Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1
Authors: Michal R. Pijak, Frantisek Gazdik, Stefan Hrusovsky
Journal: Hepatology (2004)

To the Editor: In the recent issue of HEPATOLOGY, Jeffers et al. report the results of the prospective study evaluating responses of black patients with chronic hepatitis C to peginterferon alfa-2a and ribavirin.1 We wish to comment on the role of obesity in interferon resistance in blacks and the predictability of sustained virological response (SVR) based on early virological response (EVR). The black patients in this study were heavier than white patients, a finding that was also observed in a similar study with peginterferon alpha-2b.2 This fact reinforces a hypothesis that obesity might have contributed to poor response to interferon among black patients. Obesity-related comorbidities in blacks, such as diabetes and hypertension, might have contributed to the lower rate of SVR of 19% in the Muir et al. study compared to 26% in the study of Jeffers et al. The apparent lack of body-weight effect in the regression analysis in both studies agrees with earlier observations that weight alone is not a reliable parameter to predict response.3 In fact, obesity was found to be an independent negative predictor of response to antiviral treatment only when defined as body mass index greater than 30 kg/m2.3 Obesity presumably diminishes the effectiveness of interferon by altering its distribution.4 Such a pharmacokinetic difference is supported also by an observation of reduced incidence of adverse events among black patients found by Jeffers et al. Obesity may also induce interferon resistance directly through the alteration of immune function.5 Prospective studies are needed to investigate whether weight reduction or higher doses of interferon could enhance antiviral responsiveness in black patients. With regard to the predictability of SVR, Jeffers at al. are correct in pointing out that all patients with a minimum 2-log decrease in viral load should continue antiviral therapy even if the positive predictive value of EVR defined as undetectable hepatitis C virus (HCV) RNA at week 12 is higher. This conclusion is supported by the finding that a fair proportion (16%) of the patients who had at least 2-log reduction of HCV-RNA but remained detectable achieved SVR. The authors, however, fail to point out that all such patients with genotype l should be retested with a sensitive qualitative polymerase chain reaction (PCR) assay at week 24. Several authors suggested that if HCV-RNA is detectable at week 24, treatment should be stopped because the likelihood of achieving SVR is virtually nil.6-10 For example, Davies et al. showed that of those patients who remained PCR positive at week 24, only 4% achieved SVR, compared with 33% of those who lost virus between weeks 12 and 24.6 Furthermore, the probability of achieving SVR in patients who had 2-log decrease in HCV-RNA but remained PCR positive was about 4 times lower than in those who had undetectable HCV-RNA after 12 weeks. We are curious why this information was not incorporated in the recent American Association for the Study of Liver Disease guidelines.10 Michal R. Pijak M.D.*, Frantisek Gazdik M.D.*, Stefan Hrusovsky M.D.*, * Department of Clinical Immunology Slovak Medical University Bratislava, Slovak Republic.