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In This Issue:
Minorities and Real World Treatment Results
Alan Franciscus, Editor-in-Chief
HealthWise: Hepatitis C and Brain Fog
Lucinda Porter, RN
HIV/HCV Coinfection at CROI: Cofactors and Inflammation
Disability & Benefits: Health Insurance after Diagnosis of HCV
Jacques Chambers, CLU
HCV Advocate Eblast
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Minorities and Real World Treatment Results
—Alan Franciscus, Editor-in-Chief
The difference in efficacy (clinical trials) vs. effectiveness (real world settings) is always striking. In clinical trials of pegylated interferon plus ribavirin the sustained virological response rates (SVR) ranged from about 40 to 50% in genotype 1, and up to about 70% in genotypes 2 and 3. In a real world setting, however, effectiveness has been found to be lower. But what about treatment response rates in an urban real world population that is mostly composed of African Americans and Hispanics? A recent study by Feuerstadt and colleagues1 provides us with some important information and is a real call to action to step up and improve almost every aspect of HCV care and treatment.
In this study, the medical records of 2,370 HCV patients were analyzed. The patients either received care at the Albert Einstein College of Medicine (faculty practice) or at the Montefiore Medical Center Liver Clinic Care (everyday clinical practice). In total 255 patients were treated with pegylated interferon plus ribavirin. The average patient age was 50 yo (60% male; 40% female) and 58% were Hispanic, 20% African American, 9% Caucasian, and 13% from other ethnicities; 68% were HCV genotype 1 and 32% were HCV genotypes 2 or 3.
In the intent-to-treat analysis (all patients counted if just one dose was received) the SVR rates were 14% for HCV genotype 1 patients and 37% for HCV genotype 2 or 3 patients. The SVR rates among those who were treated in the faculty setting were higher than in those patients who were treated in the clinic setting (27% vs. 15%), but the SVR rates were similar in both settings when they counted only the patients who completed treatment. They did find that in a clinic setting more patients stopped treatment due to side effects than in the faculty setting (28% vs. 17%).
The most alarming finding of this study was that only 3.3% of the 1,656 HCV patients who were seen in the clinics and who completed evaluation and treatment where able to achieve an SVR.
The authors noted that “[B]etter therapeutic strategies, drug regimens, and insurance coverage are essential to improve our ability to successfully treat hepatitis C in [an] urban setting with a high prevalence of this disease and, by implication, related morbidity and mortality.”
In the not too distant future we will have an HCV protease inhibitor to add to the current therapy of pegylated interferon plus ribavirin. While the treatment will become more efficacious it will also become more difficult in terms of side effects, adherence and drug resistance. Add in the barriers to care and treatment especially among urban minorities and the message is clear—much more needs to be done to improve education, support and access to care if we are to reap the benefits of the new drugs.
1“Effectiveness of Hepatitis C Treatment with Pegylated Interferon and Ribavirin in Urban Minority Patients,” Hepatology, Vol 51 Issue 4, Pages 1137 - 1143, April 2010.
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HEALTHWISE: Hepatitis C and Brain Fog
—Lucinda K. Porter, RN
The only time my car ever ran out of gas, I was undergoing treatment for chronic hepatitis C virus infection (HCV). I had been taking the usual HCV cocktail of pegylated interferon and ribavirin when I noticed that I was more muddled than my usual self. Determined to stay on top of my game, I became a compulsive sticky note user. Concerned that I would run out of gas, I wrote “Get Gas” on a note and posted it on the dashboard—right over the low fuel light. The next day, my car sputtered and quit, while I was headed to a massage appointment for a stress-reduction treatment.
HCV is associated with impaired cognitive function. Patients call this brain fog. This describes the experience perfectly as sometimes it feels like my brain is enveloped in a dense fog. Research tells me that it is not just in my head. In fact, it may be because of my liver.
In Hepatitis C and Cognitive Impairment, Hilsabeck and Hassanein,1 report that thinking difficulties are linked with liver disease. For many years, cognitive impairment was associated only with hepatic encephalopathy (HE). HE usually occurs in end-stage liver disease as a result of the liver’s inability to remove harmful substances from the bloodstream—particularly ammonia. However, we now know that many factors affect HE and we don’t know what causes it.
Electrolyte and metabolic abnormalities may trigger HE. Other conditions that may lead to HE are dehydration, eating too much protein, kidney problems and insufficient levels of oxygen in the body. HE is often reversible if the cause is treated. Left untreated, coma and death may occur.
Symptoms of HE include changes in mental state, consciousness, behavior, personality, and mood. Speech impairment, delirium, disorientation or coma may occur. A patient with HE may have uncontrollable movement, tremors, deterioration of handwriting or loss of other small hand movements.
There is a huge difference between HE and brain fog. HE is a medical emergency. Brain fog is frustrating. With brain fog, you may lose your car or temporarily forget where you are driving to, but with HE, you may not know what a steering wheel is for or what your name is. It’s important to understand the difference because fear and frustration can make brain fog worse.
Patients with brain fog may have problems with memory and concentration. Thinking and psychomotor skills are slowed. Performing certain tasks can be frustrating. Some patients have trouble reading or remembering what they read.
Brain fog affects approximately one-third of HCV patients. No one knows what causes HCV-related cognitive impairment. There is evidence that HCV may affect the brain directly and indirectly. Our body houses a complex neurochemical system, which is constantly producing substances to keep us healthy. These substances may affect our mood and the overall efficiency of our brain.
Although science supports the notion of brain fog, we need to guard against assuming that we have this HCV-related symptom. Cognitive impairment has many causes, some of which can be fixed. So, before sentencing yourself to a lifetime of feeling feeble-headed, make sure you rule out other risk factors. Hearing loss, sleep problems, thyroid disease, psychiatric disorders, stress, vitamin deficiency, alcohol, and drugs can make us feel fuzzy. Aging and menopause may affect our cognitive abilities. A medical evaluation may help pinpoint the source of the problem.
When HCV treatment is added to brain fog, it feels more like a brain tsunami. Pegylated interferon and ribavirin amplify mood fluctuations and cognitive dysfunction—particularly impaired concentration. Further complicating matters, HCV drugs have side effects such as depression, thyroid abnormalities, sleep disturbances, and fatigue—all of which cause cognitive difficulties. Again, if you are on HCV treatment, don’t assume that the medication is solely responsible for your foggy brain. Something else may be causing it that can be easily fixed.
No matter what the cause, the bottom line is learning how to cope with cognitive impairment. Although it is a frustrating problem, fighting against it makes it worse. Acceptance helps to open the door to finding solutions for how to live when your brain isn’t operating like it used to. Being annoyed doesn’t help matters.
Organization and consistency are essential to effective management of brain fog. Make lists. Write everything down, check the list, and keep it in the same place. I maintain my list on my phone’s memo feature and I back up my phone to my computer. I also keep a separate note pad for jotting stuff down and I add it daily to my computer and phone.
Avoid sticky notes. These get lost or fall off. Put everything in one place. Sometimes I call or e-mail myself with reminders. I use my phone’s alarm to remind me of really important things.
I have a friend who misplaces everything—her phone, car keys, purse, glasses, scissors, etc. She leaves her things wherever they land. This can be fixed by establishing good habits. Return everything to its place. If your car keys and cell phone are always kept on a table near the door, then you won’t spend time looking for them elsewhere. If your list is there, you are likely to check it.
In addition to organizing, try to prevent a pile-up of paper. If you pay your bills as soon as you get them, they won’t get lost. I pay all my bills using the secure online auto-pay feature. I feel it is safer than mailing a check and I avoid late fees.
If losing your car is a problem, write down the location. Make up a phrase to help you remember. For example, Lot B-1= Be one with the universe while I search for my car. When parking at the airport, I will deliberately drive to the “P” for Porter section.
Consistency helps with medication-taking. Choose times to take medication that both follow the instructions and fit your schedule. If you have medication that must be taken with food, store the bottle where you sit down to eat. If you need to take medication several times a day, use a pill container and set a reminder alarm on your phone, computer or wristwatch.
Don’t overlook these brain essentials—sleep, stress reduction, exercise, good nutrition, hydration, and recreation. Avoid alcohol and recreational drugs as these intensify cognitive problems. Don’t try to multi-task. You may think you are saving time, but the risk of memory loss increases when we aren’t mindful.
Exercise your brain. Physical activity is the best way to stimulate brain cells. Go for a walk but don’t talk on the phone at the same time. Puzzles, reading, learning new things, and games are all fun ways to engage the mind.
Above all, maintain a sense of humor. Yes, not being able to think clearly is frustrating. Laughter makes it bearable. Instead of brain fog, I call it hepheimers. I chuckle to myself while I search the house for my reading glasses, wondering how several pair could have disappeared. As the saying goes, the mind is a terrible thing to lose. I think losing a sense of humor is even worse.
1Hepatitis C and Cognitive Impairment, Robin C. Hilsabeck, PhD, Texas Tech University Health Sciences Center, Tarek I. Hassanein, MD, University of California, San Diego, HCV Advocate’s Medical Writers’ Circle
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HIV/HCV Coinfection at CROI: Cofactors and Inflammation
The 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010), held February 16-19 in San Francisco, featured several presentations on HIV/HCV coinfection.
This report looks at factors predicting treatment response, inflammation, and associated conditions among HIV/HCV coinfected individuals. See the April issue of the HCV Advocate for a report on disease progression and treatment outcomes.
Inflammation and HCV
Inflammation has recently become a key area of interest in the HIV field. A growing body of evidence suggests that ongoing inflammation and excessive immune activation due to HIV infection contribute to non-AIDS conditions such as cardiovascular and liver disease.
If chronic HIV infection promotes immune activation, dual infection with HIV and HCV may have an additive effect. Hans Rempel from the San Francisco Veterans Affairs Medical Center and colleagues (abstract 672) found that HIV/HCV coinfected people had higher scores on a “chronic immune activation index” composed of genes that were strongly up-regulated or down-regulated on CD14+ monocytes, a type of white blood cell that recognizes pathogens.
People with either HIV or HCV monoinfection had increased monocyte activation compared with uninfected control subjects. HIV monoinfected individuals who had suppressed HIV viral load on antiretroviral therapy (ART) showed reduced immune activation, but coinfected people with suppressed HIV still showed greater monocyte activation. These findings suggest that “HCV is amplifying the HIV effect on the immune system,” the researchers concluded. “This elevated immune activation may place these individuals at increased risk for HIV and HCV disease complications.”
One factor that contributes to persistent inflammation is “microbial translocation,” or leakage of bacteria from the gut. HIV infects CD4 T-cells in the lining of the intestines, and the resulting damage allows microbes that normally live in the intestines to escape; these bacteria produce toxins including lipopolysaccharide (LPS) that trigger a systemic inflammatory response. Laboratory and animal studies have shown that LPS exposure promotes liver inflammation and fibrosis.
Giusi Maria Bellistri and colleagues from Italy (abstract 654) reported that higher levels of soluble CD14, a receptor that binds to LPS, were associated with advanced fibrosis and having hard-to-treat HCV genotypes 1 or 4. Coinfected patients who did not respond well to interferon-based therapy had higher plasma soluble CD14 and LPS levels, evidence of greater microbial translocation. CD8 T-cell activation, however, did not differ according to treatment response. The researchers suggested these findings indicate that microbial translocation may be an “adjunctive early biomarker of HCV disease progression and treatment outcome.”
Inflammation contributes to impaired function of the endothelial lining of the blood vessels and development of atherosclerosis, or build-up of plaques (accumulations of cholesterol, white blood cells, calcium, and scar tissue fibers) in artery walls; over time, this can lead to heart attacks, and strokes.
Isabel Fernandez de Castro and colleagues from Spain (abstract 667) performed a cross-sectional study of endothelial dysfunction in 183 HIV/HCV coinfected patients on combination ART and 24 control subjects with neither virus.
The coinfected participants had significantly higher levels of two adhesion molecules that serve as biomarkers for endothelial dysfunction, sICAM-1 and sVCAM-1. HCV genotype 1 and advanced fibrosis (stage F3 or higher) independently predicted elevated sICAM-1 and sVCAM-1, and these biomarkers were also positively correlated with elevated liver enzymes. In an analysis of 32 coinfected patients treated for hepatitis C, nonresponders had significantly higher sICAM-1 and sVCAM-1 levels, while those who achieved sustained virological response (SVR) had significantly reduced sICAM-1.
Strokes can happen when pieces of plaque or blood clots break off and block small arteries in the brain, depriving it of oxygen. Jason Sico and colleagues (abstract 668) looked at data on HIV and HCV status, stroke incidence, and mortality among more than 8,500 men in the Veterans Aging Cohort Study; within this group, 1,687 (20%) had HIV alone, 701 (8%) had HCV alone, 738 (9%) were HIV/HCV coinfected, and 5,453 (64%) had neither virus.
After adjusting for confounding factors including demographics, cardiovascular risk factors, and substance use, HIV and HCV alone each increased stroke risk by about 35% (neither statistically significant), but having both viruses more than doubled the risk. In a second model treating death as a “competing risk,” HCV alone raised the risk by about 45% (still not significant), while both HIV monoinfection and HIV/HCV coinfection were associated with a two-fold increase in the likelihood of a stroke.
ART and HCV Replication
HIV/HCV coinfected individuals tend to experience more rapid liver disease progression than people with hepatitis C alone, but the reasons are not well understood. Another study at CROI suggested that changes in blood lipid levels due to antiretroviral drugs may facilitate HCV replication.
Very low-density lipoprotein (VLDL) cholesterol plays role in the HCV lifecycle, but the details are not clear; some experts think HCV may co-opt mechanisms of VLDL assembly to produce new virus particles.
Susanna Naggie from Duke University and colleagues (abstract 666) assessed the impact of ART-induced lipid changes on HCV pathogenesis in HIV/HCV coinfected individuals. They analyzed stored blood samples from 23 coinfected patients starting ART regimens containing either a ritonavir-boosted protease inhibitor (about 60%) or the NNRTI efavirenz (Sustiva); several boosted protease inhibitors are known to raise cholesterol levels.
Lipid levels were within normal ranges at study entry. After starting ART, total cholesterol, VLDL-associated apolipoprotein CIII, and apolipoprotein A1 levels all increased. Concurrently, HCV viral load also increased, by 0.5 log at six months and by 0.4 log at 12 months. This association led the researchers to conclude that, “Lipid elevations associated with ART initiation may drive increases in HCV replication in HIV/HCV coinfected patients.”
IL28B Gene in Coinfected People
Variations in the IL28B gene that were recently linked to spontaneous HCV clearance and treatment response in individuals with hepatitis C alone appear to play a similar role in HIV/HCV coinfected people¾the main topic of a CROI oral abstract session on hepatitis coinfection. Session moderator Ken Sherman said the discovery had “revolutionized the way we think about treatment and management issues.”
Last year researchers in the U.S., Europe, Australia, and Japan reported that specific single nucleotide polymorphisms (SNPs), or variations at specific positions in the human genome, could predict hepatitis C outcomes. These SNPs are located near the IL28 gene, which encodes lambda interferon. A high-risk SNP pattern, or genotype (not to be confused with HCV viral genotypes 1, 2, 3, etc.) was found most often in interferon nonresponders, less often in people who achieved SVR, and least often in those who spontaneously cleared HCV. (For more information, see “Unlocking Interferon” in the October 2009 HCV Advocate.)
Jacob Nattermann and colleagues (abstract 164) determined the IL28B genotypes of nearly 500 Europeans with HIV/HCV coinfection, HCV alone, or neither virus. The frequency of SNP patterns did not differ according to HIV status, but HIV positive people were found to have lower average serum levels of interferon lambda. Among coinfected patients, those with the high-risk IL28B genotype were less likely to achieve SVR, but the effect was not as strong as it was for HCV monoinfected people.
In a study of 189 coinfected individuals in Spain, Norma Rallon and colleagues (abstract 165) saw a strong link between IL28B SNPs and spontaneous HCV clearance. People with non-risk IL28B genotypes were also more likely to achieve SVR, but the association was only statistically significant for HCV genotype 1, with a trend for genotype 4. The researchers suggested that IL28B genotypic testing “should be part of the treatment decision algorithm in this difficult-to-treat population.”
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Disability & Benefits: Getting Health Insurance after Diagnosis of HCV
—Jacques Chambers, CLU
While the new healthcare reform law which recently was passed and signed into law will cause substantial changes, many of the provisions don’t start for some time.
While children will be able to immediately be covered under health insurance regardless of pre-existing conditions, adults with a pre-existing condition will not be able to purchase individual coverage until the year 2014.
Until then, the current rules govern, so perhaps a review of the present sources of coverage for someone diagnosed with HCV would be appropriate.
Currently, the insurance industry uses a procedure called “medical underwriting.” Loosely translated into plain English, it means “discriminating against anyone we feel may cost us money.” And this type of discrimination against people with health problems is perfectly legal.
So once a person has been diagnosed with HCV, can they ever get health coverage again? They certainly will not be able to purchase a policy that requires medical underwriting, which most health plans sold individually do; before accepting you for coverage, they get to review your entire health history and current medical condition, and anyone with HCV will be refused coverage.
Currently, there are alternatives to medically underwritten individual health insurance plans. These are some of the most common:
Employer Provided Health Insurance
Under a federal law called HIPAA, if you work for an employer who provides health insurance to its employees, you cannot be refused the insurance because of your medical condition or health history. If the employer offers it and you are full-time and otherwise qualify for it, they must let you enroll in the plan regardless of your health.
This right to health insurance is available not only to new hires, but also to persons who had originally declined the insurance and later changed their mind, although there may be some temporary limitations on coverage for these “late enrollees.”
There are advantages and disadvantages to getting health insurance through your employer. The primary advantage is the employer pays most or all of the costs of the health insurance and you can’t be turned down. Also, many employers offer a choice of plans so each employee can choose the plan that best fits his/her needs.
The primary disadvantage is that your health insurance is tied to your employment. If the employer changes plans, you have no choice but to change plans too, even if it means less coverage.
Another drawback used to be that you lost your insurance when your employment stopped. COBRA Continuation laws have helped some, but their extension of coverage is limited to between 18 and 36 months.
Now, thanks also to the HIPAA law, once you have acquired health insurance through an employer, you have the right to keep either that insurance or a private plan of similar quality, even if you terminate employment and COBRA Continuation coverage expires. This means that once you acquire health insurance through an employer you will be able to maintain some form of health insurance regardless of any change in your employment status.
Eligible Spouse or Domestic Partner: If you are the spouse of an employee who gets health insurance through an employer, you too are eligible for health insurance just as the employee is. Also, more and more employers and health insurance plans allow “domestic partners” the same rights to health insurance as a married spouse.
Because there is no standard definition of a “domestic partner,” each health plan will have its own requirements as to who can be covered as a “domestic partner.” It usually includes the partner in a committed relationship regardless of sex. Some plans require that they live together; others don’t. Many will require registering as domestic partners if the state or city offers such a program. A few employers will permit any other person to whom the employee has close ties, including a parent or sibling, to be included in the plan.
Union or Guild Health Plans
Most union employees are covered through employer provided health plans that are part of a bargaining agreement with the union. However, some unions and trade guilds provide health insurance directly to their members. This is most common in trades or occupations where the union member either works free-lance or moves frequently from employer to employer. Examples would include: musicians, actors, writers, editors, decorators, truck drivers, and some professional occupations such as attorneys, architects, or dentists.
The requirements for joining the union health plan can be fairly strict. Those unions that permit any dues-paying union member to join the health insurance will have strict requirements as to who is eligible to join the union. Many union plans are more liberal on membership but will require a minimum number of hours worked or dollars earned in that profession to be eligible for the health insurance plan. A few may offer the health insurance to anyone willing to pay the dues but virtually all of those plans are medically underwritten.
At one time, many associations made health insurance available to their members without requiring medical underwriting. Unlike the union or guild plans which required some affiliation to join, most association plans were open to virtually anyone who was willing to pay the dues. This included groups like associations for independent sales representatives, self-employed individuals, and even some fraternal and social organizations.
However, as health insurance became more difficult to find and more expensive to maintain, insurance companies largely stopped writing association plans on such a loose basis. Virtually all of the association plans that still exist require medical underwriting or other evidence of good health to join, just as if the insurance were being purchased directly.
Short Term Health Insurance
There is one health insurance product that is often included in lists such as this, but it provides no real help for anyone already diagnosed with a medical condition. These are the short term or “temporary” health insurance plans. They are written for a set period of time, usually from 30 days up to six months, and they cannot be renewed. While they rarely require answering any questions about your health, they are carefully worded so that they will never cover charges related to any condition for which you were already being treated when the coverage began. This makes them virtually worthless for our purposes.
Veterans Administration Medical Benefits
If you are a veteran of the military you may be eligible for medical benefits from the Veteran’s Administration. For more information on getting benefits through the VA, go to www.va.gov/ and click on “Health – Benefits & Services.” While this may not affect many readers, for those that are, VA benefits can be very helpful, especially for persons dealing with HCV.
If a disability is “service-connected,” you may be eligible for monthly benefits in addition to completely free medical care. Because of the methods of transmission for HCV and because of its relative newness as an identifiable diagnosis, the VA often liberally interprets HCV infection as “service connected.” Generally, proof must be shown that you were at least exposed to potential infection by HCV. If you can show that during active duty, you may have been exposed to HCV through transfusions, tattooing, or even IV drug use, or other situations that could explain the exposure, you may be approved for free medical care and some monthly disability benefits.
These federal health insurance plans can provide medical care to a person with HCV as well, assuming that you are eligible for the coverage.
Medicare is available to persons 65 or older. It is also available to persons under 65 who have collected Social Security Disability Insurance (SSD or SSDI) benefits for 24 months.
Medicaid is a federally mandated health plan based on need. In addition to being either 65 or older or disabled, you must show that your income and resources (assets) are low enough to qualify. Medicaid is administered by each state so eligibility rules will vary slightly from state to state.
State High Risk Plans
Most states offer a health insurance plan for persons who, due to their medical history, are unable to purchase one on the open market. The plans vary from state to state. Most charge a premium that is higher than regular health plans, and some offer benefits that are not as broad.
Currently at least 34 states offer some form of a high risk health insurance pool for persons who cannot otherwise purchase insurance, such as someone diagnosed with HCV. There is a website that reviews each state’s program and provides links for additional information. It can be reached at www.cobrahealth.com/statehighriskpools.html
Open Enrollment Periods
A few states require their Blue Cross – Blue Shield plan to open their enrollment at least once a year to anyone who applies for health insurance, regardless of their health history. Contact your state Department of Insurance to see if your state offers this.
Guarantee Issue by State Mandate
Finally, there are a few states that require all insurance companies to offer at least a few health insurance plans, if not all, to persons without any medical underwriting at all.
However, these few states have not been very successful as the mandate allows people to postpone purchasing health insurance until they knew they were going to need it. As a result, New York, one of the states that guarantees access, finds its health insurance premiums the highest in the nation with family coverage reaching $2,400 per month. This is the reason that current proposals have tied guaranteed access to a mandate that requires everyone to purchase insurance.
Note of Caution: You should avoid any health plan that offers guaranteed coverage including coverage for pre-existing conditions, whether you find it on line or from a licensed insurance agent. Frequently, these plans have such limited benefits, despite the flowery promises in their literature, that they are of little benefit in the event of a serious medical problem. There are also plans out there that are downright fraudulent.
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