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Hepatitis B Foundation News Update HBV: Victories and Challenges in Fighting This Silent Infection BY Marcia Holman Hepatitis B is the world’s most common, serious liver infection, affecting two billion people, a staggering figure that translates to one out of three individuals. Every year in the U.S. alone, more than 200,000 people become infected with the hepatitis B virus (HBV)–a virus that can leave them prone to cirrhosis and liver cancer yet typically wreaks damage without leaving a single clue. This is why HBV has been dubbed a "silent infection." It can be transmitted through blood, sex, intravenous needles or from an infected mother to her newborn during delivery. People at greatest risk for contracting HBV include those who practice unprotected sex with multiple partners, share needles, or who are in an occupation or situation that exposes them to blood. In addition, people who immigrate from or travel to parts of the world where HBV is prevalent are at increased risk of infection. Yet no matter how hepatitis B is contracted, the virus does its damage silently and slowly. Inside the liver cells, the virus reproduces itself at stunning rates-replicating much more rapidly than the virus that causes either hepatitis C or AIDS, but it can take decades for the destruction to the liver to manifest. That’s why many people do not even know they are infected until they test positive for the virus when undergoing a routine screening-type blood test associated with a blood donation, for example. Fortunately, most adults recover and their bodies naturally shed the virus. But ten percent of those infected are unable to shed the virus. They become chronic carriers and are vulnerable to progressive–and usually fatal– liver disease. Currently, 1.25 million Americans are chronically infected with HBV. Worldwide, that number swells to 400 million. A Vaccine Provides Vital Prevention In recent years, patient advocates and public health officials have made it a national priority to stop this stealth disease in its tracks. And the results have been encouraging. For starters, a safe and effective vaccine became available in the mid-80s. The Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics currently recommend that all infants and children up to age 18 years be vaccinated. Adults at high risk for infection are also strongly encouraged to consider the HBV vaccine. Immunizing infants and children is vitally important because they are more vulnerable to HBV. About 90 percent of those under age one who contract the virus are unable to clear their systems and will become chronic carriers of the virus. At greatest risk are infants born of mothers who have the virus. On a positive note, nationwide programs to screen high-risk pregnant women are reaching 100 percent. Certainly, the vaccine is a major strike against eradicating this deadly disease. But prevention is only part of the solution, reminds experts such as Harold Margolis, Ph.D., chief, Hepatitis Branch, CDC. Prevention represents half of what he calls "the bundle of hepatitis B." "We still have to work to cure the people who already have this disease. It’s part of the package," he says. Among prominent liver specialists concerned about finding a cure is Anna Lok, M.D., professor of Internal Medicine at the University of Michigan Medical Center. Dr. Lok cautions that the advent of a vaccine should not be perceived that this disease has been eradicated. "A disease does not disappear overnight. It takes a couple of generations," she says. "We definitely need to continue working on curing this disease." Promising Drugs in the War Against HBV The first FDA-approved drug to fight HBV-interferon alpha 2b (Intron A)-originated from research that initially focused on HIV, the virus that causes AIDS. What interferon does is mimic the natural interferon produced in the body that alters the immune system and suppresses the infectious virus. Unfortunately, the interferon drug has proved it may not be the silver bullet needed to wipe out HBV. For one thing, the drug causes flu-like symptoms. For another, it is only effective in about 20 to 40 percent of HBV-infected individuals. The good news is that as researchers have begun to zero in on how the hepatitis B virus operates, more promising drugs are becoming available. Lamivudine (Epivir-HBV), for example, is the first oral FDA-approved drug for chronic HBV. It was discovered by Raymond Schinazi, Ph.D., director of the Laboratory of Biochemical Pharmacology at Emory University and Senior Research Scientist at Emory’s V.A. Medical Center who became convinced that the key to curing HBV was in dismantling the virus reproduction factory that lies within the liver cell nucleus. This is the aim of lamivudine, which belongs to a class of drugs called nucleoside analogues. These drugs inhibit the DNA polymerase, the enzyme needed for the virus to reproduce. Inhibiting the polymerase shuts down the virus production factory, essentially stopping the HBV in its tracks. Zeroing in on New Therapies While lamivudine has few side effects and has brought hope to chronic carriers, a major concern is that taking the drug may spark mutant strains of the virus, causing resistance. This concern has spawned research into other drugs that may be added to lamivudine to boost its effects and that counter resistance. A promising anti-viral drug that appears to be effective against the lamivudine-resistant virus is Adefovir dipivoxil (GS890) which is now in Phase III clinical trials. The drug has been shown to deplete levels of HBV by 99.99 percent in patients who took the pills for three months. Other hopeful nucleoside analogue drugs in the pipeline include L-FMAU. In preliminary studies conducted at Georgetown University, L-FMAU showed anti-HBV activity and also helped reduce cccDNA, the template the virus forms to replicate itself. Elsewhere, scientists at the Jefferson Center for Biomedical Research are looking at plant sugars that alter proteins within the cell and prevent the HBV from using them to replicate. Advancing research also continues on drugs aimed to boost the immune system such as non-interferon immune enhancers. Thymosin alpha-1 (Zadaxin) is a drug that recently gained FDA-approval for the treatment of liver cancer and appears to give a general boost to T-cell immune fighters that attack infected liver cells. Thymosin also appears to prompt natural interferon production. Theradigm, now in Phase II trials, is a vaccine that enhances helper T-cell activity. Despite the excitement about these individual therapies, experts agree that the most likely successful therapy will include a combination approach. The best way to halt HBV, they say, is to employ two strategies-one aimed to attack the viral replication factory, the other to beef up the immune system. A Cure is on the Horizon The two-pronged approach, however, raises a slew of issues. Should the drugs be started together or staggered? If staggered, which drug should come first? Which patients are the best candidates for these therapies? "Despite the many unanswered questions, chronic HBV carriers have reason to hope," says Dr. Schinazi. Every year in the U.S. alone, more than 200,000 people become infected with the hepatitis B virus (HBV). Currently, 1.25 million Americans are chronically infected with HBV. Worldwide, that number swells to 400 million. About 90 percent of those under age one who contract the virus are unable to clear their systems and will become chronic carriers of the virus. Currently, there are two FDA-approved drugs for HBV, three drugs in clinical trials and at least eight compounds in the pipeline, he notes. Within two years, another drug will be on the market. Although delay in disease progression is the only possibility with the current drugs in development, suppressing viral replication by even 10 years represents a huge step forward toward turning the tide against this dreaded disease. Joan Block, president of the Hepatitis B Foundation-which has a strong mission to find a cure for chronic hepatitis B–echoes this hopeful message. "The promise of research is finally bearing fruit," she says. "But because HBV may manifest differently in people, it’s clear that many approaches must be pursued in order to find good solutions." And although the disease itself may be silent, the efforts to stamp it out must be loud and clear, she adds. "The Hepatitis B Foundation can help increase disease awareness, keep patients up-to-date about drug developments and continue to serve as vocal patient advocates" (see box at right). "But moving the Cause for a Cure takes a team effort. Government grants, biotech investment, and major pharmaceutical R & D (research and development) programs are all needed to fund the cure." Partnering For a Cure It’s critically important for those who are affected to become an active part of this team, Block adds. "Individuals and families affected by this disease can get involved. Share your stories to help eliminate the stigma of the disease." Some experts have noted that there may be some reluctance to speak out because of fear of stigmatization since the public perception may be that hepatitis B is mainly a "sex and drug" disease. Yet, approximately one-third of people become infected from unknown sources. Infected individuals can also volunteer for clinical trials if it’s medically appropriate. To find out about trials sponsored by the NIH and pharmaceutical/biotech companies, log ontowww.clinicaltrials.gov. Finally, urge industry and government leaders to respond by increasing research dollars. As one scientist notes, "we don’t want to leave it to the pharmaceutical companies to solve this problem. That holds HBV patients hostage to the market value of drugs." A cure is too close for the nearly 400 million people worldwide who have hepatitis B to be forgotten, says Block. "Raising our voices about this silent disease is an important step towards eliminating it." -------------------------------------------------------------------------------- The Hepatitis B Foundation: Cause for a Cure Founded in 1991, the Hepatitis B Foundation (HBF) is the only voluntary, non-profit organization solely dedicated to finding the cause and cure of chronic hepatitis B through research, education and outreach. The HBF is committed to raising disease awareness and promoting prevention and has a primary focus on serving as a beacon of hope for individuals and families affected by chronic HBV. Here are some of its services: • maintains a comprehensive Website (www.hepb.org) featuring information about drugs, liver specialists, useful advice and wide-ranging links, etc. • offers a telephone and e-mail Help-Line and educational literature. • publishes B Informed, a free newsletter highlighting "Drug Watch," an updated file of HBV therapies, a complete listing of print and on-line information and support resources,a calendar of events, personal stories and more. • provides a national directory of liver specialists who treat HBV The HBF’s research laboratory at Jefferson Medical College is the site of the exciting discovery of a plant sugar derived HBV antiviral compound that is expected to go into human trials late this year. The HBF also sponsors the prestigious annual Princeton Workshop where a small group of the nation’s leading researchers and clinical experts are invited to come together to discuss HBV therapeutics. In addition, the foundation testifies before state and national legislatures on behalf of the millions of HBV-infected individuals and families and remains at the forefront towards establishing a research agenda for finding a cure. *************** Fact: Every year in the U.S. alone, more than 200,000 people become infected with the hepatitis B virus (HBV). Currently, 1.25 million Americans are chronically infected with HBV. Worldwide, that number swells to 400 million. About 90 percent of those under age one who contract the virus are unable to clear their systems and will become chronic carriers of the virus. For more information, contact: Hepatitis B Foundation 700 East Butler Avenue Doylestown, PA. 18901-2697 Phone: 215-489-4900 E-mail: [email protected].