- File Under protease inhibitor
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Reported June 29, 2011
Medical Advances: Wiping Out Hepatitis C -- In Depth Doctor's Interview
Stuart Gordon, M. D., Director of Hepatology at Henry Ford Health System discusses hepatitis C and how a medical cocktail has helped cure patients of the disease before the occurrence of liver damage.
What is hepatitis C and what exactly does it affect?
Dr. Stuart C. Gordon: Hepatitis C is a virus that has been around for hundreds of years; however, it has just become more common and prevalent in recent years. The epidemic of acute hepatitis C probably took place in approximately the 1960’s, 70’s, as well as the early 1980’s in this country, although it probably took hold in other parts of the world in earlier parts of the century. Hepatitis C is a virus that attacks the liver essentially – that is why we call it hepatitis (hepar– meaning liver and –itis meaning inflammation). In due course, it is a virus that comes into the body and attacks the liver. There are different types of hepatitis (i.e. type A, type B, type C). Type C is the type that we are discussing today, and it generally enters through the blood stream, travels to the liver where it replicates, and usually causes most of its damage in the liver. In most cases, the body is unable to clear the virus on its own. There are a small percentage of individuals that are lucky enough to get hepatitis C and get rid of it on their own, nonetheless, they are the minority. The majority, once infected, remain infected.
What kind of damage can hepatitis C do in cases where the body is not able to rid itself of the virus?
Dr. Stuart C. Gordon: The damage is slow and indolent, and often occurs over a span of many years. There are rapid progressions, there are slow progressions, and there are probably patients who will never encounter some of the affects associated with the virus. It usually causes a mild degree of inflammation, and in certain individual’s cases that inflammation may progress and eventually lead to scar tissue. That scar tissue can lead to cirrhosis. Certain people are more predisposed to more advanced liver diseases (i.e. diabetic patients, overweight patients, patients that are immunocompromised in various forms), so there are myriad factors that may predict who is going to experience worse symptoms than others. Some individuals might go many, many years without ever getting into any problems, where as others may rapidly progress into more severe and detrimental lever diseases.
How does one acquire hepatitis C?
Dr. Stuart C. Gordon: Well, there are various ways that individuals acquire the infection. In the United States, there was a vast outbreak of acute hepatitis infection in the 1960’s and 1970’s, owing largely to the use of illegal drugs and narcotics. These drugs may have been taken intravenously, subcutaneously, or even inhaled (intranasal cocaine has actually served as a route of viral acquisitions). So many individuals were not even aware that they may have been at risk of viral hepatitis. That is merely one cohort – we refer to that as the ‘birth cohort’ – generally individuals that were born before 1946 – ’64. This particular age group is at an increased risk due to the illicit drug use. Another large group of individuals that acquired the disease received it from blood transfusions / blood product transfusions any time prior to 1990 – ’92. All of those individuals are at risk, and furthermore all of those individuals should be tested immediately to see if they are infected. Throughout the world, there are different risk factors. If you look at Sub-Saharan Africa, large outbreaks in Egypt for example, many parts of Asia, Eastern Europe in addition to many other parts of the world, there was the use of non-sterile glass syringes as well as non-sterile medicinal techniques that exposed large, large numbers of the population to this particular virus. Many of these individuals are just now finding out that acquired have the virus years ago, thus putting them at an even greater risk for increased liver damage.
What are some of the symptoms of hepatitis C?
Dr. Stuart C. Gordon: Well, the absence of symptoms is both good and bad. The fact that so many of these patients are asymptomatic becomes a sheer source of frustration when trying to identify the virus in patients. There may be a little bit of fatigue. Generally though, the most common symptom with liver disease may be slight fatigue, but in most cases the presence or absence of symptoms is often irrelevant. Unless an individual is tested, or unless there are some abnormalities that point you toward looking for the virus, there may be no symptoms whatsoever. As with most liver diseases, when true symptoms begin to present themselves (complications of cirrhosis), it is oftentimes far more advanced.
This is a virus that still has no vaccination or cure, am I correct in saying that?
Dr. Stuart C. Gordon: There is no vaccination. There is vaccination for type A hepatitis, which is ultimately acquired by food and/or food handlers; for type B hepatitis there is a vaccination as well that is available.. There is conversely a potential cure, which is probably an aspect of the disease that is often overlooked. The current therapy (if successful) does lead to a permanent eradication, which leads us more towards using the word “cured” far more in our profession.
Currently, what is the standard treatment for an individual with hepatitis C?
Dr. Stuart C. Gordon: The current treatment that has been implemented for the past decade has been a combination of an injectable form of interferon in addition to an oral tablet known as ribavirin. The weekly injection along with the daily pills has become the standard form of treatment for the past ten years or so. This form of therapy is evident all around the world with different durations of therapy for patients depending on the severity and strain of the virus. Essentially, that has been the standard of care for quite some time now.
Has the combination of the aforementioned injection and oral medication been successful in restoring patient’s kidney function?
Dr. Stuart C. Gordon: Overall, the success rate is roughly 50 percent. For some strains (genotypes) of the virus that number may rocket to over 80 percent effective, however, for other individuals as well as strains that number may plummet to as low as 20 – 30 percent. There may be different racial factors in addition to genetic factors that play a role in the efficacy of the treatment and moreover predicting who is going to respond to this particular therapy. The numbers, although better than they were in the 1990’s (before we used ribavirin), are still suboptimal.
Can you talk a little bit about what you are currently studying?
Dr. Stuart C. Gordon: What we have looked at is direct acting antivirals – the current standard of care of interferon and ribavirin really came about serendipitously. No one really is sure how either drug works, however, we do understand that when we use them in combination they will affect the immune system and probably help the body fight off the virus. They may have some antiviral properties on their own, but they weren’t really specifically developed for hepatitis C, they just happen to work. They aren’t direct acting antivirals, and what we have been waiting for is the availability of drugs that directly attack the virus. To answer your question, that is currently where the research arena is heading.
Talk to me a little bit about these novel treatments. Are these particular drugs being designed to directly target the virus.
Dr. Stuart C. Gordon: Yes. These drugs are designed to directly target the virus. They were first described several years ago – they were labeled as the hepatitis C protease inhibitors (these inhibit the replication of one particular portion of the hepatitis C virus) – they were remarkably effective. When they were used individually as single agents, we found that the viral levels would come down very dramatically, but found that if the drug was used solely over a period of just several days, we noticed that the virus sprung right back up. It was frustrating because we had hopes for switching over to an all-oral therapeutic approach, nevertheless, that proved not to be the case. When used by itself, it would work very well initially bu then lead to an emergence of resistant strains of the virus. So then they tried combining the direct antivirals with the interferon and ribavirin, and we were able to eliminate some of this resistance phenomenon; thus when used all together: the interferon and ribavirin . . . now plus these protease inhibitors – we witnessed remarkable success. We saw success rates that we had never seen before and offered patients with this virus a sense of hope.
When you say “remarkable success,” what exactly do you mean? Give us some specific examples of the remarkable triumphs that you have experienced in your years treating this particular virus.
Dr. Stuart C. Gordon: Let me put it in some perspective. In the 90’s we were using interferons alone –fewer than ten percent of the individuals with the virus were getting cured. When combined the interferons with ribavirin we were seeing almost a 50 percent cure rate in the genotype 1 (the most common strain of the hepatitis C virus). Now, looking at the triple agents, we are looking at numbers from upwards of 70 percent and higher. When you see numbers (cure rates) going from 10 percent to 70 percent in roughly a short period of time . . . this is cause for celebration. When we realized that most of the patients when responding were actually achieving a sustained response (cure) -- that is absolutely remarkable, and something that has not been described for any other virus before .
Researchers are often times hesitant when using the word “cured.” In this case, however, using that word is applicable?
Dr. Stuart C. Gordon: That is correct. It is the four-letter word that we have been reluctant to use, and are now becoming more comfortable saying to our patients and their family members. During the course of therapy, our goal is to sustain that response, and we define that by the absence of the virus six months to completion of the therapy. So the aforementioned numbers are ultimately in reference to the individuals that have completed the therapy. They are done with therapy. They are off of treatment for over six months and moreover they are virus free. We have looked in liver tissue and blood cells, and when we followed-up on these patients years later, we discovered that the virus was still gone. That is about as close to using the word “cured” as you are going to get. I am not aware of any other chronic viral infections where that word can be used. For hepatitis B, we have nice therapies but we have to keep people on these therapies in order to suppress the virus. This (hepatitis C) is a virus where using the word “cured,” “sustained” or “eradicated” is common after successful treatment.
Does this cure ultimately lead the individual to a better quality of life where they don’t have to incessantly worry about taking medications and treating the symptoms?
Dr. Stuart C. Gordon: It has improved quality of life, and it is translating into improving the rate of survival in the general hepatitis C population. The numbers are suggesting that if we can get rid of the virus early on then we can potentially prevent that development of cirrhosis down the road; that might potentially prevent the need for transplants as well as liver cancer. So our goal is to catch this early. The fact of the matter is this virus can take decades before causing any severe injury. On the other hand, viruses like HIV can lead from infection to grave consequences in a very brief period of time. The damage from hepatitis C is stretched out over decades, thus damage may be slow and insidious. The earlier that we are able to treat the virus, the better chance of having a favorable response and achieving cure. The individuals who have more advanced disease have a somewhat less chance of responding to the medications. So, the goal is to try and help patients pick up on the notion that they may have the virus and / or need to be checked. Treatment has shown to improve the quality of life, and there have been studies that show there are neurocognitive deficits in patients who have hepatitis C with a decreased quality of life. Successful treatment improves liver function, and has ultimately slowed down other extrahepatic manifestations. We know that hepatitis C can wreak havoc in other places of the body. It has been associated with various kidney diseases, lymphoma, diabetes, in addition to a whole host of other diseases fully unrelated to the liver. So you think of liver disease when referring to hepatitis C, however, it can cause severe damage to the body elsewhere.
Can you discuss protease as well as some of the other regions of the virus?
Dr. Stuart C. Gordon: Protease is one region of the virus (an enzyme that we are inhibiting), and there are other regions of the virus that we try to attack (targets of therapy) known as the polymerase region. So the future therapies are looking at attacking the virus at other positions along the way. Not only the protease but the polymerase region as well. The real exciting news is the potential for eliminating the need for the interferon down the road. Some of the newer research that has been coming out is looking at all oral regimens – since the use of injectable interferons are generally difficult to tolerate as well as being associated with a multitude of side effect.
Can you explain interferons?
Dr. Stuart C. Gordon: It is actually something called pegylated interferon (the “peg” stands for Polyethylene glycol) – attaching the interferon molecule to Polyethylene glycol, which allows us to use it just once weekly. Ribavirin has been around for quite some time, and we use that in addition to the interferon. That is the cocktail that we have been using right now. The third drug that we hope will gain FDA approval soon will be boceprevir and telaprevir. So, the new cocktails will consist of interferons, ribavirin and a protease inhibitor (either boceprevir or telaprevir).
What is the difference between the two aforementioned protease inhibitors?
Dr. Stuart C. Gordon: They are both hepatitis C protease inhibitors, and they are both given three times a day, so it will be yet another pill to add to the regimen. Ultimately, it will be a fairly complicated regimen that involves injection along with two separate pills that need to be taken at different times during the day. These two drugs (boceprevir and telaprevir) were developed by two different companies. They each work in a similar mechanism; each has different side effect profiles.
When will these two drugs be available to start treating patients with hepatitis C?
Dr. Stuart C. Gordon: Well, the FDA will actually be meeting tomorrow, so they will probably decide by May. We are hoping for FDA approval of boceprevir and telaprevir by May 2011.
Is there anything else that you would like to add?
Dr. Stuart C. Gordon: This is a very common virus, also a potentially deadly one. The majority of individuals infected probably don’t even know that they are. It is suspected that approximately 4,000,000 Americans are infected with the virus and the vast majority of those have yet to be tested and don’t even know about it. The goal is to detect the virus as early as possible so that you can treat it, and possibly avoid some of the consequences associated with the progression of the virus. It is a treatable disease. As exciting as these new antivirals are, even better treatments are coming. To those whose lives have been affected by this virus, there is new hope.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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