Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Narrow-band imaging in the prediction of surveillance intervals after polypectomy in community practice

Background and study aims: It has been proposed that the use of narrow-band imaging (NBI) for real-time histological assessment to determine postpolypectomy surveillance intervals is a cost-effective approach to the management of diminutive polyps. However, significant discrepancies in NBI performance have been observed among endoscopists; hence, professional societies recommend training, monitoring, and auditing. The aim of the present study was to evaluate the performance of real-time optical diagnosis for diminutive polyps after the inclusion of this approach in an internal quality assurance program, in order to assess its applicability in clinical practice Patients and methods: Four endoscopists attended periodic training sessions on NBI assessment of polyp histology before and during the study. Performance was audited and periodic feedback was provided. The accuracy of high-confidence NBI evaluation for polyps 645mm in predicting surveillance intervals according to the European and US guidelines, and the negative predictive value (NPV) for adenoma in the rectosigmoid were calculated and compared with recommended thresholds (90% agreement and 90% NPV, respectively). Results: Overall, 284 outpatients (mean age 61.3\ub118.2 years; 63% males) were enrolled. A total of 656 polyps were detected, 465 of which (70.9%) were diminutive (70.5% adenomas). Sensitivity, specificity, positive and negative predictive values, and accuracy of high-confidence NBI predictions for adenoma in diminutive lesions were 95.3%, 83.5%, 93.5%, 87.6%, and 91.9%, respectively. High-confidence characterization of diminutive polyps predicted the correct surveillance interval in 95.8% and 93.3% of cases according to European and American guidelines, respectively. NPV for adenoma in the rectosigmoid was 91.3% Conclusions: For community settings in which endoscopists are adequately trained and performance is periodically audited, real-time optical diagnosis for diminutive polyps is sufficiently accurate to avoid postpolypectomy histological examination of resected lesions, or to leave rectosigmoid hyperplastic polyps in place. Trial registered at ClinicalTrials.gov (NCT02196402)

Sofosbuvir and ribavirin for genotype 2 HCV infected patients with cirrhosis: A real life experience

Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12-16weeks duration were associated with a 90% sustained virological response at 12weeks (SVR12). Real life cohorts showed lower SVR12 rates

Diagnosis, treatment and survival of patients with hepatorenal syndrome: A survey on daily medical practice

Background & Aims: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis with ascites. The International Ascites Club recommended strict diagnostic criteria and treatment with vasoconstrictors and albumin. Aim of this prospective cohort study was to investigate the prevalence of HRS, diagnostic criteria, treatment and 3-month outcome in the daily-clinical-practice. Methods: Two-hundred-fifty-three patients with cirrhosis and renal failure consecutively admitted to 21 Italian hospitals were recruited. Results: The prevalence of HRS was 45.8% (30% type-1 and 15.8% type-2). In 36% of cases HRS was presumed because not all diagnostic criteria could be fulfilled. In 8% of cases HRS was superimposed on an organic nephropathy. Patients with HRS type-1 were younger and showed higher leukocyte count, higher respiratory rates, and worse liver function scores. Sixty-four patients with HRS type-1 received vasoconstrictors (40 terlipressin and 24 midodrine/octreotide). A complete response was obtained in 19 cases (30%) and a partial response in 13 (20%). Age was the only independent predictor of response (p = 0.033). Three-month survival of patients with HRS type-1 was 19.7%. Survival was better in patients who responded to therapy. Age (p = 0.017), bilirubin (p = 0.012), and creatinine increase after diagnostic volume expansion (p = 0.02) independently predicted death. The mortality rate was 97% among patients with at least two negative predictors. Conclusions: The diagnostic criteria of HRS in our daily-clinical-practice could not be completely fulfilled in one third of cases. The treatment with vasoconstrictors and albumin was widely implemented. Mortality was strongly predicted by simple baseline variables. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved

Adherence to European Society of Gastrointestinal Endoscopy Quality Performance Measures for Upper and Lower Gastrointestinal Endoscopy: A Nationwide Survey From the Italian Society of Digestive Endoscopy

Background: The quality of gastrointestinal (GI) endoscopy has been recently identified as a major priority being associated with many outcomes and patient's experience. Objective: To assess adherence of endoscopists to the European Society of Gastrointestinal Endoscopy (ESGE) quality performance measures for upper and lower GI endoscopy in Italy. Methods: All endoscopist members of the Italian Society of Digestive Endoscopy (SIED) were invited from October 2018 to December 2018 to participate to a self-administered questionnaire-based survey. The questionnaire included questions on demographics and professional characteristics, and the recent ESGE quality performance measures for upper and lower GI endoscopy. Results: A total of 392 endoscopists participated in the study. Only a minority (18.2%) of participants recorded the duration of esophagogastroduodenoscopy (EGD) and 51% provided accurate photo documentation in the minimum standard of 90% of cases. Almost all endoscopists correctly used Prague and Los Angeles classifications (87.8% and 98.2%, respectively), as well as Seattle and Management of precancerous conditions and lesions in the stomach (MAPS) biopsy protocols (86.5% and 91.4%, respectively). However, only 52.8% of participants monitored complications after therapeutic EGD, and 40.8% recorded patients with a diagnosis of Barrett's esophagus (BE). With regard to colonoscopy, almost all endoscopists (93.9%) used the Boston Bowel Preparation Scale for measuring bowel preparation quality and reported a cecal intubation rate ≥90%. However, about a quarter (26.2%) of participants reported an adenoma detection rate of &lt;25%, only 52.8% applied an appropriate polypectomy technique, 48% monitored complications after the procedure, and 12.4% measured patient's experience. Conclusion: The adherence of endoscopists to ESGE performance measures for GI endoscopy is sub-optimal in Italy. There is a need to disseminate and implement performance measures and endorse educational and scientific interventions on the quality of endoscopy