Arnaldo Andreoli

Stress and exacerbation in ulcerative colitis : A prospective study of patients enrolled in remission

OBJECTIVE:We sought to determine whether psychosocial factors influence the course of ulcerative colitis, hypothesizing that high perceived stress among patients with inactive disease will increase the risk of subsequent exacerbation.METHODS:Sixty-two patients with known ulcerative colitis were enrolled into a prospective cohort study while in clinical remission. Their perceived stress, depressive symptoms, and stressful life events were followed, along with potential confounders, for up to 45 months; exacerbation status was monitored for up to 68 months.RESULTS:The 27 patients who experienced an exacerbation were compared with those who remained in remission. Having a score in the upper tertile on the long-term (past 2 yr) baseline Perceived Stress Questionnaire significantly increased the actuarial risk of exacerbation (hazards ratio = 2.8, 95% confidence interval 1.1–7.2). At any given study visit, high long-term stress tripled the risk of exacerbation during the next 8 months (risk for the three tertiles, 8.3%, 16.7%, and 26.2%, p = 0.02). Shorter sleep time, briefer remission, histological activity, and use of nonsteroidal antiinflammatory drugs, antibiotics, or oral contraceptives also increased the medium- and/or long-term risk of exacerbation, but adjustment for these variables did not eliminate the associations with stress. Exacerbation was not associated with stressful life events, depressive symptoms, short-term (past month) perceived stress, smoking, disease extent or duration, or severity of recent course.CONCLUSIONS:Short-term stress does not trigger exacerbation in ulcerative colitis, but long-term perceived stress increases the risk of exacerbation over a period of months to years.

Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: Potent antiviral activity but no clinical benefit if treatment is given late

BACKGROUND We evaluated efficacy and safety of sofosbuvir and daclatasvir±ribavirin in liver transplant recipients with severe recurrent hepatitis C. METHODS Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir±ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12. RESULTS Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400mg/day+daclatasvir 60mg/day, and 6 patients (50%) also received ribavirin 200-800mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n=2; week 4, n=3) and was undetectable in all cases. Mean Child-Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed. CONCLUSION All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.

Role of ultrasonography in the diagnosis of postsurgical recurrence of Crohn's disease

Objective:Ultrasonography is a valid tool in the diagnosis of Crohns disease, but its sensitivity, specificity, and overall accuracy in the diagnosis of postoperative recurrence are still not well established. The aim of this study was to evaluate the accuracy of ultrasonography compared with endoscopy in the diagnosis of postoperative recurrence of Crohns disease.Methods:Forty-seven patients resected for Crohns ileitis were studied by ultrasonography and colonoscopy to detect possible recurrence of the disease; 10 patients operated on for cancer of the right colon were used as controls. Six patients with Crohns disease were excluded from the study because of failure to endoscopically reach the anastomosis; the remaining 41 patients had both ultrasonography and colonoscopy over a period of 14 days. Sonographic recurrence was defined as the presence of >5 mm thickness of the ileal wall.Results:Sensitivity, specificity, and overall accuracy of ultrasonography in diagnosis of postoperative recurrence were 81%, 86%, and 83% respectively. Positive predictive value was 96% and negative predictive value was 57%.Conclusion:This study is the first to assess the role of ultrasonography in comparison with endoscopy in detecting Crohns disease recurrence after surgery. Our data suggest that ultrasonography should be used first in the case of clinical suspicion of Crohns disease recurrence, reserving ileocolonoscopy for negative or uncertain cases.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM To evaluate if indolent B cell-non Hodgkins lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies. METHODS A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared. RESULTS Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%). CONCLUSION HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.

Plasma Cytokines and Portopulmonary Hypertension in Patients With Cirrhosis Waiting for Orthotopic Liver Transplantation

Portopulmonary hypertension (PPHTN) is a rare complication in patients with portal hypertension. A role of endothelin 1 (ET-1) and other cytokines was demonstrated in primary pulmonary hypertension but not in PPHTN. We evaluated the possible role of ET-1, interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α) in the pathogenesis of PPHTN. Plasmatic concentrations of ET-1, IL-6, IL-1β, and TNF-α were measured in patients with pulmonary systolic arterial pressure (PAPs) >30 mm Hg and in patients with cirrhosis. In all, Six out of 11 patients with PAPs >30 mm Hg had PPHTN on right heart catheterization. The remaining 10 patients had an hyperdynamic circulation (HC). In PPHTN patients, ET-1 and IL-6 were significantly higher compared with HC and patients with cirrhosis. Endothelin 1 and IL-6 could be implicated in the pathogenesis of PPHTN. On the basis of these results, ET-1 receptor antagonists or anti-IL-6 could have a rationale in the treatment of PPHTN.

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b.

BackgroundThe impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin.MethodsFor 48 weeks, 388 “naïve”genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000–1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR).ResultsThe rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.ConclusionDual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance.Trial registrationClinicalTrials.gov Identifier: NCT01342003

Diagnostic and therapeutic yield of single balloon enteroscopy in patients with suspected small-bowel disease: results of the Italian multicentre study

BACKGROUND Limited data are available on the clinical impact of single balloon enteroscopy. AIMS To evaluate the diagnostic and therapeutic yield of single balloon enteroscopy in patients with suspected small bowel disease. METHODS Data on patients with suspected small bowel disease based on non-invasive imaging, who were subjected sequentially to enteroscopy were prospectively collected. RESULTS 131 procedures were performed in 111 patients. The mean procedure time was 61±33min for the oral approach, and 78±41min for the anal approach. The mean insertion depth was 223±93cm beyond the ligament of Treitz, and 96±56 beyond the ileo-cecal valve. A diagnosis suspected with prior small bowel tests was confirmed in 82 patients, confidently excluded in 20, while in 9 the suspected area was not reached. Total enteroscopy was deemed clinically unnecessary in 94 patients; when total enteroscopy was attempted, it was achieved in 8 out 17 patients. Endoscopic therapeutic interventions were performed in 39 patients, medical treatment was started in 30, whereas 18 underwent to surgery. No major complications were registered. CONCLUSIONS This study shows that single balloon enteroscopy appears to be an helpful and safe procedure with a high clinical impact, especially when it is placed in decision-making as a third level examination.