I read with interest the paper by Maasoumy et al. examining the concordance between different PCR assays measuring on-treatment hepatitis C virus (HCV) RNA levels and correlating this with sustained virological response (SVR) rates.1 The importance of early PCR results in determining the success of triple therapy was established in the large phase 3 pre-licensing clinical trials and forms the basis of the clinical decision to shorten therapy to 24 weeks.2, 3 The importance of differentiating detectable but below the limit of quantification (BLOQ) vs. not detectable (ND) RNA levels was demonstrated by Harrington et al. who showed that subjects treated with both the first generation protease inhibitors had on average 20% less SVR rates if HCV RNA levels were detectable but BLOQ at the early time point, compared with those that were ND.4 The paper by Massoumy et al. further adds to our knowledge. While they did not set out to study the differences among the three assays used in this pilot, they did show that the HPS/TAQMAN Test v2.0 (used in all the clinical trials) did overestimate the proportion of patients with truly ND RNA levels. Furthermore, when the RNA levels were concordantly ND, the SVR rates were 100% compared with 50% when one assay measured the sample as detectable but BLOQ. It will be important to see if these findings can be replicated in a larger scale study. One of the strengths of the study is the high proportion of cirrhotics and treatment-experienced subjects included, reflecting everyday clinical practice in many centres. However, given the size of the study, some of the assertions made must be treated with some caution. What remains unclear is whether the authors are advocating retesting week 4 samples in difficult to treat patients using the same machine in any given institution, and if so how many times? Or are they advocating relying on more than one type of assay, something that would be very difficult to deliver in practice? Finally, although these findings are of relevance in the clinical use of the first generation of protease inhibitors, the introduction of newer and more potent directly acting anti-viral agents may make the measurement of on-treatment HCV RNA levels a thing of a past.5 Declaration of personal interests: AME has received lecture fees from Merck Sharpe Dome, Janssen-Cilaq and Abbott. Declaration of funding interests: None.
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Apr 1, 2016
Laura Rodríguez-Martín + 7
Open Access