Reply:
Authors: John F. Reinus, Allan W. Wolkoff
Journal: Hepatology (2010)

We are grateful to Dr. Ridruejo and colleagues for their comments regarding our article in the April issue of HEPATOLOGY.1 They cite their recently published study of hepatitis C virus (HCV) therapy in 235 patients treated in "routine clinical practice" over an 8-year period at four Argentinean medical centers2 and compare their per-protocol results to the intention-to-treat (ITT) analysis from our single-center study of hepatitis C therapy in U.S. urban minority patients, 56% of whom were self-identified as being of Hispanic origin. We have read their report with interest and offer the following observations that may account for the discrepancies between sustained viral response rates in the two studies. First, for methodological reasons, it is impossible to make meaningful comparisons between their per-protocol results and our ITT results. Second, the ethnic backgrounds of patients in these two studies are likely to have been quite different despite the fact that they are all described as being Hispanic; more than 90% of Argentineans are of Spanish or Italian origin, whereas our Hispanic patients are mostly from the Caribbean or Central America and likely have mixed racial backgrounds. Thus, it cannot be assumed that responses to infection and its treatment should be similar on a genetic basis, as implied. Based on their data, each of the Argentinean centers treated, on average, only seven to eight patients each year, which implies that they were caring for a highly selected group of individuals in a nation of almost 40 million people with an estimated prevalence of hepatitis C of at least 2%.3 These authors state that we believe suboptimal clinical care was the reason for the poor sustained viral response rate in our patients. This is incorrect: we think our dedicated subspecialty liver clinic offered patients better access to more resources specifically designed to help them complete HCV treatment than are available in most other clinical settings. Instead, in our opinion, this study demonstrates that the effectiveness of protracted treatment with drugs that have significant side effects and require careful patient monitoring cannot match the efficacy of such therapy, which is customarily defined by randomized prospective ITT data from carefully controlled trials that do not account for treatment problems encountered in everyday clinical practice. In particular, patients who enter efficacy trials are chosen in part because they are thought to be highly likely to comply with the treatment protocol, whereas in routine clinical practice there is an obligation to attempt therapy in any patient without a contraindication who expresses the desire to be treated. Although efficacy and effectiveness may be nearly identical for short courses of therapy with drugs that do not have significant effects on well-being, it is unrealistic to believe that expected outcomes of difficult treatment regimens like that for HCV are accurately predicted by standard efficacy trials, especially in patients with numerous socioeconomic problems, like the urban minority patients treated at our center. Clinical decisions related to treatment in the latter situations should not be made based on efficacy data alone. John F. Reinus M.D.*, Allan W. Wolkoff M.D. , * Chief of Clinical Hepatology, Montefiore Medical Center, Professor of Clinical Medicine, Albert Einstein College of Medicine, Bronx, NY, Professor of Medicine and Anatomy and Structural Biology, Associate Chair of Medicine for Research, Chief, Division of Hepatology, Albert Einstein College of Medicine, Bronx, NY.