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.
Abstract Background Gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) comprise a heterogeneous disease group. Factors that affect long‐term survival remain uncertain. Complete population‐representative cohorts with long‐term follow‐up are scarce. Aim To evaluate factors of importance for the long‐term survival. Methods and results An Observational population‐based study on consecutive GEP‐NEN patients diagnosed from 2003 to 2013, managed according to national guidelines. Univariable and multivariable survival analyses were performed to evaluate overall survival (OS) and to identify independent prognostic factors. One hundred ninety eligible patients (males, 58.9%) (median age, 60.0 years; range, 10.0–94.2 years) were included. The small bowel, appendix, and pancreas were the most common tumor locations. The World Health Organization (WHO) tumor grade 1–3 distributions varied according to the primary location and disease stage. Primary surgery with curative intent was performed in 66% of the patients. The median OS of the study population was 183 months with 5‐ and 10‐year OS rates of 66% and 57%, respectively. Only age, WHO tumor grade, and primary surgical treatment were independent prognostic factors for OS. Conclusion The outcomes of GEP‐NEN patients are related to several factors including age and primary surgical treatment. WHO tumor grading, based on the established criteria, should be routine in clinical practice. This may improve clinical decision‐making and allow the comparison of outcomes among different centers.
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.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.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.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).
Adalimumab is administered and dosed using a standardized treatment regimen. Although therapeutic drug monitoring (TDM) may help optimize treatment efficacy, the lower cut-off concentration of adalimumab needed to retain disease remission has not been established. This cross-sectional study of patients with Crohn's disease on stable medication aimed to determine a lower therapeutic drug concentration threshold of adalimumab associated with biochemical disease remission.C-reactive protein (CRP) and fecal calprotectin were used as established markers and albumin as an explorative marker of disease activity. Time since introduction, treatment interval, drug dosage, serum drug concentration and antidrug antibodies, disease duration, age, and sex were recorded.The study included 101 patients who were divided into "active disease" and "remission" groups for inflammatory markers based on cut-off levels of 5 mg/L for CRP and 50 mg/kg for fecal calprotectin. Cut-off levels for albumin of 36.5 and 41.5 g/L were also added as further indicatives of remission. Receiver operating characteristic analysis found optimal thresholds for adalimumab associated with remission at 6.8-7.0 mg/L for the combination of CRP and fecal calprotectin and when combining CRP, fecal calprotectin, and albumin.In patients with Crohn's disease, serum adalimumab of at least 6.8 mg/L was associated with biochemical disease remission based on CRP and fecal calprotectin, supporting the use of TDM to ensure disease control. Albumin should be further tested in this setting.
Background: Mucosal healing has become a primary target in the treatment of inflammatory bowel disease (IBD), as it is associated with an improved disease course. However, real life data concerning mucosal healing after conventional treatment are scarce. Methods: Our aim was to assess the rate of mucosal healing and clinical remission after 3 months of conventional treatment in a cohort of newly diagnosed IBD patients. 171 patients with ulcerative colitis [UC; N=123 (72%)] or Crohn's disease [CD; N=48 (28%)] aged 16 years and above, were consecutively included in a prospective study. Demographic data, medication, Partial Mayo Score (PMS) for UC or Harvey Bradshaw Index (HBI) for CD, fecal calprotectin and CRP were obtained, and colonoscopy performed at baseline and after 3 months of conventional treatment. Inflammatory activity was assessed according to the Mayo Endoscopic Score (MES-UC) for UC and the Simple Endoscopic Score (SES-CD) for CD. Baseline data are given in Table 1. Mucosal healing was defined as MES-UC ≤1 or SES-CD ≤2, clinical remission as PMS ≤2 or HBI <5. Results: Mucosal healing was achieved by 101 (59%) and clinical remission by 100 (58%) of all patients, whereas 74 (43%) reached a combined endpoint of mucosal healing and clinical remission (Figure 1A). Eighty-six (70%) UC patients achieved mucosal healing, 68 (55%) clinical remission and 60 (49%) combined mucosal healing and clinical remission (Figure 1B). Median PMS was reduced from 5 to 1 (p<0.001), CRP from 6.4 to 1.9 mg/L (p<0.001) and f-calprotectin from 620 to 67 mg/kg (p<0.001). Fifteen CD patients (31%) achieved mucosal healing, 32 (67%) clinical remission and 14 (29%) combined mucosal healing and clinical remission (Figure 1C). Figure 1. Outcomes. Median HBI was reduced from 5 to 3 (p=0.01), CRP from 7.9 to 4.1 mg/L (p=0.002) and f-calprotectin from 160 to 38 mg/kg (p<0.001). The mucosal healing rate was higher in UC than in CD patients (p<0.001); no difference in clinical remission was observed (p=0.18). Conclusions: Nearly 60% of newly diagnosed IBD patients achieved mucosal healing as well as clinical remission following three months of conventional treatment in a real life setting. Mucosal healing rate was significantly higher in UC than in CD patients. Conventional treatment appears effective for mucosal healing in UC patients.
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.
AIMS Iron deficiency anemia (IDA) is among the most common extraintestinal sequelae of inflammatory bowel disease (IBD). Intravenous iron is often the preferred treatment in patients with active inflammation with or without active bleeding, iron malabsorption, or intolerance to oral iron. The aim of the present study was to evaluate the cost-utility of ferric derisomaltose (FDI) versus ferric carboyxymaltose (FCM) in patients with IBD and IDA in Norway.
Abstract Background In ulcerative colitis (UC), faecal calprotectin (FC) correlates with endoscopic severity and disease extent, and low levels are associated with histological remission [1, 2]. The effect of mucosal inflammatory activity versus disease extent on the FC levels, remains poorly understood. We aimed to compare FC levels in patients grouped by endoscopic and histologic scores of the inflammatory activity. We also grouped patients according to active disease extent based on endoscopic or histological evaluations. Methods This was a post hoc analysis of patients diagnosed with UC or with confirmed UC at Stavanger University Hospital, Norway, from 2012 to 2020. Visits were performed at diagnosis, and after 3 and 11 months. FC was analysed in samples collected from 4 weeks before until 3 days after visits (EliA Calprotectin or EliA Calprotectin 2, Thermo Scientific). At each visit, colonoscopy was performed, and biopsies were collected from three colorectal segments (rectum, left colon, right colon). Mucosal inflammatory activity was scored endoscopically by Mayo Endoscopic Score (MES 0 – 3) and histologically by Nancy Histological Index (NHI 0 – 4). The highest value of the segmental NHI scores were reported. Disease extent was defined by Montreal classification. Distribution of acute inflammation was defined by the number of colorectal segments with NHI ≥ 2 (presence of neutrophilic infiltrates). Results In total 554 visits of 249 patients were analysed. FC levels increased significantly for every stepwise increase in MES, and median FC was 30-fold (range 19-49) higher in MES 3 than in MES 0 subgroups. The largest difference was observed between MES 1 and MES 2 (Figure 1a). FC levels also increased significantly for every stepwise increase in NHI, except between NHI 3 and NHI 4. Median FC level was 54-fold higher in NHI 4 group compared with the NHI 0 group, and the largest difference was observed between NHI 1 and NHI 2 (Figure 1b). Disease extent showed little effect on FC, and significant difference was only observed between proctitis and pancolitis with 3-fold (range 1.6 – 4.5) higher levels in the latter groups (Figure 2a). Median FC level was 3-fold higher in patients with acute inflammation in all 3 segments compared to patients with acute inflammation in only 1 colorectal segment (Figure 2b). Conclusion FC increased significantly by increasing mucosal inflammatory activity, whereas disease extent showed a modest effect on the FC levels. FC is an accurate and useful biomarker of both endoscopic and histological inflammatory activity in patients with ulcerative colitis. References: 1. Kawashima K. et al, BMC Gasteroenterology 2016 2. Magro F. et al, Gut 2019
The relationship between the disease activity of ulcerative colitis and fatigue is unclear. We investigated how reaching deep remission versus remaining in active disease influenced the severity of fatigue.We included 149 consecutive patients in a longitudinal study. Patients were re-examined after 3 months of conventional treatment and dichotomized into A: Active disease or B: Deep remission. The Partial Mayo Score (PMS) was recorded in all patients. Fatigue was rated using the fatigue visual analog scale (fVAS), Fatigue Severity Scale (FSS), and Short Form-36 Vitality Subscale (SF-36vs). A control group of 22 age and sex-matched healthy subjects were included as controls for patients reaching deep remission.After 3 months there were no significant differences in fVAS, FSS and SF-36vs scores in patients with active disease compared to patients reaching deep remission, when adjusting for baseline fatigue scores. Patients in remission based on MES-UC scores had no significant reduction in fatigue scores, whereas patients in remission based on PMS had all three fatigue scores reduced. However, patients reaching deep remission still had higher fVAS and lower SF-36vs scores compared to healthy control subjects.After 3 months of conventional treatment there were no differences in fatigue severity in patients reaching deep remission compared with patients still having active disease. Fatigue was more pronounced in patients in deep remission than in healthy subjects, and was associated with subjective and not objective measures of disease activity. This indicates that other potent factors than inflammation influence fatigue in UC.
A young man was hospitalised with acute abdomen and signs of pancreatitis. He became seriously ill and required surgery to address the underlying cause.
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