Black patients with chronic hepatitis C have a lower sustained viral response rate than non‐Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin*

Bräu, Norbert; Bini, Edmund J.; Currie, Sue; Shen, Hui; Schmidt, Warren N.; King, Paul D.; Ho, Samuel B.; Cheung, Ramsey; Hu, Ke; Anand, B S; Simon, F. R.; Aytaman, Ayse; Johnson, David; Awad, Joseph; Ahmad, Jawad; Mendenhall, Charles L.; Pedrosa, Marcos; Moseley, Richard H.; Hagedorn, Curt H.; Waters, Bradford; Chang, Kyong–Mi; Morgan, Tim; Rossi, Stephen J.; Jeffers, Lennox J.; Wright, Teresa L.

doi:10.1111/j.1365-2893.2005.00682.x

Cited by 39 publications

(41 citation statements)

References 22 publications

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“…[4][5][6]16 Our results confirm studies that found that African Americans had significantly lower SVR rates than did whites [17][18][19] and that patients who had not responded to a prior course of nonpegylated interferon also had a lower SVR rate. 20 Our finding of a decreased SVR rate among patients with diabetes supports recent work indicating that insulin resistance impairs the response to PEG-INF/ ribavirin.…”

Section: Discussionsupporting

confidence: 80%

Predictors of response of U.S. veterans to treatment for the hepatitis C virus

et al. 2007

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The currently recommended treatment for hepatitis C virus (HCV) infection is pegylated interferon alfa (PEG-INF) and ribavirin, which can be difficult to tolerate. More information about predicting sustained virologic response (SVR) may allow more informed treatment decisions to be made. This retrospective observational cohort study identified predictors of SVR to PEG-INF and ribavirin in routine medical practice at 121 Department of Veterans Affairs facilities. Among 5,944 patients infected with HCV genotypes 1, 2, or 3 who had been treated with PEG-INF and ribavirin, SVR rates were 20%, 52%, and 43%, respectively, and discontinuation rates were 68% (prior to 48 weeks), 34% (24 weeks), and 41% (24 weeks), respectively. In multivariate analysis, significant predictors of decreased likelihood of genotype 1 patients having an SVR were being African American, clinical liver disease, diabetes, low cholesterol, low hemoglobin, low platelet count, and treatment at a low-volume facility. Predictors of increased likelihood of genotype 1 patients having an SVR were low-level HCV viremia, elevated ALT quotient, and receiving PEG-INF 2A (rather than 2B). For genotype 2 patients, increasing body mass index, prior use of interferon, and low platelet count were negative predictors; only low-level HCV viremia was a positive predictor. For genotype 3 patients, only receiving PEG-INF 2A affected the likelihood of an SVR; its effect was positive. Conclusion: Among patients for whom HCV treatment is initiated during routine medical care, multiple factors including form of PEG-INF received affect the SVR rate for genotype 1 patients. Few of these factors affect the rate for genotype 2 patients, and even fewer do so for genotype 3 patients. (HEPATOLOGY 2007;46:37-47.)

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Section: Discussionsupporting

confidence: 80%

Predictors of response of U.S. veterans to treatment for the hepatitis C virus

et al. 2007

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“…Because low treatment rates in African American patients may be explained by the high prevalence of genotype-1 HCV, we also entered an interaction term between race and genotype in the model. 29 Provider factors included provider type, clinical experience, and continuity of primary care. We identified provider type based on the clinics where PCP (clinic codes 323, 322, 348, 350) and specialists (clinic codes 307, 454) provided care for the study cohort.…”

Section: Predictorsmentioning

confidence: 99%

Predictors of treatment in patients with chronic hepatitis C infection-Role of patient versus nonpatient factors

et al. 2007

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Treatment with interferon and ribavirin is effective in patients with chronic infection with hepatitis C virus (HCV). Previous data indicate that treatment rates are suboptimal. We sought to identify patient and provider-level predictors of treatment receipt in HCV by conducting a retrospective cohort study of 5701 HCV patients in a large regional Veteran's Administration (VA) healthcare network. We also determined the degree of variation in treatment rates attributable to patient, provider, and facility factors. Three thousand seven hundred forty-three patients (65%) were seen by a specialist and 894 ( C hronic hepatitis C virus infection (HCV) is a prevalent and expensive condition affecting more than 1.3% of the U.S. population at a cost of over $700 million annually. 1-3 HCV is the leading cause of cirrhosis, hepatocellular cancer, and death of liver disease in the United States and is the primary indication for liver transplantation worldwide. 3,4 The economic burden of HCV is multiplied by the negative impact of HCV on health-related quality of life. 5 Treatment with interferon and ribavirin is effective and results not only in reducing liver disease progression, but also improving health-related quality of life among patients with sustained viral response. [6][7][8][9] Given the burden of illness, several professional societies have published evidence-based guidelines defining the best practices and standards of treatment in HCV. These include the American Association for the Study of Liver Disease, the National Institutes of Health, the American Gastroenterology Association, and the Veterans Administration (VA). 10-13 Despite these well-disseminated guidelines, recent data indicate deficits in HCV care. Several reports demonstrate that antiviral treatment rates among HCV patients are lower than 30%, generally attributed to the high prevalence of treatment contraindications. 14-18 However, even among patients otherwise eligible for treatment, the reported treatment rates range from 45% to 75%, suggesting that factors other than treatment contraindications may be important determinants of treatment receipt. [14][15][16]18 Recent studies suggest

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“…African Americans (AA) are infected with HCV genotype 1 at a much higher rate than Caucasian Americans (CA) (91% vs. 70%, respectively) (4), and SVR rates are lower in AA (19-28%) compared to CA (39-52%) (9)(10)(11). These racial differences are not likely explained by differences in frequency of ribavirin dose reductions or PEGIFN systemic exposure (12,13). Although IL-28B polymorphism is a known predictor of SVR, the interaction between ribavirin exposure, race, IL-28B genotypes (CC, CT, and TT), and SVR has not been fully explored.…”

Section: Introductionmentioning

confidence: 96%

Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

Jin

Fossler

McHutchison

et al. 2012

AAPS J

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Abstract. We report a population pharmacokinetic (PK) and pharmacodynamic (PD) model of orally administered ribavirin in patients with chronic hepatitis C virus (HCV) infection enrolled in a multicenter clinical trial, including the estimation of covariate effects on ribavirin PK parameters and sustained viral response (SVR). Ribavirin concentrations obtained from 144 patients, consisting of n=71 African American (AA) and n=73 Caucasian Americans (CA), during 24 weeks of therapy were best described by a twocompartment model with first-order absorption and elimination parameterized in terms of apparent oral clearance (CL/F), apparent central volume (Vc/F), apparent peripheral volume (Vp/F), and apparent intercompartmental clearance (Q/F). The typical population parameters were CL/F (19.0 L/h), Vc/F (1,130 L), Vp/F (4,020 L), and Q/F (38.6). The Vp/F was approximately 50% greater in AA compared to CA. Significant covariates in the SVR model included IL-28B genotype, homeostasis model assessment of insulin resistance, and ribavirin exposure during the first week (AUC 0−7 ). The population PK and logistic regression models both described the observed ribavirin concentration data and SVR data well. These findings suggest that optimization of ribavirin plasma concentrations during the first week of ribavirin dosing is most critical in AA patients in order to increase the rate of SVR, especially those with the IL-28B TT genotype.

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Black patients with chronic hepatitis C have a lower sustained viral response rate than non‐Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin*

Cited by 39 publications

References 22 publications

Predictors of response of U.S. veterans to treatment for the hepatitis C virus

Predictors of response of U.S. veterans to treatment for the hepatitis C virus

Predictors of treatment in patients with chronic hepatitis C infection-Role of patient versus nonpatient factors

Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

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