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

Pegylated interferon-alpha2b plus ribavirin for the treatment of chronic hepatitis C virus genotype 4 infection in patients with normal serum ALT

Background. Approximately one-third of patients with chronic hepatitis C virus infection have persistently normal liver enzymes reflected by a normal serum alanine transaminase (ALT). Data with regards the efficacy and safety of treatment in patients chronically infected with Hepatitis C virus genotype 4 and normal serum ALT are limited. Aim. To evaluate the efficacy and safety of peginterferon alfa-2b plus ribavirin combination therapy in this population.Material and methods. Twenty-two patients with chronic hepatitis C virus genotype 4 infection were enrolled in an open-labeled, uncontrolled pilot study. All patients had biopsy proven chronic hepatitis and persistently normal serum ALT levels. Patients were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 μg/kg body weight once per week plus oral ribavirin (15 mg/kg/day) for 48 weeks. Patients were followed for 24 weeks post-treatment.Results. Sixteen patients out of twenty two completed the study (9 [40.9%] females, mean age 43.8 years). The ALT level were normal in all patients, with a mean of 38.6 U/L. Sustained viral response was achieved in 13 patients (59%), 4 patients (18.1%) were non-responders and 2 patients (9%) relapsed while 1 patient had a viral breakthrough during treatment. Two patients (9%) discontinued the treatment because of adverse events.Conclusions. Combination therapy of pegylated interferon-alpha2b and ribavirin is safe and resulted in a sustained viro-logical response in a significant number of patients with chronic Hepatitis C, genotype 4, and persistently normal serum ALT

Emergent endovascular stent grafting for saccular arch aneurysm complicated by aorto-esophageal fistula

Aneurysms of aortic arch are rare but amenable to endovascular therapy. Arch aneurysm presenting with aorto-esophageal fistula and hematemesis is a feared, but relatively rare complication. The extrapolation of the safety and rapidity of emergent endovascular repair for bleeding arch aneurysms has been infrequently reported. A bovine arch anatomy confers distinct advantages for endovascular therapy often avoiding a preceding debranching surgery. However, its endovascular treatment might be complicated by the nonhealing of fistula and potential risk for mediastinitis. Here, we report a case of a bovine aortic arch cystic aneurysm complicated by bleeding aorto-esophageal fistula, which warranted an emergent endovascular therapy. The prevertebral part of LSCA was plugged to interrupt the retrograde filling and a future endoleak. A nonhealing aorto-mediastinal fistula at follow-up was successfully treated by covered esophageal stenting. This report reiterates the importance of multidisciplinary approach with multispecialty collaboration to such complex spectrum of diseases

Plasma vitamin A is reduced in active ulcerative colitis

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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