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Ribavirin Plus Interferon Is Effective For Hepatitis C Virus Clearance In HCV-HBV Coinfected Patients
By hivandhepatitis.com
Ribavirin and interferon are an effective treatment in 30 percent to 60 percent of patients with chronic hepatitis C. Whether they are also effective in dually infected patients with hepatitis B and C is unknown.
Twenty-four patients with chronic hepatitis seropositive for both hepatitis B surface antigen and antibody to HCV received ribavirin 1,200 mg daily for 6 months, together with 6 million units IFN-alfa 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks.
Serum HCV RNA was positive in 21 patients and negative in 3 patients by Amplicor (Cobas Amplicor Monitor, Roche Diagnostics, Branchburg, NJ). Serum alanine aminotransferase, HCV RNA, and hepatitis B virus DNA were monitored regularly for 12 months.
Another 30 patients with chronic hepatitis C alone receiving the same regimen, served as controls.
The serum HCV clearance rate in group I
patients (43%) was comparable with that in controls (60%, P =
.63) 24 weeks post-treatment. The serum ALT normalization rate in group I and group II patients was 43% and 0%, respectively, 24 weeks post-treatment. After treatment, resurgence of HBV and HCV was encountered in 4 group I patients and 1 group II patient, respectively.
In conclusion, in hepatitis B and C dually infected patients, combination of IFN with ribavirin can achieve a sustained HCV clearance rate comparable with hepatitis C alone. In dually infected patients, the treatment may alter the dominant, ruling hepatitis virus.
Reference
L Chun-Jen and others. Ribavirin and interferon is effective for hepatitis C virus clearance in hepatitis B and C dually infected patients. Hepatology 37 (3):568-576. March 2003.
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Influence of Ethnicity in the Outcome of HCV Infection and Cellular Immune Response
By hivandhepatitis.com
This study was performed to examine the immunologic basis for the apparent ethnic difference in clinical outcome of hepatitis C virus infection between African Americans and Caucasian Americans.
To this end, the researchers recruited 99 chronically HCV-infected and 31 spontaneously HCV-cleared subjects for clinical, virologic, and immunologic analysis. In particular, CD4-proliferative T-cell response to genotype 1-derived HCV antigens (core, NS3-NS5) was examined in 82 patients chronically infected with genotype 1 (54 AA, 28 CA) and in all HCV-cleared subjects (14 AA, 17 CA).
HCV-specific Th1 response also was examined in 52 chronic and 13 recovered subjects. Our results showed that HCV clearance was associated with a vigorous HCV-specific Th1 response irrespective of ethnic origin.
Although the HCV-specific CD4 T-cell response clearly was weaker during chronic infection, AA ethnicity in this setting was associated with a significantly greater CD4-proliferative T-cell response to HCV, particularly to the nonstructural antigens (22% AA vs. 0% CA, P = .007) as well as better clinical parameters of liver disease.
Interestingly, most HCV-specific CD4 T-cell proliferative responses in AA patients were unaccompanied by concurrent interferon (IFN- ) production, suggesting a dysregulated virus-specific, CD4 T-cell effector function during chronic HCV infection.
In conclusion, the study results suggest that host ethnicity does influence the clinical outcome and antiviral T-cell response during HCV infection. AA ethnicity is associated with a more robust antiviral CD4 T-cell response than CA ethnicity, although these T cells are limited in direct virus or disease control due to their dysfunctional nature.
Reference
S Kazushi and others. Influence of ethnicity in the outcome of hepatitis C virus infection and cellular immune response. Hepatology 37 (3): 590-599. March 2003.
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April 17th, 2003
New Drugs Block Hepatitis C
By Maggie Fox, Health and Science Correspondent
New experimental compounds may be able to help the body fight off hepatitis C-an incurable virus that infects millions around the world and causes liver failure and cancer, researchers said.
The research, done by separate teams in Canada and the United States, also led to new discoveries about how hepatitis infects the body-and how the body fights off infection.
Hepatitis C was identified only in 1989. It is spread through blood transfusions and the reuse of needles-including those used for drugs and tattoos.
It infects an estimated 175 million people around the world, about 4 million in the United States, many of whom do not know they are infected. About 8,000 die every year from hepatitis C in the United States alone.
Viruses such as influenza are eventually cleared by the immune system. But hepatitis C can stay in the body forever, eluding the various weapons of the immune system.
The U.S. Centers for Disease Control and Prevention says 75 percent to 85 percent of those infected have chronic, or permanent hepatitis C infection. Seventy percent of these will develop liver damage leading to cirrhosis and liver cancer.
An antiviral drug called ribavirin, used along with an immune system booster called alpha interferon, can help some patients control hepatitis C infection but does not cure it.
"Just a year ago, the hepatitis C virus field had no leads," said Michale Gale, a virologist at the University of Texas Southwestern Medical Center in Dallas who led one of the studies. "We were totally clueless."
Gale's team and a team led by John Hiscott at McGill University in Montreal, Canada found out how the virus de-activates a cell's defenses, so that it can stay in the cell virtually forever.
Virus Blocks a Cell's Defenses
Writing the in journal Science, both teams said they found the virus can block a cell's production of interferon regulatory factor 3 or IRF3-produced by cells to defend against infection and call in more immune system help. The McGill team found it blocks a second compound called IRF-7.
"This really gives us the first evidence of how it is the virus can cause lifetime infection, as opposed to influenza which infects you for a week," Gale said in a telephone interview.
Gale's team also discovered that individual cells have their own immune responses, a finding his team has published in the April issue of the Journal of Virology.
"The whole thing works by IRF3 turning on genes in the human cell that fight off infection. We are going to find out what those genes are, what their products are," Gale said.
This in turn could lead to new ways to battle a number of different viruses, from the AIDS virus to herpes.
In the meantime, two drug companies-Schering-Plough and privately owned German company Boehringer Ingelheim-have developed compounds they hope will work against hepatitis C.
Gale's team tested the Schering product, called by its experimental name SCH-6, and found it could protect the cell's defenses.
"We found that the new protease inhibitors could actually prevent the virus from blocking this immune response and basically restore the innate antiviral response in human cells," Gale said.
The work reported in Science was all done in the laboratory and Gale said the drugs will be difficult to test because no animals are naturally infected with hepatitis C the way humans are.
But Boehringer has reported on Phase I clinical trials, designed to test the safety of a drug in people, that suggest its protease inhibitor is both safe and may at least greatly reduce levels of the virus in the body.
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April 18th, 2003
PEG-Intron (peginterferon alfa-2b) Plus Ribavirin Shows Poor Response Rate as Therapy for Chronic Hepatitis C in HIV Coinfected Patients
By hivandhepatitis.com
Treatment of hepatitis C virus (HCV) has become a major challenge in HIV-infected individuals. No data exist on the efficacy and tolerability of pegylated interferon alfa plus ribavirin in HIV coinfected patients.
Subcutaneous peginterferon alfa (150 micrograms weekly during the first 12 weeks and 100 micrograms weekly thereafter) plus ribavirin (400 mg twice a day) was given to 68 HIV-infected patients with chronic hepatitis C, having CD4 cell counts greater than 300 cells/microliter, plasma HIV-RNA less than 5000 copies/ml, and elevated aminotransferase levels. All were naive for interferon alfa, and 73% were receiving antiretroviral drugs.
Plasma HCV-RNA levels greater than 800 000 IU/ml were seen in 50%, and 35% carried HCV genotype 3.
Adverse events leading to treatment discontinuation occurred in 10 patients (15%). One patient taking didanosine developed pancreatitis. Severe weight loss occurred in 70% of patients.
Clearance of HCV-RNA at the end of therapy (6 months for HCV-3 and 12 months for HCV-1/4) occurred in 50% of patients (81% with HCV-3 versus 30% with HCV-1/4).
As 30% relapsed, the overall sustained response rate was 35% (28% in the intent-to-treat analysis). The main predictors of response were infection with HCV-3 and low HCV load.
Treatment with peginterferon alfa and ribavirin is relatively well-tolerated in HIV-HCV coinfected patients, although new side-effects, including pancreatitis and severe weight loss, may result from the interaction of ribavirin with antiretroviral drugs.
Overall, therapy provides cure to one third of patients, a rate significantly lower than that seen in HCV-monoinfected individuals. Given that relapses are common, extended periods of therapy should be investigated.
Editor's Note: Higher doses of interferon and ribavirin and a longer treatment period may have improved outcomes. However, the pancreatitis and severe weight loss seen in some patients argue against use of higher doses of ribavirin in patients concomitantly using ddI. These study results suggest it will be very challenging to treat HIV-HCV coinfected patients, and that the choice of the anti-HIV regimen must be made with great care to avoid serious toxicities.
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Drugs Could Undo Hepatitis C Damage-UT Southwestern Tests Revive Cells' Immune Response to Virus
By Laura Beil
Texas scientists have discovered how the hepatitis C virus can disarm the body's defenses, allowing it to become a permanent occupant inside cells.
Laboratory experiments published online Thursday in the journal Science Express also suggested that drugs already being tested in patients could restore the crippled immune response, allowing a cell to rid itself of the virus within days.
The discovery offers a blueprint for new treatments of the deadly infection.
Hepatitis C, which is most commonly spread through contaminated blood or intravenous drug use, often leads to a chronic infection. It is the leading cause of liver transplants in the United States. Under the best circumstances, current drugs-which must be taken for months and come with sometimes-brutal side effects-cure only about half the people who take them. An estimated 3.9 million Americans have been infected.
"There's a desperate need for new, more effective drugs to fight hepatitis C," said Michael Gale, a researcher with the University of Texas Southwestern Medical Center at Dallas. Dr. Gale and colleagues from the University of Texas Medical Branch at Galveston conducted the new experiments.
The research team discovered that the hepatitis C virus drops a kind of precision bomb once it invades a cell, releasing an enzyme that disables a molecule called interferon regulatory factor 3, or IRF-3. Without IRF-3, the cell's immune response stalls. With the immune system no longer around to restrain it, hepatitis C gains free reign of the cell, making copies of itself and moving on to infect other cells.
But the UT Southwestern scientists were able to restore IRF-3 by exposing the cells to drugs called protease inhibitors. Once the cell was awash in protease inhibitors, the hepatitis C virus was unable to take over. The cell's immune system was resurrected, and the virus vanished.
"This is, I think, the weak link in the virus's ability to persist, "Dr. Gale said.
And pharmaceutical companies are already testing protease inhibitors in small groups of patients, Dr. Gale said, so experts should know soon how the drugs fare in patients, not just cells.
A second paper published with Dr. Gale's study explains more about how IRF-3 and its team of molecules protect cells. "This is a mechanism that is actually used by many viruses," said John Hiscott of McGill University in Montreal. The fact that protease inhibitors restored IRF-3, he said, has implications for many viral infections other than hepatitis C.
Hepatitis C experts, meanwhile, are pleased to have a new avenue to pursue. "We found something else that may give us a handle on getting rid of this virus," said Leslye Johnson, who heads research into liver infections at the National Institute of Allergy and Infectious Diseases. If Dr. Gale's discovery leads to a better, easier treatment for hepatitis C, she said, "It will be a blessing for the population."
Other UT Southwestern researchers involved in the study were Eileen Foy, Chunfu Wang and Rhea Sumpter.
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Adherence and Mental Side Effects During HCV Treatment with Interferon Alfa and Ribavirin In Psychiatric Risk Groups
Psychiatric disorders or drug addiction are often regarded as contraindications against the use of interferon alfa in patients with chronic hepatitis C. The objective of the current study was to obtain prospective data on adherence to as well as efficacy and mental side effects of treatment with interferon alfa in different psychiatric risk groups compared with controls.
In a prospective trial, 81 patients with chronic hepatitis C (positive hepatitis C virus [HCV] RNA and elevated alanine aminotransferase [ALT] level) and psychiatric disorders (n = 16), methadone substitution (n = 21), former drug addiction (n = 21), or controls without a psychiatric history or drug addiction (n = 23) were treated with a combination of interferon alfa 2a 3 (Roferon A) MU 3 times weekly and ribavirin (1,000-1,200 mg/d).
Sustained virologic response (overall, 37 percent) did not differ significantly between subgroups. No significant differences between groups were detected with respect to interferon alfa-related development of depressions during treatment. However, in the psychiatric group, significantly more patients received antidepressants before and during treatment with interferon alfa (P < .001).
Most of those who dropped out of the study were patients with former drug addiction (43 percent; P = .04) compared with 14 percent in the methadone group, 13 percent in the control group, and 18 percent in the psychiatric group. No patient in the psychiatric group had to discontinue treatment because of psychiatric deterioration.
In conclusion, our data do not confirm the supposed increased risk for interferon alfa-induced mental side effects and dropouts in psychiatric patients if interdisciplinary care and antidepressant treatment are available.
Preexisting psychiatric disorders or present methadone substitution should no longer be regarded as contraindications to treatment of chronic hepatitis C with interferon alfa and ribavirin in an interdisciplinary setting.
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April 20th, 2003
Genetic "Smart Bomb" Knocks out Hepatitis
Human liver cells harbouring the hepatitis C virus can be selectively targeted and destroyed by a new gene therapy approach, according to new research.
The key is a genetically-engineered "suicide" gene, delivered aboard a harmless virus, which is triggered only when it enters a hepatitis-infected cell.
The two current treatments for the debilitating liver disease - alpha interferon and ribavarin - can reduce the level of infection, say researchers, but the virus usually comes back.
The new gene therapy approach could one day "offer the potential of a total cure" for many people, says virologist Christopher Richardson, at the Ontario Cancer Institute in Toronto, Canada, and one of the research team. It might also help tackle other viruses, such as HIV.
About 200 million people worldwide are affected by hepatitis C and infections are increasing. In advanced cases, the virus causes the liver to fail completely or become cancerous.
Achilles Heel
The research began when Richardson and colleague Eric Hsu identified an "Achilles heel" in hepatitis C - a unique protease enzyme produced by the virus.
Some proteases in human cells trigger proteins to kick-start the process by which the cell commits suicide. So the team removed the genetic code that allows the protein to recognize the human protease and replaced it with code specific to the hepatitis C protease.
The DNA for the modified protein was then smuggled into cells using a harmless adenovirus. If a cell is infected, then the viral protease causes it to order its own death. "It's like a suicide vector, a smart bomb," Richardson told New Scientist.
No Rebound
The therapy successfully cleared low and medium level hepatitis C infections in mice with implanted infected human liver cells. In mice suffering high levels of infection, the gene therapy slashed levels of the virus by a factor of 1000.
Importantly, the virus did not "rebound" after the gene therapy, as it can do with existing treatments. This is true for at least 28 days after gene therapy and the team is now doing further work to see if this effect lasts longer.
"It's an incredibly novel approach," said Nigel Hughes, chief executive of the British Liver Trust and an adviser on the UK government's strategy to tackle hepatitis C. "But I have some reservations. If you had this massive cascade of cells dying in the human liver, what would the body's response be? Would you create more harm?"
The approach is "futuristic", admits Richardson: "It is very drastic and we would say it should not be used immediately for human trials." An intermediate approach could be to apply the therapy outside the body, he says.
In an ex vivo therapy, relatively healthy liver cells could be extracted from patients with an advanced infection, cultured and then exposed to the gene therapy. This would kill any infected cells, meaning healthy cells could be transplanted back and restore some of the liver's function.
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April 21st, 2003
Pure Protein L.L.C. Launches Hepatitis C Vaccine Discovery Project
Pure Protein L.L.C. has licensed three Hepatitis C transfected cell lines from the National Institutes of Health to use in a Hepatitis C vaccine discovery project.
Pure Protein will use soluble HLA protein in its Proteome Expression Profiling (PEP) technology to discover virus-associated antigens from inside the HCV infected cells. By comparing differences between peptides in
the HCV cell lines and healthy cell lines, Pure Protein can directly discover which proteins and antigens are unique to diseased cells. Promising targets will be licensed to vaccine and drug designers.
Pure Protein CSO, William Hildebrand, Ph.D., commented, "This project expands on our HIV work in which we discovered a range of novel virus associated antigens and will allow us to move forward in the effort to
characterize viral-host interaction for all the major virus families. In the first phase alone, the HIV project has yielded over 15 new targets for immunotherapy or drug intervention."
Tony Taylor, Business Development Vice President, added: "Pure Protein has enjoyed an excellent reception rolling out its suite of vaccine validation and discovery services. Pure Protein's use of HLA/MHC molecules
as a natural proteome sampling tool has enabled us to quickly and efficiently find relevant antigens for immunotherapeutics as well as targets for drugs and diagnostics."
Pure Protein L.L.C. is commercializing innovative HLA-based technologies for discovery and development of novel immunotherapeutics and small molecule drug targets. The company has research and business
collaborations with several major corporate and academic partners in North America and Europe. For more information, visit the Pure Protein Web site at www.pureproteinllc.com..
Pure Protein L.L.C. was founded in 1999 by Emergent Technologies Inc. (ETI) and its investment partnerships. ETI is a venture capital firm that specializes in forming, funding, commercializing, and managing biotech
companies for the purpose of converting institutional and university-based technology into high return ventures. Its unique process matches breakthrough technology with commercialization partners who can validate
the market potential and expeditiously bring the technology to market. Visit its Web site at www.emergenttechnologies.com
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Protease Inhibitors: Restoring Immune Response in Hepatitis Patients
By John C. Martin, hepatitisneighborhood.com
A new generation of drugs may be the key to restoring immune response blocked by the hepatitis C virus, reducing the virus to what researchers describe as nearly undetectable levels in a matter of days.
The finding could lead to additional effective treatments for liver disease caused by HCV, they say.
A Dual Efficacy
"We found that the new protease inhibitors could actually prevent the virus from blocking this immune response and basically restore the innate antiviral response in human cells," said Michael Gale, Ph.D., an
assistant professor of microbiology at the University of Texas Southwestern Medical Center at Dallas, and senior author of the study.
"Our conclusion is that these new drugs will have a dual efficacy," he said.
The immune system has many ways to detect and fight off invading microbes, and microbes have just as many ways to elude and disarm immune system components. Through a series of experiments on cells grown
in a laboratory, Gale and co-researchers Stanley Lemon, M.D., of the University of Texas Medical Branch at Galveston, defined the strategy that HCV uses to evade the immune response.
As HCV begins to replicate in the body, it manufactures enzymes, called proteases which it needs to transform viral proteins into their functional forms.
Protease inhibitors, which are being scrutinized in clinical trials as therapies to treat chronic hepatitis C infections, target the enzyme activity of the viral protease. "If you block the protease, it neutralizes the virus, and
restores the host response to infection, allowing the cell to clear the virus naturally," Gale explained. "That type of mechanism of the drug was completely unexpected."
Hepatitis C Affects 3.9 Million People
Hepatitis C virus, which is primarily transmitted by intravenous drug use, blood transfusions or blood products, as well as through sexual contact, affects approximately 3.9 million Americans. About 2.7 million are
chronically infected, and the number of new infections has declined from approximately 240,000 in the 1980s to about 25,000 in 2001.
Hepatitis C virus is also the leading cause of liver cirrhosis and liver cancer.
Treatment for the disease includes interferon and the anti-viral medicine, ribavirin. Pegylated, or longer-lasting, interferon combined with ribavirin is the current main line of treatment for HCV. Combination therapy can
clear the virus in 5 out of 10 people with the genotype 1 strain, and 8 out of 10 persons with genotypes 2 and 3.
HCV Persistence
The aim of the study was to determine why hepatitis C virus is so persistent in human cells. Some 85 percent of individuals exposed to the virus develop chronic infections that are non-responsive to therapy. Seventy
percent of those with chronic infections develop chronic liver disease, and nearly 3 percent with long-term infections die of related illnesses.
Gale and his team of investigators discovered that the virus persists, in part, because it blocks the innate immune response in infected cells. "We believe that is a major reason why hepatitis C virus causes chronic
infection," Gale explained.
The identification of this viral protease, Gale explained, opens new avenues in both clinical and basic research on hepatitis C. Until now, scientists had not considered the possibility that inhibiting the protease enzyme
did anything more than halt viral replication. "Now that we know [protease] inhibition essentially restores the hosts immune response to the virus, we can assess hepatitis drug candidates for this ability as well," he
said.
Scrutinizing Protease Inhibitors
Two different protease inhibitor drugs are currently in different stages of clinical trials. These medications will likely be evaluated relative to the latest findings, Gale said. "As opposed to just studying how much the drug
knocks down the virus, now we will evaluate how the drug impacts the host cells response to the infection," he explained.
Protease inhibitors are already well known as effective drugs against HIV, the virus that causes AIDS. They work by interfering with the protease enzyme that HIV uses to make infectious viral particles. Some experts
believe protease inhibitors may now have a new role, based on the findings of studies like this one.
"These new findings with hepatitis C virus suggest that protease inhibitors will become an important addition to existing interferon treatments for hepatitis C, and that they will have equal if not greater impact on the
treatment of this important form of liver disease," said Stanley Lemon, M.D., dean of medicine at the University of Texas Medical Branch at Galveston, whose researchers also took part in the study.
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April 23rd, 2003
Predicting Steatosis in Chronic Hepatitis C
By John C. Martin, hepatitisneighborhood.com
In people with chronic hepatitis C, a condition known as steatosis can also be diagnosed. Steatosis is one of various forms of nonalcoholic fatty liver disease, which is manifested in a range of conditions.
Steatosis essentially means simple fatty liver, which is the accumulation of fat in your livers cells. The condition usually does not damage the liver, and is not associated with liver abnormalities like scarring or
inflammation. Most people who have simple fatty liver have no symptoms.
Another form of non-alcoholic fatty liver disease is known as nonalcoholic steatohepatitis (NASH), which is the most common. Though the prevalence of NASH is not exactly known, some estimates suggest that as
many as 30 million obese adults in the U.S. may have fatty liver disease. NASH is an inflammation of the liver due to the accumulation of fat, which may also lead to scarring of the liver known as cirrhosis.
Cirrhosis is the final form of non-alcoholic fatty liver disease. When inflammation continues for years in the liver, it may progress into cirrhosis of the liver, which can cause progressive and irreversible liver damage.
Steatosis and Its Relationship to HCV
Steatosis is not uncommon in people with HCV, particularly in patients with a strain of the virus known as genotype 3. In addition, non-alcoholic steatohepatitis may co-exist with hepatitis C, and may help to
accelerate the diseases progression.
But it has not been clear about whether steatosis linked with chronic HCV is merely fat accumulation in and around the liver, or whether it may progress to the standard features found in NASH.
Based on that, researchers with the National Institutes of Health released the findings of a study last year during a meeting of the American Association for the Study of Liver Diseases (AASLD), and published in the
journal Hepatology, that could help doctors better diagnosis steatosis and steatohepatitis in HCV patients.
The objective of the study was to determine the frequency, and clinical and virological factors linked to steatosis and NASH in these patients. David Kleiner, M.D., Ph.D., of the National Institute of Diabetes & Digestive
& Kidney Diseases (NIDDK) led the study that first identified all patients with chronic hepatitis C examined at the NIH Clinical Center who had undergone liver biopsy, and whose genotype and clinical information were
available.
The researchers then examined data obtained from liver biopsies performed on 248 patients. The tissue had been examined for three distinctive features of NASH: ballooning degeneration, an abnormal swelling of liver
cells; Mallory bodies, which are accumulations of white blood cells known as eosinophils in damaged liver cells; and sinusoidal fibrosis.
Those findings were then correlated with facts about each persons hepatitis infection, such as genotype, height and weight, and evidence of inflammation, fibrosis and steatosis.
Steatosis and Steatohepatitis Incidence
Approximately 5.6 percent of the patients had features consistent with steatohepatitis. When that was broken down, those with genotype 3 faced higher odds of steatosis and increased fibrosis, the scientists reported.
Steatohepatitis was seen in about 3.5 percent of genotype 1 patients, compared to 13.5 percent of genotype 2 patients, and 18 percent of those with the strain of genotype 3 hepatitis.
In cases of steatohepatitis, the scientists also found that steatosis, liver inflammation, and fibrosis were more common, as were higher levels of two enzymes that can indicate liver damage: alanine aminotransferase
(ALT), and aspartate aminotransferase (AST). The investigators found no association between higher risk of steatohepatitis and weight, age, sex or race.
They concluded that steatosis and fibrosis appear to occur more often in patients with genotype 3 HCV, while steatohepatitis is apparently more prevalent in those with genotypes 2 and 3. "Patients with genotype 2 or
3 may be at increased risk for both NASH and disease progression," they wrote. "The occurrence of steatohepatitis in chronic hepatitis C appeared to be independent of obesity."
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Impact of Estrogens on Liver Disease Progression Considered
From Newsrx.com
"As of this writing, the most common cause of hepatic fibrosis is chronic hepatitis C virus infection (HCV), the characteristic feature of which is hepatic steatosis," state University of Tokushima researchers.
"Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which in turn activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory stimuli, and
produce extracellular matrix components," they continued.
"It should be noted," wrote I. Shimizu and colleagues, "that estradiol (E2) is a potent endogenous antioxidant. A recent study has shown that hepatic steatosis became evident in an aromatase-deficient mouse and
was diminished in animals, after treatment with E2.
"Our studies showed that E2 suppressed hepatic fibrosis in hepatic fibrosis models, inhibited the activation of activator protein 1 and nuclear factor-kappaB in cultured hepatocytes undergoing oxidative stress, and
attenuated HSC activation in primary culture."
Men appear to be more adversely affected by liver disease than women, with clinical data suggesting chronic HCV disease progresses faster in men than women, for example, and liver cirrhosis occurring more often in
men and postmenopausal women.
Shimizu and colleagues noted that recent work has shown that men with chronic liver disease have higher expression of variant estrogen receptors (Ers) than women patients, while ER levels are diminished in
postmenopausal women and both men and women with liver cirrhosis.
"The actions of E2 are mediated through ER alpha and beta. HSCs have also been found to possess functional ER beta but not ER alpha," the researchers said.
They concluded that "a better understanding of the basic mechanisms underlying the gender-associated differences observed in the development of hepatic fibrosis would provide valuable information relative to the
search for effective antifibrogenic therapies."
Shimizu and coauthors published their study in Liver International (Liver Int, 2003;23(1):63-69)).
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U.S. Warns Drug Makers on Illegal Sales Practices
By Robert Pear
The Bush administration told drug companies today that many of the techniques they use to sell their drugs run a high risk of violating federal fraud and abuse laws.
The warning came as the government issued a compliance guide for the drug industry, telling manufacturers that they must not offer any financial incentives to doctors, hospitals, insurers or pharmacists to encourage
or reward the prescribing of particular drugs.
Such payments have "a high potential for fraud and abuse," said the guide, issued by Janet Rehnquist, inspector general of the Department of Health and Human Services.
Federal law prohibits payments intended to generate business under Medicare or Medicaid, the federal health programs for 80 million older, disabled or poor people.
The law, known as the anti-kickback statute, forbids some practices that are common in other industries, Ms. Rehnquist said.
She said she was particularly concerned about marketing practices that drive up federal costs, interfere with clinical decision making and lead to overuse or inappropriate use of drugs.
Medicaid and Medicare spend more than $30 billion a year on prescription drugs. The amount would soar if President Bush and Congress agreed on a plan to provide comprehensive outpatient drug benefits to older
people.
Drug companies objected to many provisions of the compliance guide when the government invited public comment on its ideas in October. The final version of the document clarifies the government's interpretation of
the law and explains why federal officials oppose some drug company practices, including offering doctors gifts, payments and entertainment.
"Any time a pharmaceutical manufacturer provides anything of value to a physician who might prescribe the manufacturer's product, the manufacturer should examine whether it is providing a valuable tangible benefit to
the physician with the intent to induce or reward referrals," the compliance guide says.
"A lawful purpose will not legitimize a payment that also has an unlawful purpose," it adds.
It also says drug companies risk prosecution when they encourage the use of their products by making payments to health plans and to the companies that manage drug benefits for millions of Americans. Such
companies, known as pharmacy benefit managers, often receive money from the manufacturer of a drug if sales of that drug reach a certain level-say 40 percent of the prescriptions for drugs that lower cholesterol.
The inspector general said such payments could violate the law.
To help control costs and improve the quality of care, many health plans and benefit managers establish lists of recommended drugs, known as formularies.
If a drug is on such lists, its sales can rise rapidly. Given the importance of formularies, Ms. Rehnquist said, "some unscrupulous manufacturers and sales representatives" offer payments to the people who develop
them. The payments "are suspect," she said.
Ms. Rehnquist said consumers could benefit from legitimate discounts, defined as a reduction in the price of a prescription drug "properly disclosed and accurately reported."
Drug companies and benefit managers can protect themselves, she said, by disclosing their financial arrangements to the people who pay for prescription drugs, including employer-sponsored health plans.
Those arrangements have long been shrouded in secrecy. But in advertisements last week, one benefit manager, Express Scripts, promised to "provide our clients with a detailed disclosure of our sources of revenue
and financial relationships with drug manufacturers."
Ms. Rehnquist also warned drug companies that their research and education grants must be divorced from their marketing, or they risk violating the law.
If a drug company has any influence over the content of a professional education program or the choice of speakers, "there is a risk that the program may be used for inappropriate marketing purposes," the compliance
guide says.
It also says that when drug companies pay doctors to conduct research, they must make sure the research is legitimate, "not simply a pretext to generate prescriptions of a drug."
Research and education grants are suspect if they are "based in any way, expressly or implicitly," on a doctor's ability to generate business for a drug maker, the guide says.
Ms. Rehnquist said drug makers might violate the law when they pay doctors for the opportunity to observe the treatment of patients. Drug companies defend these programs as a way to educate their sales agents.
But Ms. Rehnquist said the payments could also be a subtle way to encourage or reward the use of particular medicines.
Ms. Rehnquist also condemned a new arrangement under which drug companies pay doctors for the time they spend listening to sales pitches. The pitches are typically made by a sales representative who visits
doctors in their offices.
These payments "are highly suspect under the anti-kickback statute, are highly susceptible to fraud and abuse and should be strongly discouraged," the guide says.
Medicare and Medicaid often pay for prescription drugs based on price and sales data reported to the government by drug makers. Ms. Rehnquist said drug companies had often tried to maximize their income by
reporting inaccurate data in violation of the False Claims Act.
Under federal law, state Medicaid programs are often entitled to the "best price" a drug company offers to other buyers. But, Ms. Rehnquist said, companies sometimes conceal the discounts they give other buyers.
"Manufacturers have a strong financial incentive to hide de facto pricing concessions to other purchasers, to avoid passing on the same discount to the states," the compliance guide says. Drug companies are
responsible for the integrity of the data they report to the government, and the data must take account of any discounts, rebates, price concessions or other benefits offered to private purchasers, it says.
Ms. Rehnquist said a drug company's commitment to fighting fraud and abuse could be measured by the way it trains and pays its sales agents. Excessive compensation can be evidence of "improper intent," the
compliance guide says.
"For example," it says, "if a manufacturer provides sales employees with extraordinary incentive bonuses and expense accounts, there may well be an inference to be drawn that the manufacturer intentionally
motivated the sales force to induce sales through lavish entertainment or other remuneration."
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April 28th, 2003
Schering-Plough Reducing Dependence on "Single Blockbusters"
Schering-Plough's newly elected CEO, Fred Hassan, plans to reduce the company's previous dependence on a single blockbuster and look instead to five or six growth products that together represent 50 percent to 60
percent of revenues.
The move, part of an action agenda unveiled at Schering-Plough's annual meeting, is a tacit admission that excessive reliance on one top-selling product - Claritin - has failed. Claritin is now sold over the counter in the
US, and the switch, together with the entry of generic loratadine, is a major reason for the company's present woes.
Mr Hassan also hinted that some shifting around in the company's senior management might occur, although he plans to work with existing Schering-Plough people. He said he had made a commitment to having an
effective team of people at the top within several months, and that this team would provide "the necessary energy and direction" to improve flagging sales figures and turn the company around.
Nevertheless, cutbacks in sales staff are not expected, nor will arbitrary redundancies be made across the board, said Mr Hassan. Instead, a "cost-consciousness" will prevail and all activities will be reviewed based
upon return on investment and risk. Results will begin to show by the year's end, although it will take five or six years to achieve most of the planned goals, Mr Hassan told shareholders on his second day in the job.
His overall approach will focus first on people and then on products and processes. "I will count on the company's worldwide team of talented employees to accomplish the new agenda and build on all that is good in
Schering-Plough," said Mr Hassan, who will receive a minimum salary of $1.5 million per year as well as stock options and incentive pay.
He said he would "make the most" of marketed products through better sales promotion and the pursuit of additional indications. For example, sales of the incontinence treatment, Detrol (tolterodine), grew
substantially at Pharmacia, where Mr Hassan was previously CEO, after the product was marketed to general practitioners as well as urologists.
Schering-Plough will also seek to expand its portfolio through product licensing and acquisitions. As for the manufacturing issues that have dogged the company for two years, Mr Hassan plans to be personally
involved with the FDA to demonstrate the company's commitment to the terms of its consent decree.
He said he will review and evaluate the company's product portfolio, which most analysts believe to be weak. Schering-Plough is investing heavily in R&D but has not made public its R&D budget for 2003. It expects its
recently launched cholesterol-lowering product, Zetia (ezetimibe), co-marketed with Merck & Co, to become its next best-selling product.
Schering-Plough's Product Pipeline Product
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Schering Turnaround Needs 5 Years, CEO Hassan Says; First Step: Buy Time
THE-PINK-SHEET
Schering-Plough CEO Fred Hassan's turnaround plan for the company relies on a careful balance of near-term markers coupled with a message of patience to buy time to execute a five- to seven-year plan.
In his inaugural presentation to shareholders during Schering's April 22 annual meeting, Hassan declared that "there will be no quick fixes" for the company. Rather, he intends to move through a five-phase turnaround
process "that we plan to implement over the next several years. The timeframe is maybe five to seven years."
Hassan was confirmed as Schering's pick to succeed retiring CEO Richard Kogan April 20. The former Pharmacia CEO emerged as the leading candidate for the post soon after Schering began the search process in
November, but a formal announcement awaited the closing of the Pfizer/Pharmacia merger ("The Pink Sheet" April 21, p. 8).
The unusual succession process contributes to the unusual challenge Hassan faces at Schering.
Hassan was a logical choice for the post. He is regarded as the savior of Pharmacia, having joined the company in 1997 during a difficult period following the Upjohn merger. He turned P&U around and then engineered
the acquisition and integration of Searle.
The long period as unannounced heir-apparent, however, may have led to unrealistic expectations among investors that the arrival of the new CEO would signal the end of the turnaround process. Instead, Hassan
outlined a five-phase plan in which "turnaround" is prominently listed third. The five phases outlined are "stabilize," "repair," "turnaround," "build the base," and "break out."
Hassan stressed the need for "long-term" changes at Schering. "A long-term action agenda demands that we be engaged in a major change process over a long period of time. It will not be enough simply to do the
things that brought success in the past; we must do things in a new way to respond to a new environment."
After Schering's dismal performance over the past two years, however, shareholders are likely to demand immediate signs of improvement, and Hassan's five-phase plan offers some early markers over the first year of
his tenure.
"We see the first two phases [i.e., stabilize and repair] lasting about a year," he said. "Meantime, beginning around month six to month nine, we'll start to see the beginning of phase three."
The first phase is already under way, Hassan declared, with the company focusing on a more open communications strategy to "rebuild confidence."
"I've already launched a number of communication actions, including a personal message to all our people worldwide," he said. In addition, "our customers will see a lot of me."
Hassan will also host Schering's second quarter earnings call in July. At that time, "I will update you on the early action steps" being taken. Schering's first quarter call will be delayed until May 13 from its original April
22 date to give Hassan the opportunity to review the company's most recent financial numbers.
Schering has been known for delivering scripted presentations to investors and usually declining to take analysts' questions on its quarterly "quick calls."
Schering's reputation in the investment community hit a low point after a closed-door meeting between former CEO Kogan and select analysts days before the firm announced it was lowering its third quarter 2002
earnings guidance. The fallout from that meeting prompted the acceleration of Kogan's retirement ("The Pink Sheet" Nov. 18, 2002, p. 15).
In addition to building a new communications strategy, the first phase of Hassan's action plan includes getting "on top of the immediate legal and compliance issues."
Schering has already taken steps in that direction. The company entered into a consent agreement with FDA regarding good manufacturing compliance difficulties at the end of 2001 (although a criminal investigation is
ongoing). In addition, the firm reserved $150 mil. to reflect its "minimum liability" in ongoing investigations by the Boston and Philadelphia U.S. Attorney's offices of its marketing practices ("The Pink Sheet" March 3, p.
4).
The "repair" phase will include efforts to "embed a behavior of business integrity and compliance" into the company. Hassan will "reach out to our stakeholders to listen, learn and take actions to reduce our risk
exposure and fix problems."
At Pharmacia, Hassan created an "in-house prosecutor" position that reported directly to the board ("The Pink Sheet" Dec. 2, 2002, p. 13). As chairman of the Pharmaceutical Research & Manufacturers of America in
2002, he oversaw the adoption of codes of conduct covering marketing practices and clinical trials.
In the "turnaround" phase, Hassan envisions "making progress on selling more of our products, reducing costs and improving product flow, and establishing the basics of strategy, structure and longer-term action
programs."
From an operational standpoint, Schering will be working through the loss of the prescription Claritin line over the course of 2003, and then appears to be well-positioned to deliver growth based on the performance of
the cholesterol agent Zetia and other potential new launches.
However, there are other potential difficulties to overcome. The Intron-A franchise is facing tougher competition from Roche with Pegasys, and the potential launch of generic versions of Rebetol (ribavirin) could erode
sales. Another challenge could be protecting the prescription-only status of Clarinex.
Schering has several late-stage compounds in its pipeline, including the pending metered-dose inhaler Asmanex; Noxafil for opportunistic fungal infection; and Sarasar, an oral anticancer agent in Phase III for non-small
cell lung cancer.
The "turnaround" phase is "also when we begin building a superior top team," Hassan added. Hassan is in a good position to recruit outside executives to Schering based on his extensive network of contacts from
three decades in the industry.
An obvious starting point will be the pool of former senior Pharmacia managers who were not offered slots at Pfizer. That list includes former Chief Financial Officer Christopher Coughlin; Co-President-Global
Prescriptions Business Carrie Cox (who Hassan brought with him to Pharmacia from Wyeth); Chief Scientific Officer Phillip Needleman (credited with the development of COX-2 inhibitors); and Senior VP-Corporate
Affairs Timothy Cost.
Several other members of the Pharmacia group, including R&D head Goran Ando, Pharmaceutical Co-President Tim Rothwell and VP-Global Specialty Operations Stephen MacMillan, have moved to other companies
(see following story).
Hassan began his career at Sandoz and spent 17 years at the Swiss company, becoming head of its U.S. pharma business. He joined American Home Products (Wyeth) in 1989 before leaving for P&U in 1997.
Hassan's familiarity with the senior executive teams around the industry may also prove useful in accomplishing phase four of the action plan: to broaden Schering's product base. Hassan is already speaking publicly
about a formula where half of Schering's product line represents in-licensed or otherwise acquired research.
Finally, in the "break-out" phase, Hassan envisions Schering moving from "good to best," by identifying "actions that will bring transformational change."
At Pharmacia, Hassan sought transformation through acquisition in the Searle deal. An exact replica of that strategy would be difficult at Schering, since there are fewer like-sized firms left in the industry. However,
there are still potential acquisition targets on a smaller scale in the biotech and specialty pharma areas.
Hassan also learned first hand the intricacies of managing a mega-partnership deal at Pharmacia, where the Searle/Pfizer COX-2 inhibitor agreement ultimately led to Pfizer's buyout of the company.
At Schering, the Zetia copromotion with Merck will again have Hassan working with a senior partner on a key product. The intense competition between Merck and Pfizer/Pharmacia in the COX-2 category should make
for an interesting transition period, particularly if Hassan recruits former Pharmacia marketing execs like Carrie Cox to Schering.
Overall, Merck is a less threatening partner than Pfizer, based on the repeated declarations by Merck CEO Ray Gilmartin that mega-mergers are not in the company's best interests. Nevertheless, the Merck
relationship may set a competing timeline running against Hassan's five to seven year plan: Gilmartin is 62 and will presumably retire as CEO in the next three years. Depending on the course of the transition at
Merck, the no-merger pledge could be revisited.
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April 29th, 2003
AIDS Drugs Offer Hope for Hepatitis C Patients-Virus All But Destroyed in Three Days
Researchers have found that new drugs can reduce the hepatitis C virus to nearly undetectable levels in as few as three days and restore the cells' ability to clear the infection from the body naturally.
Protease inhibitors, which have revolutionized the treatment of AIDS, could dramatically improve the lives of the estimated four million people in the United States and 275,000 in Canada who have hepatitis C, University
of Texas researchers in Dallas and Galveston said.
"Just the thought of something like this that could treat a disease that is this horrid that fast is inconceivable," said Paula Parsons, an Irving resident who was diagnosed with hepatitis C three years ago. "It would
change my life most definitely."
In the study to determine why hepatitis C is so persistent, researchers at the University of Texas Southwestern Medical Center at Dallas and the University of Texas Medical Branch at Galveston found that protease
inhibitors prevented the virus from blocking the immune response. The inhibitors also restored the natural anti-viral response in human cells.
The research brings new hope to the millions of patients worldwide who have hepatitis C, said Dr. Michael Gale, assistant professor of microbiology and an author of the study. His study was published online in
Science, a magazine by the American Association for the Advancement of Science, based in Washington, D.C.
"Today, less than half of all patients are cured because the virus is so resistant to therapy," Gale said. "With 200 million people in the world infected, we desperately need new drugs."
Protease inhibitors boost a person's ability to respond to the hepatitis C virus, said Eileen Foy, a student in UT Southwestern's Medical Scientist Training Program and the study's lead author. When used to treat
AIDS, protease inhibitors stop the body's reproduction of HIV.
The drugs neutralize the virus and allow cells to clear the virus from the body naturally, Gale said. Protease is an enzyme that is required to process viral proteins into their functional forms.
Protease inhibitors are at least a couple of years away from Food and Drug Administration approval for the treatment of hepatitis C but are being tested in clinical trials.
The research holds promise for patients such as Parsons.
"The worst part of living with this disease is there's always the fear you'll get liver cancer," she said. "Or you're wondering from day to day if you'll need a liver transplant."
About 85 per cent of those exposed to the virus develop chronic infections that are unresponsive to therapy, Gale said. Chronic hepatitis C can cause cirrhosis, liver failure and liver cancer.
At least 75 per cent of patients diagnosed with hepatitis C develop chronic liver disease; nearly 3 per cent with long-term infections die of related illnesses, according to the Centers for Disease Control and Prevention.
The virus is primarily transported by sexual contact, intravenous drug use and blood transfusions. The disease can exist for 10 to 15 years before symptoms such as fatigue, jaundice and nausea appear, Gale said.
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EU Health Authorities Revise Peg Intron Labeling To Include 12-Week Predictability For Success In Treating Chronic Hepatitis C.
Schering-Plough Europe today reported that the European Agency for the Evaluation of Medicinal Products (EMEA) has revised the EU labeling for Peg Intron(R) (peginterferon alfa-2b).
The new labeling includes clinical trial results that demonstrate the predictability of a patient achieving a sustained virologic response (SVR) at week 12 of a 48-week treatment regimen with Peg Intron and Rebetol(R)
(ribavirin) combination therapy. SVR, the accepted criterion for efficacy, is the sustained undetectability of the HCV virus six months following the end of treatment. In this 48-week clinical trial, patients who did not
achieve an early virologic response (EVR) did not become sustained responders (100 percent negative predictive value), indicating that doctors can predict with a high degree of certainty after 12 weeks of therapy which
patients will not achieve SVR; this is referred to as negative predictive value. EVR is defined as achieving either undetectable virus (HCV-RNA) levels or a significant (greater than 2 log10) drop in viral load at week 12 of
therapy. Positive predictive value is equally important in encouraging patient compliance with the prescribed treatment regimen. In this study, 80 percent of patients treated with Peg Intron and Rebetol who achieved
EVR at week 12 went on to achieve SVR. The predictability of Peg Intron and Rebetol combination therapy can help physicians to reduce uncertainty in managing each patient's treatment.
"The predictive value of the early virologic response rates seen with Peg Intron and Rebetol combination therapy provide a real incentive to many patients who are responding at week 12 to continue their treatment
regimen and achieve a sustained virologic response," said Prof. Christian Trepo, head of Service d'Hepato-Gastroenterologie, Hotel Dieu, Lyon, France. "Likewise, for those patients who do not achieve an EVR or take
longer to respond to therapy, doctors might discontinue therapy or consider continuing treatment based on other prognostic factors," he said.
"Schering-Plough is committed to providing quality care and support for patients with chronic hepatitis C," said Thomas C. Lauda, executive vice president, Schering-Plough Pharmaceuticals. "For more than a decade,
we have researched and refined innovative products such as Peg Intron and Rebetol to achieve this goal, and we are committed to continuing our leadership in discovering and developing new therapies for patients with
this disease. "Peg Intron is a longer-acting form of Intron(R) A (interferon alfa-2b) that uses proprietary PEG technology developed by Enzon, Inc. of Bridgewater, N.J., USA.
Peg Intron, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy dosed according to patient body weight that is designed to achieve an effective balance
between antiviral activity and elimination half-life. Schering-Plough holds an exclusive worldwide license to Peg Intron.
Rebetol is an oral formulation of ribavirin, a synthetic nucleoside analogue with broad-spectrum antiviral activity. It is approved worldwide for use in combination with Peg Intron or Intron A for the treatment of adult
patients with chronic hepatitis C. Schering-Plough has rights to market oral ribavirin for hepatitis C in all major world markets through a licensing agreement with Ribapharm Inc. of Costa Mesa, Calif., USA.
Chronic hepatitis C is estimated to affect more than 10 million people in major world markets. In Europe, chronic hepatitis C is a leading cause of chronic liver disease and one of the most common reasons for liver
transplant. Schering-Plough Europe, based in Brussels, Belgium, is a subsidiary of Schering-Plough Corporation of Kenilworth, N.J., USA, a research-based Company engaged in the discovery, development,
manufacturing and marketing of pharmaceutical products worldwide.
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New test May Help Hepatitis B Patients
By Randy Dotinga, HealthScoutNews
Researchers think they've discovered a way to tell if patients infected with a type of hepatitis will eventually fail to respond to a powerful drug.
If the researchers are right, their test could help doctors do a better job of adjusting medications for people with hepatitis B, a deadly type of liver disease.
"About half to two-thirds of patients will basically fail the therapy after two to three years because they acquire drug resistance," says study co-author Brent Korba, a professor of microbiology at Georgetown University
Medical Center. "It would be nice if you could predict those who are most likely to fail so you don't treat them (with the drug)."
Hepatitis B is one of several types of liver diseases that share little but the same name. An estimated 1.25 million Americans are infected with chronic cases of hepatitis B, which is typically spread through sex,
needle-sharing and transmission from mother to baby during birth. Liver disease kills as many as one in four of those who suffer from the chronic form of the disease.
Hepatitis B, like AIDS, responds to antiviral drugs. One of them, called lamivudine, is commonly used to keep hepatitis B under control. "It's probably the first treatment choice for chronic hepatitis B today," Korba
says.
But in many patients, the hepatitis B virus mutates into forms that become immune to lamivudine and other drugs. For that reason, many doctors are hesitant about giving patients the drug until they are in the later
stages of infection.
Korba and his colleagues decided to study the hepatitis B virus's genetic makeup in 26 patients who had undergone treatment with lamivudine to see if there were any early warning signs of trouble. They reported their
findings Monday at the 16th International Conference for Antiviral Research in Savannah, Ga.
The researchers found DNA "markers" in the genetic makeup of the virus in the patients who either developed an immunity to lamivudine or never responded to it at all. They couldn't find the markers in the virus in
patients who responded well to the drug, says study co-author John Gerin, a professor of microbiology and immunology at Georgetown University Medical Center.
The test for the DNA markers is cost-effective, he adds. Alternatives to lamivudine are scarce, however. Only two other drugs are licensed for use in hepatitis B patients.
But Gerin says new drugs are on the horizon: "We do hope there will be options."
Frank Myers, an epidemiologist at Scripps Mercy Hospital in San Diego, says the findings are promising, especially if they can be extended to predict potential drug resistance in other diseases such as AIDS.
"We can not know if this new technique could be used with other viruses like HIV, but if it could, the benefits could be enormous," Myers explains.
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May 01st, 2003
Levels of IgM anti-HCV in liver transplant patients with ALT flares
Quantitative monitoring of IgM anti-HCV may be a diagnostic tool for distinguishing recurrent hepatitis C from acute graft rejection, find researchers in the May issue of the Journal of Viral Hepatitis (J Viral Hepatitis
2003; 10 (3): 168-73).
Recurrent hepatitis and acute rejection share common features which diagnosis difficult in liver transplant hepatitis C virus (HCV) positive patients.
In this study, researchers from Italy assessed quantitative monitoring of HCV RNA and immunoglobulin (Ig)M anti-HCV in the differential diagnosis between recurrent hepatitis and acute rejection.
They studied 98 consecutive anti-HCV positive liver transplant patients.
The research team measured aminotransferase levels, serum HCV RNA and IgM anti-HCV at the time of transplantation, and monthly thereafter.
Furthermore, the researchers obtained a liver biopsy (LB) when serum aminotransferase levels increased to greater than twice normal.
The research team observed 86 aminotransferase flares, during a mean follow-up of 16 months.
They found that histology was compatible with recurrent hepatitis C in 44 cases, with acute rejection in 28, and inconclusive in 14.
The fluctuations of HCV RNA serum levels were not significantly different in the 3 groups.
Serum IgM anti-HCV levels increased in 82% of cases with recurrent hepatitis C.
However, serum IgM anti-HCV levels increased in 36 of 44 cases with recurrent hepatitis C at the time of the alanine aminotransferase (ALT) flare.
Furthermore, IgM anti-HCV remained unchanged in all rejection cases.
It also increased in 10 of 11 histologically doubtful cases that were diagnosed as hepatitis at a second LB.
Increasing serum levels of IgM anti-HCV at the time of ALT flares are significantly associated with recurrent hepatitis C in liver transplant patients.
Dr Ciccorossi's team concluded, "Quantitative monitoring of IgM anti-HCV appears to be an additional diagnostic tool for distinguishing recurrent hepatitis C from acute graft rejection with a 100% specificity, 100%
positive predictive value and 89% diagnostic accuracy".
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Adenovirus Expressing Modified Apoptotic Molecule Thwarts HCV Infection in Mice
By Megan Rauscher
In mice with chimeric human livers and hepatitis C virus infection (HCV), an adenovirus vector expressing a genetically engineered apoptosis-inducing molecule called BID targets and kills HCV-infected cells, effectively
halting progression of disease.
Dr. Christopher D. Richardson, of the Ontario Cancer Institute in Toronto, and colleagues describe their gene therapy strategy in the May issue of Nature Biotechnology, published online April 21st.
"Originally my postdoctoral fellow, Dr. Eric Hsu, and I were looking for an approach to target the protease of HCV using gene therapy," Dr. Richardson told Reuters Health. "We felt that this viral molecule could be the
'Achilles heel' of the virus since its function is essential for viral replication."
They engineered a proteolytic cleavage site into a number of apoptotic precursor molecules including procaspase 3 and BH3-interacting death domain death agonist (BID), "both of which are normally activated by host
cellular proteases in the cascade leading to programmed cell death," Dr. Richardson said.
BID, modified to contain the NS5A/NS5B cleavage site, proved "most efficacious," Dr. Richardson said, effectively activating apoptosis when HCV NS3/NS4A protease resides in the cell.
In culture, modified BID rapidly killed cells containing HCV or its protease, but was nontoxic to healthy neighboring cells. "In a sense, the modified BID was a 'smart bomb' which targeted the infected cell for
destruction," Dr. Richardson said.
Modified BID also prevented infection in a Sindbis virus model of HCV. And, in HCV-infected SCID mice transplanted with human liver xenografts, intrajugular injection of the modified BID therapeutic adenovirus vector
targeted the liver efficiently, activated apoptosis, and cleared viral infection.
"Although the initial HCV titers varied mouse to mouse, depending on how well the transplanted human liver was infected with the pathogenic virus, adenovirus containing the modified BID gene cleared HCV completely
from the liver, and at least decreased the serum levels of the mouse by 2-3 logs," Dr. Richardson told Reuters Health.
Further experiments are underway to see how long the treatment effects last and whether HCV levels rebound. In the current experiments, there did not appear to be viral rebound up to 28 days following treatment.
"I believe that these experiments attest to the power of gene therapy in treating human disease," Dr. Richardson said.
A targeted therapeutic approach using modified BID "may be useful as a prophylactic against accidental virus exposure, in the early stages of hepatitis, during limited infection of the liver, or for ex vivo therapy of
hepatocytes," the investigators write in the journal. "It may also reduce virus loads in chronically infected patients, and in conjunction with interferon and ribavirin therapy, might eradicate HCV from the infected host."
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May 05th, 2003
Class-Action Lawsuit by Inmates Demands Treatment for Hepatitis C
By hivandhepatitis.com
Oregon inmates allege in a pending class-action lawsuit that treatment for hepatitis C is so woefully inadequate in the state's 12-prison, 11,800-inmate system that it violates the constitutional ban on cruel and unusual
punishment.
Prisoners say health care managers systematically deny treatment to hold down costs.
The federal lawsuit seeks $17.5 million for inmate medical expenses, including drug therapy, chemotherapy and potential liver transplants. "It's just unconscionable what's going on," said Phyllis Beck, director of the
Hepatitis C Awareness Project in Eugene, Ore. "They're letting prisoners die of hepatitis C." Beck said, "The main reason a lot of these prisoners aren't getting treatment is because of the cost."
Portland lawyer Michelle Burrows filed the suit on behalf of 11 current and former inmates. District Court Judge Anna Brown recently granted Burrows' motion to expand the suit into a class action. All Oregon inmates
with hepatitis C now are considered plaintiffs. Corrections Department spokesperson Perrin Damon said, "Treatment protocol is both medically appropriate and conforms with the state's legal obligation to provide
medical care to state prison inmates. We look forward to responding to the plaintiffs' claims in court."
Corrections officials estimate that about 30 percent of all Oregon inmates - roughly 3,500 - are infected with hepatitis C. Corrections Department Medical Director Dr. Steve Shelton, who oversees the prison system's
management of hepatitis C, declined to provide complete data on the number of prisoners given medication for the infection.
In 2001, the only data made available by the department, a dozen inmates received the drug therapy. At a low-end cost of $18,000 per inmate, providing treatment for 10 percent of the infected inmates in Oregon would
cost taxpayers at least $6.3 million. At a high-end cost of $30,000 per inmate, the total bill would rise to $10.5 million.
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May 06th, 2003
Blood Donation Surge after 9/11 Waned Fast
By Adam Marcus, HealthScoutNews
In the aftermath of the Sept. 11 terror attacks, Americans who'd never before given blood flocked to blood banks with their arms bared.
But as the immediacy of the deadly events faded, the sleeves came down again, says a new study that highlights the difficulty of encouraging people in this country to become regular blood donors.
"Americans are quick to respond in times of national emergency," says study author Dr. Simone Glynn. "During the Sept. 11 events, there was a tremendous national outpouring of public support that included
thousands of people wanting to donate blood."
But only about 30 percent of those people ever came back to give again. "Many first-time donors may not realize that blood is needed every day to save the lives of accident victims or patients with cancer," Glynn
says.
The study, reported in the May 7 issue of the Journal of the American Medical Association, tracked blood supplies at five regional centers, which together make up about 8 percent of the nation's blood pool.
In the month before the terrorist attacks, the centers collected roughly 20,000 units of blood per week. That number hit 49,000 in the week following Sept. 11, and remained at about 27,000 or so for several weeks, or
about 40 percent more than normal. Nationally, blood banks collected 572,000 units more than usual in the three-month period after the attacks, a larger spike than was seen during the first Gulf War or the 1995
Oklahoma City bombing.
First-time donors usually account for about one-fifth of all blood donated at the five sites. But in the wake of Sept. 11, that figure soared to almost half.
Compared with the month before the attacks, the number of first-time donors jumped more than fivefold in the week after Sept. 11. Repeat donations rose 50 percent, while the rate of repeat donors who had taken a
10-year or longer hiatus from giving blood tripled, from 2 percent to 6 percent of the supply at the banks. As with the San Francisco quake of 1989, the majority of new donors were women.
Despite the encouraging outpouring after the attacks, first-time donors were no more likely to become repeat givers than in the past, with this rate hovering around 30 percent.
The influx of new donors was accompanied by a tripling in the number of blood units infected with potentially serious microbes, including HIV, hepatitis C and hepatitis B. Almost all the increase was due to more
detection of hepatitis C, a potentially deadly liver virus. Yet the researchers say this increase wasn't significant and didn't threaten the safety of the blood supply. Nor was it the result of a surge in risky donors, but
rather reflected having so many more people willing to give blood.
Dr. Linda Chambers, senior medical officer for the American Red Cross in Washington, D.C., says the study shows the nation's blood screening system worked well both before and after Sept. 11. The Red Cross didn't
see an increase in people acquiring infections from blood in the weeks and months after the terrorist attacks, she says.
Although blood banks greatly appreciated the good will and effort of the new donors, Chambers says their donations wouldn't have helped mass casualties on Sept. 11. Instead, these people would have required blood
collected in the weeks before the attacks, since blood needs time to be tested and processed.
"The bottom line is that blood donation and the continuous need for blood is not something that's right in front of people day to day," she says. "They think what they give today is going to be available tomorrow."
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3M Seeks FDA Approval for Drug Aldara
3M Co. has asked the U.S. Food and Drug Administration for permission to sell its genital warts drug Aldara to treat a precursor to skin cancer that affects an estimated 10 million Americans a year.
"Aldara represents an entirely new approach to treating this precursor to skin cancer," said Barry Labinger, 3M pharmaceuticals vice president.
Labinger said Monday that company scientists are very encouraged by recent clinical data that support the use of Aldara in treating actinic keratosis, a condition caused by overexposure to the sun that often appears
as red scaly patches, crusts or sores on the top layer of skin.
Untreated, actinic keratosis can lead to squamous cell carcinoma, the nation's second-leading cause of skin cancer death.
If the FDA grants approval within the next year as expected, Aldara's new applications "have pretty substantial potential for $500 million to $600 million in combined sales," said Deutsche Bank analyst David Begleiter.
During clinical trials, patients were treated with Aldara or a placebo cream twice a week for 16 weeks. After eight weeks, 3M said half of the patients treated with Aldara had at least an 83 percent reduction in the
number of skin lesions, while the placebo group had no reduction.
3M also plans to submit new data to the FDA for the use of Aldara as a treatment for superficial basal cell carcinoma, a common form of non-melanoma skin cancer, Labinger said. That application probably will not be
submitted until summer.
3M began selling Aldara cream in 1997 to treat external genital and perianal warts. Sales for wart treatment alone are approaching $200 million a year.
3M is exploring other treatment uses for Aldara, such as for hepatitis C and a precursor condition to cervical cancer.
3M stock is down $2.30 to $122.51 a share in afternoon trading on the New York Stock Exchange
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Normal Liver Enzyme Levels in HCV Carriers May Still Spell Liver Damage
By John C. Martin, hepatitisneighborhood.com
The controversy persists over the proper care and management of hepatitis C (HCV) patients with normal liver enzyme levels. A study published recently in the Journal of Hepatology points to the debate, and warns
that while the majority of patients with normal liver enzyme levels may have only mild inflammation and liver fibrosis, some of them can still progress to more severe liver disease.
Liver Enzyme Analyses
In addition to tests conducted to measure levels of antibodies in the bloodstream as a diagnostic indicator that a person is infected with hepatitis C, doctors also perform tests to detect an individuals liver enzyme
levels.
These enzymes, known as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are normally released when liver cells are injured or killed.
ALT is an enzyme involved in the metabolism of the amino acid alanine. The enzyme is embedded in a number of tissues, but is at its highest levels in the liver. Injury to the liver results in the release of these enzymes
into the bloodstream. AST is in high concentrations in heart muscle, liver cells, skeletal muscle cells, and to a lesser degree, in other tissues. Although elevated blood levels of AST by itself are not normally an
indicator of liver disease, they are used in combination with other enzyme measurements to monitor the course of liver disease.
Thus, high levels of ALT or AST in the blood can help doctors determine that a patient has liver disease. In chronic hepatitis, liver enzyme levels can be elevated consistently for six months or more.
However, there are exceptions. Some patients can have liver disease, or hepatitis infection, and have normal liver enzyme levels.
Normal Liver Enzymes and Fibrosis
In the study, doctors at a San Francisco V.A. hospital compared fibrosis progression rates in patients with normal liver enzymes and those with elevated enzyme levels.
Forty patients with normal ALT levels were recruited along with 41 patients with persistently elevated enzymes. Only patients with early stage fibrosis were included.
About 22 percent of the patients in the first group and 41 percent of those in group 2 had fibrosis progression, the researchers reported. But those with elevated enzyme levels in the second group had "a significantly
higher cumulative probability of fibrosis progression."
The authors concluded that persons with persistently normal ALT levels were less likely to develop fibrosis progression as compared to those with higher ALT levels, but patients with normal levels "may have
histologically and clinically progressive disease."
Treatment Controversy
In an editorial accompanying the study, Claudio Puoti, M.D., in the department of gastroenterology and internal medicine at E. De Santis General Hospital in Rome, Italy warns of the risks that patients with normal ALT
levels may still face: "Although formerly referred to as healthy or as asymptomatic HCV carriers, it has now become clear that the majority of these patients have some degree of histological liver damage." Histology is
the study of cells and tissue on a microscopic level.
According to Puoti, about one-third of patients with chronic HCV have persistently normal ALT levels, while another 40 percent have "minimally raised" ALT values.
The controversy still exists, he says, regarding the definition of "persistent" liver enzyme normality, the state of the liver and virus levels in these individuals, and the best way to manage and treat HCV in people with
normal ALT levels.
Other questions that remain to be answered include whether certain factors like viral load, genotypes, gender, age and host immune response to HCV-infected cells differ between HCV patients with normal or abnormal
enzyme levels, and whether liver disease is milder in patients with normal versus elevated enzyme levels.
While the majority of hepatitis C patients with normal liver enzyme levels have only a mild form of liver inflammation, fibrosis, and non-progressive disease, some do progress to severe liver disease anyway, Puoti
writes. "These patients should be followed up at regular intervals in order to identify ALT flares or disease progression."
Antiviral combination treatment has shown effectiveness similar to that of patients with high levels of liver enzymes, but there have been too few clinical trials to assess the risks of treatment in those with normal liver
enzymes, and determine the outcomes of the milder and slower progression of disease in these patients, he says.
Puoti also questions whether routine liver biopsies and antiviral treatment are even necessary in people with hepatitis who have normal ALT levels.
"Until the results of studies with peginterferon plus ribavirin are available, and the cost effectiveness of these new options has been investigated, HCV carriers with normal ALT should not receive antiviral treatment
outside of clinical trials," Puoti stresses.
NIH Consensus
He cites a recommendation from a 1997 National Institutes of Health (NIH) Consensus Conference that patients with persistently normal ALT levels not be prescribed interferon treatment. It was based on studies that
showed the overall sustained virological response (SVR) in patients with normal ALT was very low, though not unlike that of patients with higher ALT levels., and the fact that many patients showed ALT flares during
treatment.
It was concluded, therefore, that interferon monotherapy in patients with normal enzyme levels "was not beneficial and may actually worsen the underlying disease."
Since then, combination treatment with ribavirin, and a longer-lasting form of therapy-pegylated interferon-have been developed, achieving much higher sustained virological responses of more than 50 percent, with even
more success in patients with viral genotypes 2 and 3.
Given those facts, last years NIH Consensus Conference stated that treatment for patients with normal ALT levels should be re-evaluated, and that the focus should be on whether patients with mild disease should be
treated.
"ALT levels may have less importance in deciding who should be treated," Puoti wrote. "Many other factors might influence the decision to treat, such as the age of the patient, HCV genotype, liver histology, patients
motivation, symptoms, extra-hepatic manifestations, and co-morbid illness."
The controversy even exists over whether to perform liver biopsies on patients with normal ALT levels. The San Francisco V.A. study recommended it to accurately determine the stage of fibrosis.
Emmet Keeffe, M.D., chief of hepatology and co-director of the transplant program at Stanford University Medical Center says he does not perform liver biopsies on patients with normal ALT levels, nor does he
prescribe treatment, unless the patient asks for it.
"I think it is not wrong to treat patients, but in general, the patient does not need treatment, said Keeffe, who is regular participant in the Hepatitis Neighborhoods weekly chats.
Keeffe points to data that show only about 15 percent of patients with normal enzyme levels have more advanced disease, meaning treatment may not be necessary.
Still, more questions about outcomes in patients with persistently normal ALT levels must first be answered, Puoti maintains. "The solution of these conundrums will come from well-sized, long-term prospective
studies."
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May 07th, 2003
ACLU Study: Virginia Prisoners Denied Adequate Medical Care
A study by civil liberties lawyers found that health care for Virginia's more than 30,000 prisoners is woefully inadequate and has left some inmates dead or maimed.
The study by the American Civil Liberties Union of Virginia also charged that the Department of Corrections broadly used exceptions in Virginia's open-government law to keep secret potentially widespread failures to
provide treatment and services to prisoners.
"Virginia promotes cruelty and indifference by walling off the truth about prison health care from the public,'' Kent Willis, executive director of the ACLU of Virginia, said in the preface to the report, "Accountable to No
One."
"What we discovered, first and foremost, was that bad attitudes, bad laws and bad policies make getting to the bottom of health care in Virginia's prisons an arduous, if not impossible, task,'' Willis said.
Larry Traylor, chief spokesman for the Virginia Department of Corrections, said Wednesday he had not seen the report, but he denied its major allegations.
"Inmates receive the same community standard of care'' as other Virginians, Traylor told the Richmond Times-Dispatch. ``Oftentimes, they receive better medical care than they received on the street.''
While the department denied access to complete medical records about treatment and deaths, the ACLU's investigator argued that Virginia's prisons are "breeding grounds'' for the potentially fatal hepatitis C virus.
Laura LaFay, who conducted the investigation that began last summer, wrote that an estimated 39 percent of the state's prisoners are infected one of the highest prison infection rates in the country. The virus is spread
primarily through needles and sexual acts.
Half the infections can be cured, she said, but only 50 inmates out of an estimated 12,800 infected inmates had been treated as of November.
Such lack of treatment is hazardous to inmates and to the public, LaFay wrote, but there appears to be little governmental interest in dealing with the growing epidemic.
Virginia's budget crisis has limited the use of a treatment regimen for hepatitis C that can cost up to $15,000 per inmate annually.
The report recommended 10 changes to help the public, prisoners and health providers.
Among other things, it urged repeal of the state law that permits the prison agency to withhold all records about an inmate's imprisonment.
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High Rate of Infection Found in Maryland Prisons
By Avram Goldstein
Nearly one in three inmates entering the Maryland prison system is infected with HIV, syphilis, hepatitis B virus or hepatitis C virus-many of them with more than one infection-according to a blood survey released
yesterday by state health officials.
Infection rates among prisoners were dramatically higher than among the general population, based on blood tests of 3,914 people entering the state penal system during a 60-day period in 2002.
The most prevalent infection in Maryland state prisons was hepatitis C, a blood-borne virus that can cause liver disease, including cancer and cirrhosis, and other serious complications, according to the report by the
Maryland AIDS Administration.
At a time when less than 2 percent of the U.S. population is infected with hepatitis C, 29.7 percent of Maryland prisoners had it, said Liza Solomon, the agency's director.
The higher rate of disease among prisoners has major public health implications beyond prison walls, she said, because inmates eventually are released into the community, where they can spread the infections.
Reaching undiagnosed inmates in prison is an important opportunity for the state to limit diseases that can disrupt or prematurely end lives.
"Many people move in and out [of prison], and when they are outside, they frequently fall to us in publicly funded programs to provide care and treatment," she said. "We need to make sure we have a coordinated
approach. If someone is released in the middle of treatment, we need to make sure treatment continues."
Solomon said her agency's study is the first to show systematically that prisoners often have several of the infections simultaneously. Such "co-infections" are harder to manage, and the symptoms are more severe,
she said.
In Virginia, studies show that about one-third of prison inmates have hepatitis C, but no statistics have been released on multiple infections. The District Health Department's chief medical officer, Michael S.A.
Richardson, said that the city has not done a comprehensive survey of multiple infections in jail inmates but that if it did, the results probably would be similar to Maryland's.
Inmates in Maryland are treated for syphilis and HIV, but the prisons do not routinely give hepatitis B vaccinations, which are highly effective, to inmates or staff members, Solomon said. The prisons offer no routine
treatment of inmates with hepatitis C, for which there is no vaccine, she said.
Richardson said that diagnosing hepatitis C may not be worthwhile because it is not clear that the expensive treatments are effective. "Diagnosing stuff you aren't going to treat is always questionable," he said. "We
have not aggressively tried to diagnose hepatitis C."
Top officials at the Maryland Division of Correction were unavailable to discuss the study yesterday, but spokesman Mark Vernarelli said they are reviewing it with an eye toward new medical policies. "Health and
treatment issues are a priority for this administration," he said. "Preventing the spread of communicable diseases among inmates is critical."
Corrections officers worry about acquiring blood-borne viruses on the job and have pushed for legislation that would make it easier to collect workers' compensation for such infections, but their efforts have been
unsuccessful.
Sue Esty, legislative director for Maryland state employee bargaining units of the American Federation of State, County and Municipal Employees, said a bill got nowhere last year in the General Assembly.
Syphilis is caused by a sexually transmitted bacterium. The other infections in the study are blood-borne viruses whose spread in Maryland can be attributed mainly to the sharing of tainted needles by drug users, the
report said.
The study also concluded that women entering the Maryland prison system are far more likely than men to be infected with HIV, syphilis and hepatitis C, though not hepatitis B virus.
For the study, inmates were tested upon admission to a Baltimore detention center and a statewide receiving facility for inmates headed to state prisons across Maryland.
In February and March 2002, every detainee or inmate submitted to a blood test for syphilis and received appropriate follow-up treatment if the test was positive. Blood samples were then stripped of identifying
information and run through additional tests for the viruses.
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One in Three Inmates Has HIV, Syphilis, Hepatitis
Nearly one in three inmates entering the Maryland prison system is infected with HIV, syphilis, hepatitis B virus or hepatitis C virus, many of them with more than one infection, according to a survey released Tuesday
by state health officials.
The survey was based on blood tests of 3,914 people entering the state penal system during a 60-day period in 2002.
The most prevalent infection in Maryland state prisons was hepatitis C, a blood-borne virus that can cause serious complications, including liver cancer, according to the report by the Maryland AIDS Administration.
Less than 2 percent of the U.S. population is infected with hepatitis C, while 29.7 percent of Maryland prisoners had it, said Liza Solomon, the agency's director.
The higher rate of disease among prisoners has major public health implications beyond prison walls, she said, because inmates eventually are released into the community, where they can spread the infections.
Reaching undiagnosed inmates in prison is an important opportunity for the state to limit diseases.
Solomon said her agency's study is the first to show that prisoners often have several of the infections simultaneously. Such ``co-infections'' are harder to manage, and the symptoms are more severe, she said.
Inmates in Maryland are treated for syphilis and HIV, but the prisons do not routinely give hepatitis B vaccinations, which are effective, to inmates or staff members, Solomon said. The prisons offer no routine treatment
of inmates with hepatitis C, for which there is no vaccine, she said.
Top officials at the Maryland Division of Correction were unavailable to discuss the study Tuesday, but spokesman Mark Vernarelli said they are reviewing it with an eye toward new medical policies.
"Health and treatment issues are a priority for this administration,'' he said. "Preventing the spread of communicable diseases among inmates is critical.''
The study also concluded that women entering the Maryland prison system are far more likely than men to be infected with HIV, syphilis and hepatitis C, though not hepatitis B.
For the study, inmates were tested upon admission to a Baltimore detention center and a statewide receiving facility for inmates headed to state prisons.
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Crackdown on Drug Dealers Draw Complaints
By JEREMY HAINSWORTH, Associated Press Writer
VANCOUVER, British Columbia - A police crackdown on drug dealers in downtown Vancouver is causing more harm than good for the neighborhood's AIDS hepatitis epidemic, a Human Rights Watch report says,
asserting addicts are being driven away from needle-exchange programs and other services.
Called Operation Torpedo, the crackdown has gotten some pushers off the streets, "but at a high cost," said the report issued Wednesday by the New York-based rights group. Its findings were echoed by health care
workers, activists and addicts in the city, known for its progressive drug policies.
"The flouting of due process in this crackdown is shocking for a country with Canada's strong commitment to human rights," said Joanne Csete, director of the HIV/AIDS Program of Human Rights Watch. "Vancouver
risks making its HIV/AIDS crisis much worse and it's already the worst on the continent."
Illegal searches and arrests, excessive force and other abuses committed by police on addicts not accused of dealing drugs have worsened the already dire situation in the 15-block neighborhood on Vancouver's east
side, which is frequented by more than 5,000 addicts, the report said.
"These actions, which violate Canadian and international human rights guarantees, contributed to driving drug users underground and away from lifesaving HIV prevention and other health services," it said.
Vancouver police denied officers abuse their power, saying the crackdown is aimed at dealers, not users, with a goal of ridding the area of pushers while keeping addicts near the services they need.
"This whole report lacks credibility," Inspector Doug LePard said Wednesday.
"There's no reason for addicts to be worried," he said. "We're focusing on disorder and we're focusing on traffickers."
Still, health workers fear a new wave of HIV and hepatitis C cases in Vancouver, which already has the highest infection rate in North America. The British Colombia Center for Disease Control puts the AIDS rate
among area addicts at more than 30 percent, while well over half the intravenous drug users are infected with hepatitis C.
The problem seems ironic for Vancouver, a coastal city known for its magnificent mountain and ocean vistas and laid back West Coast lifestyle, along with progressive policies for drug addicts.
More than 2.5 million needles are handed out to addicts each year in the city's east end, a warren of dilapidated buildings and filthy streets believed to be the stalking ground of a suspected serial killer accused of
murdering at least 15 prostitutes and drug addicts from the area.
Mayor Larry Campbell, a former police officer and coroner, won last year's election on a platform that included the promise of safe injection sites as part of a "four pillar" drug policy involving treatment, prevention, harm
reduction and enforcement.
So far, Operation Torpedo is the only visible step taken, with regular police patrols on foot and in squad cars.
On streets littered with orange needle caps and stinking of urine, users and those trying to help them complain of police intimidation or worse.
"I've seen a guy down and three cops on top of him with a knee in his forehead," said Chantal Brunet, 37, who called herself a recovering heroin addict. "They're abusing their authority."
Addicts fearful of being confronted by police use dirty needles they find on the ground instead of going to needle exchange sites, she said, while others may be fleeing the area in violation of bail conditions.
At a corner near a known heroin market called "the shooting gallery" by locals, two men handed out needles, clean water and condoms for the Vancouver Area Network of Drug Users, a local support group.
"It's going to increase the human tragedy tenfold," the group's president, Rob Weppler, said of the police operation.
Needle distribution has dropped by half and condom handouts to prostitutes are down 60 percent since the crackdown began April 7, according to Weppler. That will fuel the AIDS and hepatitis spread in the area, he
said.
The Human Rights Watch report called for a halt to abusive police tactics, public hearings on abuses and creation of an independent commission to investigate complaints of police misconduct.
"The system is not conducive to people who file these grievances, and I don't think we'd have to write this report if it were," said Jonathan Cohen, a Human Rights Watch HIV/AIDS researcher.
With Vancouver a finalist for the 2010 Olympics, there are fears of a broader crackdown before the July decision by the International Olympic Committee. When an IOC evaluation team visited in March, it was kept far
from the downtown east side.
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Doctors Eye Damaged Organs for Some Transplant Patients
The tragic death of Jessica Santillan at Duke University Medical Center earlier this year focused attention on the shortage of precious donor organs. She died after receiving an incompatible heart/lung transplant.
NewsCenter 5's Liz Brunner has news of a new medical technique that could help others get the organs they need to survive.
Last year, more than 6,000 Americans died waiting for an organ transplant. There simply aren't enough healthy organs to go around, Brunner said.
But now, doctors in California are hopeful a new procedure will be able to make use of more available organs than ever before.
Last fall, Anne Cunha was on life support -- given just weeks to live. After a long illness, the Harvard student's lungs had collapsed, and she was considered too sick to be put on a transplant list for a new set of healthy
lungs.
"I had been turned down for transplant which is why I was so scared," Cunha said.
Doctors at UCLA suggested an experimental procedure. They took lungs considered too damaged for a normal transplant and put them into Cunha. Then they flushed them with a mixture of nutrients that allowed the
lungs to repair themselves.
So far, 50 patients have undergone the surgery.
"In our experience, the result has been quite encouraging in that our one-year survival rate has exceeded 90 percent," UCLA Medical Center Dr. Abbas Ardehali said.
The same type of procedure is being used to resuscitate substandard hearts and there are other encouraging developments. Organs from older donors, and donors with diseases such as Hepatitis C once considered of
no use, are now being successfully transplanted.
Cunha is now in therapy, building up her strength and lung capacity. She plans to finish her law degree at Harvard this fall and for the first time in a long time, is counting on a future.
"I'm giddy. It's frustrating I'm not 100 percent strong because I'm so ready to dive back into life and drink it up," she said.
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May 08th, 2003
PegIntron and Rebetol Combination Therapy for Hepatitis C Receives Fundamed-El Global Award For Best Pharmacoeconomic Profile
Research demonstrates cost effectiveness and impact of patient compliance
Schering-Plough Europe today announced that PegIntron(R) (peginterferon alfa-2b) and Rebetol(R) (ribavirin) combination therapy for chronic hepatitis C has been awarded the prestigious Fundamed-El Global award for
the "Best Pharmacoeconomic Profile" among therapeutic innovations. The award is based on an economic analysis demonstrating that combination therapy with PegIntron and Rebetol, adjusted for patient body weight
and with good patient compliance, is more cost-effective than many medical treatments for other serious diseases.
The analysis, published in Alimentary Pharmacology and Therapeutics 2003: 17: 687-694, compared four antiviral regimens for chronic hepatitis C to estimate the cost-effectiveness of treatment with PegIntron and
Rebetol in previously untreated patients, and to examine the effect of patient compliance on treatment outcome.
"In patients achieving a sustained virologic response, 48 weeks of weight-based PegIntron and Rebetol therapy with good therapeutic compliance was shown to have better cost-effectiveness than many other
well-accepted medical interventions, according to the analysis," explained Dr. Maria Buti, Professor of Medicine, Department of Hepatology, Hospital Vall d'Hebron, Barcelona, Spain, and lead author of the study.
An economic model was used to evaluate the natural history of hepatitis C and the costs and benefits of combination therapy. Investigators analysed clinical data obtained from published studies involving treatment
with PegIntron and Rebetol. Costs associated with hepatitis C were derived from a database of health care costs and the Catalogue of Medicinal Products in Spain.
The analysis demonstrated that treatment with weight-based PegIntron and Rebetol combination therapy is a highly cost-effective strategy for managing chronic hepatitis C and that its cost-effectiveness improves with
good patient compliance.
"Therapeutic compliance is a key parameter that can not only have a positive effect on the rate of sustained virologic response, but also reduce the overall cost of the disease," explained Dr. Rafael Esteban, Professor
of Medicine and Head of the Department of Hepatology, Hospital Vall d'Hebron, Barcelona, Spain, and a co-author of the study.
"We are very proud to be recognized by El Global and Fundacion Fundamed for this research and the efforts of our scientific team to bring the best quality care and support to patients with hepatitis C," said Marcelo R.
Siedlarek, Vice President and General Manager, Schering-Plough Spain. "PegIntron and Rebetol combination therapy is just one example of Schering-Plough's longstanding history of research and patient support in
the effort to eradicate the hepatitis C virus."
The Fundamed-El Global Award is granted by Spain's El Global newspaper and Fundacion Fundamed, an international non-profit philanthropic foundation. Established in 2001, the award recognises outstanding
achievement in pharmaceutical research and development in a variety of categories, including health care initiatives and therapeutic innovations.
PegIntron is a longer-acting form of Intron(R) A (interferon alfa-2b) that uses proprietary PEG technology developed by Enzon, Inc. of Bridgewater, N.J., USA. PegIntron, recombinant interferon alfa-2b linked to a 12,000
dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy dosed according to patient body weight that is designed to achieve an effective balance between antiviral activity and elimination half-life.
Schering-Plough holds an exclusive worldwide license to PegIntron.
Rebetol is an oral formulation of ribavirin, a synthetic nucleoside analogue with broad-spectrum antiviral activity. It is approved worldwide for use in combination with PegIntron or Intron A for the treatment of adult
patients with chronic hepatitis C. Schering-Plough has rights to market oral ribavirin for hepatitis C in all major world markets through a licensing agreement with Ribapharm Inc. of Costa Mesa, Calif., USA.
Chronic hepatitis C is estimated to affect more than 10 million people in major world markets. In Europe, chronic hepatitis C is a leading cause of chronic liver disease and one of the most common reasons for liver
transplant.
Schering-Plough Europe, based in Brussels, Belgium, is a subsidiary of Schering-Plough Corporation of Kenilworth, N.J., USA, a research-based company engaged in the discovery, development, manufacturing and
marketing of pharmaceutical products worldwide.
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May 09th, 2003
Interferon Activity against HCV Is Associated with Interferon Responsive Genes
By Brian Boyle, MD. Hivandhepatitis.com
Hepatitis C virus (HCV) infection is an affliction borne by 170 million people worldwide. Chronic HCV infection can cause a number of medical problems that involve the liver, e.g., chronic hepatitis, cirrhosis, liver failure,
and hepatocellular carcinoma and other organ systems, e.g., essential mixed cryoglobulinemia, Sjogrens syndrome, and porphyria cutanea tarda.
Unfortunately, treatment options for HCV remain somewhat limited and of marginal effectiveness, especially in patients with HCV genotype 1, the most common genotype in the United States.
The current treatment of HCV generally involves the concomitant use of interferon (IFN) and ribavirin. Despite the widespread use of interferon, the molecular mechanisms for the effectiveness of IFN-a- based treatment
are largely unknown.
While IFN- a has well-established immunoregulatory effects, which in some viral infections has been shown to involve multiple interferon-stimulated genes (ISGs), such as double-strand RNA-dependent protein kinase
(PKR), ribonuclease L, the functions of other host genes are still unknown.
The recent development of an HCV replicon cell culture system has made it possible to investigate the molecular bases of IFN-induced direct antiviral activity in hepatocytes. In a study published in Hepatology,
investigators reported that IFN- a can effectively inhibit HCV subgenomic RNA replication and suppress viral nonstructural protein synthesis.
Several host genes were found to play a role in this inhibition and to be inducible by IFN- a. One of the genes, 6-16 (G1P3), appears to enhance IFN- a antiviral efficacy. In addition, IFN- a can significantly activate
STAT3 in hepatoma cells, suggesting that this pathway plays a role in IFN- a signaling.
The authors conclude,
- Our study has demonstrated that the IFN- a inhibition of HCV RNA replication in the human hepatoma cell line containing HCV replicons is associated with activation of the JAK-STAT3-signaling pathway and a
number of IFN- a responsive genes.
- We have shown that one of the IFN- a responsive genes, 6-16 (G1P3), moderately enhanced IFN- antiviral efficacy, although expression of this protein alone did not significantly inhibit HCV RNA replication in
transient transfection assay.
- These results support the notion that certain intracellular molecules play key roles in IFN- a antiviral activity. In addition, HCV replication per se did not induce a significant interferon-dependent gene expression in
this model.
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May 12th, 2003
UK Team Transplants Liver Cells in Babies
By Richard Woodman
Doctors at a London hospital said on Monday three babies were "doing very well" after receiving pioneering liver cell transplants.
The technique, called hepatocyte injection, avoids the difficulty of finding enough organs for whole-liver transplantation as well as the trauma of surgery.
It involves taking healthy cells from donor livers and injecting them into the livers of patients with life-threatening diseases. The patients' own cells then regenerate and are eventually replaced by new healthy ones.
Dr. Anil Dhawan of Kings College Hospital, the research leader, told Reuters it was the first time the technique had been used to correct two rare pediatric disorders.
The team had also proved for the first time that liver cell transplants could work even when all the cells had previously been frozen.
"All three babies are doing very well and without the hepatocyte injections one of the children would certainly have died," he added in a statement.
The hospital said that in one "world first," it operated last year on Mansoor Al Housani, a six-week-old boy from an unnamed Middle Eastern country who was born with factor 7 deficiency, a blood clotting disorder
which had claimed the life of his oldest brother.
"He received three injections of hepatocytes at the age of six weeks. Following this, we have been able to reduce his factor 7 requirement by 80 percent," the hospital said.
Last month, 18-month-old Lawrence Robinson from London became the first person to receive new liver cells because he could not clear bile acids from his liver.
"Healthy liver cells have been injected into his liver, which will divide and eventually replace the defective cells, allowing the liver to function normally," the hospital said.
The third baby, Billy Corfield, from Liverpool, was treated two days after being born with a defect that causes a dangerous build-up of ammonia.
"He is now seven months old and is progressing very well, although he may need further injections," the hospital said.
King's said there were huge implications for the future.
"If the technique does provide long-term success, then 20 to 40 children could avoid liver transplantation each year in the UK," Dhawan said.
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Hispanics launch hepatitis C Campaign: Vulnerable community hit hard by 'silent killer'
By Javier Erik Olvera, Rocky Mountain News
It's a deadly disease that crosses economic, racial and social boundaries, affecting 1.8 percent of the country's population. But in Colorado, hepatitis C may have targeted Hispanics with a particular vengeance. Two
local nonprofit organizations estimate that Hispanics comprise up to 30 percent of the 77,400 Coloradans infected. The Hep C Connection and the Latino American Research and Service Agency this week will launch
an awareness campaign to target the ethnic group, which makes up 17 percent of the state's 4.3 million residents. "My hope, my goal, is that people will take care of themselves more," said Julissa Molina Soto,
multicultural outreach manager for the Hep C Connection. The disease, one of the most common causes of liver disease in the country, was identified in the late 1980s. It's called a "silent killer," slowly deteriorating 80
percent of its victims' livers for decades without any symptoms such as fatigue, jaundice or nausea. Each year in the country, nearly 35,000 people are infected and another 12,000 die from disease complications,
such as liver cirrhosis and cancer.
Infection requires direct blood-to-blood contact with an infected person, said Mauricio Palacio, hepatitis C coordinator for the state health department. High-risk candidates include anyone who received contaminated
blood transfusions before screening for the disease began in 1992. Also at risk are newborns whose mothers are infected and anyone who has multiple sex partners. No vaccine exists, but treatment is available
through injections and pills that are taken for up to a year. The exact number of Hispanics infected is unclear, largely because there's limited data on victims' ethnicity and race. Molina Soto has noticed a lack of
resources in Spanish, something she hopes will change with the campaign that begins by educating Hispanic leaders about the disease.
The goal? - That leaders will take the information back into the community and encourage residents to get examined. She also has noticed that non-English speakers don't know where to go for help or are unaware
that, if they qualify, financial assistance is available for treatment. "My dream is that we'll have a vaccine," Molina Soto said. "I don't like seeing families go through this. I say families because it affects everyone in a
household." The biggest problem may be woven in beliefs that date back to the old country, where people still use curanderas, or folk healers, to cure ailments through rituals. One of Molina Soto's clients recently
asked if a curandera - Spanish for "the curer" - could help take away the hepatitis C making her sick, she said. As the multicultural outreach manager, Molina Soto is charged with breaking barriers with the Hispanic
community and teaching them to trust modern medicine. Another issue is health insurance, which roughly one in every three Hispanics lacks, said Rosario C. de Baca, health coordinator for LARASA. Said de Baca:
"If we're serious about tackling something this big, everyone has to hear about it." For information about hepatitis C, call the Hep C Connection at (800) 522-4372. Information in Spanish is available at (720) 917-3967.
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Genetic Attack Slows Hepatitis
The technique may help people with hepatitis B
Scientists may have found a new way to treat the virus that causes hepatitis B - launching a strike on the genetic material it needs to spread.
The study, on mice, is further evidence of the promise of the technique, called "RNA interference". Some experts are hoping it will eventually have a role against HIV.
Hepatitis B is the most common serious liver infection in the world, causing up to a million deaths worldwide a year.
Although a vaccine is available against hepatitis B, once infected, the range of treatments available is limited.
A team of researchers from California injected a biochemical called RNA into mice infected with hepatitis B.
This binds with RNA which is part of the virus, effectively "silencing" a key part of the virus' genetic machinery.
This hampers the virus' efforts to replicate itself, and spread to infect other cells. While the RNA treatment managed this in mice, there is no certainty that the effects would be the same in humans.
Side-effects
The researchers wrote: "Here, we show that RNA interference can inhibit all the steps of hepatitis B virus replication that occur in cell culture and in mice."
Further studies will be carried out to ensure that side-effects from the treatment are minimised. But the researchers warned that care must be taken to avoid producing viral strains resistant to the treatment.
Nigel Hughes, the chief executive of the British Liver Trust, said that the treatment was promising, although he cautioned that this "very early" research might not translate into human treatments.
He told BBC News Online: "Our current therapies do have drawbacks - the 'holy grail' is a one pill cure."
The study was published in the journal Nature Biotechnology.
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May 13, 2003
Hepatitis C Drug Market to Grow from $2.5 Billion in 2002 to More than $9 Billion in 2012
Schering-Plough and Roche Will Capitalize on Growth in this Market, but Considerable Opportunity Remains for Competitors, According to a New Study from Decision Resources
Decision Resources, Inc., one of the world's leading research and advisory firms focusing on pharmaceutical and health care issues, finds that the hepatitis C virus (HCV) drug market will grow from $2.5 billion in 2002
to more than $9 billion in 2012. A major factor contributing to growth over the next ten years will be an increase in the number of diagnosed patients, as patients who have been infected with HCV for more than 15 years
present with advanced liver disease. Additional growth will come from the ever-expanding population of patients who did not respond to initial therapy, and are increasingly being retreated with a second course of
interferon/ribavirin therapy and/or emerging antivirals, according to a new Pharmacor study entitled Hepatitis C.
The study also found that Schering-Plough and Roche's PEG-IFN-alpha products will benefit from increased uptake in the near term owing to their improved clinical efficacy.
"Hepatitis C represents a high-growth opportunity for the biopharmaceutical industry over the next decade," said John Lebbos M.D., senior analyst at Decision Resources. "The HCV diagnosed patient population is
expected to expand significantly and there remains a high unmet need: the combination PEG-IFN/ribavirin, which is the current standard of therapy, is associated with significant side effects and is not effective in a
large subset of patients."
Disease Facts-Hepatitis C The vast majority of HCV-infected individuals have few or no symptoms and therefore remain unaware of their disease. In fact, a significant proportion of individuals infected with HCV die with
rather than from this infection. The fact that HCV is associated with a relatively low direct mortality contributes to the continued debate among experts about who should and should not receive treatment for chronic
hepatitis C.
About Pharmacor
Pharmacor is a unique family of studies based on primary and secondary research conducted by Decision Resources' on-staff experts. Each comprehensive study assesses a host of market-impacting factors and
analyzes the commercial outlook for drugs in research and development. Cardium, Cognos, Immune and Inflammatory Disorders, Infectious Disease, Metabolic Disorders, Psychiatric Disorders, and Onkos concentrate
on specific therapeutic areas. Mosaic covers high-interest disease states. Hepatitis C is an Infectious Disease study.
About Decision Resources
Decision Resources, Inc. is a world leader in research publications, advisory services, and consulting designed to help clients shape strategy, allocate resources, and master their chosen markets. The company has
provided strategic information services for 30 years, assessing international pharmaceutical and health care industry trends. Visit Decision Resources at www.decisionresources.com.
All company, brand, or product names contained in this document may be trademarks or registered trademarks of their respective holders.
For more information, contact:
Elizabeth Marshall
Decision Resources, Inc.
781-296-2563
emarshall@dresources.com
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Battery-Powered Esophagoscope for Detecting Esophageal Varices
The diagnostic accuracy of a battery-powered esophagoscope for diagnosing esophageal varices is the same as that for esophagogastroduodenoscopy, find researchers in the April issue of the American Journal of
Gastroenterology (Am J Gastroenterol 2003; 98(4): 807-12).
Standard esophagogastroduodenoscopy (EGD) is expensive. It also requires conscious sedation which may be poorly tolerated by cirrhotic patients.
In this study, researchers from the United States assessed un-sedated esophagoscopy, using an ultrathin battery-powered endoscope (BPE), for diagnosing esophageal varices (EV).
Initially, the team retrospectively evaluated 199 cirrhotic patients undergoing liver transplant evaluation.
Both procedures were well tolerated by all patients.
They determined the prevalence of significant gastroduodenal pathology, which could be missed if patients only underwent esophagoscopy. Of these patients, 3 had gastric ulcers, and 2 had duodenal ulcers.
The team then performed a prospective study to evaluate a BPE in EV screening. They evaluated 28 cirrhotic patients.
An un-sedated per-oral endoscopy was performed by a single endoscopist using a BPE. This was followed by an EGD, performed by a second endoscopist who was blinded to the results of the BPE.
The research team used a visual analog score was used to determine patient tolerance to the procedure.
In addition, patients were questioned about their preferred method for endoscopy in the future.
The researchers diagnosed EV in 14 patients using a BPE, and 13 of these were confirmed by standard EGD.
EV were graded as large in 1 patient and small in 13 with a BPE, however small varices diagnosed in 1 patient were not confirmed on EGD.
Both procedures were well tolerated by all patients.
Overall, 27 of 28 patients preferred un-sedated endoscopy with a BPE over EGD.
Dr Ravi Madhotra's team concluded, "Unsedated endoscopy with a BPE is safe and well tolerated".
"The diagnostic accuracy of a BPE for diagnosing EV is the same as by EGD".
"Esophagoscopy with a BPE is a potential alternative to EGD for EV screening".
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Liver Research Institute to Deliver AdherePlan(TM) Hepatitis C Content via Health Hero Network Technology Platform
Combination of LRI's Clinical Expertise and Health Hero's Technology Utilizes Health Hero Platform to Deliver Treatment Program
Health Hero Network, Inc., the developer of award-winning technology solutions for health monitoring, today announced that the Liver Research Institute (LRI) has joined Health Hero. as a solution partner. LRI and
Health Hero will develop and resell partnered content with a concentration on Hepatitis C, other liver diseases, and HIV. The content will be delivered via the Health Hero platform.
Hepatitis C constitutes a worldwide epidemic, affecting nearly 4 million people in the United States alone. Improved treatment strategies are rapidly evolving and the success rate (measured as sustained viral response)
is approaching 60%. The treatment, however, is arduous, and many patients are unable to complete the $30,000-40,000 course of therapy.
LRI's AdherePlanT content will be used with the Health Hero technology platform to collect, analyze, and report data such as side effects, quality of life, and medication compliance to care providers. The combined
program, available from both LRI and Health Hero, provides a support and management system to increase treatment adherence and success while controlling the costs of Hepatitis C therapy.
"Health Hero is pleased to partner with LRI and leverage our success in health monitoring technology to benefit Hepatitis C-positive patients," said Geoffrey Clapp, CTO/COO, Health Hero Network.
"By delivering our AdherePlan content over the Health Hero platform, we can dramatically improve patients' quality of life," noted Kevin Kearney, President of LRI. "The educational interactions, reminders, and incentives
provided to the patient through the combination of products will give patients a substantial support system and provide caregivers with vital feedback to direct appropriate intervention."
About Health Hero Network
Health Hero Network, Inc., founded in 1988, develops and licenses technology solutions for health monitoring and management. The Health Hero technology platform offers Internet-enabled care management tools,
multiple patient interfaces, and a secure environment for data communications. The Company's products include Health Buddy., BuddylinkT, Health Buddy. Web, other licensee devices for data collection and
communications with patients, and iCare DesktoT, an Internet-based care management and research tool for health care professionals. Health Hero offers over a dozen standard health management programs
delivering daily monitoring & education, and promoting positive behavioral change for better chronic care with lower costs to the health care system. Buddylink allows patients to upload device-reported data from a
variety of peripheral devices. Health Hero Network technology is protected by over 50 issued U.S. patents. Company headquarters are in Mountain View, California. On the Net: www.healthhero.com.
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May 14th, 2003
Schering-Plough Profit Plunges 71%
By Peter Landers
Schering-Plough Corp. went into free fall in the first quarter as profit plummeted 71% and sales of key drugs declined across the board.
New Chief Executive Fred Hassan withdrew Schering-Plough's earlier predictions of a quick profit recovery and warned of possible job cuts as the company deals with the loss of patent protection on allergy-drug Claritin
in the U.S.
Net income fell to $173 million, or 12 cents a share, from $600 million, or 41 cents a share, in the first quarter of 2002. World-wide sales were down 19% to $2.1 billion as the company's U.S. pharmaceuticals business
lost more than half of its sales, one of the steepest plunges ever for a major pharmaceuticals company.
Schering-Plough, formerly known for its solid balance sheet, also disclosed that it plans to borrow money during 2003 because its cash from operations is likely to fall short of covering capital investments, dividends
and other expenses. In February, the company filed papers with the Securities and Exchange Commission enabling it to issue as much as $2 billion in bonds. It also can draw on two credit lines with banks totaling $1
billion.
In March, Schering-Plough had warned that profit would be weak in the first quarter but predicted improvement in the remaining quarters of 2003, leading to net income for the year of 75 to 85 cents a share. Mr.
Hassan, who joined the company in April after six years at the helm of Pharmacia Corp., withdrew that prediction, saying he wants to review the business for himself.
In a message to employees, Mr. Hassan said Schering-Plough "must move swiftly and effectively to improve our sales and earnings performance, both of which have declined dramatically versus the prior year." He said
he will sharply reduce hiring and possibly cut jobs as well, if overstaffing is found in lower-priority areas.
Mr. Hassan named longtime lieutenant Carrie Cox to lead Schering-Plough's global pharmaceuticals business and said the company's key functions will be managed globally from headquarters in Kenilworth, N.J.,
rather than splitting U.S. and international operations, as currently. In the first quarter, 60% of Schering-Plough's pharmaceuticals sales came from outside the U.S.
Schering-Plough has been struggling with the expiration of Claritin's patent last November, but the first-quarter results brought bad news about its remaining lineup of prescription drugs, especially a group of medicines
that treat hepatitis-C infection. World-wide sales of the hepatitis-C lineup fell to $516 million, down 7% from the first quarter of 2002, and U.S. sales dropped 18%.
The company blamed a buildup of inventories in the fourth quarter of 2002 for the drop in sales. But it also cited competition from Roche Holding AG of Switzerland, which introduced a pair of competing drugs last year
and grabbed market share by offering the drugs for free for a trial period.
The first-quarter results also underscored Schering-Plough's failure to establish Clarinex, an allergy drug launched in January 2002, as a successor in the prescription market to Claritin, which is now available over the
counter at U.S. pharmacies for a fraction of its old price. Clarinex sales totaled $173 million world-wide, which was above the year-earlier first quarter but slightly below sales in the fourth quarter of 2002.
At 4 p.m. in New York Stock Exchange composite trading, Schering-Plough shares were up 41 cents at $18.71 apiece.
Schering-Plough said Clarinex is experiencing "intense competition" in the U.S.market, in part from Claritin, which is chemically similar.
In a recent interview, Mr. Hassan said his first short-term priority is to deal with manufacturing problems that forced Schering-Plough to agree to pay $500 million in fines to the Food and Drug Administration. The
company could have to pay as much as $175 million more if it fails to convince the FDA that it has cleaned up its act.
Mr. Hassan said he wants a blockbuster to replace Claritin and intends to look harder at licensing other companies' drugs. He is forming a division of global licensing whose head will report to him.
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Debate over Hepatitis C Drug Heats Up
By Tiffany Kary
Enzon Pharmaceuticals Inc. shares tumbled as much as 8% Wednesday after the company's latest quarterly results reinforced concerns over the sales trend for one of its main products, PEG-Intron.
The stock's decline comes on the heels of a sell-off Tuesday, after marketing partner Schering-Plough Corp. disclosed lower worldwide and U.S. sales of Intron during the March quarter. The news also hurt shares of
Enzon's prospective merger partner NPS Pharmaceuticals (NPSP).
PEG-Intron is a therapy for hepatitis C that combines Enzon's polymer, PEG, with Schering Plough's Intron. The PEG polymer helps Intron remain in the blood longer.
In its fiscal third-quarter report, Enzon said total royalty revenues rose 15%, to $16.2 million from the same time a year earlier. But that's down from $22.9 million in the fiscal second quarter. The company doesn't
break out the contribution of PEG-Intron royalties.
But Enzon acknowledged Schering-Plough's previous-day remarks on the drug, igniting further debate over its outlook.
Analysts were divided on reasons for Schering-Plough's lower sales of PEG-Intron, citing temporary inventory issues at Schering-Plough, impinging competition from Roche Holding AG and possible declining demand
for that class of drugs overall.
Enzon's chairman and chief executive, Arthur J. Higgins, said in a statement that "...prescription trends for PEG-Intron continue to indicate that although the product faces competitive pressure from Roche's product,
Pegasys, demand for PEG-INTRON remains strong and the overall market for pegylated alpha interferon products used to treat hepatitis C has expanded since the launch of Pegasys."
The company's press release then addressed Schering-Plough's previous-day comments, saying information revealed that "PEG-Intron royalties were negatively impacted, as compared to the December quarter, by a
reduction in trade inventories, as a result of Schering-Plough's elimination of its Access Assurance Program and the related transition from sole to multi-source distributors."
Enzon Chief Financial Officer Kenneth J. Zuerblis told nervous investors to "look beyond quarterly fluctuations and focus on PEG-Intron long-term potential."
Some company watchers agreed with Enzon's analysis of the situation.
"Enzon's third quarter earnings shortfall appears driven by a correction in PEG-Intron inventories," said WR Hambrecht analyst Louis Webb. Webb remained upbeat on shares however, maintaining his buy rating and
saying he expects a rebound in manufacturing sales in the fourth quarter.
Webb said Schering-Plough had used multiple distributors for the drug in the December quarter, making inventory "excessively strong," and leading to a spike in sales. Schering said sales of the drug were $305 million
in the December quarter, up from $244 million in the previous quarter.
Webb said the decline to $216 million in PEG-Intron sales in the March quarter resulted from inventory corrections.
Webb doesn't own shares in any of the companies mentioned and WR Hambrecht makes a market in Enzon.
Enzon said its fiscal third-quarter revenue was $43.2 million, slightly below Thomson First Call's consensus estimate for $46.83 million. Earnings were 21 cents a share excluding a 4-cent expense related to the
proposed merger. First Call had predicted earnings of 31 cents a share.
On Tuesday, sell-sied analysts said they doubt that the PEG-Intron issue presents an obstacle to the pending merger between Enzon and NPS Pharmaceuticals.
Enzon shares recently traded at $12.95, down 6% or 82 cents on volume of 2.8 million shares. Average daily volume is 1.1 million shares.
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Combination Regimen Helps Quell Refractory Hepatitis C
Triple therapy for chronic hepatitis C using alpha interferon, ribavirin and amantadine may be effective in many patients who do not respond to alpha interferon alone, Italian researchers report in the May issue of Gut
(Gut 2003;52;701-705)
Lead investigator Dr. Luigio E. Adinolfi told Reuters Health that although half of chronic hepatitis C patients do not show a response to interferon, "there are no recommended therapeutic options for these subjects, who
remain at risk of progression of the disease."
Dr. Adinolfi and colleagues at the Second University of Naples studied 114 such patients, who were randomized to 3 treatment groups. All received interferon alpha 2b and ribavirin 1000 mg/day.
In the first group, the interferon dosage was 3 million units (MU) 3 times a week, the two other groups received 3 MU daily for the first 4 weeks and then 3 MU 3 times a week. The third group was also given oral
amantadine hydrochloride 200 mg per day.
At the end of the 12-month treatment period, the response was 25% in the first group, 29% in the second and 68% in the triple therapy group (p < 0.005). Follow-up, a year later, showed corresponding sustained
responses to be 2%, 4% and 25% (p < 0.002).
The researchers, call for larger trials. Summing up, Dr. Adinolfi said the study demonstrates "that amantadine acts synergistically with interferon and ribavirin in chronic hepatitis C patients, who were non-responders to
interferon alone, without any increase of side effects."
