From Medscape Education Infectious Diseases
Michael W. Fried, MD CME Released: 03/28/2012; Valid for credit through 03/28/2013
Introduction
Hepatitis C virus (HCV) infection has been called both the silent epidemic[1] and the silent killer;[2] it is both. Recent estimates are that there are at least 5.2 million people in the United States with HCV infection.[3] Although the Institute of Medicine report "Hepatitis and Liver Cancer" predates the availability of the HCV protease inhibitors for the treatment of genotype 1 chronic HCV infection, it underscores an important observation -- that advancements in the treatment of viral hepatitis in general will not in and of themselves decrease the burden of disease if people are not screened for both risk factors and presence of infection; diagnosed; or once diagnosed, referred to specialists and provided appropriate care.[4] In other words, the best treatments cannot benefit those who have no access to them, regardless of the reason. Lack of awareness among the general public and primary care providers (PCPs) about the prevalence of chronic HCV infection and failure to appreciate the serious burden of HCV will continue to impede efforts to prevent and control HCV infection in the era of the HCV protease inhibitors. The gap between the millions of people in the United States with untreated chronic HCV infection and the available treatments has been referred to as a treatment bottleneck, in which the capacity of healthcare providers with expertise in the treatment of these patients is overwhelmed. Thus, even when patients are screened and diagnosed, they may either not be referred for treatment, or if referred, they may wait as long as a 8 months for an appointment.[5]
Medscape spoke with Michael W. Fried, MD, Professor of Medicine and Director of Hepatology at the University of North Carolina School of Medicine, Chapel Hill, North Carolina, about various solutions to enhanced coordination of care and linkage of HCV-infected persons with treatment services.
Medscape: What is meant by the term "HCV bottleneck," and what problems does it create?
Michael Fried, MD: The HCV bottleneck can refer to several issues. Not everyone with chronic HCV infection is aware of his/her HCV status. When we talk about barriers to getting treatment for chronic HCV infection, 1 of the biggest barriers is that the vast majority of Americans living with chronic HCV infection have not been diagnosed.
A study published in the February 21, 2012 issue of Annals of Internal Medicine found that it was cost-effective to target HCV screening at the baby-boomer generation -- those born between 1945 and 1965.[6] It is very cost effective to use birth-cohort screening for HCV since, with the current program we are using -- a risk-based screening program -- very few of those patients are actually being identified as having HCV infection. By screening an age cohort, in which we know that older patients have the highest prevalence of chronic HCV infection, we might diagnose an additional 1 million cases that were not diagnosed otherwise.
Part of the bottleneck is the initial diagnosis. By the way, the issue with diagnosis is partly related to the lack of awareness of chronic HCV infection. Even though we had screening recommendations based on risk for many years, sometimes patients do not admit to risk factors that would trigger screening. Other times, primary care providers (PCPs) may not be familiar with the screening guidelines or the next steps in management. PCPs may not inquire about risk factors because they feel uncomfortable with asking these questions. Finally, PCPs may not test for HCV infection (even when they know that their patients have risk factors or even when they find an abnormal alanine transaminase level). Birth cohort screening would also obviate the need to inquire about risk factors and could lead to increased screening and diagnosis. The first steps in addressing the bottleneck issue are raising patients' and PCPs' awareness of chronic HCV infection and making the diagnosis in infected patients.
Still, once you identify all these patients, the questions then become, "What do you do with them? How do you get them into appropriate evaluation, provide education about the disease, and properly treat those patients who are candidates for therapy?" Those are also big challenges. There is a large backlog at most offices to see patients with chronic HCV infection; there are a lot of patients and there are not a lot of providers who will give the specialized care and treatment that are needed. Right now we can have a big impact on disease outcomes if we identify the patients at risk who have chronic HCV infection. There are strategies that PCPs can use to mitigate the disease while patients are waiting to be seen by specialists. PCPs can counsel at-risk patients on minimizing the risk for liver disease progression through lifestyle modification (eg, minimizing alcohol intake, maintaining an ideal body weight) to prevent the additive effects of fatty liver disease.
Medscape: Is the present model of liver specialist care sustainable? And if not, why?
It is probably not sustainable. Specialists -- ie, hepatologists, gastroenterologists -- are overwhelmed by the number of patients that are seeking care. One of the reasons for the increased number of patients seeking care is the availability of new treatments. With treatment using these new medications, many patients have an increased likelihood of achieving a sustained virologic response (SVR), so more patients are interested in hearing about new treatments.[7-10] We have to disseminate the care beyond the liver disease specialist, if possible.
Medscape: It goes back to the 2 prongs of the bottleneck that you outlined. People are not being diagnosed, and they are not being treated, so if you fix that problem of people being diagnosed, will you make the bottleneck worse?
Dr Fried: It increases 1 of the other problems: having the PCP capacity to see and to treat all these patients.
Medscape: Are you saying that the model is not sustainable because it already is not working?
Dr Fried: It is working to some extent, but it is clear that there are more people out there with chronic HCV infection. And even those who are diagnosed now have long wait times for appointments to see specialists. Fortunately, the natural history of chronic HCV infection is that it is not immediately life threatening. Although HCV can be appropriately self-concerning to patients when they are diagnosed, its natural history does not change in 1 week, 1 month, or even 1 year. So, patients can wait to see specialty providers. Again, as more and more people are diagnosed and more and more patients are interested in being treated, we need to find other ways to improve the capacity of PCPs to care for these patients.
Medscape: You mentioned mitigating disease progression; I find that very interesting. Most of the literature that I have seen talks about the 2 prongs: that people need to be aware of chronic HCV infection and that PCPs need to refer patients to specialists in order for patients to get linked to care. I have not seen much about the need for the PCPs to, as you said, mitigate disease progression. It is a really important point.
Dr Fried: It is. PCPs can do a lot. As I mentioned, PCPs can counsel about lifestyle; that is very important. It is also important to note that PCPs are not always aware that chronic HCV infection is not uniformly fatal -- that it is a slowly progressive disease that can be treated; those messages of hope need to be given to patients at the time of diagnosis. Secondly, when patients are diagnosed with chronic HCV infection, they are usually very concerned about the impact on their family, spouses, partners; it is very important to explain to patients that HCV infection is not easily transmitted outside of direct blood-to-blood contact. Reassuring patients about the small risk for transmission of HCV infection to sexual partners and the virtual absence of risk for transmission to household contacts and family members is really important. Then, PCPs can address making sure that appropriate contacts (eg, spouses, partners, children) are tested for HCV infection, if it is recommended. PCPs can also verify immunity to hepatitis A virus and hepatitis B virus and perform appropriate vaccinations in those patients. Those things, if done before referral, will help the specialists and also provide great reassurance to patients.
Medscape: Prevention and health maintenance strategies are right up the alley, so to speak, of the PCP. Why are those strategies being missed by PCPs?
Dr Fried: A lot of it is a question of education and time. I want to stress that there are a lot of really excellent PCPs who use these strategies to educate patients -- don't get me wrong -- but I think there needs to be a specific conversation, with the PCP saying, "You have chronic HCV infection; here are the things you need to know and here are the things I need to do. And when you get to the specialty care provider, he/she will have all of this information." It will help specialty care providers focus more on some of the positive messages about disease outcomes as well as the treatment issues.
Medscape: There are algorithms for diagnosis and treatment; is there something analogous to that for counseling during the evaluation and diagnosis process? For example, is there a pocket guide or an algorithm that PCPs can look up on their iPad or iPhone and say, "Okay, it is HCV. I need to ask about this, this, this, and this."
Dr Fried: That is a good point. I do not know of any resource other than the guidelines from the Centers for Disease Control and Prevention and specialty organizations, such as the American Association for the Study of Liver Diseases. I'm not familiar with the primary care literature, so I do not know what is out there.
Medscape: It is been suggested that physicians in other specialties (ie, primary care, infectious diseases) begin treating patients with chronic HCV infection. What are your thoughts about this as a potential solution to the bottleneck? Is it feasible for a PCP who sees 30 patients a day to add care of patients with chronic HCV infection to his or her practice?
Dr Fried: We touched upon this a bit. Those early stages of education and disease mitigation fall within the PCP's realm. At the present time, I do not believe that with the complexities of the treatment regimens that involve pegylated interferon plus ribavirin, and now the addition of a protease inhibitor -- either boceprevir or telaprevir -- to the regimen, that it is feasible for a PCP to treat chronic HCV infection.
Although the protease inhibitors substantially increase the SVR over dual-therapy regimens of peginterferon plus ribavirin, these regimens are complicated; there is a learning curve. There are a lot of adverse events that need to be very closely managed. Unless this is a major focus of their practice, I think it would be very difficult for a PCP to manage the treatment of patients with chronic HCV infection. It would certainly be feasible and important for PCPs to comanage their patients with chronic HCV infection on treatment.
That said, there are some interesting models being demonstrated to determine if PCPs, with the right mentoring, can provide highly specialized care. I think the most promising model is Project ECHO (Extension for Community Healthcare Outcomes)[11] developed by Sanjeev Arora, MD, at the University of New Mexico. Over the past year, this model has received a lot of interest from various stakeholders. Project ECHO involves a Web-based mentoring program where Dr Arora and his team discuss actual cases on a 2-way Webcam-based system; the PCPs in rural New Mexico are presenting cases to the specialty providers at the University of New Mexico. They have a team of people that they meet on a weekly basis, and they review all the cases. They do not actually see the patients, so this is not strictly telemedicine, in which a single doctor is providing Web-based care directly to a patient. It is telementoring, where the University of New Mexico team is working with what it calls "a knowledge network," to comanage these patients in the rural PCP practices.[11] Over time, because of this mentoring, the PCPs become more highly skilled at managing patients with chronic HCV infection.
Dr Arora compared outcomes of the specialty team at University of New Mexico to the Project ECHO rural PCPs;[5] PCP outcomes, in terms of SVR and adverse event management, were nearly identical to the outcomes of the University of New Mexico specialty teams. With effective mentoring, the PCPs can manage HCV. Initially, Project ECHO focused on treatment with pegylated interferon plus ribavirin. Dr Arora is now looking at how this mentoring is working with triple therapies, peginterferon plus ribavirin and the protease inhibitors. Triple therapy adds a level of complexity, and it will be a challenge.
Medscape: It has also been suggested that nurse practitioners (NPs) and physician assistants (PAs) could play a bigger role; what are your thoughts about this as a potential solution?
Dr Fried: Absolutely; those individuals are critical to managing chronic HCV infection, and I think that they do an outstanding job. No one comes into that job with a lot of experience managing chronic HCV infection, so if physicians spend the time mentoring NPs and PAs, NPs and PAs will do an outstanding job in the management of patients with chronic HCV infection. We use NPs and PAs extensively in our practice here at University of North Carolina. We are very fortunate to have 4 of these providers who work with patients with chronic HCV infection; I cannot say enough good things about their roles in managing this disease. If there is 1 group that I think we should particularly try to get involved in practices that have an interest in chronic HCV infection, it is certainly NPs and PAs. They are excellent healthcare professionals and ideally suited for managing chronic HCV infection.
Medscape: I think that most people understand the role of NPs and PAs. What do you think is the biggest value in making these providers an integral part of the patient care team for patients with chronic HCV infection?
Dr Fried: The initial evaluations are performed in a team environment; the attending physician, NPs, and PAs evaluate patients about their candidacy for treatment and develop a treatment plan. In our experience, NPs and PAs are often primarily responsible for managing patients with chronic HCV infection on a daily basis -- of course with our oversight and supervision -- and help make decisions about issues such as adverse-event management. They play a very pivotal role in the management of patients with chronic HCV infection; in my experience, they develop great rapport with the patients. I don’t think there is any other way to do it; the role of NPs and PAs should be expanded in the care of patients with chronic HCV infection.
Medscape: What about in states where NPs and/or PAs have prescriptive authority?
Dr Fried: In North Carolina, NPs and PAs have prescriptive authority. They work under the supervision of attending physicians. Management of chronic HCV infection during the treatment phase is very amenable to the role of NPs and PAs. Practitioners in other states would be familiar with their local regulations.
Medscape: The treatment algorithms are fairly clear?
Dr Fried: Yes, the treatment algorithms are clear, but -- make no mistake -- this is a complex disease with complex treatment and adverse-event management. You cannot just hand an algorithm to a clinician and say, "Here; go treat this patient with chronic HCV infection." They need to have backup support and ongoing mentoring because there are nuances to every case. Specialists have to continue to work with their team of multidisciplinary providers; everyone needs continuing medical education in this regard. As you do that, NPs and PAs become quite expert in managing this disease.
I think you can glean from my answers where we have to be; it is definitely a multidisciplinary model. As long as we are dealing with interferon-based therapies, it goes beyond just an NP or PA and the attending physician; because of drug-drug interactions, it is best to involve pharmacists and pharmacologists. Also, because all treatment including triple therapy is interferon based, there are issues related to the neuropsychiatric side effects of those drugs. Having a psychiatric healthcare provider (a psychiatrist or psychologist) can help with the evaluation and management of patients on interferon-based therapy. Multidisciplinary models are definitely important. How practical they are for solo providers is a different story, but at least they need to have resources in their communities that they know they can draw from.
Medscape: Treatment paradigms are changing: they are more complex on 1 hand, and the efficacy is greater on the other. What immediate changes are needed to optimize triple therapy? What will the future of treatment of chronic HCV infection look like?
Michael Fried, MD: We have been waiting a very long time for the introduction of the protease inhibitors into treatment. We are happy that they are here, because they improve SVR rates significantly over pegylated interferon plus ribavirin.[2-5] I mentioned that they represent treatment challenges due to adverse events, but nevertheless, they have also shortened the duration of therapy by 50% in patients with genotype 1 infection.[12]
Optimizing triple therapy involves understanding the treatment algorithms and knowing when these medications are not effective and need to be discontinued prematurely. This involves making sure that adherence to the medications is complete, optimizing management of side effects and adverse events, and optimizing therapeutic outcomes without premature discontinuation of these medications.
Researchers are also looking at certain subpopulations where perhaps even 6 months of therapy may be more than enough treatment; maybe we will be able to get away with shorter durations of treatment in certain populations -- for example, a patient with IL28B CC genotype who has mild disease. Maybe those patients only need 12 or 16 weeks of treatment; these studies are going on now.
Also, very exciting, is what is coming down the pipeline. We are talking about second-generation protease inhibitors that appear to have improved side effect profiles. They only need to be taken once or twice daily vs 3 times a day; that will help with adherence.
In 3 to 5 years we may be looking at all-oral regimens; that would be a complete game-changer. An all-oral regimen for chronic HCV infection will mean several things. First, PCPs could potentially treat chronic HCV infection because they would not be dealing with the interferon injectables and some of the adverse events. Of course, it will depend on the side-effect profiles of these all-oral regimens. Second, an all-oral regimen could extend treatment options for a large portion of the HCV-infected population that currently are not candidates for interferon-based regimens (eg, patients with underlying psychiatric disease). If you take interferon out of the mix, the treatment could be expanded quite extensively to patients who have no other contraindications to therapy. Once that occurs, there will be an even greater impact on the natural history of chronic HCV infection, and the likelihood of progression to cirrhosis, hepatocellular carcinoma, and the need for liver transplantation will be decreased. This will have a huge positive impact on the healthcare burden 10 and 20 years from now.
The possibility of all-oral regimens is very exciting, and it is happening faster than many of us predicted. However; a note of caution: although there are many drugs in the pipeline and researchers will ultimately discover which combinations will be very effective for most patients with chronic HCV infection, we are not there yet. Clinical trials are necessary to determine how to combine these medications to achieve the greatest efficacy with the least side effects, and in the most cost-effective ways in the most patients. We have a lot of work to do, but it is really exciting. I am very optimistic about the future of management of patients with chronic HCV infection.
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