January 6, 2010
Being infected with chronic hepatitis C (HCV) presents challenges no matter who you are. For instance, HCV has nowhere near the wealth of treatment options that we have for HIV. The HCV meds that are available can cause harsh side effects, and in many cases they don't work. Furthermore, there's a fact that has baffled HCV-positive people and their caregivers for years: It has long appeared that, if you're of African descent (as most black people are), as opposed to European descent (as most white people are), HCV treatment is considerably less likely to work for you.
Now, in a landmark study published in the journal Nature, U.S. researchers say they have discovered that people with a specific genetic variation appear to have better outcomes on standard HCV treatment. Here's the twist, however: About 39 percent of the whites in the study had the beneficial variation, compared with only about 16 percent of African Americans. As a result, the researchers believe that this variation (which occurs near the IL28B gene) may explain some of the differences between how African Americans and whites respond to HCV treatment.
(It's worth mentioning that African Americans who had the variation did significantly better on treatment than whites who did not have it -- further evidence that it is the presence of this variation, and not race alone, that's associated with doing better on treatment.)
Of course, finding a major clue in a mystery as vexing as this one is cause for celebration. But what can people with HCV do with this information right now? We caught up with two of the researchers on this study -- David Goldstein, Ph.D., and John McHutchinson, M.D., both of Duke University -- and asked them everything we thought you'd want to know about this new research and what it means for the future of HCV treatment.
Olivia Ford: Had it been documented previously that African Americans did not do as well on HCV treatment as European Americans?
David Goldstein: This has been well known for a long time, and very well documented. It is one of the factors that persuaded us that there could well be a gene variant or variants that contribute to response.
Olivia Ford: Do you take into account the fact that many people of African descent are unaware that they have African ancestry and therefore don't self-identify as such?
David Goldstein: One of the most important points about this discovery is that the effect of IL28B status appears to be the same across different racial and ethnic groups. Hence it does not matter whether an individual is African American, Hispanic, European or [belongs to] presumably any other group. We still know that IL28B status will be informative about treatment response regardless of what group an individual is classified in.
Olivia Ford: Can someone be tested for the IL28B gene variation?
David Goldstein: I am hopeful that a test will be made available sooner rather than later so that both doctors and patients can incorporate that genetic information as treatment options are evaluated for individual patients.
Olivia Ford: Should everyone who's HCV positive be tested for this variation?
Olivia Ford: How soon do you think it will be before testing for the IL28B variation is recommended in the guidelines for HCV screening and care? In other words, when do you anticipate it becoming part of the basic workup for people with HCV?
John McHutchinson: Guidelines always lag behind the field, and they have just been revised for 2009 for HCV treatment. Nonetheless, updates and important changes can be made fairly quickly. I believe this will occur once a larger body of clinical evidence develops.
David Goldstein: I am hopeful this will happen within a very short period of time, hopefully only months. ... There does seem to be a very high level of interest in this, and I believe a test should indeed be made available.
Olivia Ford: Does this genetic variation equally affect treatment outcomes on every currently available treatment for HCV?
David Goldstein: So far, we have only studied pegylated interferon [Pegasys, Peginterferon, PEG-Intron] and ribavirin [Copegus, Rebetol] -- the standard of care.
Olivia Ford: Is there alternative treatment for HCV that people can take if they turn out not to have the IL28B gene and existing treatments don't work for them?
David Goldstein: There are new treatments that are in late-stage evaluation. It will be a priority to determine how IL28B status influences response to these treatments.
John McHutchinson: In the future, direct antivirals (protease and polymerase inhibitors, for example) may be available. Some of these drugs are in phase 3 clinical trails globally now, and response rates appear higher. We have recently published on this in the New England Journal of Medicine. Telaprevir [VX-950] is the name of the newest drug coming through the pipeline.
Olivia Ford: What does the discovery of this IL28B variation mean for the development of future HCV treatments?
David Goldstein: One of the more interesting questions is whether one could develop add-on therapies that might help to make individuals with the "poor response" IL28B type respond more like individuals with the good response type.
Olivia Ford: Since no IL28B test is currently available, should a person who's African American -- and therefore has a lesser likelihood of having this protective gene variation -- delay starting treatment?
John McHutchinson: Not at all. But they can now be armed with additional information that will help them decide whether to undergo therapy now or defer therapy, depending on their degree of liver disease, IL28B type and other factors.
Olivia Ford: If someone is already on HCV treatment and is wondering about his or her IL28B status, should he or she consider stopping treatment?
John McHutchinson: No -- we would never do that once we had committed to starting to treat someone, based on many other factors.
Olivia Ford: In light of the findings of your study, what can a person infected with HCV do today, right now, with this information -- particularly if they're considering starting treatment?
David Goldstein: We definitely do not foresee that IL28B status would be used to either deny anyone therapy or to stop in mid-course. As far as African Americans go, I think one point to consider is that some African Americans may be reluctant to start therapy because they know, or are told, that as African Americans they have a relatively low chance of being cured.
But we can now do much better than that. We can determine their IL28B status and give them information that is specific to their individual genetic makeup, instead of the more crude proxy of their racial/ethnic grouping.
John McHutchinson: When such a test becomes available, providers will be armed with a pretty powerful additional piece of information to share with their patients, before therapy, about the likelihood of responding. No doubt this will help inform the decision-making process.
This interview has been lightly edited for clarity.
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