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 peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

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 peginter-feron alfa-2a/ribavirin

Response of Black African patients with hepatitis C virus genotype 4 to treatment with peg-interferon and ribavirin

Aim : To compare responses to therapy of Black African (BA) and non-Black African (non- BA) patients with hepatitis C virus genotype 4 (HCV-4) residing in Belgium. Methods : In this retrospective multicenter study, 473 patients with HCV-4 were selected from databases at 7 Belgian centers ; 209 treatment-naïve patients (154 BA) had received treatment with peg-interferon (peg-IFN) plus ribavirin (RBV) and were included in the study. Results : There was a greater percentage of female patients in the BA group than in the non- BA group ; BA patients were also older, had a greater body mass index, and more frequently had abnormal glucose metabolism. The route of contamination was more frequently unknown in BA than in non-BA patients and BA patients had more HCV-4 subtypes. There were no differences in other demographic factors between the groups. Sustained viral response (SVR) and complete early viral response rates were significantly lower and relapse rates significantly higher in BA than in non-BA patients. There were no differences between groups in rates of dose modification or in drug tolerance. Conclusion : In our cohort, treatment-naïve BA patients with HCV-4 who were treated with peg-IFN and ribavirin had a much lower SVR rate than treatment-naïve non-BA patients with HCV- 4 who were treated with peg-IFN and ribavirin, and a higher relapse rate, possibly related to a weaker response to interferonbased therapy. Treatment may need to be adapted in this population

HBV infection in Belgium: results of the BASL observatory of 1456 HBsAg carriers.

Introduction : Nationwide studies are mandatory to assess changes in the epidemiology of HBV infection in Europe. Aim : To describe epidemiological characteristics of HBsAgpositive patients, especially inactive carriers, and to evaluate how practitioners manage HBV patients in real life. Methods : Belgian physicians were asked to report all chronically infected HBV patients during a one-year period. Results : Among 1,456 patients included, 1,035 (71%) were classified into one of four phases of chronic infection : immune tolerance (n = 10), HBeAg-positive hepatitis (n = 248), HBeAgnegative hepatitis (n = 420) and inactive carrier state (n = 357 HBeAg-negative patients with ALT < upper limit of normal (ULN) and HBV DNA < 2,000 IU/mL). Using less restrictive criteria for ALT (1-2 ULN) or HBV DNA (2,000-20,000 IU/mL), 93 unclassified patients were added to the group of inactive carriers. These 93 additional inactive carriers were younger, more frequently males, with similar risk factors for HBV infection and histological features compared to inactive carriers according to recent guidelines. Recent guidelines on management of HBV patients were generally followed, but systematic HBV DNA measurements and HDV coinfection screening should be reinforced. Conclusion : In Belgium, an inactive carrier state was a common form of chronic HBV infection. Using less restrictive criteria for classification of inactive carriers did not modify their main characteristics and seemed better adapted to clinical practice. Recent guidelines on management of HBV patients should be reinforced

Sofosbuvir in combination with simeprevir +/- ribavirin in genotype 4 hepatitis C patients with advanced fibrosis or cirrhosis: a real-life experience from Belgium

Background: All-oral, interferon-free regimens that combine direct-acting antiviral drugs have significantly advanced the treatment of hepatitis C (HCV), especially for genotype 1(G1) patients. However, efficacy and safety data of interferon-free regimens in HCV genotype 4 (G4) patients are scarce. In Belgium, Sofosbuvir (SOF) and Simeprevir (SMV) treatment is available since January 2015 for G4 patients with advanced fibrosis (F3-F4 METAVIR) for 12 weeks. Methods: analysis of HCV G4 patients receiving SOF and SMV treatment in Belgium. The aim of the study was to evaluate the safety and efficacy of the treatment. Results: 73 G4 patients were enrolled in this data collection including 32 (43.8%) patients with severe fibrosis F3 and 41(56.2%) cirrhotic patients. The study population comprised 58.9% male, 77.8% treatment experienced patients. Median age was 59 [51-66] years and 5 patients were HCV/HIV co-infected. 24 patients received the treatment associated with ribavirin, 11/32 (34.37%) of patients with advanced fibrosis and 13/41 (31.71%) of cirrhotic patients. In cirrhotic patients, median MELD and Child-Pugh score were 9 [7-12.5] and 5 [5-6], 46.2% had platelet below 100.000/mm and 28.6% had albumin below 35 g/L. W4 HCV RNA was undetectable in 31.25% (15/48). 9 of the 15 patients with undetectable W4 HCV RNA received RBV. At W12, 100% (23/23) had HCV RNA below the limit of quantification, with 6/23 still detectable. All SVR12 data will be available at the time of presentation. No patient experienced serious adverse event. Conclusions: these preliminary results in difficult-to-treat G4 HCV patients show that SOF/SIM +/- RBV treatment is safe and seems promising, in line with that was observed in G1 HCV patients