Update on Hepatitis C Virus

Editor's Notes

• #41: BID, twice daily; QD, once daily. Paul Y. Kwo, MD: Our discussion covers a number of investigational DAAs representing a variety of drug classes, as outlined in this slide.
• #67: BOC, boceprevir; HCV, hepatitis C virus; pegIFN, peginterferon; TVR, telaprevir. Stefan Zeuzem, MD: Formal clinical guidelines are challenging to generate and take, on average, 6-12 months to complete. Because of the rapid developments in HCV therapy, currently the field has chosen to switch to reliance on guidelines based on expert opinion. In 2013, EASL established formal guidelines, which proved to be outdated by the time they were published. For the 2014 annual meeting, EASL presented a revised guidance document based on expert opinion,[1] an approach that would not fulfill strict methodological criteria for practice guidelines but functions better in the rapidly evolving field. EASL has summarized treatment options for patients with genotype 1-6 HCV according to the availability of HCV therapies in European countries.   The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), in collaboration with the International Antiviral Society-USA, were effective in publishing updated guidelines almost immediately after the US Food and Drug Administration (FDA) approvals of simeprevir and sofosbuvir in late 2013.[2] EASL has gone a step further by including drugs that are not yet available but whose approval is anticipated, such as the NS5A inhibitor daclatasvir, whose approval is anticipated this fall in Europe. The EASL guideline does not include any recommendation on additional combination therapies that are anticipated to be approved in Europe in late 2014 or early 2015, including sofosbuvir/ledipasvir and ABT-450/ritonavir/ombitasvir and dasabuvir.   Jordan J. Feld, MD, MPH: The EASL guidelines, in contrast to the AASLD/IDSA guidelines, acknowledge that not every country gets approval and access to new drugs at the same time. Specifically, EASL has included the option of using telaprevir and boceprevir, and dual therapy with peginterferon and ribavirin alone, in settings where newer agents are not yet available. I applaud EASL for taking treatment access into account because the AASLD/IDSA guidelines are much stricter in that regard.   Stefan Zeuzem, MD: The difference, of course, is that the AASLD/IDSA guidelines are written with one country in mind. The European guidelines need to cover approximately 30 countries.   Jordan J. Feld, MD, MPH: Absolutely. I think EASL was right to include the older regimens because it makes for a more universal guideline. Even though the AASLD/IDSA guidelines are written for the United States, it is certainly the case that many non-Americans read them and rely on them, and so it is useful to have some guidance on other options.   Paul Y. Kwo, MD: As new HCV therapies continue to be introduced, it will be helpful for the AASLD/IDSA and EASL guidelines to evolve into living documents that will be revised online periodically rather than waiting for the period of time it usually takes for guidelines to be developed. This is an approach that AASLD/IDSA have already adopted and will ensure that practicing clinicians can access expert treatment advice for their patients.
• #68: HCV, hepatitis C virus; pegIFN, peginterferon. Stefan Zeuzem, MD: In addition to the 6 options recommended for genotype 1 HCV infection, EASL has recommended a range of treatment options for patients with genotypes 2-6 HCV. These include varying durations of sofosbuvir plus ribavirin with or without peginterferon (depending on genotype). Daclatasvir is included as an option for genotypes 3 and 4, and sofosbuvir plus simeprevir is a further option for genotype 4.
• #69: BOC, boceprevir; GT, genotype; HCV, hepatitis C virus; pegIFN, peginterferon; RBV, ribavirin; TVR, telaprevir; WHO, World Health Organization. Paul Y. Kwo, MD: WHO also took the opportunity to present revised guidelines on HCV management at the EASL annual meeting.[3] Significantly, by publishing recommendations on HCV treatment, WHO has demonstrated that it recognizes the importance of treating those with hepatitis C around the world and that all people who are infected should be assessed for candidacy for antiviral therapy.   Jordan J. Feld, MD, MPH: The WHO guidelines have put hepatitis C on the radar screen at an international level, which was not previously true. The specific therapy recommendations contained in the EASL and AASLD/IDSA guidelines are more detailed than the WHO guidelines. However, the fact that WHO is taking hepatitis seriously is very important.   Stefan Zeuzem, MD: I agree, although now that these different guidelines have reinforced the importance of therapy, it also becomes important to find ways to identify patients with HCV. Therefore, EASL and WHO should now consider making further recommendations on how to implement screening strategies across different countries.