Equally poor outcomes to pegylated interferon-based therapy in African Americans and Hispanics with chronic hepatitis C infection
ABSTRACT Treatment response to pegylated interferon based regimen is different between African Americans and Whites, but little comparable data is available comparing Hispanics and African Americans.
We retrospectively evaluated the rate of success in the treatment completion and response to peginterferon alpha-2a or alpha-2b plus ribavirin in 103 (male:female-69:34) hepatitis C virus (HCV)-polymerase chain reaction positive patients that included 68 Hispanic and 35 African Americans.
Patients were treated with peginterferon alpha-2a 180 mcg/wk (n=25) or peginterferon alpha-2b 1.5 mcg/kg/wk (N=78) and ribavirin 1000 to 1200 mg/d for 24 weeks (genotype 2 and 3) or 48 weeks (genotype 1 and 4) based on the genotype of the patient. Treatment was discontinued if the patients failed to have a 2-log drop in viral load after 12 weeks of treatment. Primary aim of the study was to evaluate success in completing a scheduled duration of pegylated interferon and ribavirin treatment in patients with chronic HCV infection and the reasons for discontinuation of the treatment. The secondary aim was to look for the end of treatment virologic response and sustained virologic response. The analysis was conducted by intention-to-treat.
Of the 103 patients included in the study, 50 (48.5%) patients dropped out of the treatment because of side effects of the drug or noncompliance to the treatment protocol or alternate reasons; 44 (42.7%) of them could not continue beyond 12 weeks of therapy. There were no significant differences in the drop out rate between the African American [15 (43%)] and Hispanic [35 (51.5%)] patients (P=0.41). Overall, 41% of the patients completed the scheduled 24 week or 48 week treatment. HCV genotype-1 was the most prevalent genotype in both African Americans and Hispanics (88.6% vs. 75%, P=0.10). Overall end of the treatment response (ETR) was 29.1% (30/103) and sustained virologic response (SVR) was 23.3% (24/103) in this population. No significant differences were noted in the ETR (20% vs. 34%, P=0.14) and the SVR (20% vs. 25%, P=0.57) between the African Americans and Hispanics. When data were analyzed by genotype, overall SVR rates were 14.6% (12/82) in genotype 1 versus 57% (12/21) in genotype 2/3/4 (P<0.0001). Both these ethnic groups had comparable response rates when only patients with genotype-1 were considered 5/31 (16.1%) versus 7/51 (13.7%, P=0.76).
A significant proportion of the African Americans and Hispanics referred for HCV treatment with pegylated interferon dropped out early in the therapy, suggesting possible racial, socioeconomic, and cultural barriers in successful treatment for chronic HCV infection. Overall, both groups had similar poor response rates, well below those reported for White patients. As is true for the general population, patients with nongenotype 1 infection had a significantly better ETR and SVR.
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ABSTRACT: The global prevalence of hepatitis C virus (HCV) infection exceeds that of HIV but only has a 40% response rate to the currently available standard of care. In contrast to HIV infection, eradication of HCV is possible, with cure rather than viral suppression the goal of treatment. Specifically targeted antiviral therapy against hepatitis C (STAT-C) hopes to improve this low rate of response using small molecules designed to inhibit key viral processes. Protease and polymerase inhibitors are the most studied of the STAT-C small molecules with protease inhibitors being the closest to commercial availability. The most promising of these new approaches to therapy rely on a persistent need for pegylated interferon and ribavirin and may be limited by the development of viral resistance. KeywordsHepatitis C virus (HCV)-Specifically targeted antiviral therapy against hepatitis C (STAT-C)-Polymerase inhibitors-Protease inhibitors-Chronic hepatitis C-Telaprevir-BoceprevirCurrent Hepatitis Reports 08/2010; 9(3):125-132. DOI:10.1007/s11901-010-0043-5
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ABSTRACT: Nowadays the standard of care for hepatitis C therapy is based on pegylated interferon alpha and ribavirin (Peg IFN/RBV). This combination has led to a sustained virological response rate (SVR) of 50 to 80% depending on genotype. This is still low, considering the side effects, overall costs and duration of therapy. So far, strategies to foresee SVR have been described such as genotype, fibrosis stage, viral load and gammaglutamyltransferase.In addition, new data has recently been provided on predictive factors of SVR like genetic polymorphism related to race, insulin resistance and viral kinetics. This review aims to discuss these predictive factors of therapy that might help the decision about starting or discontinuing therapy in chronic HCV infected patients.Annals of hepatology: official journal of the Mexican Association of Hepatology 01/2010; 9 Suppl(supplement):54-60. · 2.19 Impact Factor
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ABSTRACT: Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV therapy but there is little information about safety and efficacy of peginterferon alpha-2a and ribavirin combination therapy in these patients. In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 microg of Pegasys and 800-1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56-66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1-3.1), genotype non-1 OR=1.8 (95% CI 1.1-3.2), BMI<25 OR=2.1 (95% CI 1.3-3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1-3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation. Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients.Liver international: official journal of the International Association for the Study of the Liver 09/2010; 30(8):1173-80. DOI:10.1111/j.1478-3231.2010.02296.x · 4.41 Impact Factor