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 incidence and mortality of hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) is higher in African Americans (AA) than other racial/ethnic groups in the U.S., but the reasons for this disparity are unknown. There is an urgent need for the discovery of novel molecular signatures for HCV disease progression to understand the underlying biological basis for this cancer rate disparity to improve the clinical outcome. We performed differential proteomics with isobaric labeling tags for relative and absolute quantitation (iTRAQ) and MS/MS analysis to identify proteins differentially expressed in cirrhotic (CIR) and HCC as compared to normal tissues of Caucasian American (CA) patients. The raw data were analyzed using the ProteinPilot v3.0. Searches were performed against all known sequences populating the Swiss-Prot, Refseq, and TrEMBL databases. Quality control analyses were accomplished using pairwise correlation plots, boxplots, principal component analysis, and unsupervised hierarchical clustering. Supervised analysis was carried out to identify differentially expressed proteins. Candidates were validated in independent cohorts of CA and AA tissues by qRT-PCR or Western blotting. A total of 238 unique proteins were identified. Of those, around 15% were differentially expressed between normal, CIR & HCC groups. Target validation demonstrates racially distinct alteration in the expression of certain proteins. For example, the mRNA expression levels of transferrin (TF) were 2 and18-fold higher in CIR and HCC in AA as compared to CA. Similarly; the expression of Apolipoprotein A1 (APOA1) was 7-fold higher in HCC of AA. This increase was mirrored in the protein expression levels. Interestingly, the level of hepatocyte nuclear factor4a (HNF4a) protein was down regulated in AA, whereas repression of transcription is seen more in CA compared to AA. These data suggest that racial disparities in HCC could be a consequence of differential dysregulation of HNF4a transcriptional activity. This study identifies novel molecular signatures in HCV-induced HCC using iTRAQ-based tissue proteomics. The proteins identified will further enhance a molecular explanation to the biochemical mechanism(s) that may play a role in HCC racial disparities.Journal of Translational Medicine 01/2013; 11(1):239. DOI:10.1186/1479-5876-11-239 · 3.99 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the real outcomes of chronic hepatitis C patients, who treated with interferon plus ribavirin (INF-RBV) and peg-interferon plus ribavirin (PEG-RBV). Despite the PEG-RBV has become a standard treatment of hepatitis C virus (HCV) around the world; and in Iran too, but in developing countries like as Iran, INF-RBV is still used among some patients for treating HCV, due to the high costs of treatment with PEG-RBV. The present cross-sectional study was conducted on 77 naïve patients referred to a private gastroenterology clinic between years 2007 through 2009 in Tehran. Patients had participated in this study taking two types of combination therapies, based on standard protocol of the Iranian Ministry of Health. At the end of the treatment, sustain virological response (SVR) rate was evaluated. The outcomes showed in INF-RBV treatment; 11.6%, 16.3% and 34.9% patients were suffered from relapse, lost follow-up their treatment and non-responder, respectively, and finally 37.2% of the patients reached SVR. In PEG-RBV treatment outcomes were as follows; 2.9%, 14.7% and 14.7% patients were non-responder, lost follow-up their treatment and suffered from a relapse, respectively, and 67.6% of the patients reached SVR. The multivariate-adjusted odds ratios of outcomes showed that treated with PEG-RIB and also genotype 3a than the others genotypes in this treated had more chance to achieved SVR. The findings of the present study showed that the rate of SVR in patients who treated with PEG-RBV significantly was higher than patients who treated with INF-RBV. Also in PEG-RBV the chance of achieving SVR is higher among the patients with genotype 3a than among those with other genotypes.01/2013; 6(Suppl 1):S58-64.
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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:10.1186/1756-0500-7-266This article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.