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In This Issue:
Telaprevir & Boceprevir: Priority FDA Review
Alan Franciscus, Editor-in-Chief
Alan Franciscus, Editor-in-Chief
Lucinda K. Porter, RN
HealthWise: Hepatitis C and Your Heart
Lucinda K. Porter, RN
HCV Advocate Eblast
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Telaprevir & Boceprevir: Priority FDA Review
—Alan Franciscus, Editor-in-Chief
In January, 2011, both Merck and Vertex announced that the Food and Drug Administration (FDA) had granted Priority Review to boceprevir (Merck) and telaprevir (Vertex). Priority Review is granted to a drug that offers a significant advancement in treatment for a certain condition. This means that their applications for marketing approval will be reviewed within a six month time-period instead of the standard review period of 10 months. Merck and Vertex are seeking approval of their HCV protease inhibitors (in combination with pegylated interferon plus ribavirin) to treat people with chronic hepatitis C—genotype 1. Additionally, both HCV protease inhibitors have been granted priority review in Europe and Vertex announced that it had been granted Priority Review in Canada—this could shorten the review period to 6 to 9 months.
Regardless of which drug is approved first, people with chronic hepatitis C and their medical providers will have two more options to choose from that will greatly increase the chances of being cured. FDA approval for both HCV protease inhibitors are expected mid-year.
A looming question is the cost of the new medications. Current treatment with pegylated interferon plus ribavirin can range from $25,000 to $30,000 or higher depending on the contracted price. This does not include office visits and the various laboratory tests needed during treatment. Add in $500 to $600 a dose to treat certain serious side effects (erythropoietin—anemia; granulocyte-colony stimulating factor (G-CSF)—neutropenia) if needed and it’s clear that an add-on drug is going to have an effect on insurance coverage and even more importantly on what patients will have to pay out of pocket. Hopefully, Merck and Vertex will offer generous patient assistance programs to help people who have limited medical insurance coverage (large co-pays; low coverage caps) or people who have no medical insurance at all. Another concern over the pricing is the effect it will have on Medicare since some of the Hep C Baby Boomer Generation will qualify for Medicare now and many more in the near future.
Finally, what affect will the cost of the new medications have on Healthcare Reform? These are just a few of the important and complex issues that will need to be factored into the price equation when the new HCV protease inhibitors are marketed.
For more information about boceprevir and telaprevir see our respective fact sheets which discuss top-line treatment results:
Sources: Merck Press Release; Vertex Press Release
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—Alan Franciscus, Editor-in-Chief
Collaboration of Two HCV Pharmaceuticals
It was announced on January 10th, 2011 that Bristol-Myers Squibb (BMS) and Pharmasset will collaborate on a new study that will test BMS’s HCV NS5A inhibitor BMS-790052 and Pharmasset’s HCV polymerase inhibitor PSI - 7977 with and without ribavirin to treat HCV. This collaboration is a tremendous move forward for the development of more medications to treat hepatitis C.
Collaborations between pharmaceutical companies to explore different various combinations of drugs has been encouraged by the FDA and many HCV advocates. This is a win-win situation for everyone – it will speed up the testing of various combinations of medications that will eventually lead to better treatment options for people with chronic hepatitis C.
Hopefully, other pharmaceuticals will take notice and begin to dialogue and work together to develop other combination drug regimes to treat HCV.
Source: BMS & Pharmasset Press Release
FDA: New Acetaminophen Rules
The Food and Drug Administration (FDA) is finally acting on the recommendations of its advisory board and is asking drug manufacturers to limit the amount of acetaminophen (brand name Tylenol) used in prescription painkillers to 325 mg per dose—tablets and capsules.
The FDA will also require that drug manufacturers label their prescribed drugs with a Boxed Warning about the potential for severe liver injury. The FDA stated that almost half of the cases of liver failure in the United States are the results of acetaminophen overdosing.
The new FDA requirements will not affect any over-the-counter medications containing acetaminophen. Acetaminophen is an ingredient in over 300 over-the-counter medications including painkillers, cold and flu medications, fever reducers, etc. Currently, OTC medications contain specific labeling including a warning about the potential risk of liver injury when people exceed the maximum recommended doses and warnings about when acetaminophen is combined with more than three alcoholic drinks a day. It is expected however, that stronger labeling will be required in the future.
- Note that on prescription medications that contain acetaminophen physicians use the abbreviation of “APAP.”
- Acetaminophen is currently in many prescribed painkillers including codeine, oxycodone (Percocet), and hydrocodone (Vicodin). The FDA action is not expected to affect prescription painkiller supplies since the new dose restrictions will be phased in over 3 years. In addition some prescription pain medications are already available in combination with other types of medications for pain relief such as ibuprofen.
- Acetaminophen is an extremely safe drug when used as directed—even in people with liver disease.
- In 2005 it was estimated that more than 28 billion doses of medications (including over-the-counter medications) were purchased. This included 182 million acetaminophen prescriptions that were filled.
- Since 1997, the most frequently prescribed medication that contained acetaminophen was Vicodin (combination of hydrocodone and acetaminophen).
- From 1998 to 2003 acetaminophen was the leading cause of fulminate or acute liver failure, accounting for 1600 cases.
- An estimated 56,000 emergency room visits, and 26,000 hospitalizations and 458 deaths PER YEAR were related to acetaminophen overdoses from 1990 to 1998. During the same period 48% of cases of acetaminophen overdosing were considered accidental.
Everyone with liver disease should talk with their medical providers about a safe dose to take of acetaminophen based on their degree of liver damage or function, how and when to take it and also discuss what medications, including over-the-counter medications, they are taking that include acetaminophen as an ingredient.
Source: FDA Press Release
Testing for hepatitis C based on a risk factor only catches a fraction (25 to 30%) of the estimated 4 million plus Americans who are infected with hepatitis C. Risk factor testing would seem to be the best avenue for testing and diagnosing the hepatitis C population, but it hasn’t been effective in identifying the majority of people with hepatitis C. There are a couple of reasons for this: lack of provider and patient knowledge of the risk factors, and the stigma and shame people face when disclosing a risk factor. To overcome these limitations there has been talk of screening for hepatitis C based on age—that is, testing everyone at a certain age based on the ages when it is believed that the majority of people became infected with hepatitis C. It is believed that this type of approach would identify the vast majority of people who are infected with hepatitis C. And of course, if we can identify the majority of people who are infected with hepatitis C, they can seek medical care and monitoring that would save thousands of lives.
Many times, talk goes nowhere, but in this instance talk is turning into action. It was announced recently in a news story that the Centers for Disease Control (CDC) is piloting aged based testing in New York, Detroit, MI, Houston, TX, and Birmingham, AL. This means that everyone of a certain age would be tested once for hepatitis C. Hopefully, these sites will provide information that will take the aged-based model to a national level.
Preventing Re-infection Post Transplant
The consequences of hepatitis C (HCV) infection are the leading cause of liver transplantation in the United States. When a healthy liver is transplanted into someone with hepatitis C the new liver will become infected with HCV. Unfortunately, post-transplant HCV disease progression can be very fast and severe—an estimated 20% of liver transplant patients will progress to cirrhosis in five years.
A news story on January 19, 2011 from www.news-medical.net detailed a new study about monoclonal antibodies—MBL-HCV1—that has entered into phase 2 trials to find out if re-infection with HCV post-transplant can be prevented. The results from a phase I study of 31 healthy volunteers conducted in 2009 found that MBL-HCV1 was well-tolerated with no side effects, and the researchers were able to set up a protocol and find the best dose to use for the phase II study.
The study sites are located in MA, CT, and NYC and 16 patients will be enrolled in the first phase. The administration of MBL-HCV1 by infusion is carried out at certain time points—the first infusion is given 1 to 4 hours prior to surgery, a second infusion when the diseased liver is removed, but before the new liver is implanted, and a third dose after the surgery is completed. Daily infusions are given post-transplant for the first week and the final infusion is given on the 14th day after the transplant. The primary goal of the study is to measure the effectiveness (HCV RNA negative) and safety of MBL-HCV1.
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—Lucinda K. Porter, RN
February’s Snapshots is devoted to exploring research related to HCV, stroke and heart disease.
Article: Hepatitis C Virus Infection and Increased Risk of Cerebrovascular Disease — Mei-Hsuan Lee, Hwai-I Yang, Chih-Hao Wang, Chin-Lan Jen, Shiou-Hwei Yeh, Chun-Jen Liu, San-Lin You, Wei J. Chen, MD, Chien-Jen Chen
Source: Stroke December 2010
This long term study enrolled 23,665 participants between the ages of 30 to 65, beginning in 1991-92 and followed until 2008. Subjects were interviewed and tested for HCV viral load and genotype. The risk of death from stroke for those who were HCV-positive was 2.7% and 1% for those who were HCV-negative. The risk of stroke-related death increased to 3.16% for those with high viral loads. Genotype was not associated as a risk factor for stroke. The researchers concluded that HCV is associated with an increased risk of death from stroke, particularly for those patients with high viral loads.
The Bottom Line: The presence of HCV, particularly for those with high viral loads, is associated with a higher risk for stroke.
Editorial Comment: An association between HCV and stroke does not mean that HCV causes cerebrovascular disease; it might, it might not. Also, this community-based research used a fairly homogenous cohort (Taiwanese) which may have factors that don’t apply to everyone in other places in the world. However, the results of this large, prospective study are very compelling.
Article: Hepatitis C Infection and Clearance: Impact on Atherosclerosis and Cardiometabolic Risk Factors — Aya Mostafa, Mostafa K Mohamed, Mohamed Saeed, Abubakr Hasan, Arnaud Fontanet, Ian Godsland, Emma Coady, Gamal Esmat, Mostafa El-Hoseiny, Mohamed Abdul-Hamid, Alun Hughes, Nish Chaturvedi
Source: Gut August 2010
One of the mysteries about HCV is how patients with this virus tend to have low cholesterol despite having an increased risk of diabetes. There are a number of theories about the association between HCV and cholesterol, but nothing concrete has surfaced to explain the connection. Recent research suggests that lower cholesterol levels do not mean lower risk of heart disease. This Egyptian study compares cardiovascular risk factors of those who have never been infected with HCV with those who have HCV, and with those who have cleared HCV.
This cross-sectional study enrolled 795 participants who were never infected with HCV, 329 with chronic HCV infection and 173 who cleared HCV. The prevalence of diabetes was higher in those who had HCV, whether or not they cleared it, compared to those who never had HCV (10% vs. 6.6%). Those who had a history of HCV, either active or cleared, had more mesenteric fat (abdominal fat found around the small intestines). LDL cholesterol (the “bad” cholesterol) was lower in those with active HCV, compared to those who had cleared or never had HCV. Atherosclerosis, a build-up of fat along the wall of the arteries, was measured, and was similar in all three groups. However, when adjustments were made for cardiovascular risk factors, those with HCV had more atherosclerosis than those who had never been infected.
The Bottom Line: The presence of chronic HCV infection may increase the risk of atherosclerosis.
Editorial Comment: This study is important because it adds weight to the growing body of evidence that there may be a link between heart disease and HCV. More research needs to be done, but until then, it won’t hurt to adopt a heart-healthy lifestyle.
Article: Hepatitis C Virus Infection and the Risk of Coronary Disease —Adeel A. Butt, Wang Xiaoqiang, Matthew Budoff, David Leaf, Lewis H. Kuller, Amy C. Justice
Source: Clinical Infectious Diseases July 15, 2009
Although this is the oldest study featured in this month’s Snapshots, it stands out and deserves mentioning. Looking at veterans from 2001 to 2006, this study enrolled 89,582 participants without HCV and 82,083 with HCV. (Note: HCV infection was defined as being positive for HCV antibody or viral load; traditionally HCV infection is defined as a positive HCV viral load.)
Those with HCV were less likely to have high blood pressure, high cholesterol or diabetes, and were more likely to abuse drugs or alcohol, or have anemia or kidney failure. Those with HCV had a significantly higher risk for coronary artery disease, even when adjustments were made to neutralize the effect of traditional cardiac risk factors.
The Bottom Line: Because the risk of coronary artery disease was higher after adjustment for the traditional risk factors, the researchers concluded that HCV infection or other unknown factors may be responsible for an increased risk of heart disease.
Editorial Comment: This very large study reinforces the notion that HCV may increase the risk of heart disease. The study’s researchers speculate about the role of inflammation, a known event common to both HCV and cardiac disease. The influence of lifestyle choices, such as diet and exercise, need to be explored to see if these can reduce inflammation or lower the risk of coronary artery disease in those with HCV.
Article: Hepatitis C Virus RNA Localization in Human Carotid Plaques — Maria Boddia, Rosanna Abbateb, Benedetta Chellinia, Betti Giustib, Carlo Gianninic, Giovanni Pratesid, Luciana Rossib, Carlo Pratesid, Gian Franco Gensiniae, Laura Paperettia, Anna Linda Zignegoc
Source: Journal of Clinical Virology January 2010
This Italian study, although small, is noteworthy. First, it was prospective. Second, the researchers actually assessed the plaque found in the carotid arteries of patients with coronary artery disease. HCV RNA was found in the carotid plaque tissue of those who were HCV-antibody positive (7 subjects); HCV was not found in patients who were HCV-antibody negative (9 subjects). HCV RNA was found in carotid plaque samples of 3 patients who were HCV-antibody positive but had undetectable serum HCV RNA.
The Bottom Line: The researchers suggest that HCV may play a part in the development of carotid plaque.
Editorial Comment: The presence of HCV RNA in the carotid plaque is interesting. Since this study was small and only looked at patients with existing heart disease, it seems unrealistic to make an association between HCV and heart disease based solely on this research. However, there are many more studies showing a link between HCV and increased risk factors for heart disease. The fact that there are too many to list in this newsletter is sobering.
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HEALTHWISE: Hepatitis C and Your Heart
—Lucinda K. Porter, RN
The month of February is set aside to promote heart disease awareness. It makes sense that this would occur in the month when Valentine hearts are prominently displayed in all the stores. I am more of a liver fan, but we can’t live without a heart or a liver.1
Heart disease is the number one cause of death in the United States, reports the Centers for Disease Control and Prevention (CDC). Claiming more than a quarter of all deaths in the U.S., more than 631,000 people died of heart disease in 2006. Death from heart disease is split evenly between men and women.
In December 2010, the American Heart Association2 reported that from 1997 to 2007 the mortality rate from heart disease dropped nearly 28%; the stroke death rate fell 44.8 percent. Unfortunately, that does not tell the complete story because during the same period, the total number of heart-related surgeries and procedures increased 27 percent. Mortality rates are going down, but probably from advances in medical intervention—not from people making health changes.
A number of studies provide evidence that those with chronic hepatitis C virus infection (HCV) may have an increased risk of heart disease. When discussing heart (cardiovascular) disease it is also important to mention its close cousin—stroke (cerebrovascular disease). Both types of disease have many of the same risk factors. Added together, heart disease and stroke are the cause of one in every three deaths.
In addition to this month’s Healthwise, this month’s Snapshots focuses on stroke and heart disease in those with HCV. A study in Stroke (December 2010) suggests an increased stroke risk for those with HCV. An Italian study (Journal of Clinical Virology January 2010) found HCV RNA in the plaque lining the walls of the carotid arteries of HCV patients. In fact, there is so much research showing that HCV patients have an increased risk of cardiovascular disease, that the topic could only be briefly summarized.
Stroke and heart disease prevention all come down to lifestyle. These and other diseases, such as diabetes and some types of cancers are often preventable. In “Heart Disease and Stroke Statistics– 2011,” Veronique L. Roger3 reported that:
- More than two-thirds of U.S. adults are either overweight or obese.
- More than a third of U.S. adults have high blood pressure.
- 23% of adult men and 18% of adult women smoke cigarettes.
- 15% of adults have total serum cholesterol levels of 240 mg/dL or higher. The recommended level is 200 mg/dL or lower.
- 8% of the U.S. adult population have diabetes and nearly 37% have prediabetes.
When I talk to others about heart disease, I am surprised by how many people think they aren’t at risk because there is no heart disease in their family. Granted, family history is a red flag for an increased risk of a cardiac event, however, an absence of cardiovascular disease in your family does not mean no risk. Again, it is a question of lifestyle and how it affects your health.
The CDC website lists the main risk factors for heart disease; inactivity tops the list. Nearly 40% of those who had heart attacks were inactive. Other risk factors are: obesity (34%), high blood pressure (31%), cigarette smoking (21%), high cholesterol (16%), and diabetes (10%).
So, if you have HCV and are inactive, or have other risk factors, especially a family history, perhaps it is time to make some lifestyle changes. Here are some to consider:
- Exercise regularly – You don’t need to go overboard. Aim for 30 minutes a day of something to which you can commit. For example, you can walk, dance, swim, bike, or garden. The American Heart Association website states that for every hour of walking you may increase your life expectancy by 2 hours.
- Don’t smoke – Do I really need to say anymore about this? I don’t want to nag or make you feel bad. I used to smoke, so I know we quit when we are ready. I hope it is soon, because it is affecting your precious life.
- Maintain a normal weight – Another one that we all know we need to do. To see if you are a healthy weight, calculate your body mass index at www.nhlbisupport.com/bmi.
- Follow a healthy diet – Aim for vegetables, fruit, whole grains, nuts, seeds, lean meats, fish, poultry and low fat dairy. The American Heart Association (AHA) recommends limiting sodium to no more than 1500 mgs daily; less if medically advised. AHA guidelines for sugar are less than 100 calories per day for women (6.5 teaspoons) and no more than 150 calories per day for men (9 teaspoons, roughly the amount in 12 oz can of Coke).
- Limit alcohol use – Those with HCV are advised to abstain completely. Turns out that excess alcohol isn’t so great for the heart either. If you don’t need to totally abstain for medical reasons, women may drink up to one standard-size drink a day; men up to two.
- Manage or reduce stress – Just 15 minutes a day of meditation can do a world of good. Don’t have time? Here’s something you can do right now: Close your eyes, take a deep breath in and then let it out. Do it again, this time letting go of the tension in your body. Repeat one more time, this time focusing only on your breath as it enters and leaves your nostrils.
- Get enough sleep. This is an important one. Sleep-deprivation leads to more eating, an inability to manage stress, and other health problems.
If you look over this list, resist the temptation to try to change too much. We all have areas that could use improvement. Beware of the “should” list, such as I should lose weight, I should exercise more, etc. We can beat ourselves up with this list, also known as shoulding all over ourselves.
Start with just one or two concrete and obtainable goals. For instance, if my goal was to lose 20 pounds in the next two months, I’d never make it. It’s too vague and too big. I am more likely to be successful if the goal is to limit myself to 1800 calories a day and keep a log of what I eat. Setting a goal of getting more sleep is too abstract. Saying I will go to bed at 10 pm every night is more concrete.
When I set a goal, I write it down and look at it every day. If I don’t meet my goal, I don’t berate myself. I try to look at why I am not meeting it and adjust accordingly. If my goal is to eat more vegetables, I may not be able to meet that goal because by the time I think about eating them, I am already hungry; heating up last night’s leftovers is faster. Perhaps I need to cut up veggies every few days so they are readily available, or roast up a pan of delicious root vegetables and reheat them in the microwave.
There are many online tools to help me stay on track; some are listed at the end of this article. Online daily logs help me to stay honest. To keep me from slacking, I set up goal reminders to be emailed to me periodically via FutureMe.
On Valentine’s Day, roughly 1200 people will die from heart disease. Don’t be one of them.
Spend some time finding out what you can do to help your heart and brain as well as your liver.
Make a commitment to improve one thing in your life. In matters of the heart, all these things matter.
1 In Stiff: The Curious Life of Human Cadavers, author Mary Roach wrote that some ancient cultures believed that the liver was the most important organ, more so than the heart. The Greeks believed that the soul resided in the liver. It was the source of love and passion. Roach noted that if the liver maintained this prestige, we would be seeing bumper stickers declaring “I (liver symbol) New York” rather than “I ♥ New York.” Imagine Cupid’s arrows impaling livers instead of hearts.
2 Heart Disease and Stroke Statistics – 2011, Veronique L. Roger and colleagues; Circulation: Journal of the American Heart Association
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