained unchanged, whereas hemoglobin levels increased after 3 months. Increased fVAS scores were associated with higher ferritin, Mayo and HADS-D scores. There were no associations between fVAS scores and CRP, fecal calprotectin, or Mayo endoscopic scores. Colonic disease distribution did not influence fatigue significantly. Conclusions: Disease activity and fatigue improved after 3 months of conventional ulcerative colitis treatment. Over time, more severe fatigue was associated with more ulcerative colitis symptoms, but not with objective disease activity markers or colonic disease distribution. A clinical setting of standard treatment regimens and medical attention may alleviate fatigue in IBD patients.

TWEAK is not elevated in patients with newly diagnosed inflammatory bowel disease

Abstract Objective: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) may be involved in the pathogenesis of inflammatory bowel disease. The aim was to investigate if TWEAK may reflect disease activity in inflammatory bowel disease. Materials and methods: In this cohort study, 139 consecutive patients with newly diagnosed and previously untreated inflammatory bowel disease – 95 with ulcerative colitis (UC) and 44 with Crohn’s disease (CD) – underwent colonoscopy. Disease activity was assessed by the Mayo score and the Mayo endoscopic score (MES) for UC, or the Simple Endoscopic Score (SES) for CD. Serum C-reactive protein (CRP) and fecal calprotectin were measured in IBD patients, as were plasma TWEAK levels in patients and 85 healthy subjects. Associations between TWEAK levels and disease activity markers were explored. Results: In the total IBD group, the median (interquartile range) TWEAK level was 430 pg/ml (109–6570), in UC 502 pg/ml (109–4547) and in CD patients 352 pg/ml (101–9179), respectively. Healthy subjects had a median (IQR) TWEAK of 307 pg/ml (63–3492). There were no significant differences in TWEAK levels between the total IBD group and healthy control subjects, nor between UC and CD, or between UC/CD and healthy subjects. Furthermore, we found no significant associations between Mayo scores, MES-UC, SES-CD, CRP, and fecal calprotectin with plasma TWEAK levels. Conclusions: Plasma TWEAK levels do not reflect disease activity or the grade of inflammation in patients with newly diagnosed inflammatory bowel disease. NCT01551563.

Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease:

Background: Low anti-tumor necrosis factor α (TNFα) serum concentrations may result in lack of treatment response in patients with inflammatory bowel disease. We determined the anti-TNFα drug concentrations in patients with inflammatory bowel disease and investigated whether or not subtherapeutic drug concentrations were associated with increased levels of disease activity. Methods: In a single-center cross-sectional study, we included patients with ulcerative colitis or Crohn’s disease who were receiving infliximab or adalimumab maintenance therapy. Demographic data, disease activity symptom scores (Partial Mayo Score, Harvey Bradshaw Index), inflammatory markers [C-reactive protein (CRP), fecal calprotectin], antidrug antibodies and serum drug concentrations were recorded. Therapeutic drug concentrations were defined as 3–8 mg/liter for infliximab and 5–12 mg/liter for adalimumab. Results: Of 210 patients included, 137 (65.2%) had Crohn’s disease. In the adalimumab group, subtherapeutic drug concentrations were measured in 16.7% of patients with ulcerative colitis and in 27.7% of patients with Crohn’s disease. In the infliximab group, subtherapeutic drug concentrations were found in 23% (ulcerative colitis) and 30.3% (Crohn’s disease) of patients. In Crohn’s disease, subtherapeutic adalimumab concentrations were associated with higher fecal calprotectin and CRP concentrations compared with therapeutic concentrations. Subtherapeutic infliximab concentrations in patients with Crohn’s disease were also associated with higher CRP concentrations compared with therapeutic concentrations. Conclusions: The prevalence of subtherapeutic drug levels ranged from 17% to 30%. In patients with Crohn’s disease, subtherapeutic serum drug concentrations were associated with significantly higher disease activity with both anti-TNFα agents. These findings were not observed in patients with ulcerative colitis. Clinicaltrials.gov identifier [NCT02134054]

Intramural gastric pseudocyst: A case report and a comprehensive literature review

Rationale: Intramural pseudocyst, although first reported several decades ago, is a rare entity. Scientific knowledge regarding its clinical management is sparse. Patient concerns: We present three cases to show the diverse clinical patterns of patients diagnosed with an intramural gastric pseudocyst. Diagnosis: A final diagnosis should rest on proper evaluation by cross sectional imaging, including computer tomography and magnetic resonance imaging. Endoscopic ultrasound adds to the work-up. Interventions: Previously, identified “lesions of the gastric wall” were not well recognized as an intramural pseudocyst, and treatments including resectional surgery were employed. Contemporary proper diagnostics should provide support to a less aggressive treatment approach. Outcomes: While an indolent natural history without any clinical symptoms or discomfort could be expected in most cases, individual clinical evaluation should be applied. Lessons: A heterogeneous information pattern from the limited number of cases in the literature makes it difficult to draw any firm conclusions. Attention to this rare condition should be increased to help clinicians arrive at a correct diagnosis and possibly prevent some patients from being over treated or from the use of unnecessary surgery.

Hepatitis C treatment at three Norwegian hospitals 2000-2011.

BACKGROUND In the period 2000 – 2011, chronic hepatitis C virus infection (HCV infection) was primarily treated with a combination of pegylated interferon and ribavirin. New antiviral drugs, which are effective but very expensive, are in the process of replacing this regimen. We have investigated the results pegylated interferon and ribavirin have yielded in ordinary clinical practice and examined the part this treatment may play in the near future. MATERIAL AND METHOD We included in this retrospective study HCV-RNA-positive, treatment-naive patients at Stavanger University Hospital, Akershus University Hospital and Østfold Hospital who received at least one dose of pegylated interferon in combination with ribavirin in the period 2000 – 2011. The primary endpoint was sustained virologic response (SVR). Predictors for SVR were identified by means of logistic regression analysis. RESULTS Of 588 included patients, 69.6% (409/588) achieved SVR, 14.3% (84/588) suffered relapse and 16.1% (95/588) showed non-response. In a multivariate analysis, genotypes 2 or 3 and low age at treatment start were independent predictors of SVR. A total of 85.4% of patients aged ≤ 40 years with genotype 2 or 3 had SVR. INTERPRETATION We found good results for treatment of young patients with genotype 2 or 3 with pegylated interferon and ribavirin. Low age and viral genotype were predictors of sustained virologic response (SVR).