In a response to the Cochrane Group Review entitled “Direct acting antivirals for chronic hepatitis C,” the European Association for the Study of the Liver (EASL) released a statement pointing out the Group’s “flawed methodological approach” and “ignorance of the natural history of hepatitis C virus (HCV) infection and associated systemic diseases.” The editorial response by EASL was published online in The Journal of Hepatology.
In the Cochrane review by Jakobsen et al., the researchers stated that “DAAs [direct acting antivirals] on the market or under development do not seem to have any effects on risk of serious adverse events [but] we could neither confirm nor reject that DAAs had any clinical effects.” The review deemed all studies and outcome results to be at high risk of bias and the quality of evidence to be “very low.” Moreover, the review did not accept sustained virologic response (SVR) as a critical treatment outcome and did “not accept the likelihood that an SVR will reduce the risks of long-term outcomes of hepatitis C.”
The EASL expressed that these conclusions could negatively impact policymaking and impede the progress for diagnosis, testing, and patient care. The authors added, “It will create dangerous confusion in the mind of patients treated or about to be treated and their families.” Without an available vaccine to prevent HCV, the EASL felt that the Cochrane Review “jeopardises treatment as a necessary intervention.”
SVR, defined as undetectable HCV RNA 12 or 24 weeks post-treatment, has been the primary endpoint in DAA drug development trials. The EASL explained that the benefits of achieving an SVR “cannot be measured in these trials” due to the slow progression of HCV complications and the varying stage of liver disease. The studies analyzed in the Cochrane Review were intended to establish whether infection could be effectively and safely eradicated, and were not adequately powered to assess long-term outcomes. In addition, the EASL felt the Cochrane Review overlooked the possibility of reducing risk of transmission from viremic individuals as well as recent trials that demonstrated an improved quality of life with DAA therapy.
The Cochrane Review also called for randomized clinical trials evaluating the direct effects of DAAs which the EASL felt posed an “ethical anathema of leaving patients untreated to accrue increasing hepatic fibrosis, in the face of treatments that are likely to arrest viral replication in the overwhelming majority.” To illustrate their point, they reference the Tuskegee study, where syphilis patients were left untreated, rather than given penicillin, so that disease progression could be observed.
“Overall, the Cochrane Review displays a lack of understanding of hepatitis C and drug development in the context of a transmissible infectious disease with a long natural history.”
For more information visit journalofhepatology.eu.