A young man with acute abdomen and anaemia. / En ung mann med akutte magesmerter og anemi.

A young man was hospitalised with acute abdomen and signs of pancreatitis. He became seriously ill and required surgery to address the underlying cause.

The influence of disease activity on fatigue in patients with ulcerative colitis - a longitudinal study.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial.

Importance: Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear. Objective: To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM. Design, Setting, and Participants: Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019. Interventions: Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204). Main Outcomes and Measures: The primary end point was clinical remission at week 30. Results: Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, -8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively. Conclusions and Relevance: Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03074656.

Diagnosis and treatment of autoimmune hepatitis. / Diagnostikk og behandling av autoimmun hepatitt.

Autoimmune hepatitis is a chronic liver disease which, if untreated, can lead to cirrhosis of the liver and liver failure. The majority of patients respond well to standard immunosuppressive therapy, but some experience adverse effects, or lack of treatment efficacy. Diagnosis, assessment of therapeutic response and choice of second-line therapy may be challenging. This article provides a summary of updated knowledge concerning diagnosis and treatment of patients with complex autoimmune hepatitis.

Endoscopic retrograde cholangiopancreatography (ERCP): lessons learned from population-based national registries: a systematic review.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) was introduced more than four decades ago as a diagnostic tool for biliary and pancreatic diseases. Currently, ERCP is mainly used as a therapeutic approach to relieve biliary or pancreatic duct obstruction. Clinical practice has been based on a few large reports and some randomized controlled trials. These data are valuable and important, but the external validity of these reports is limited. Implementation into routine practice should be balanced with the knowledge that these studies were conducted under very specific circumstances. This review was undertaken to describe ERCP results from population-based national registries recorded during routine clinical practice. METHODS: A systematic literature search of the electronic databases Medline Ovid and Embase was conducted. Eligible papers were selected and data were recorded according to the PRISMA criteria. RESULTS: Thirty-one studies were included: 15 true national population-based and 16 population-level studies. Most studies originated from countries with a governmental public health care system. At least three-quarters of the ERCP procedures are currently therapeutic, and the technical success rate is high (> 90%). The postprocedure 30-day mortality rate ranged between 1 and 5% and was strongly correlated with older age, male sex, emergency admission, and noncancer comorbidities, but exhibited a lower correlation with the annual ERCP volume. Patients with primary sclerosing cholangitis or liver cirrhosis should receive particular attention. The risk of developing a bile duct, liver, or pancreas malignancy after ERCP tended to increase, but endoscopic sphincterotomy did not affect this risk. CONCLUSION: ERCP is currently mainly used as a therapeutic approach, and the results are generally likely to improve patients' conditions. A nationwide registry enables better monitoring of routine clinical practice. The collection of valuable information from routine clinical practice in population-based databases may help to improve patient care from best evidence to best practice.

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

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.

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.

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

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.

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).

Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B.

BACKGROUND: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. AIM: To assess whether it is beneficial to undergo a prolonged flare after NA cessation. METHODS: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. RESULTS: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. CONCLUSIONS: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.

Histologic healing and factors associated with complete remission following conventional treatment in ulcerative colitis.

Background: Endoscopic and histological activity scores in ulcerative colitis (UC) are associated with clinical outcomes and have become important targets of clinical trials. However, these endpoints have been scarcely investigated in patients receiving only conventional treatment. Objective: We aimed to assess the deep and complete remission rates after 3 months of conventional treatment in patients with newly diagnosed UC with moderate to severe endoscopic activity. We also aimed to investigate whether selected clinical and biochemical variables at baseline were associated with complete remission status after 3 months. Design: This was a prospective cohort study. Methods: Newly diagnosed patients with active UC commencing 5-aminosalicylate, corticosteroid, and/or azathioprine treatment were consecutively included. Clinical, biochemical, endoscopic, and histological data were collected at baseline and after 3 months. Rates of clinical remission (Partial Mayo Score ⩽ 2), mucosal healing (Mayo Endoscopic Score ⩽ 1), and histologic healing (Nancy Index ⩽ 1) were determined. Deep remission was assessed as clinical remission plus mucosal healing and complete remission as deep remission plus histologic healing. Predictors of complete remission were identified by logistic regression. Results: A total of 180 patients were included in the study. Deep remission and complete remission occurred in 62.8% and 42.2% of patients, respectively. Thus, of patients in deep remission one-third had persistent histologic activity. Histologic activity in mucosally healed patients was associated with higher symptom scores and faecal calprotectin levels. Of baseline variables, less endoscopic distribution and disease activity showed strongest association with achieving complete remission, and limited distribution in combination with moderate activity gave highest odds for complete remission (odds ratio: 4.1, 95% confidence interval: 7.69-2.18). Conclusion: In patients with mucosal healing, persistent histologic activity was a common finding and was associated with increased disease activity. Pancolitis and severe inflammatory activity at baseline were associated with lower complete remission rates.

The overriding role of surgery and tumor grade for long-term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population-based cohort study.

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.

Determination of lower cut-off levels of adalimumab associated with biochemical remission in Crohn's disease.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Palliative surgical outcome score (PSOS) in patients treated palliatively with self-expanding metal stent (SEMS) for malignant incurable colorectal obstruction.

AIM: The palliative surgical outcome score (PSOS) was proposed for evaluation of the effect of palliative surgical interventions. As a surrogate measure for successful symptom control, it is defined as the proportion of days outside the hospital of the remaining life time up to six months after a palliative intervention. In this study we evaluate the PSOS in patients treated palliatively with self-expanding metal stents (SEMSs) for incurable malignant colorectal obstruction. METHODS: All eligible patients endoscopically treated with palliative intent with SEMSs were identified. Demographics and clinical characteristics, including complete follow-up, were recorded, and the PSOS was calculated. Non-parametric tests were used for comparisons, and survival was evaluated by univariable and multivariable analyses. RESULTS: Between 2005 and 2013, 116 patients (median age 71.5 years; 53.4% women) were identified. Most obstructions were caused by primary colorectal cancers. Technical- and clinical success rates were 94.0% and 87.1%, respectively. Procedure-related complications occurred in 17 (14.7%) of the patients, and most were minor. A PSOS>70 (regarded as excellent palliation) was achieved in 79 (68.1%) patients. This goal was significantly more often achieved in patients who survived at least 6 months than in those with shorter survival (p < 0.001). No clinical variables at the time of the endoscopic palliative procedure could predict a PSOS>70. However, in patients who survived at least 6 months (n = 69), a PSOS>70 was independently associated with better survival in the multivariable Cox analysis. CONCLUSIONS: PSOS could be used as a practical proxy or a pragmatic tool for the effectiveness of palliative interventions, when such interventions are compared. Clinical factors that could significantly add to the clinical decision-making and predict a PSOS>70 in an individual patient were not identified for this specific group of patients.

A case of Ménétriere´s disease treated with the monoclonal antibody cetuximab.

Ménétriere´s disease is a rare disorder of the body and fundus of the stomach, characterized by a massive proliferation of the foveolar cells and subsequent excess mucous secretion. This results in hypoproteinemia due to loss of serum proteins across the gastric mucosa. The cause of Ménétriere´s disease is unknown, and due to the irreversible and premalignant character of the disorder, the patients affected have been subdued to gastrectomy as the only curable treatment. Epidermial growth factor (EGF) has been implicated in the pathogenesis, a finding that makes the disorder receptive to monoclonal antibody treatment against the EGF receptor. In this case report, we present a 41-year-old woman referred to our emergency department due to dizziness, nausea, and vomiting. A thorough medical investigation, combining clinical history, laboratory investigations, an upper endoscopy with full-thickness snare biopsies, and a CT scan confirmed Ménétriere´s disease, and she was successfully treated with the monoclonal antibody cetuximab.

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.

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.

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 Crohn's 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.