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

Risk factors for intrafamilial spread of hepatitis B in northeastern Bosnia and Herzegovina.

<b>Background: </b> Accurate estimations of hepatitis B virus transmission risk for any region in Bosnia and Herzegovina are not clearly established. We aimed to determine levels of risk associated with intrafamilial transmission of hepatitis B infection within families in our region. <b> Patients and Methods: </b> Family members of 81 chronic carriers of hepatitis B surface antigen (>6 months positive and considered as index case) were tested for hepatitis B markers. For family members, we recorded their age, sex, and family relationship to the index case, and vaccination status. <b> Results: </b> The proportion of HBsAg positive family members was 25/207 (12.1&#x0025;), while the proportion of family members with evidence of exposure to HBV was 80/207 (38.6&#x0025;). Only 17/207 (8.2&#x0025;) family members had evi--dence of past HBV vaccination. Age was found to be a significant predictor of HBV exposure of family members (odds ratio 1.05, 95&#x0025; CI 1.03-1.07, P&#60; .001). In a multivariate analysis, HBsAg positivity was associated with a female index case (odds ratio 11.31, 95&#x0025; CI 3.73-34.32, P&#60; .001), HBeAg positivity in the index case (odds ratio 5.56, 95&#x0025; CI 1.80-17.23, P&#60; .005) and being a mother of the index case (odds ratio 9.82, 95&#x0025; CI 2.43-39.68,P&#60; .005). A female index case (odds ratio 4.87, 95&#x0025; CI 2.21-10.72, P&#60; .001), HBeAg positivity in the index case (odds ratio 3.22, 95&#x0025; CI 1.15-9.00, P&#60; .05) and being a mother of the index case (odds ratio 3.72, 95&#x0025; CI 1.19-11.64, P&#60; .05) were also risk factors for HBV exposure among family members. The combination of HBeAg positivity and female index case was a significant predictor for HBsAg positivity of family members (odds ratio 70.39, 95&#x0025; CI 8.20-604.61, P&#60; .001). <b> Conclusions: </b> Children of HBeAg positive mothers are at highest risk for becoming chronic carriers them--selves and generally, the combination of female sex and HBeAg positivity dramatically increases the chances of HBV transmission within the family

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