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

Fecal microbiota transplantation in recurrent Clostridium difficile infection: the first prospective study of 30 patients in Romania

Introduction: The infection with Clostridium difficile has increased in incidence worldwide and it raises many problems with regard to therapy, resistance to treatment and especially recurrence. Recurrence is frequent in patients treated for Clostridium difficile infection, requiring vancomycin by mouth, with limited alternatives. The literature shows that one of the most efficient treatment methods in Clostridium difficile infection is the transplantation of gut microbiota, also known as fecal microbiota transplantation. Aim: We present our results following FMT performed in patients with recurrent Clostridium difficile infection, and propose a simple and effective protocol for fecal microbiota transplantation. Study design: The study was prospective. The phases of the FMT procedure: assessment of patient eligibility, patient’s consent, identification and screening of donors, discontinuation of antibiotics (vancomycin, metronidazole) 3 days prior to the procedure. Methods: Between 2013 and 2015, FMT was performed in 30 patients with recurrent Clostridium difficile infection, by direct infusion of extensively processed donor fecal matter via colonoscopy. We followed up the patients for 12 months. Results: Immediate post-transplantation outcome in what concerns stool frequency during the follow-up period (7 days) was encouraging in 93.33% of patients. The donors were healthy individuals (53% 1st degree relatives), previously screened for possible infections and infestations. This result was sustained at 6-month and 12-month follow-up. Post-transplantation recurrence occurred in 6.67% (2 patients), which responded well to treatment and did not require a new vancomycin course. Conclusions: Fecal microbiota transplantation via colonoscopy is effective, safe, easy to perform, it yields lasting results and is therefore a good option for recurrent or treatment-resistant Clostridium difficile infection

The role of narrow band imaging in colorectal polyp detection

Colonoscopic detection and removal of polyps represent the most important prevention method for colorectal cancer. We aimed to investigate the diagnostic yield of narrow band imaging (NBI) colonoscopy for polyp detection compared with standard colonoscopy. In this prospective study, 505 patients that underwent total colonoscopy were randomized into two groups: 226 patients in NBI group and 279 in non-NBI group (standard colonoscopy). The primary endpoints were polyp detection rate (PDR) and adenoma detection rate (ADR) in both groups. Polyps detected with NBI technique were characterized according to the NBI International Colorectal Endoscopic (NICE) classification. The total number of polyps detected in NBI group was significantly higher compared with non-NBI group (325 polyps in 226 patients versus 189 polyps in 279 patients, respectively). PDR in NBI group was 55.3%, versus 43.3% in non-NBI group. ADR in NBI group was significantly higher compared with non-NBI group (35.3% versus 20%, respectively). The proportion of detected adenomas in the left-sided colon was significantly higher in NBI group (72.8% versus 61.06% in non-NBI group), which was related to an increased number of small adenomas detected in NBI group. Also, in NBI group, a significant number of flat adenomas were detected (28 versus 9 in non-NBI group). A total of 147 (45.2%) polyps were classified according to the NICE classification, and showed a good correlation with histological analysis. In conclusion, this study demonstrated increased PDR and ADR for NBI colonoscopy. A good correlation between the NICE classification and histological analysis was also observed

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 ≥1 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 ≥1 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 ≥5. 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 peginter-feron alfa-2a/ribavirin