Provided by NATAP
Jürgen K. Rockstroh M.D., Professor of Medicine
University of Bonn, Germany
Correspondence:
Prof. Dr. J.K. Rockstroh
Department of Medicine I
University of Bonn
Sigmund-Freud-Str. 25
53105 Bonn
Germany
Introduction
Ever since the first DAA based triple therapy for HCV became available treatment paradigms for HCV therapy have subsequently changed significantly and promise cure of HCV infection in around two thirds of treatment naïve HCV-genotype-1 infected patients undergoing triple therapy. Nevertheless, with more widespread use of boceprevir and telaprevir based triple therapy the current challenges of HCV therapy have become quite evident: Adherence issues due to high pill burden and food requirements with tablet intake, high rate of adverse events particularly in patients with more advanced liver disease, multiple drug-drug interactions and finally also significantly lower response rates in more challenging patient populations (cirrhosis, previous null-response to dual therapy, post-transplant treatment etc.). So not so surprisingly after an initial euphoria to offer triple therapy to HCV patients who had waited a long time for more efficacious HCV treatment options, many physicians and patients likewise now seem to wait for easier to take and potentially better tolerated and at best even interferon free new treatment options in the near future. At this year's EASL in Amsterdam with over 9600 delegates the phase III study results for the two "second wave HCV protease inhibitors" faldaprevir and simeprevir each in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) for HCV genotype 1 patients were presented as well as the phase III findings for the polymerase inhibitor sofosbuvir again in combination with PEG-IFN/RBV for treatment of genotypes 1,4,5 and 6. In addition phase III results of the first interferon free combination of sofosbuvir with ribavirin for treatment of genotype 2 and 3 were presented. As these new drugs have been or are about to be filed for licensing it can be expected that at least for the US, approval of these new HCV drugs can be expected 2013/2014. Therefore, with most likely less than a year ahead before these new drugs hit the market the question who to treat now and in whom to wait for improved HCV treatment options has become even more pertinent.
But clearly there is an even more promising future behind these new HCV agents, suggesting interferon free regimens will become available even in more difficult to treat patient populations and for all genotypes in the upcoming years. Again several studies which were presented at EASL allowed a glimpse into this highly promising future. Nevertheless, issues around the potential cost of the HCV drugs to come as well as the question which prediction factors allow us to decide which patient needs how many DAAs and what kind of combination suits which type of patient remain unanswered to the very day. Indeed the high number of compounds and combinations makes it increasingly difficult to follow all studies. Also 100% sustained virological response rates in easy to treat naïve HCV patients with early fibrosis stages and an IL28b CC genotype as well as a 1b infection cannot be automatically transferred to more challenging patient populations. In summary, the HCV field is moving fast and new HCV compounds promising simpler treatment regimens with increased tolerability and shortened treatment durations can be expected soon. In addition first interferon-free treatment approach for genotype 2 and 3 will be available shortly. A successful interferon-free HCV treatment strategy for all patients however, still has not yet arrived.
Why treat hepatitis C?
In consideration of the high costs of HCV therapy many countries in Europe have restricted the use of HCV protease inhibitor based triple therapy to more advanced fibrosis stages. Therefore, it is important that studies look at the impact of HCV therapy on survival in HCV infected individuals in order to demonstrate the benefits of HCV therapy and ultimately demonstrate cost-effectiveness of these treatment approaches. Interesting data in this context was presented at the EASL conference from a retrospective cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) (1). Within this study the predictors of mortality among US HCV infected veterans were evaluated. Overall they were able to compare an impressive number of 195,585 HCV Patients with 202,739 non-HCV infected veterans. The all-cause mortality rate among Veterans with HCV infection was much higher with 43.9 (43.4-44.3) per 1000 person-years (PY) than in Veterans without HCV infection (all-cause mortality was 24.0 (23.7-24.4) per 1000 PY). The table 1 shows the relevant predictors found to impact mortality. Among Veterans with HCV infection, decompensated liver disease, anemia, cancer, chronic kidney disease and COPD were the strongest predictors of higher risk of mortality, while HCV treatment was associated with over 50% reduction in mortality in this group. These findings once again underline the importance of HCV therapy to significantly lower risk of mortality in HCV infected individuals.
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