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Chronic hepatitis C virus (HCV) infection is a major public health burden in the United States and worldwide. Between 2% and 3% of the world’s population has chronic HCV infection, although significant geographic variation results in a prevalence of chronic HCV of 10% in certain countries. As a result, complications of chronic HCV infection (mostly end-stage liver disease and hepatocellular carcinoma) comprise the leading indications for liver transplantation worldwide. Phylogenetic analysis has led to the description of 6 major viral genotypes, numbered 1 through 6, that differ from each other by 30% at the nucleotide level over the viral genome. The major genotypes can, in turn, be divided into subtypes (e.g., 1a or 1b) that differ by 20%. Interferon (IFN)– based regimens have been the mainstay of HCV treatment for nearly 2 decades [1, 2]. Patients with genotype 1 infection experience substantially lower rates of sustained virologic response (SVR), defined as an undetectable serum HCV RNA level 24 weeks after the end of treatment, compared with patients with HCV genotype 2 or 3 infection. With best current therapy consisting of peginterferon and ribavirin, genotype 1 infection is associated with a 45%–55% rate of SVR, whereas genotype 2 or 3 infection is associated with a 75%– 80% rate of SVR. This observation underscores the importance of viral factors in determining the response to IFN-based therapy. It has also become apparent that host factors influence the response to antiviral therapy. Several independent studies have shown that African Americans experience consistently lower rates of SVR to IFNbased regimens, compared with white persons [3– 6]. In the Study of Viral Resistance to Antiviral Therapy of Hepatitis C (Virahep-C), a multicenter trial comparing the rates of response to peginterferon and ribavirin among 205 white and 196 African American patients with chronic genotype 1 infection, only 28% of African American patients attained SVR, compared with 52% of white patients [5]. The association between African American race and decreased IFN responsiveness remained significant even after adjustment for baseline HCV RNA level, sex, age, weight, stage of hepatic fibrosis, or amount of peginterferon or ribavirin taken. Intriguingly, this study also showed that only 10% of African American patients had an undetectable HCV RNA level after 4 weeks of therapy, compared with 22% of white patients, demonstrating that at least some of the difference in IFN responsiveness between African American and white patients could be explained by differences in early viral kinetics. The article by Hoofnagle et al. [5] in this issue of the Journal extends this observation by analyzing HCV early viral kinetics in response to peginterferon and ribavirin in 301 patients (of whom 154 were African American and 187 were white) from the Virahep-C study population. Three kinetic measurements were assessed: the first-phase response, defined in this study as the decrease in HCV RNA levels between baseline and 24 or 48 h after the first dose of peginterferon, whichever was greater; the second-phase response, defined as the maximum weekly decrease in HCV RNA levels between days 7 and 28 or days 14 and 28, whichever was greater; and the total decrease from baseline to week 28. All 3 responses were predictive of SVR, although the 28-day decrease was most predictive by receiver operating curve analysis. The most striking finding of the study was that the ultimate antiviral efficacy of a 48-week course of IFN-based therapy for chronic HCV infection was, to a significant degree, determined by the viral kinetics only 24 – 48 Received 4 November 2008; accepted 4 November 2008; electronically published 24 March 2009. Potential conflicts of interest: none reported. Financial support: none reported. Reprints or correspondence: Dr. Raymond T. Chung, Gastrointestinal Unit, Massachusetts General Hospital, WRN 1007, 55 Fruit St., Boston, MA 02114 (rtchung@partners.org). The Journal of Infectious Diseases 2009; 199:1101–3 © 2009 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2009/19908-0001$15.00 DOI: 10.1086/597385 E D I T O R I A L C O M M E N T A R Y

Racial Differences in Response to Interferon‐Based Antiviral Therapy for Hepatitis C Virus Infection: A Hardwiring Issue?