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: Human leukocyte antigen (HLA) alleles are associated with both the progression of chronic hepatitis C (CHC) and the sustained virological response (SVR) to antiviral therapy. HLA-A*02 is the most common HLA allele in people of European/Caucasian descent and the Chinese and Japanese population. Therefore, we investigated whether HLA-A*02 expression is associated with disease outcome in Chinese CHC patients. Three hundred thirty-one treatment-naïve CHC patients were recruited in this study. The expression of HLA-A*02 was tested by FACS and LABType SSO assays. All patients were treated weekly with pegylated interferon plus ribavirin (PEG-IFN/RBV) according to a standard protocol. Virological response was assessed by TaqMan assay at the 4th, 12th, 24th, and 48th week of therapy, and again at the 24th week post-therapy. By the end of the study, 293 CHC patients, including 144 HLA-A*02-positive patients and 149 HLA-A*02-negative patients, were evaluable for analysis. There were no statistical differences in clinicopathological parameters between HLA-A*02-positive and negative patients before antiviral therapy (P > 0.05). The HLA-A*02-positive patients had a higher rapid virological response (RVR, 74.3 % versus 62.4 %, P = 0.03) and SVR (78.5 % versus 64.4 %, P = 0.01) and a lower relapse rate (4.2 % versus 11.9 %, P = 0.03) than HLA-A*02-negative patients. Multivariable logistic regression analysis showed that HLA-A*02 expression, liver fibrosis stages <S3, HCV genotype 2a, IL-28B rs8099917 TT, and RVR were independent predictive factors of SVR (P < 0.05). Host HLA-A*02 allele expression is associated with SVR, highlighting the importance of considering HLA-A*02 as a predictor of the response to PEG-IFN/RBV treatment in the Chinese population with CHC.Archives of Virology 02/2015; 160(4). DOI:10.1007/s00705-015-2361-y · 2.28 Impact Factor
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ABSTRACT: Patients with chronic hepatitis C (HCV) frequently discontinued dual therapy with pegylated interferon alfa (Peg-IFN) plus ribavirin (RBV) before reaching the recommended duration of 48 or 24 weeks for genotypes (G) 1/4 or 2/3, respectively. We quantified rates of discontinuation despite efficacy (non-LOE) versus lack of efficacy (LOE) versus discontinuation for unknown reasons in a national database of United States veterans. We identified a population-based cohort of U.S. veterans with encounters from 2004 through 2009 who had lab-confirmed HCV infection and initiated therapy with Peg-IFN plus RBV in Veterans Health Administration medical centers. Pharmacy data were used to determine therapy duration, defined as the sum of Peg-IFN days supplied. Patients "discontinued" if they failed to receive at least 44 (G1/4) or 20 weeks (G2/3) of therapy. We classified discontinuations as due to non-LOE, LOE, or unknown reasons using a classification rule based on treatment duration and laboratory confirmed response. Of 321,238 diagnosed HCV patients during the evaluation period, 9.7% initiated therapy and 6.4% met all other inclusion criteria. 54.9% of patients discontinued early; of these, 41.2% discontinued due to non-LOE reasons, 12.5% discontinued for LOE reasons, and 46.3% discontinued for unknown reasons. Among non-LOE discontinuers, most (60.1%) discontinued in the first 4 weeks of therapy, which constitutes 13.6% of all treated patients. We observed a high proportion of early discontinuations with dual-therapy regimens in a national cohort of HCV-infected veterans. If this trend persists in the triple-therapy era, then efforts must be undertaken to improve adherence.BMC Research Notes 04/2014; 7(1):266. DOI:10.1186/1756-0500-7-266
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ABSTRACT: Hepatitis C is a major reason of morbidity and mortality among hemophilia patients. Although combination therapy with peginterferon (peg-INF) and ribavirin is considered as standard treatment for chronic hepatitis C (CHC), but more evidence of the efficacy and safety is needed. In this study, efficacy and tolerability of combination therapy with peginterferon α-2a-ribavirin was investigated among hemophilia HCV infected patients. In a quasi-experimental, 45 naive hemophilia patients with chronic HCV received 180 mg of pegylated interferon (Pegasys) by subcutaneous injection weekly plus an oral dose of 800-1200 µg ribavirin daily according to body weight. The treatment continued 48 weeks in patients with genotype one and 24 weeks in those with genotype 3. Sustained virological response (SVR) was considered as efficacy of treatment. Forty three patients (95.6%) reached to end of treatment response (ETR); only two (4.4%) patients did not respond and were discontinued from treatment. None of 43 patients relapsed. SVR obtained in 43 of 45 patients (95.6%), in multivariate logistic regression model, third month's treatment WBC (WBC > 2000) remained the only significant predictor of SVR. Regimen dose reduced in three patients; two of those because of ALT increasing and other one for his retinal bleeding. In repeated measurement analysis, alanine aminotransferase (ALT) and hemoglobin (Hb) decreased significantly during treatment, but reduction of platelet (PLT) was not significant. CONCLUSONS: Results show high efficacy and safety of combination therapy of Peg-IFN-α 2a plus ribavirin among hemophiliacs with chronic hepatitis C.08/2012; 14(8):466-9.