March 21, 2014

New HCV Guidance: Rapid Updates for Clinicians

Medscape Gastroenterology

Laura A. Stokowski, RN, MS, Helen W. Boucher, MD, Paul Martin, MD
March 21, 2014

HCV Science Catching Up to Medical Need

In just 2 or 3 years, the pace of progress in the treatment of hepatitis C virus (HCV) infection has been fairly dramatic. A swift and steady stream of new drugs has challenged clinicians to keep up with the latest recommendations for therapy, and the pipeline is far from dry. The next wave of direct-acting antivirals will continue to target the HCV life cycle from different angles, and combining molecules with different mechanisms of action, different resistance profile, and high antiviral activity will be the name of the game.[1]

Safer, shorter, and more durable treatments are anxiously awaited by many patients already infected with HCV, who have been forestalling treatment or retreatment while waiting for all-oral, interferon-free regimens that will cure their infections without the adverse effects associated with previous drugs. For the rest of the estimated 2-3 million individuals infected with HCV in the United States, all the new drugs in the world are of scant worth if these infections remain undiagnosed.

The recommendation to add a 1-time HCV birth cohort screening for "baby boomers" to exposure risk-based screening[2] is expected to identify more than 800,000 new cases of chronic HCV infection in the United States.[3] Many clinicians -- from those on the frontlines of primary care to the specialists who are experienced in managing HCV and its complications -- will be needed to cope with the burgeoning newly diagnosed population.

The rapid advances in the field of HCV prompted the Infectious Diseases Society of America (IDSA) and the American Association for the Study of Liver Diseases (AASLD), in collaboration with the International Antiviral Society-USA (IAS-USA), to sponsor an effort to synthesize the current evidence in the field, from which was derived a set of expert-developed recommendations for the management of HCV infection, a feat that was accomplished remarkably quickly. The first phase of the HCV guidance, available online at HCVguidelines.org, details the methodology used to develop the guidance, and covers the following sections related to diagnosis, referral, and management:

  • HCV Testing and Linkage to Care;

  • Initial Treatment of HCV Infection in Patients Starting Treatment;

  • Retreatment of Persons in Whom Prior Therapy Has Failed; and

  • Unique Patient Populations (HIV/HCV coinfection, cirrhosis, transplantation, renal impairment).

Sections ("coming soon") that are now being developed for updates of the guidance include:

  • In Whom and When to Initiate Treatment;

  • Monitoring Patients Who Are On or Have Completed Therapy; and

  • Management of Acute HCV Infection.

Clinicians will appreciate the color-coded treatment guidance within the report, allowing them to distinguish at a glance "recommended" (outlined in green) from the "not recommended" (outlined in red) treatment regimens. Each section of the report ends with a quick reference summary of recommendations, and useful resources are provided at exactly the point they might be needed. For example, the section on testing includes a table of commercially available, US Food and Drug Administration-approved anti-HCV screening assays, and a simple algorithm of the recommended sequence for screening, testing, and linking patients to care for ongoing evaluation and management.

Medscape Talks to Paul Martin, MD, and Helen W. Boucher, MD, for Perspectives on New HCV Guidance

Medscape recently spoke with Dr. Paul Martin, a hepatologist and member of the guidance writing panel, and Dr. Helen W. Boucher, an infectious diseases specialist, about the new HCV guidance, including key points of emphasis about the content of the guidance, the implications for clinical practice, and what clinicians can expect in the way of updates.

Medscape: HCV treatment is still in flux -- it almost seems impossible to settle on treatment guidelines. How did the HCV guidance first come about?
Dr. Boucher: The HCV guidance was sponsored by the IDSA and the AASLD, with IAS-USA as the collaborating partner. The 2 societies have decided that the best way forward with the treatment of hepatitis C infection is to collaborate, and I think what is so exciting about this new guidance is the partnership behind it. We have recognized the need to provide up-to-date information, and that is what our societies have done with this guidance. The speed with which the guidance document was achieved was extremely noteworthy.

Medscape: You refer to the HCV guidance as a "living document." How does this differ from the model that we are accustomed to in medicine?

Dr. Martin: The whole area of hepatitis C treatment is evolving so rapidly that we felt that it was crucial that treating healthcare providers have access to up-to-date information. The more traditional practice guidelines go through a detailed process and take some time to appear in print. Clearly, however, this whole field is moving so rapidly that we felt that it was best to have our recommendations online as soon as possible. As far as updating it, the same panel will be involved, and additional experts may be invited to participate for specific topics. The idea is that this will be updated on a regular basis. We plan to add additional sections later on. Clearly, however, the HCV guidance reflects treatment options in the United States, as these new drugs may not yet be licensed in other countries where different standards of care exist.

I think this is probably going to be the wave of the future, because we are all now so dependent on the Internet for information. We use the Internet in the office to research clinical questions when a patient is being seen, and I think practice guidelines in the future will reflect what we have done and mirror this sort of model. Speed and completeness are going to be the watchwords of the future.

Medscape: Is it significant that the document is called "HCV Guidance" rather than "HCV Guidelines"?

Dr. Martin: Yes. We view it that guidelines are typically developed after a protracted process, and the word "guidance" reflects the need to make recommendations available to potential treaters in a relatively short period. The recommendations are still based on a combination of review of the literature and consensus of expert opinion, but we view guidance as reflecting an up-to-date process.

Dr. Boucher: We were (and still are) experiencing an explosion of information about how best to treat patients with HCV, similar to what happened with HIV years ago The IAS-USA has done something similar, in a very high-quality way, for HIV/AIDS.

Medscape: With the recommendation to test all "baby boomers" (people born between 1945 and 1965) in addition to risk-based screening, the numbers of individuals with active hepatitis C infection are going to climb in the near future, and concerns have been raised about having enough healthcare providers to evaluate and treat all of these individuals.

In the section on testing and linkage to care, it says, "All patients with current HCV infection and a positive HCV RNA test result should be evaluated by a practitioner with expertise in assessment of liver disease severity and HCV treatment." Does this mean that primary care/internal medicine practitioners should refer all newly diagnosed patients to liver specialists?

Dr. Martin: We didn't restrict management of HCV to any particular discipline. The key thing is in managing hepatitis C is that although you are managing a viral disease, you are also managing the liver disease. We didn't seek to preclude any type of healthcare practitioner from caring for these patients, but we wanted to recommend that patients be seen by somebody who can not only treat the viral infection but also understands that the severity of the liver disease needs to be addressed -- because ultimately that is going to determine, or be an important component of determining, the patient's prognosis.

Dr. Boucher: The important point is that the patient ends up with a healthcare practitioner who is expert in managing his or her disease. Many physicians are expert in treating HCV. Some are infectious diseases trained, and some are gastroenterology/hepatology trained. It differs by medical center; there are no absolutes.

Medscape: In the section about initiating treatment, as written today, what would you most like to draw clinicians' attention to?

Dr. Martin: The most important point is endorsing the use of the combination of sofosbuvir and simeprevir in the treatment of hepatitis C and discouraging the use of telaprevir- and boceprevir-containing regimens. These drugs are still approved for use, although they are associated with higher rates of adverse effects, such as rash and anemia.

Medscape: If a patient has already been started on a regimen involving either telaprevir or boceprevir, would you switch to a different combination, or allow the patient to complete the treatment?
Dr. Martin: If a patient is already doing well on treatment, there is no need to switch therapy.

Medscape: How important is genotyping in tailoring treatment to the patient?

Dr. Martin: Genotyping is key to picking the optimal regimen.

Medscape: Can you speak a little about the progress toward an all-oral, interferon-free treatment for hepatitis C?
Dr. Martin: In my mind, it has already arrived. We are in the first phase of it already. Obviously, interferon is still part of a number of regimens, but as we speak, many patients are receiving all oral therapies

It depends on the genotype. For patients with genotype 1, we have the COSMOS protocol, which is a combination of simeprevir and sofosbuvir. For patients with some non-genotype 1 infections, there is the option of using sofosbuvir with ribavirin, for instance.

In general, therefore, we are seeing an increased use of these all-oral regimens. This reflects what has been approved as of the date that the guidance was generated. A drug such as the NS5A replication complex inhibitor daclatasvir will be part of the revised treatment strategy if and when it has been approved.

Medscape: We hear talk of an "avalanche" of drugs in the HCV pipeline, and that some of the drugs are pan-genotypic: For example, a drug such as the NS5A replication complex inhibitor daclatasvir might become part of a revised treatment strategy if approved. Can we really expect this many new drugs, and how will you keep this manageable for clinicians who must keep up to date with new drugs all the time?

Dr. Martin: "Avalanche" might be overstating it. I would describe it as a very good developmental pipeline, and I think we are going to see continued advances related to the licensing of new drugs. We will probably see several more drugs licensed in the next 1-2 years. It will certainly be challenging to help clinicians keep them all straight, but that is one of the reasons we were interested in developing these guidelines and, in fact, the reason that they are called hepatitis C "guidance" rather than "guidelines." It is a huge amount of information, and it needs to be updated frequently.

Medscape: How much concern do you have about the development of resistance to these drugs?

Dr. Martin: When we are seeing sustained virologic response rates now routinely in excess of 90%, clearly resistance is going to be substantially less of a concern, because most patients are going to be cured by a single course of treatment. That being said, I don't think anybody thinks resistance is going to go away. However, the key to managing or preventing resistance is to very effectively treat the infection with the best drug combination available and to eradicate the infection the first time around.

Medscape: In the guidance document, you don't mention cost of treatment at all. It is understandable that you wouldn't want to get into that, but would you be willing to comment on the reports about the high cost of these drugs?

Dr. Martin: It is fair to say that the more treatment options that there are, the more price pressure there will be on the individual companies to license or sell their drugs at a competitive price. It is very expensive to take care of a patient with advanced liver disease -- not just the cost of a liver transplant, but a patient with advanced liver disease who is in and out of hospital with one complication after another is enormously resource-intensive for the system. If we can abort the progression of liver disease, we are ultimately going to have a major impact on healthcare costs related to hepatitis C. Many patients with hepatitis C may elect to wait for less expensive regimens if their liver disease is mild.

Medscape: Is there anything else practice-changing about the guidance document, as it stands today, that you would like to mention?

Dr. Martin: It is critically important that patients are seen by practitioners who are comfortable managing and treating hepatitis C. We don't want to restrict anyone from taking care of these patients, but we want to make sure that patients have the appropriate work-up. Patients with advanced liver disease who may need additional consideration, such as a liver transplant, should be referred for specialty care. Another group of patients who might need referral are those who are coinfected with HIV, who might need expertise in HIV management.

Dr. Boucher: We hope that primary care practitioners will use the guidance to help them decide who needs a referral and when.

Medscape: How do you plan to disseminate the guidance to clinicians, both now and when there is updated guidance that you want to make them aware of?

Dr. Boucher: I believe that the plan is to use the Website www.hcvguidelines.org as the major point of dissemination.

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