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October 2000's Advocate:

News Brief

FDA Approves Fast Track Designation for Pegasys & Ribavirin
HCV Ribozyme Phase I Study Completed
Ortho's New Antibody Test
HCV Saliva Test In The Works

HealthWise: Getting the Most Out of Your HMO
How to make better use of your time in the "system"

Hepatitis C Challenges The Prison System
Issues of Testing and Treatment for Prisoners with HCV Will Tax Correctional Facilities for Years

Selenium - Wonder Mineral?
Selenium, Found in A Variety of Foods, May Have Many Health Benefits

Triple Whammy - New Hope for Interferon Nonresponders
The combination of three drugs could prove to be an effective addition to the current list of medications to fight HCV.

News Briefs

FDA Approves Fast Track Designation for Pegasys & Ribavirin

Hoffmann-La Roche, Inc., has been granted Fast Track development for the combination of Pegasys and ribavirin. Roche is expected to complete the filing process soon.

Under the FDA Modernization Act of 1997, designation as a Fast Track product for a new drug or biological product means that FDA will take such actions as are appropriate to expedite the development and review of the application for approval of such product. The FDA will only designate drugs that are generally considered an improved medical treatment for serious illnesses.

Maxim Reports 48-Week results from Phase II Study

Maxim Pharmaceuticals announced the 48-week results from a Phase II dose-ranging study of Maxamine (by injection) in combination with interferon for naive (patients that have never been treated) HCV+ patients. Patients in the group that were treated with higher, twice daily doses of Maxamine, achieved a 61% response rate. This study was conducted in United Kingdom, Belgium, Israel and Russia. Maxim is collaborating with Hoffman-La Roche for Phase III clinical trials using the combination of Maxamine with Pegasys and ribavirin.

Source: BW HealthWire

HCV Ribozyme Phase I Study Completed

Ribozyme Pharmaceuticals, Inc. and Eli Lilly and Company announced the successful completion of a safety and pharmacokinetic (the action of the drug in the body - absorption, duration of action, distribution in the body, and method of excretion) study of LY466700, the Anti-Hepatitis C ribozyme compound (by injection). This is a safety trial only and did not establish the effectiveness of the drug. Results indicate that the drug was well tolerated over a 28-day period. Ribozymes are synthetically engineered to act as 'scissors'- cutting up viral proteins, thereby making it impossible for the virus to replicate itself.

Source: PRNewswire, Sept. 11

Ortho's New Antibody Test

Ortho-Clinical Diagnostics, Inc. has submitted an investigational new drug (IND) application to the United States Food & Drug Administration for a new HCV antibody test - ELISA. According to company sources, Ortho's new test will detect the HCV antibody in blood samples within a 45-50 day window, which is 49 days earlier than existing HCV antibody tests. Ortho's antibody test is already available in Spain and Belgium and registered in France and Hungary. It is believed that this will be a superior test and would help make the blood supply safer.

Source: PR Newswire

HCV Saliva Test In The Works

Epitope and LabOne are developing a test to detect HCV antibody by measuring the HCV anti-body in saliva. The test will feature Epitope's OraSure oral fluid collection device, which is already used in tests for HIV-1 antibody and for five common drugs of abuse. Measuring antibody to HCV in saliva could lead to wide scale testing since it would be cheaper, more convenient and less painful than the current method by obtaining a sample of blood.

The saliva test would detect the presence of HCV antibody only. Antibodies are developed within 6 months of exposure to HCV. 10-20% of individuals infected with HCV clear the virus on their own - that is their immune system eliminates the virus from their body. A saliva test would not indicate acute or chronic infection or presence of the virus. Viral load tests would be required to identify active infection.

According to a company press release, approval of the saliva test is expected within a year.

Source: Company press release

HealthWise: Getting the Most Out of Your HMO
How to make better use of your time in the "system"
By Lucinda K. Porter, RN

The relationship between a patient and her physician is a sacred one. It requires a tremendous amount of trust. This trust is expected to bloom under the most inadequate circumstances. We meet our doctors when we are sick and vulnerable. There is a social expectation that we are to turn over our bodies to a complete stranger. We barely understand their language and we need to communicate our ailments. The time and attention we often need is usually far less than we are allotted.

It is no surprise to most that there is a crisis in the health care system. "Managed care" is definitely an oxymoron. Physicians are forced to see more patients, thus having less available time with each individual. Insurance sometimes ties the hands of physicians, regulating diagnostic tests, procedures, medications, and number of allowable office visits.

As someone who is both patient and health care professional, I am able to see both sides of the situation. Patients and physicians are frustrated by the inadequacy of the system. The following are some guidelines to help maximize your relationship with your health care provider.

Looking for a new physician:

Find referrals - If you are currently satisfied with one or more of your health care practitioners ask for a referral. You can also ask family, friends, and co-workers for suggestions.

Making an appointment - After you have collected names, you will need to call the office and inquire if s/he is accepting new patients. Also ask if your insurance covers the services of that provider. Verify billing practices in order to avoid any last minute unwelcome financial misunderstandings. You may also want to find out how soon you can get an appointment to be seen. Many people are shocked to learn that new appointments are booked months in advance. If that is the case and you really want to be seen earlier, ask if the office maintains a waiting list. Last minute cancellations are common. If you have a flexible schedule, consider this option. Also, if your medical condition is truly urgent, you can sometimes ask your referring physician to call and attempt to find an earlier appointment. Some offices reserve time for medical emergencies.

Set aside enough time - If your situation is complicated, tell the receptionist. A 15- minute appointment is not the place to bring a long list of complaints. You and the doctor will feel hurried and you may start to lose the doctor's attention if s/he is concerned about running behind time.

In a recent article appearing in Health magazine, the author offered the following based on suggestions from Don't Let Your HMO Kill You by Jason Theodosakis. A few more suggestions have been added. Be sure you make eye contact before speaking to your physician. Once you begin speaking, your doctor may take notes. This does not mean s/he is not listening.

When describing your symptoms, begin with the general picture and end with the specifics. Example: My stomach hurts. I feel nauseous in the morning.

Discuss subjective information first and then move to the objective and/or quantifiable. Example: I feel tired. I have slept 15 hours nearly every night for the past 3 weeks.

Relate the impact the problem has on your life. Example: I am so tired I am unable to exercise.

Be succinct. Start with the most important details and if there is time, you can add the less important information in at the end.

Ask for clarification. If your doctor uses words or explanations you do not understand, ask her to clarify or simplify her words.

Take notes - If the doctor makes suggestions, write them down. Ask him to spell any words you might want to refer to later, such as a diagnosis, medication or procedure.

Take a friend - This is especially important for appointments that may be long, complicated, or not routine. Ask your companion to take notes for you.

Express your reservations - If your doctor suggests a treatment plan that you have some concerns about, let her know. Sometimes these concerns can be easily addressed.

Ask if there are any alternatives - If your doctor makes a treatment suggestion and it is not one that you are prepared to follow, ask about the alternatives.

Keep an open mind - This can be your strongest ally. It is amazing how many people will not try a medication because of their fear of side effects, only to find out later that the reality was not anywhere near their imagination.

Maintain your own health records - It can really help expedite matters if you bring copies of your most recent pertinent laboratory and biopsy results.

Discuss the follow-up plan - If you are scheduled to have diagnostic tests, ask the doctor when you can expect the results and how these results are conveyed to you. If the results are going to be disclosed at your next appointment and if there is going to be a long interval between appointments, ask how you can obtain earlier results.

It usually takes more than one appointment to establish trust. First impressions are not always right. Even the most personable and capable physician's have bad days. Patients do not always make great first impressions either. We are often scared and hide our fear with defensiveness or other mechanisms that inhibit a good relationship. If you do the groundwork, in time the relationship will strengthen. If it does not, look for another doctor. It is your right. Remember that you are the leader in your health care team. You are managing your care, not your physician and not your insurance company.

Further reading:
Theodosakis, Jason Don't Let Your HMO Kill You Routledge, 2000
Groopman, Jerome Second Opinion Viking Press 2000
Jetter, Alexis Help Health magazine July/August 2000 pps. 119-121,160-5

Copyright 2000
Lucinda K. Porter, RN
All Rights Reserved

Hepatitis C Challenges The Prison System: Issues of Testing and Treatment for Prisoners with HCV Will Tax Correctional Facilities for Years
By Alan Franciscus
Editor

Recent estimates indicate that between 40-60% of the US prison population in the United States is infected with HCV and that 1/3 of the estimated 4 million Americans infected with HCV pass through the prison system each year. A disproportionate number of prisoners are people of color; many are locked up for drug-related crimes. In view of the fact that new HCV infections are most frequently spread by sharing drug injection works (needles, cottons, cookers, etc) and minorities have a higher rate of HCV infection, it is easy to see why prisons have such a large population infected with HCV. Now, many prisons around the country are just starting to address the enormous financial and ethical issues that threaten to bankrupt many state budgets.

Many prison systems are starting to tackle the problems of testing and treating HCV. California, Texas, New York, Florida, Virginia and Pennsylvania have adopted testing policies. The larger and more important issue is treatment guidelines on HCV. Many prisons have adopted the treatment guidelines based on the National Institutes of Health (NIH) Consensus guidelines, but have added more restrictions within their prison system. The big challenge will be instituting these adopted medical guidelines in states with a large prison population such as California, New York and Texas.

Testing

There has been sporadic testing in some states to establish HCV prevalence rate. However, routine testing of HCV in prison does not currently exist. When routine testing does become available it is hoped that counseling will be included. "Ideally, there should be pre and post counseling around testing" comments Judy Greenspan, 47, Chairperson of the HIV in Prison Committee of California Prison Focus. "Unfortunately, this is not being done. In fact, some prisoners have been tested and were not told they are HCV+ until years later". This seems to be a recurring theme in letters received by the Hepatitis C Support Project (HCSP) from prisoners. "Many prisoners write that when they inquire about being tested for HCV, they are told that a test had already been performed years earlier, but they were never told they tested positive for HCV", comments Marie, 74, a volunteer with the HCSP. Marie receives between 10-15 letters a week from prisoners around the country. "It's very sad, because many prisoners we hear from are infected with HCV, and are living in complete fear." This is in large part due to the lack of education about HCV.

In California, testing for prisoners or the staff is not routine. According to the California Department of Corrections (CDC), inmates are medically evaluated upon entry and are periodically monitored for ongoing health conditions, and may request medical attention when they have health questions or concerns. Hepatitis testing is done when medically appropriate as indicated by history, physical examination, laboratory testing showing abnormalities, or by inmate request. Involuntary testing of an inmate may be ordered under California Penal Code 4501.1, if an inmate has been involved in "gassing" (throwing of body fluids) at an employee. CDC prison staff is given annual and periodic staff education on all blood-borne pathogens, which includes hepatitis.

CDC is planning a pilot project using a new HCV screening test process with $1 million appropriated by the Legislature. The CDC hopes this program will help to evaluate the cost-effectiveness and efficiency of the screening process in reception (incoming) centers and subsequent treatment prevention measures and costs.

Prevention

Effective disease prevention strategies that include harm reduction models that use bleach and condoms are virtually non-existent in the nation's prisons. Since hepatitis C is most commonly transmitted by sharing HCV infected needles and any drug paraphernalia it is impossible to implement these types of effective prevention measures while inmates are locked up.

Education

Very little attention has been focused on educating inmates or the prison staff. Most prisoners and the general prison staff know very little about this disease and are not being informed about the general issues of transmission, prevention or how to live with HCV.

This may change in California as Centerforce gears up to provide education to prisoners and prison staff. Centerforce, a San Francisco based non-profit, contracts with the State of California, Department of Corrections to provide services for visitor centers and prison health services. The health services piece provides education, prevention and case management to the prison population. These services are broken into three basic educational components-reception (incoming) prisoners, workshops to the general prison population and re-entry services for inmates prior to release. "Centerforce has incorporated hepatitis C prevention into its existing health education prevention programs. This includes hosting Hepatitis C specific workshops for men and women, who are about to be released from custody, with messages on prevention, testing, and treatment, as well as basic hepatitis information to all inmates entering the prison system" comments Mick Gardner, Program Director of Centerforce Health Programs Division.

Treatment

Historically, medical care in prisons has been less than optimal. Prison officials generally chalk this up to limited funding and an under trained staff. Conversely, prison activists claim that it is due to a general disinterest and malice on the part of the prison administration.

Currently, it is believed that 20-25% of people infected with HCV have serious illness or disease progression and these people may require medical treatment. The majority of people (75%-80%) infected with HCV do not have serious disease progression and treatment for these individuals is usually not recommended. If medical treatment is deemed appropriate - the standard medical treatments for HCV include interferon and the combination of interferon and ribavirin. Most medical authorities believe that individuals with elevated liver enzymes, mild to moderate disease progression, low viral load (under 2 million), younger age and a short duration of infection will have a more favorable response to treatment. Exclusionary criteria usually include - severe uncontrolled psychiatric disorders, decompensated (end stage liver disease) cirrhosis, underlying autoimmune disease, underlying cardiovascular disease and recent alcohol/ illegal drug use. As well, individuals with an uncontrolled major illness are excluded from treatment. Additionally, most prisons will not start a person on HCV medication unless the will be incarcerated for the entire length of treatment.

Cost and Effectiveness of Treating HCV

Cost and effectiveness of treating HCV has long been debated, but it has been proven that treatment is cost effective. Additionally, combination therapy produces long term response rates up to 45%. Thus treatment can lower future patient care costs and lower HCV transmission. Two FDA approved treatment protocols are currently available. Interferon mono-therapy (3 mu, injected 3 times a week) and the combination of interferon (3mu, injected 3 times a week and ribavirin (1,00-1,2000 mg pill taken daily). The sustained response rate (clear the virus during and at the end of treatment) for mono-therapy is 10-15% while the sustained response rate of combination therapy is approximately 40-45%. Most physicians agree that since the response rate is so low for mono-therapy, most individuals should be treated with the combination therapy unless contra-indicated for medical reasons.

The cost of mono-therapy is approximately $4,800/yr, while combination therapy averages approximately $16,000 - $18,000 a year. These figures do not include the additional expense of extra medical personnel and the cost of monitoring patients on treatment for side effects from these potent drugs.

Treating HCV with interferon or the combination therapy involves many complex issues, complicated even further if the patient is in prison. For instance, managing the side effects of interferon requires monitoring blood work for signs of potential adverse effects such as interferon induced auto-immune disease, low white blood counts and anemia. Ribavirin can increase the side effects experienced with interferon with an additional risk of severe anemia. The physical side effects vary from patient to patient but many patients require pain medications to help ease some of the potential side effects such as headaches and muscle/joint pain. The physical side effects seem to diminish with time. However, psychological side effects from these medications can be very difficult to control. Depression, anxiety and suicidal ideation can occur and patients need to be monitored carefully. Treatment with anti-depressants and/or anti-anxiety drugs may need to be initiated. In prisons, all mediations and over-the-counter drugs are closely monitored. In some, prisoners must be observed as they take each medication. Taking into account the amount of medications needed to treat the disease and side effects, and the potential number of prisoners needing treatment, the implications are staggering.

California's prison system is currently treating about 400 patients per month, but has not tracked the number of inmates who have completed treatment. The funds allocated for HCV is $485K while the budget only allows for $325K - the remainder $165k is taken from the general health care budget which is used for all medical needs and treatments. The CDC estimates that treatment costs could be greater than $8 million as screening tests continue to be done and as patient numbers continue to rise. The CDC also estimates that a comprehensive program for diagnosis, treatment, prevention, training and education of HCV could climb to an estimated $60,000,000. This would be a big chunk out of the CDC health care services budget of $585,080,000 for fiscal year 2000-2001.

Part of the solution to California's problem may come from Senator Polanco's SB 1256 - a bill that will help fund the Hepatitis C Education, Screening, and Treatment Act. A portion of the funds will be targeted for HCV in prisons. It has passed the California Legislature and is waiting for signature from Governor Gray Davis. Some critics of this measure fear that the CDC will emphasize testing, not treatment and education, thus increasing prisoner's fear without providing any meaningful solutions.

"As the broader community struggles with the pressing issues surrounding HCV testing and treatment", Cynthia Skow, (42), of the HIV in Prison Committee of California Prison Focus says, "special care must be taken to ensure that people in prison have access to competent, compassionate care."

Sources: California Department of Corrections Health Services Division

HEPP News, June 2000 Vol. 3, Issue 6

Selenium - Wonder Mineral?
Selenium, Found in A Variety of Foods, May Have Many Health Benefits
By Alan Franciscus
Editor

Selenium is an essential trace mineral needed in small daily amounts for proper health maintenance. Selenium is also believed to act as an antioxidant to fight viral infections and other diseases. Unfortunately, it has also been touted as a cure all for a variety of diseases from HIV to HCV and even cancer. Unfortunate because it raises false hopes and can be harmful if taken in large doses. Let me repeat this - selenium is not a cure for HCV and can be toxic if taken in high doses. However, some evidence does suggest that selenium can have many health benefits if taken in the proper dosage and under the guidance of a trained health care practitioner.

Selenium can be found in many foods. The amount of selenium in the soil varies from region to region and country to country, which impacts the amount of selenium available in the food we eat from plant and animal sources as well as in the water we drink. Good sources of selenium include grains, cereals, brewer's yeast, wheat germ, liver, butter, and most fish especially shellfish. Additionally, broccoli, tomatoes, radishes, Swiss chard, garlic and mushrooms are rich in selenium. Another excellent source can be obtained from the herb Astragalus which accumulates selenium from the soil. In the United States, regular and healthy meals tend to meet the nutritional requirements of selenium for healthy individuals.

Selenium toxicity is well known although debate continues on the amount needed to induce toxic effects. Toxicity can manifest as visual, muscular or heart problems, increased tooth decay, loss of hair or nails as well as nausea and fatigue.

Deficiencies are more common in areas with low concentrations of selenium in the soil. Selenium deficiencies can occur in association with an increased risk for certain diseases such as cancer, cardiovascular disease, hypertension, strokes, kidney and liver disease. In China, where selenium intake averages 10 to 15 mcg., a day, selenium deficiency occurs in association with Keshan disease, an endemic viral cardiomyopathy affecting children and young women in that country. Treatment with selenium in the form of Astragalus manages Keshan disease, but does not cure it.

Some evidence suggests that vitamin C may inactivate selenium in the stomach or small intestine if taking sodium slenite rather than the organic selenium, selenocysteine or selenomethione. On the other hand, Vitamin E is believed to increase selenium's effectiveness.

The July issue of The Lancet, a leading medical journal, reviewed data on selenium and its importance and potential in fighting disease. Highlights include:

• Hepatitis B or C - Selenium appears to be protective against disease progression to liver cancer.
• Immune function - Studies suggest that a deficiency of selenium can lead to a compromised immune system. Supplements of selenium have been shown to increase immune system response.
• Viral infection - Selenium plays a role in immune response to a viral infection and low selenium levels may influence infection and disease progression.
• Reproduction - Selenium is essential for male fertility. Some studies have suggested that supplementation with selenium may increase sperm stability and motility or movement.
• Mood - Selenium seems important for brain function. Some studies indicate that when selenium intake is marginal or low, mood changes, depression, anxiety, confusion and hostility may occur.
• Thyroid - A low intake of selenium may compromise thyroid-hormone metabolism.
• Cardiovascular disease - Selenium may be protective against cardiovascular disease.
• Cancer - Selenium deficiencies may be related to some cancers - notably lung, prostate and liver cancer.

Another study published in Medline, 1999 reports the results of a small study of three patients with cirrhosis, portal hypertension and esophageal varices secondary to chronic hepatitis C infection. The three patients were treated with 3 antioxidants (alpha-lipoic acid [thioctic acid], silymarin, and selenium) and recovered quickly and their laboratory values improved. While it is a small study, it does suggest the potential for antioxidant therapy, which should be researched further.

The American Recommended Dietary Allowance (RDA) for selenium was revised in April 2000. Taken from two conservative studies, The Panel on Dietary Antioxidants and Related Compounds arrived at a new RDA of 55 mcg., per day. A well-balanced diet will supply the necessary selenium in healthy individuals. Supplements of selenium are believed to be safe as long as the total daily intake is no more than 400-450mcg.,from all sources.

There are many exciting studies that are being planned or already underway. The PRECISE (Prevention of Cancer by Intervention with Selenium) study will recruit about 33,000 Europeans to examine the effect of selenium on mood and quality of life. In addition, The US National Cancer Institute has agreed to fund a 12-year study - SELECT (Selenium and Vitamin E Cancer Prevention Trial). SELECT will recruit 32,000 men to investigate the effect of selenium and vitamin E on prostate cancer.

Selenium's low cost and its potential to improve the health of those suffering from a variety of conditions such as hepatitis C, make it a very appealing subject for future research.

Sources:
The Lancet, Vol 356, July 15, 2000, Margaret P Rayman
Selenium: Important New Review of Health Findings, AIDS
Treatment News & Selenium, Elson M. Haas, MD
Medline, 2000 - Liver, Oct;19(5):381-8, Lirussi, F.

Triple Whammy - New Hope for Interferon Nonresponders The combination of three drugs could prove to be an effective addition to the current list of medications to fight HCV.
By Alan Franciscus
Editor

The combination of interferon, ribavirin and amantadine shows promise for interferon non-responders.

The vast majority of individuals treated with interferon do not clear the hepatitis C virus (HCV). Additionally, these individuals are unlikely to clear the virus when treated with the combination of interferon and ribavirin. Now the results of a new study on the combination of three drugs - interferon, ribavirin and amantadine may hold the key to successfully retreating these individuals.

Interferon is a genetically engineered product based on a natural protein found in our body. Interferon alone is not very effective for treating HCV with only a 10-15% end of treatment response rate (clear HCV). Ribavirin is an antiviral medication that does not work when used as single or mono-therapy, but is effective when used in combination with interferon with a 40-45% end of treatment response rate. Amantadine is also an antiviral that is used to treat influenza A. Like ribavirin, amantadine is not effective when used as a mono-therapy for treating HCV. However, the combination of these three drugs could prove to be an effective addition to the current list of medications to fight HCV.

In the September 2000 issue of Hepatology, scientists reported the results of a new study that treated interferon nonresponders (individuals who did not clear the hepatitis C virus) with the combination of interferon, ribavirin, and amantadine. Participants of this trial were required to be previously treated with 3 mu to 6 mu of interferon, three times a week for at least 6 months, but did not have a sustained virologic response (clear virus) (SVR) or a sustained biochemical (normalization of ALT, a liver enzyme) response (SRB). The sixty patients were divided into two groups:

• 40 patients were treated with interferon (5 mu daily), ribavirin (800-1,000 mg daily) and amantadine (200 mg daily)
• 20 individuals were treated with interferon (5 mu daily) and ribavirin (800-1,000 mg daily), but not amantadine.

Duration of treatment was 12 months with 6 months follow-up for both groups. Approximately 55% of the study participants were genotype 1, the most difficult genotype to treat. Both groups reported similar side effect profile. The end of treatment results for this trial is very impressive:

• triple therapy (interferon, ribavirin, amantadine- 57% (SRB) and 48% (SVR)
• combination therapy (interferon, ribavirin only) - 10% (SRB) and 5% (SVR)

The results of this study clearly indicate that further research is needed. The combination of interferon, ribavirin and amantadine could offer a substantial improvement in HCV therapy for individuals who do not respond to interferon alone. Furthermore, the addition of amantadine is very appealing due to the low cost and commercial availability.

Sources:
Hepatology, September 2000 32:634