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Alan Franciscus
Editor-in-Chief
- Immtech Compounds Show
Promise Against Flavivirus (Hepatitis C and BVDV) And Animal
Market Applications
- Interferon Induction Therapy
Does Not Enhance SVR and Relapsers with Genotypes 1 and
4 Retreated with High Dose Interferon Plus Ribavirin for
48 Weeks Have 50% Response Rate
- HCV Infection of the Central
Nervous System May Cause Neuropsychological Symptoms and
Cognitive Impairment
- Austrian Study Recommends
Twice-Weekly Dosage of PEG-Intron
- Time on Anti-HIV Therapy
Is a Protective Factor for Liver Fibrosis in HIV-HCV Coinfected
Patients
- Antiviral Therapy of Patients
for Patients Awaiting Lliver Transplantation: A Strategy
to Prevent Hepatitis C Recurrence After Transplantation
- Liver Transplant Recipients
Over 60 Years Old Have Lower Survival and Higher Incidence
of Malignancy
- Defective Memory Function
in Early Hepatic Encephalopathy
- Previous HBV Infection
Does Not Affect Liver Histology or the Response to Interferon-based
Therapy in HCV Patients
- Schering-Plough Says It
Is Running Out of Cash
- HBV Detected in Livers
of Patients Said 'Cured'
- In Vivo Immunization
Following Suppression of HBV: A New Approach for Inducing
Immune Control in Chronic Hepatitis B
- Are HBV Vaccine Booster
Doses Unnecessary in Immunocompetent Persons?
- Task Force Formed to
Combat Hepatitis
- Biochemical Markers of
Liver Fibrosis and Activity Can Be Used as Surrogate Markers
for Liver Biopsy in Patients with Chronic Hepatitis C
- Recommendation of Future
Management of Chronic Hepatitis C Without Liver Biopsies
- Hepatitis C on the Rise:
US Based Doctor
- Roche Replenishing Hepatitis
C Medicine
- Regeneration of Hepatocytes
From Intrabiliary Stem Cells in Cirrhosis
- Unique Scholarship Program
Aims to Support African-American and Hispanic Students Challenged
by Hepatitis C
- Preventive Treatment for
HCV Recurrence in Patients with Decompensated Post-hepatitis
C Cirrhosis Before Liver Transplantation: An Editorial
- Treatment of HCV Patients
Awaiting Liver Transplantation Helps to Prevent HCV Recurrence
Following Surgery
- Geneva Pharmaceuticals
Prepares Generic Rebetol(R) - U.S. District Court Rules
Patent Non-Infringement
- Prevalence of Hepatitis
C Virus Infection in Urban Children in the USA
- Histoacryl Injection
or Beta-blockers for the Eradication of Esophogastric varices
- College Students Ignoring
Risks of Unprotected Sex
- Schering-Plough Slashes
Costs. Jobs, Dividend and Perks Among Cutback Targets
- Wane of Hepatitis C Drugs
Wound Schering-Plough
- Vaccination and Anti-HIV
Therapy Lower Hepatitis B Infection Rates
- Hyperlipasemia and/or
Subclinical Pancreatitis May Represent Extrahepatic Manifestations
of HCV Infection
- Twice Daily Dosing with
Interferon Beta Improves Viral Kinetics and Enhances Antiviral
Efficacy
- Management of Hematologic
Disorders Associated with Hepatitis C Virus Infection
- Chinese Scientists Decode
New Hepatitis B Virus Genes
- Antioxidants May be Beneficial
For Transplant Patients
- Risk of Cancer Higher
in Patients with Fatty Liver, Say Japanese Doctors
- Accelerated Schedules
for Vaccinations Against Hepatitis A and B
- High Dose Infergen (consensus
interferon) Produces Sustained Response in Low Percentage
of Nonresponders to Interferon Alfa and Ribavirin
- Prediction at Week 4
of Treatment Effect with Interferon Alfa and Ribavirin in
HCV Patients Identifies One-half of All Nonresponders and
Allows Them Benefit of Early Cessation of Therapy
- Early Response to Individualized
Weight-Based PegIntron(R) and Rebetol(R)
- Early Virologic Response
to Treatment in Patients with Chronic Hepatitis C
- Outcomes and Indicators
of Upper Digestive Bleeding in Cirrhosis
- Factors Influencing the
Outcome of Liver Retransplantation
- Britain Says It Will
Pay Hepatitis C Victims
- Patients with HBV Genotype
B Infection Have More Severe Exacerbations of Disease and
Higher Risk of Hepatic Decompensation and Mortality Compared
with Patients with HBV Genotype C Infection
- Clinical Features and
Outcome in HCV-positive Patients with Aggressive Non-Hodgkin's
Lymphoma
- Retreatment with Interferon
Is Effective in Some Partial Responders and Nonresponders
with Chronic Hepatitis C
- Finding the Right Combination
to Fight Hepatitis C
August 15th, 2003
Immtech Compounds
Show Promise Against Flavivirus (Hepatitis C and BVDV) And
Animal Market Applications
Immtech International, Inc. (Amex: IMM) announced today
publication of scientific data describing the activity of
aromatic cationic molecules against the Bovine Diarrhea Virus
(“BVDV”). BVDV is an RNA Flavivirus genus commonly
found in cows, and is similar to both the human hepatitis
C virus and the virus that causes West Nile infections.
In the paper, published in Antimicrobial Agents and Chemotherapy,
July 2003, Volume 47, entitled “Detection of Inhibition
of Bovine Diarrhea Virus by Aromatic Cationic Molecules,”
the lead authors, Daniel Givens, (Auburn University) and David
Boykin, (Georgia State University) presented data on the activity
of compounds screened in an assay that evaluates the total
life cycle of viral propagation. The scientists identified
five Immtech compounds demonstrating exceptional efficacy,
inhibiting propagation of the BVDV virus at low (nanomolar)
concentrations with low toxicity. Such activity makes these
compounds excellent candidates for advanced testing against
the
hepatitis C virus.
Stephen Thompson, President & CEO of Immtech said, “The
results observed
by our scientists demonstrate the promise of cationic molecules
as anti-viral agents and possibly against hepatitis C. We
believe that there is an advantage in having a reliable assay
system that evaluates the complete viral life cycle for screening
compounds for anti-hepatitis C activity. We are using the
information generated from these studies to further evaluate
specific cationic compounds for anti-hepatitis C activity.”
While the exact mechanism by which these compounds exert anti-viral
activity is unknown, their known capacity to interact with
nucleic acids and inhibit proteases suggests multiple modes
for anti-viral activity. Potential outcomes from this research
include developing a drug to treat Bovine Diarrhea Virus infections
in calves and preventing viral contamination of embryos during
in vitro fertilization, placing Immtech in the multi-billion
dollar animal health market. One of the lead candidates has
advanced into research using bovine embryos to determine if
the compound could prevent BVDV contamination of the embryos
during in vitro fertilization and embryo transfer (BVDV infections
are a common cause of abortion in cows). The study demonstrated
that the compound was safe to use during in vitro fertilization
and that embryos developed after transfer resulted in the
birth of normal calves. The successful elimination of BVDV
from embryos implanted in cows can greatly reduce the abortion
rate of calves during the in vitro fertilization process.
This market can potentially be very profitable because in
vitro fertilization is the most common method used to impregnate
cows. This BVDV research was supported by a grant from the
National Institutes of Health. Immtech International, Inc.
is a pharmaceutical company focused on the commercialization
of oral treatments for infectious diseases such as pneumonia,
fungal infections, malaria, tuberculosis, hepatitis and tropical
diseases such as African sleeping sickness and Leishmania.
The Company has worldwide, exclusive rights to commercialize
a dicationic pharmaceutical platform from which a pipeline
of products may be developed to target global markets.
Back to top
Interferon Induction
Therapy Does Not Enhance SVR and Relapsers with Genotypes
1 and 4 Retreated with High Dose Interferon Plus Ribavirin
for 48 Weeks Have 50% Response Rate
by hivandhepatitis.com
Retreatment of relapser patients with chronic hepatitis C
with the standard dose of interferon (IFN) of 3 million units
(MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves
a sustained response in 30 and 73% of patients with genotype
1 and 2 or 3, respectively.
The aim of this study was to evaluate the efficacy and safety
of IFN alfa-2b (Intron A) induction therapy, followed by prolonged
treatment with a high dose of IFN alfa-2b plus ribavirin in
relapser patients.
A total of 119 patients were randomized to receive IFN alfa-2b
5 MU daily (Group A: 59 patients) or IFN alfa-2b 5 MU tiw
(Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw)
and ribavirin (1000-1200 mg/day) for 48 weeks in both groups.
The primary end point was hepatitis C virus (HCV)-RNA clearance
at week 24 after the end of treatment.
A sustained virological response (SVR) was achieved in 68
and 60% of Group A and B patients, respectively (P = 0.37).
Logistic regression analysis identified genotype 2 or 3 as
the only independent factor associated with response, whereas
induction regimen and baseline viremia levels did not affect
the response.
The overall SVR was 53 and 72% in patients with genotype 1
or 4 and 2 or 3, respectively.
In conclusion, induction IFN therapy does not enhance the
SVR to a 48-week combination therapy. Our study suggests that
relapsed patients with genotype 1 or 4 may achieve significant
response rates of approximately 50%, if retreated with 5 MU
tiw IFN plus ribavirin for 48 weeks.
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HCV Infection of
the Central Nervous System May Cause Neuropsychological Symptoms
and Cognitive Impairment
by hivandhepatitis.com
A number of studies have reported an association between chronic
hepatitis C (HCV) infection and significant impairments in
health-related quality of life (QOL). These impairments are
independent of the severity of liver disease.
There are numerous reports documenting the prevalence of symptoms
such as fatigue and depression in chronic HCV infection, which
may in part account for the reductions in quality of life.
Although there are a large number of potential explanations
for these symptoms, including depression and anxiety associated
with the diagnosis of HCV infection or substance abuse, there
has been recent interest in the possibility of a biological
effect of HCV infection on cerebral function.
There is emerging evidence of mild, but significant neurocognitive
impairment in HCV infection, which cannot be attributed to
substance abuse, coexistent depression or hepatic encephalopathy.
In vivo magnetic resonance spectroscopy and neurophysiological
studies have suggested that a biological mechanism may underlie
these cognitive findings.
The recent detection of HCV genetic sequences in post mortem
brain tissue raises the intriguing possibility that HCV infection
of the central nervous system may be related to the reported
neuropsychological symptoms and cognitive impairment.
Back to top
Austrian Study
Recommends Twice-Weekly Dosage of PEG-Intron
by newsrx.com
University of Vienna internists are recommending at least
twice-weekly dosing of peginterferon-alpha-2b for their patients
with chronic hepatitis C.
They say this schedule is necessary to continually expose
the virus to the drug and to improve initial viral clearance.
“The decline in hepatitis C viral load on treatment
with peginterferon-alpha-2b is not continuous,” said
E. Formann and colleagues. “The aim of this study was
to investigate whether twice weekly dosing of peginterferon-alpha-2b
[PEG-IFN-a-2b] may improve viral kinetics.”
Study subjects were 10 interferon-naive patients with chronic
hepatitis C - genotype 1a or b. They were “randomized
to receive either 10 mcg/kg PEG-IFN-a-2b once (group A) or
twice weekly (group B) for 4 weeks.”
Formann and colleagues reported that “ PEG-IFN-a-2b
reached maximal blood concentrations 24 hours after the first
dose, followed by a linear decline during the subsequent days.
On the day before administration of the next dose, PEG-IFN-a-2b
was undetectable in nine patients in group A (once-weekly
dosing). The same pattern was observed during the next 3 weeks
of therapy.”
They could detect PEG-IFN-a-2b at any time point in patients
under the twice-weekly regimen, the researchers said, adding
that the drug levels always were “higher than in group
A (p between 0.01 and <0.0001).”
“Viral load decreased in all patients within 2 days
after the first dose of peginterferon-alpha-2b, but increased
again on day 3. In group A, it further increased until day
7. A similar pattern was observed in the second week.
“In contrast, in group B, viral load decreased again
on day 4 and remained lower until the end of the study (p<0.001),”
reported Formann’s team.
“To achieve continuous drug exposure and to improve
initial viral clearance, peginterferon-alpha-2b has to be
given at least two times weekly,” they concluded.
Formann and coauthors published their study in the Journal
of Viral Hepatitis (Twice-weekly administration of peginterferon-alpha-2b
improves viral kinetics in patients with chronic hepatitis
C genotype 1. J Viral Hepatitis, 2003;10(4):271-276).
Back to top
Time on Anti-HIV
Therapy Is a Protective Factor for Liver Fibrosis in HIV-HCV
Coinfected Patients
by hivandhepatitis.com
To assess the factors associated with liver fibrosis in HIV
and hepatitis C virus (HIV/HCV) co-infected patients eligible
for anti-HCV therapy, researchers performed an observational,
single-centred, cross-sectional study of 180 HIV/HCV co-infected
patients who underwent liver biopsy between May 1998 and November
2001.
A total of 126 patients with a known date of HCV infection
were evaluated. Liver fibrosis was defined as a Knodell stage
of fibrosis 1-4.
The mean age was 36.7 (3.8) years, 81% were male and had a
mean age of 20.5 (3.8) years at HCV infection. Mean CD4 cell
count and plasma HIV-1 RNA load at the time of biopsy were
552 cell/mm3 (239) and 2.5 log10 (0.9), respectively; 118
patients had been on antiretroviral therapy (ART) for a median
of 45 months (Q1-Q3: 21-75) and 84 on protease inhibitor for
a median of 12.0 months (Q1-Q3: 0-29.5); 55 had an AIDS event
or a CD4 cell count nadir < 200 cells/mm3 prior to biopsy.
Median histological activity index was 6 and 27% had a Knodell
stage of fibrosis 0. On the multivariate analysis time on
ART, CD4 cell count at the time of liver biopsy, age at HCV
infection acquisition and alcohol intake (> 50 g/day) were
associated with liver fibrosis.
The authors conclude, “ART should be a priority in HIV-HCV
co-infected patients eligible for anti-HCV treatment as it
is a protective factor for liver fibrosis.”
Back to top
Antiviral Therapy of Patients for
Patients Awaiting Lliver Transplantation: A Strategy to Prevent
Hepatitis C Recurrence After Transplantation
by gastrohep.com
The utilization of antiviral therapy in hepatitis C virus
infected patients awaiting liver transplantation is a useful
strategy to prevent hepatitis C recurrence after transplantation,
according to a study published in The Journal of Hepatology
(Journal of Hepatology 2003; 39(3): 389-396).
After liver transplantation infection of the graft with the
hepatitis C virus is almost universal. This leads to the development
of chronic hepatitis and cirrhosis in a significant proportion
of patients.
One of the possible strategies to prevent recurrence of hepatitis
C is to eradicate hepatitis C virus prior to liver transplantation.
A team of Spanish doctors evaluated the efficacy and safety
of antiviral therapy to prevent hepatitis C recurrence in
30 patients with hepatitis C and cirrhosis awaiting liver
transplantation.
Antiviral therapy was initiated when the expected time for
liver transplantation was less than 4 months away and continued
until the transplant took place. The median duration of treatment
was 12 weeks.
Antiviral therapy consisted of interferon-2b (3 MU/day) and
ribavirin (800 mg/day).
9 out of the 30 patients achieved a virological response and
21 did not respond to therapy. Viral load decreased in 9 of
the 21 non-responders during treatment.
The 9 patients who responded to antiviral therapy have since
undergone liver transplantation. 6 of the 9 patients remain
free of infection after a median follow-up of 46 weeks, while
hepatitis C viral infection recurred in the remaining 3.
30% of patients had a virological response to antiviral therapy.
Side effects were frequent and dose reduction was necessary
in 19 of the 30 patients.
The authors of the study conclude “Our data support
the utilization of antiviral therapy in hepatitis C-infected
patients awaiting liver transplantation as one of the strategies
to prevent hepatitis C recurrence after liver transplantation.”
However, in an editorial which appears in the same issue of
The Journal of Hepatology, Dr Jean-Pierre Zarski
adds a note of caution.
“Antiviral therapy should be considered experimental
and not be administered outside of prospective trials.”
Back to top
Liver Transplant Recipients
Over 60 Years Old Have Lower Survival and Higher Incidence
of Malignancy
by gastrohep.com
Older liver transplant recipients have a significantly lower
survival than younger patients and malignancy is responsible
for this decreased survival, concludes a study in the American
Journal of Transplantation.
Older age is not considered a contraindication for liver transplantation.
A team of Doctors in Spain reviewed 111 liver transplants
to compare the survival of patients over 60 years old who
undergo liver transplantation with the survival of younger
patients.
They also investigated any factors involved in a potential
difference in mortality.
After transplantation, older patients had a significantly
lower survival.
Of the 111 patients analysed 54 were older than 60 years of
age and 57 were younger.
After transplantation, older patients had a significantly
lower survival. Higher age was associated with increased mortality
independent of other variables.
The incidence of de novo neoplasia and nonskin neoplasia was
significantly higher in older patients.
Malignancy was the cause of death in 12 patients older than
60 years, but only 1 patient younger than 60 years.
Higher age as well as smoking were significantly associated
with the incidence death due to de novo neoplasia.
Increased frequency of malignancy in older transplant patients
appears to lead to increased mortality.
Back to top
Defective Memory Function
in Early Hepatic Encephalopathy
by gastrohep.com
A study in the September issue of The Journal of Hepatology
(Journal of Hepatology 2003; 39(3): 320-5) finds
that although patients with early hepatic encephalopathy score
lower than controls in memory tasks, this is predominantly
due to deficits in attention and visual perception.
Early hepatic encephalopathy is characterized by deficits
in motor performance, visual perception, visuo-constructive
abilities and attention.
Whether defective memory is a feature of early hepatic encephalopathy
remains controversial.
Dr Karin Weissenborn and colleagues in Hannover, Germany,
attempted to resolve this controversy by analysing memory
function in 45 patients with early hepatic encephalopathy.
Memory tests were applied to cirrhotic patients with minimal,
grade 0, or grade 1 hepatic encephalopathy and the results
were compared with those seen in 52 control subjects.
Tasks included short and long term memory tests requiring
free recall or recognition.
Patients’ deficits were in attention and visual perception,
rather than memory.
Patients with early hepatic encephalopathy scored lower than
the controls in all of the memory tasks.
Dr Weissenborn’s team conducted a detailed analysis
of test performance, which revealed that the patients’
deficits were in attention and visual perception, rather than
memory.
Dr Weissenborn concludes “Although patients with early
hepatic encephalopathy score lower than controls in memory
tasks, this is predominantly because of deficits in attention
and visual perception.”
Back to top
Previous HBV Infection Does
Not Affect Liver Histology or the Response to Interferon-based
Therapy in HCV Patients
by hivandhepatitis.com
Patients with chronic hepatitis C frequently have antibodies
to the hepatitis B core antigen (anti-HBc), indicative of
prior hepatitis B virus (HBV) infection. In these patients,
persistence of HBV may exacerbate liver injury and diminish
the response to treatment.
The aim of this study was to evaluate the relationship between
previous HBV infection and liver histology and the sustained
virologic response (SVR) to interferon (IFN)-based therapy
in patients with chronic hepatitis C.
A total of 132 HBsAg-negative, treatment-naive patients were
evaluated. Using multiple logistic regression analysis, the
impact of anti-HBc-positivity on the rate of SVR was determined.
Progression to bridging fibrosis or cirrhosis was assessed
using Cox proportional hazards regression and Kaplan-Meier
survival analysis.
The median age of the patients was 47 years (IQR, 37-60),
57% were male, and 73% had genotypes 1, 4, 5, or 6. Fifty-one
patients (39%) were anti-HBc-positive. The prevalence of moderate
to severe necroinflammatory activity (P = 0.36) and progression
to bridging fibrosis or cirrhosis (log-rank P = 0.83) was
similar between anti-HBc-positive and -negative patients.
After a median of 48 weeks (IQR, 26-52) of therapy (IFN, n
= 116; IFN and ribavirin, n = 16), 23 patients (17%) achieved
a SVR; the rate of response was similar in anti-HBc-positive
and -negative patients (18%vs 17%, P = 1.00).
After controlling for age, gender, genotype, fibrosis, and
treatment regimen, anti-HBc status did not independently affect
the rate of SVR (P = 0.58).
In conclusion, previous HBV infection does not affect liver
histology or the response to IFN-based therapy in patients
with chronic hepatitis C.
Back to top
Schering-Plough Says It Is
Running Out of Cash
by Lewis Krauskopf
In the latest fallout from its waning Claritin franchise,
Schering-Plough Corp. warned investors Tuesday it may have
to borrow to fund this year’s cash needs.
The Kenilworth-based drug maker said that for the rest of
2003 -- and “possibly beyond”—cash from
its operating activities may not be enough to fund working
capital, capital expenditures, and dividends. The situation
particularly relates to its U.S. operations.
Schering-Plough, which has a solid, investment-grade credit
rating, said it plans short-term borrowing to cover its needs.
But the company has not ruled out job cuts or reducing its
dividend. Schering-Plough employs about 7,000 people in New
Jersey, and nearly 30,000 worldwide.
Sales of the allergy pill Claritin—once a $3 billion-a-year
cash cow making up more than 30 percent of company sales—have
evaporated after the company lost marketing exclusivity and
converted it to an over-the-counter product. In the second
quarter alone, prescription Claritin sales in the United States
dropped to $13 million from $677 million in the 2002 period.
Other products, such as its Intron hepatitis C franchise,
have failed to pick up the slack.
Schering-Plough gave its cash warning as part of an SEC document
filed Tuesday designed to answer frequently asked questions
by investors. The company had described the situation in previous
filings. Shares slipped 15 cents to $16.10, recovering after
falling as much as 11 percent early in the day.
Schering-Plough’s net cash from operating activities
totaled $429 million in the first six months, compared with
$870 million in the first half of last year.
Cash from operations was sufficient in the first quarter.
But in the second quarter, the company paid $250 million as
part of a fine levied by the U.S. Food and Drug Administration
over manufacturing practices. That payment offset cash flow
from operations, the company said, so the company borrowed
to pay for capital expenditures and dividends.
“For the remainder of 2003 and possibly beyond, cash
provided by operating activities will not be sufficient to
fund working capital, capital expenditures, and dividends
if these items remain at levels comparable to that in the
first and second quarters,” the company said.
However, the company also said it has “adequate internal
and external resources” to meet its financial requirements.
Further, the company said it might have further payments related
to other legal and regulatory problems. For example, the SEC
may bring action against the company and its previous CEO,
Richard Jay Kogan, for meetings with investors and analysts
last fall. And the company is a target of a criminal investigation
by the U.S. Attorney’s Office in Massachusetts for its
sales and marketing practices.
During Schering-Plough’s earnings slide, the company’s
dividend has come under scrutiny. At 17 cents per common share,
the quarterly dividend is costing Schering-Plough about $1
billion a year. Schering-Plough has increased its dividend
19 times since 1986.
As the company has stated before, Fred Hassan, the new chief
executive, has been asked to do a “360-degree review”
of the company’s operations, including its dividend.
“The company is generating cash to pay capital expenditures,”
said Todd Lebor, an analyst with Morningstar Inc. “What
it’s not doing is generating enough cash at the end
of the day to pay the dividend as well.” However, Lebor
said, the company’s hole is temporary and it should
be generating enough cash to do both within two years. He
said the company’s new cholesterol treatment Zetia is
expected to be a bigger revenue contributor by then.
Hassan said last month he would seek to wring out $200 million
in annual savings from the company’s current cost structure.
Schering-Plough hired Hassan, the former CEO of Pharmacia
Corp., in April to turn around the company’s fortunes.
Back to top
August 17th, 2003
HBV Detected in Livers of Patients
Said 'Cured'
Yomiuri Shimbun
The hepatitis B virus (HBV) lingers in the liver for a longer
time than previously believed and can reemerge in a carrier’s
blood after a sufferer of the disease is thought cured, according
to findings of research conducted by the Osaka National Hospital
and other medical organizations.
It was widely believed that the disease would not become chronic
in adult carriers more than six months after acute symptoms
had been cured. Such carriers were then allowed to again donate
blood.
The team said that it is unlikely the liver virus would have
an adverse effect on carriers’ health, but it may be
a source of infection in a virus-free blood transfusion recipient.
The finding is likely to have a significant impact on the
blood donation screening system.
Adults with normal immune systems carry antibodies in their
blood to attack HBV and prevent it from becoming a chronic
disease.
Once the antibodies in a carrier’s blood system have
been activated, it was previously believed that the carrier
could not be reinfected with the disease.
However, in a reexamination of 14 former carriers whose livers
have been functioning normally for between 2 and 9 years after
contracting the disease, Nobukazu Yuki, head of the hospital’s
Department of Gastroenterology, and other researchers detected
the virus in the blood of three of the former patients.
Furthermore, an examination of liver tissue from nine of the
14 former carriers, who consented to biopsies, revealed that
all had the virus, and seven were suffering from a slight
inflammation of the liver.
In the Japanese Red Cross Society’s safety checks on
donated blood, it is difficult to detect HBV unless the viral
count is above 1,000 HBVs per milliliter of blood.
However, there have been cases in which carriers with a viral
count thought lower than 50 died from the disease.
The counts in the three former patients found to have the
virus were 770, 1,300 and 24,000, respectively.
Blood donated by the two with the lowest counts could have
slipped through the society’s safety tests and subsequently
infected transfusion recipients.
There have been reports in recent years that the virus would
linger in the liver after carriers were believed to be cured,
but this is the first time the virus was found to have survived
in nine former patients who underwent posttreatment check-ups.
After treatment, it was believed that the viral count could
not rise as antibodies in the immune system had been activated
and were thought to keep the count down. Therefore, it was
not expected that a viral count as high as 24,000 HBVs per
milliliter would have been detected in a previously cured
patient’s blood.
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August 18th, 2003
In Vivo Immunization Following Suppression
of HBV: A New Approach for Inducing Immune Control in Chronic
Hepatitis B
by hivandhepatitis.com
Antiviral treatment of patients with active chronic hepatitis
B may lead to a significant reduction in morbidity and mortality.
However, after stopping nucleoside analogue therapy, relapse
rates are high in those without acquired specific immunity.
Researchers at the University Medical Center Rotterdam, The
Netherlands have treated two chronic hepatitis B patients
with in vivo immunization. In vivo immunization aims to optimize
conditions for an effective immune response: following rapid
and profound virus suppression by interferon-lamivudine combination
therapy, lamivudine is withdrawn intermittently for 4 weeks
during continued interferon therapy.
In both patients with profound virus suppression a rapid rebound
in viral replication was observed after lamivudine withdrawal,
despite continued interferon. These periods of renewed viral
replication were followed by rises in hepatitis activity.
After re-introduction of lamivudine, HBV DNA became undetectable
by PCR followed by normalization of serum ALT. These observations
are a stimulus to further explore the concept of in vivo immunization
as a novel therapeutic approach for chronic hepatitis B.
Clearly, these results in two patients require confirmation
in a larger study.
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Are HBV Vaccine Booster Doses Unnecessary
in Immunocompetent Persons?
by hivandhepatitis.com
This review analyses the cumulated data
from a number of long-term follow-up studies among infants,
children and adults vaccinated against hepatitis B in industrialized
and developing countries.
Despite low or undetectable antibody responses years after
vaccination, the development of HBsAg was a rarity and, if
present, only transient. Some vaccinees developed anti-HBc
responses but none developed an HB carrier state or clinical
manifestations of disease.
Studies demonstrating anamnestic responses among those with
low or undetectable anti-HBs levels following challenge with
HB vaccine, together with the production of anti-HBs in circulating
B-cells by spot ELISA, confirmed the presence of immune memory
among vaccinees.
Anamnestic anti-HBs responses all correlate close in kinetics
and magnitude with proliferative T-cell responses.
The accumulated data from studies assessed in this review
indicate that protection is dependent on immune memory, rather
than declining anti-HBs responses and add additional weight
to the European Consensus recommendations that following a
complete course of vaccination, booster doses are unnecessary
in immunocompetent persons.
If implemented, this recommendation will have considerable
cost benefits world-wide.
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Task Force Formed to Combat Hepatitis
Islamabad: A task force has been established in North West
Frontier Province as part of a province-wide campaign to combat
rapidly spreading hepatitis, an official said on Wednesday.
“It is a one week campaign with different components,
including seminars, workshops, display posters and walks to
create awareness. The NWFP is the first region in Pakistan
to launch such a campaign,” Provincial Health Secretary,
Dr Ihsan-Ul-Haq, said from Peshawar. He added that the federal
government is working on a similar idea for the whole country.
A private pharmaceutical company has pledged to provide discounted
vaccines, he said.
“Cases of hepatitis C have risen dramatically, making
it twice as prevalent as hepatitis B,” said the chairman
of the hepatitis task force in Peshawar, Dr Najibul Haq.
“The main objective of the campaign is to increase awareness
in people about the simple ways to avoid hepatitis. We are
targeting different groups to spread the message,” he
said, noting that the task force is also working on legislation
with the government in respect to preventative measures.
All the districts in NWFP were involved. The three main components
of the campaign were intended to raise awareness among health
workers, to hold public meetings in hospitals and arrange
walks, Najibul Haq said. He added that his task force wanted
to see the activities continue even after the campaign ended.
He said the campaign should involve local religious and community
leaders, members of parliament, heads of local government,
councillors and health workers.
At present, 18 percent of all patients admitted to general
wards in hospitals in the NWFP suffer from some type of hepatitis,
the chief of NWFP government’s Health Sector, Research
and Reform Unit, Dr Mohammed Rafiq, said. “There are
nine million hepatitis B carriers in Pakistan.” IRIN
Back to top
Biochemical Markers of Liver Fibrosis
and Activity Can Be Used as Surrogate Markers for Liver Biopsy
in Patients with Chronic Hepatitis C
by hivandhepatitis.com
In patients infected with hepatitis C virus (HCV), recent
studies have demonstrated the predictive value of combinations
of simple serum biochemical markers.
Abbreviations:
HCV - hepatitis C virus
FT - Fibrotest
AT - Actitest
ALT - alanine aminotransferase
SVR - sustained virologic response
GGT - glutamyl transpeptidase
ROC - receiver operating characteristic AUROC - area under
the ROC curves
These markers include Fibrotest (FT) for the diagnosis of
significant fibrosis (ranging from few septa to cirrhosis)
and Actitest (AT) for the assessment of necroinflammatory
activity fibrosis and activity. Such results were not obtained
by other diagnostic tests.
The usual indication for liver biopsy in patients with chronic
hepatitis C is to aid in the discussion of treatment options
with the patient and for the long-term follow-up of patients
to determine whether their disease is stable or whether it
has progressed.
Prior data suggest that FT-AT, if accurate, could act as a
surrogate and lead to a significant reduction in the number
of liver biopsies performed.The aim of this study was to validate
the usefulness of FT-AT as surrogate markers of histologic
features using the data generated from a recent randomized
trial of peginterferon alfa-2b and ribavirin.
Three hundred fifty-two patients who had had 2 interpretable
liver biopsies and stored serum sample before and after treatment
were selected. Two hundred eight patients received peginterferon
alfa-2b 1.5 mcg per kg and ribavirin and 144 patients interferon
alfa-2b 3 MU three times a week and ribavirin for 48 weeks.
A fibrosis and an activity index combining 5 and 6 biochemical
markers were assessed at baseline and at end of follow-up
(24 weeks after treatment).
The biochemical markers have significant predictive values
both for the diagnosis of fibrosis and for activity. For the
diagnosis of bridging fibrosis and/or moderate necroinflammatory
activity, the area under the receiver operating characteristics
curve of the activity index was 0.76 1 0.03 at baseline and
0.82 1 0.02 at end of follow-up. A cutoff of activity index
at 0.30 (range, 0.00-1.00) had 90% sensitivity and 88% positive
predictive value for the diagnosis of bridging fibrosis or
moderate necroinflammatory activity.
Sensitivity analyses with biopsy specimens of size greater
than 15 mm suggest that a part of discordances between biochemical
markers and histology were due to biopsy specimen sampling
error.
In conclusion, these biochemical markers of fibrosis and activity
could be used as surrogate markers for liver biopsy in patients
with chronic hepatitis C, both for the initial evaluation
and for follow-up.
This study is the seventh demonstrating that a combination
of 5 (FT) or 6 biochemical markers (AT) can have high positive
or negative predictive values for diagnosing significant fibrosis
and significant activity in patients with chronic hepatitis
C. Although retrospective, the analyses of this study were
made with an independent assessment of FT-AT, of fibrosis
stages, and of activity grades.
These scores are derived from tests that are not yet routine
in many countries. However, all the 6 components are available
in most countries. When compared with routine laboratory tests
found to be predictive of activity or fibrosis, the researchers
found better diagnostic values for their scores. In addition
to superior diagnostic power, FT is not genotype dependent,
whereas the Forns et al. index includes serum cholesterol,
which varies with HCV genotype.
The results show that FT-AT can also be used as surrogate
markers of the histologic impact of treatment. Both indexes
were associated with the virologic responses and with the
histologic variations.
In chronic hepatitis C, the impact of treatment on fibrosis
progression and activity is related to the virologic response
and, for virologic nonresponders, to the baseline stage of
fibrosis and to the duration of treatment. Therefore, FT-AT
could be used as surrogate markers in trials evaluating the
risk-benefit of maintenance therapy, without increasing the
risk and the cost because of repeated liver biopsies.
Back to top
Recommendation of Future Management
of Chronic Hepatitis C Without Liver Biopsies
From the previous results and those presented here, a simplification
of the management of chronic hepatitis C is possible, particularly
using a cutoff of 0.30 for AT. Because this analysis is retrospective,
a randomized trial of 2 strategies comparing a strategy without
and with biopsy is certainly the best scientific comparison
of the respective utilities. However, this type of trial would
require a very large number of patients to estimate the severe
adverse events.
The authors conclude, “Because of the improvement of
biochemical markers and the limits and the risk of biopsy,
liver biopsy should not be mandatory anymore. It is perhaps
time to leave the decision regarding liver biopsy to the physician
and to the patient. There is, worldwide, a lack of screening
and an under prescription of treatment despite its efficacy.
A simplification of liver damage assessment should accelerate
the management of chronic hepatitis C.”
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Hepatitis C on the Rise: US Based
Doctor
Staff Report
LAHORE: A US based Pakistani physician Dr Farrukh Ali Khan
has cautioned that hepatitis C is on the rise in Pakistan
and could lead to liver failure or cancer for most of the
affected if they were not diagnosed early.
Dr Khan, who is on a short visit to Pakistan, was speaking
at a Free Hepatitis Camp arranged by the Mumtaz Bakhtawar
Memorial Trust Hospital on Raiwind road. He said the hepatitis
virus leads to cirrhosis of the liver, causing it to scar
and shrink, and eventually, liver cancer.
He said the Hepatitis C virus was transmitted through improperly
screened blood transfusions, inadequately sterilized surgical
instruments and syringes, ear piercing and hair salon instruments.
To prevent the spread of the disease it is vital to ensure
the blood is screened properly, that disposable syringes,
razors, needles be made standard practice and sterilized equipment
used. He said Hepatitis C has infected three percent of the
total world’s population with 180 million carriers worldwide.
Early and effective treatment is vital to arrest the infection,
he said.
Dr Khan said there are six genotypes of the Hepatitis-C virus
of which genotype 3 is present in 80 per cent of those infected
with the disease in Pakistan. Genotype 1 is more common in
the West. Genotype 3 is the most curable form of the virus
with around 80 percent cure rate, he said.
Unchecked the Hepatitis B and C will triple in 10 years. Pakistan
needs to take drastic measures to block its growth. Health
experts maintained that hepatitis carriers in Pakistan are
rapidly increasing due to ignorance about the virus.
In Pakistan, a sense of complacency in the general public
and the medical community prevents a holistic approach towards
diagnosis and treatment of liver diseases, including hepatitis
and different progressive liver ailments.
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Roche Replenishing Hepatitis C Medicine
The pharmaceutical company Roche is offering samples of Pegasys
(peginterferon alfa-2a) to physicians in the Memphis area
through a program designed to replenish vials of the hepatitis
C medication that may have been lost as a result of power
outages following the July 22 storm.
Patients undergoing treatment for hepatitis C who lost one
or more vials of Pegasys should contact their physicians,
who can request samples.
Roche will be making samples of Pegasys available until Aug.
15 to physicians in Shelby, Fayette, and Tipton counties.
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August 19th, 2003
Regeneration of Hepatocytes From
Intrabiliary Stem Cells in Cirrhosis
by gastrohep.com
The biliary tree, from at least its smaller branches up to
the canals of Hering, is composed of or at least harbors facultative
hepatic stem cells, finds a study in the Journal of Hepatology
(Journal of Hepatology 2003 ; 39 (3) : 357-64).
After massive liver cell necrosis, reactive ductules at the
periphery of the necrotic area are thought to contain hepatic
stem cells which differentiate into intermediate hepatocytes,
regenerating the damged area. In cirrhosis, it is still debated
whether the reactive ductules are activated stem cells (so
called ‘buds’) or ductular metaplasia of cholestatic,
injured hepatocytes.
Dr.Olga Falkowski and colleagues investigated the differentiation
of intermediate hepatocytes from reactive ductules in cirrhosis.
The research team examined tissue explants from patients with
cirrhosis associated with alcohol, hepatitis or with primary
sclerosing cholangitis and from patients with primary biliary
cirrhosis.
“Intraseptal heaptocytes largely represent ‘buds’
of newly formed hepatocytes,” said Dr.Olga Falkowski
777 out of 830 (94%) intraseptal heaptocytes (intermediate
hepatocytes) were associated with reactive ductules.
In 3-D reconstructions, intermediate hepatocytes were seen
to bud directly from the biliary tree.
Intermediate hepatocytes were rarely found to be cholestatic.
Reactive ductules throughout the biliary tree are though to
contain stem cells which give rise to new intermediate hepatocytes
in cirrhosis.
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Unique Scholarship Program Aims to Support African-American
and Hispanic Students Challenged by Hepatitis C: Thurgood
Marshall Scholarship Fund and Hispanic Scholarship Fund Partner
On New Horizons Scholars Program
The Thurgood Marshall Scholarship Fund (TMSF) and the Hispanic
Scholarship Fund (HSF) announced today the launch of the second
year of the New Horizons Scholars Program which will provide
college scholarships to Hispanic and African-American students
entering college in 2004 who have hepatitis C or are dependents
of a person with the disease. The New Horizons Scholars Program
is funded by The Roche Foundation.
These scholarships will help support the
educational imperatives of African-American and Hispanic students
in this country. According to a recent report by American
Council on Education’s Office of Minorities in Higher
Education, college participation rates for African-American
high-school graduates, ages 18-24 was at 39.4 percent in 2000
while the college participation rate for Latinos reached 36.5
percent in 2000. “The New Horizons Scholars Program
is a unique partnership that was established last year, and
aims to create additional financial resources to cover the
costs of higher education for Hispanic and African-American
students impacted by hepatitis C,” said Nicole Lee-Haley,
major gift officer for TMSF. “We’re very excited
to continue this program with our partners and hope to positively
impact the lives of these students through this important
scholarship program.”
The New Horizons Scholars Program will
provide up to 50 scholarships to students planning to enroll
for the first time in a four-year college during the fall
of 2004. Scholarships will be awarded to students of Hispanic
or African-American heritage who are infected or are dependents
of someone infected with hepatitis C. Students will be eligible
for $2,500 per year for four years, and must maintain the
program’s academic standard of 2.5 G.P.A.
Scholarship winners will be notified in
the late spring of 2004. Applications
are available at http://www.hsf.net or http://www.thurgoodmarshallfund.org
or by calling Toll-Free 1-866-346-7496. Applications must
be postmarked no later than February 20, 2004.
“Supporting the higher education
of Hispanics and African Americans is a critical investment
in America’s future,” said Mario De Anda, HSF
director of scholarship programs. “The New Horizons
Scholars Program is a strong partnership with the Thurgood
Marshall Scholarship Fund to help provide educational opportunities
to our communities and make a difference in the lives of our
students.”
“The Roche Foundation is committed
to helping create specialized educational opportunities for
students impacted by hepatitis C,” said Vivian Beetle,
Executive Director of The Roche Foundation, “This program
is part of The Roche Foundation’s ongoing efforts to
help lessen the long term impact of hepatitis C on patients
and their families.”
About Hepatitis C
Hepatitis C virus, a blood-borne disease of the liver, is
the leading cause of cirrhosis and liver cancer and the number
one reason for liver transplants in the U.S. Hepatitis C is
transmitted through body fluids, primarily blood or blood
products, and by sharing needles. Unfortunately, most people
infected with hepatitis C are unaware of it because it may
take years for symptoms to develop. Approximately 2.7 million
Americans are chronically infected with hepatitis C with an
estimated 30,000 new infections yearly.
Hepatitis C disproportionately affects the African-American
and Hispanic community. In the United States, 3.2 percent
of African Americans are infected with hepatitis C, as compared
with 2.1 percent of Hispanics and 1.5 percent of Caucasians.
About the Thurgood Marshall Scholarship Fund
The Thurgood Marshall Scholarship Fund, the first and only
national organization of its kind, supports 45 public historically
black colleges and universities through merit scholarships,
programmatic and capacity-building support. Scholarships are
awarded based on merit and need. Since 1987, the organization
has distributed over $20 million in scholarships and programmatic
support. TMSF serves as an economic gateway to thousands of
students who may not otherwise have the opportunity to go
to college.
About the Hispanic Scholarship Fund
The Hispanic Scholarship Fund (HSF) is the nation’s
leading organization supporting Hispanic higher education.
Founded in 1975, HSF’s vision is to strengthen the country
by advancing college education among Hispanic Americans, the
fastest-growing segment of the U.S. population. In support
of its mission to double the rate of Hispanics earning college
degrees, HSF, a 501©3 not-for profit organization, provides
the Latino community more college scholarships and educational
outreach support than any other organization in the country.
Headquartered in San Francisco, HSF has opened regional offices
in Southern and Central California, the Northeast, the Southeast,
Midwest and Texas. In addition, HSF launched the Washington,
D.C.-based Hispanic Scholarship Fund Institute to generate
public partnerships in support of its work. During its 28-year
history, HSF has awarded more than 61,000 scholarships in
excess of $115 million to Latinos from all 50 states, Puerto
Rico and the U.S. Virgin Islands who have attended more than
1,700 colleges and universities.
About The Roche Foundation
The Roche Foundation (formerly known as the Hoffmann-La Roche
Foundation) was created in 1947 as an independent charitable
entity, solely funded by the company. Today, it continues
to complement the corporate contributions program and helps
support selected community organizations and initiatives.
The Roche Foundation focuses its support on health promotion
and science and math education. The establishment of The Roche
Foundation over 50 years ago demonstrated the company’s
commitment to the importance of good corporate citizenship—a
belief that remains today.
For More Information on the New Horizons Scholars Program
Go To:
http://www.hsf.net
http://www.thurgoodmarshallfund.org
Back to top
August 20th, 2003
Preventive Treatment for HCV Recurrence
in Patients with Decompensated Post-hepatitis C Cirrhosis
Before Liver Transplantation: An Editorial
by hivandhepatitis.com
There is no consensus or compelling evidence for a single,
standard approach to treatment for the prevention of HCV recurrence
following liver transplantation, which unfortunately occurs
almost universally.
In the following editorial, published in the Journal of
Hepatology (September 2003), researchers in the Gastroenterology
Department at the Michallon Hospital in Grenoble, France review
the most recent therapeutic approaches to this serious post
transplantation complication:
After liver transplantation (LT), hepatitis C virus (HCV)
recurrence is almost universal, particularly if HCV RNA is
detectable at the time of transplant and can lead in a great
number of patients to recurrent cirrhosis and graft failure.
This recurrence is often rapid. Several studies have shown
that combination therapy using interferon alfa and ribavirin
is possible after liver transplantation but the virological
response rate is low and the treatment is usually associated
with major side effects, requiring dose reduction or stopping
treatment.
Another strategy is the eradication of HCV RNA before LT in
order to prevent HCV recurrence after LT and reduction in
the level of HCV RNA to reduce the severity of post-transplantation
liver disease.
Forns et al evaluated the efficacy and safety of antiviral
therapy in 30 patients with post-hepatitis C cirrhosis awaiting
liver transplantation. Only patients having an expected time
on the waiting list shorter than four months were included.
Patients with hepatic encephalopathy, renal failure or co-infection
by hepatitis B virus or human immunodeficiency virus were
excluded. Patients were treated with interferon alfa-2b (Intron
A) 3MUI/day and ribavirin 800 mg/day. Dose reductions were
utilized according to the laboratory recommendations.
Fifty patients were screened during a 15-month period, but
19 (38%) were excluded due to contra-indication or refusal.
The median duration of treatment was 12 weeks (2-33). Virological
response was observed in nine patients (30%). Variables associated
with a good response to treatment were age, ALT level, genotype
non 1 and low viral load. A decrease of viral load > or
= 2 log had a positive predictive value of 100% at week 4.
After liver transplantation, among the nine patients with
virological response, HCV infection recurred in only three
patients at week 2, 4, 5, respectively after liver transplantation.
All these patients were infected with genotype 1b.
Six patients became HCV RNA negative after a mean follow-up
of 46 weeks (24-80). Indeed, 4/5 patients also tested in the
liver were HCV RNA negative. Side effects were frequent. Two
patients developed sepsis; in both cases, neutrophil counts
were above 1.2W109/l at the time of hospital admission.
Interferon dose reduction was necessary in 60% of cases and
ribavirin dose reduction in 24% of cases. Eleven patients
required filgrastim due to neutropenia and eight erythropoetin
due to anemia. No patients died during therapy.
Assessment of interferon in patients with decompensated chronic
hepatitis C was until now based on limited small case series.
A gradually increasing dose regimen of combination therapy
with interferon and ribavirin has been used in patients with
both compensated and decompensated cirrhosis due to hepatitis
C by Everson et al.
Patients were started on low dose of interferon (1.5 MUI,
tiw) and ribavirin (600 mg/day) with slowly increasing dose
of both drugs every 2 weeks as tolerated. Preliminary results
of treating 91 patients, the majority infected with genotype
1, were recently reported.
On-treatment virological responses occurred in 38% and a sustained
virological response in 22% of patients. Sustained responses
were more common in patients treated for more than 6 months.
Eight patients who were treated and were HCV RNA negative
at the time of transplantation remained virus free post-transplantation.
On the other hand, recurrent and persistent HCV infection
of the allograft was observed in all patients with detectable
HCV RNA at the time of transplantation. No significant change
was observed regarding the hepatic synthetic function and/or
Child Pugh score. Indeed, 27 of non-responders were reported
to develop adverse events.
Less favorable outcome has been reported by Crippin et al.
(6) in a collaborative study of five US liver transplant centers.
Patients were treated with a common protocol using low dose
of interferon with or without low dose of ribavirin. Only
half the patients screened for the study were enrolled, many
being excluded because of severe cytopenias. All patients
had advanced liver disease with a mean Child-Pugh score of
12, as well as elevated serum bilirubin, prolonged prothrombin
time and moderated impaired renal function.
On treatment, 33% of patients became HCV RNA negative. Two
patients underwent liver transplantation and both developed
recurrent infection. Adverse events were common and sometimes
severe, including profound thrombocytopenia, marked neutropenia,
new-onset hepatic encephalopathy and life-threatening infections
that ultimately led to the early termination of the study.
Of course, because both studies did not include an untreated
control group for comparison, it is unclear whether interferon
and ribavirin combination therapy per se precipitated these
life-threatening infections or whether they merely represented
complications of end stage liver disease.
All together these three studies suggest that antiviral therapy
with post-hepatitis C cirrhosis awaiting liver transplantation
is possible and can prevent HCV disease recurrence in several
patients, especially in patients with favorable predictive
factors of response.
However, recurrence of HCV infection after LT is possible
even if HCV RNA is negative in the serum or the liver at the
time of transplantation. Two explanations can be proposed
to explain this discrepancy: first the method of detection
of HCV RNA was not sensitive enough; in this case it would
be interesting to compare this result with a more sensitive
method of detection such as real-time PCR.
The second explanation could be the persistence of the virus
in a second compartment such as peripheral blood mononuclear
cells; to confirm this hypothesis, it is necessary to study
quasispecies distribution in each compartment.
The best results observed by Everson et al. and Forns et al.
suggest that the treatment is better tolerated in patients
with Child A and B than in patients with Child C and leads
to less severe complications such as neutropenia and thrombocytopenia.
All these studies clearly show also that it is necessary in
some cases to use growth factors including GM-CSF and erythropooetin
to boost peripheral blood cell counts in patients with severe
neutropenia and erythropenia to prevent profound cytopenias
and infections.
From these studies, it seems very difficult to define the
best regimen. In Forns et al. study, authors used daily dose
of recombinant interferon. By contrast, Everson et al. as
well as Crippin et al. used low doses of interferon three
times a week.
There are no data on the safety and/or efficacy of peginterferon
with or without ribavirin in patients with decompensated post
hepatitis C cirrhosis. Indeed, the combination of peginterferon
plus ribavirin was only tested in patients with severe fibrosis
(F3 and F4) and was well tolerated.
However, because peginterferon regimens are associated
with higher rate of neutropenia and thrombocytopenia, treatment
is likely to be associated with even greater infection complications
than regimens using standard infection interferon and slower
recovery from these complications when the interferon is stopped
[emphasis added--Ed.]
It will be very interesting in the future to compare these
different regimens. Indeed, the best duration of treatment
remains to be defined.
The rationale for Forns et al. (4) to treat for a short time
was that most virological responders had a viral load decrease
of > or = 2 log 10 at week 4 and were HCV RNA negative
by week 12. However these results are very surprising, especially
in patients with genotype 1b and were not found by others,
and we do not know which treatment schedule is more convenient.
In conclusion, in patients with decompensated HCV cirrhosis,
antiviral therapy as suggested by Wright et al. in the last
American consensus conference should be considered experimental
and not be administered outside of prospective trials.
If the results of these prospective trials are confirmed,
this strategy could be then used in patients with post-hepatitis
C cirrhosis without severe hepatocellular insufficiency awaiting
LT.
Back to top
Treatment of HCV Patients Awaiting
Liver Transplantation Helps to Prevent HCV Recurrence Following
Surgery
by hivandhepatitis.com
After liver transplantation (LT) infection of the graft with
the hepatitis C virus (HCV) is almost universal and chronic
hepatitis and cirrhosis develop in a significant proportion
of patients. One possible strategy to prevent HCV infection
recurrence is to eradicate HCV before LT.
Researchers at four liver transplant units in Spain evaluated
the efficacy and safety of antiviral therapy to prevent HCV
recurrence in 30 HCV-cirrhotic patients awaiting LT. At the
time of inclusion 15 patients were Child-Pugh A and 15 Child-Pugh
B/C. The infecting genotype was 1b in 25 patients. Treatment
with interferon alfa-2b (Intron A) 3 MU/day and ribavirin
800 mg/day was initiated when the expected time for LT was
less than 4 months and continued until LT. The median duration
of treatment was 12 weeks.
Study Results
Nine patients (30%) achieved a virological response and 21
did not respond to therapy. In nine (43%) of the 21 non-responders
viral load decreased \ge 2 log10 during treatment. A viral
load decrease \ge 2 log10 at week 4 of treatment was the strongest
predictor of virological response.
All nine virological responders have already undergone LT;
six patients remain free of infection after a median follow-up
of 46 weeks and HCV infection recurred in three patients after
LT. In one of these patients HCV-RNA was still detectable
in the explanted liver.
Side effects were frequent and dose reduction was necessary
in 19 (63%) of the 30 patients; no patient died while on therapy.
The authors conclude, “Our data support the utilization
of antiviral therapy in HCV-infected patients awaiting LT
as one of the strategies to prevent hepatitis C recurrence
after transplantation.”
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Geneva Pharmaceuticals Prepares
Generic Rebetol(R) - U.S. District Court Rules Patent Non-Infringement
Geneva Pharmaceuticals, Inc. (“Geneva”), an affiliate
of Novartis AG, announced today that on July 14, 2003, the
U.S. District Court Judge for the Central District of California
granted Geneva’s motion for summary judgment of non-infringement
on U.S. Patent No. 5,767,097; 6,063,772; and 6,150,337 concerning
Rebetol® (Ribavirin.) Rebetol® (Ribavirin) is used
for the treatment of hepatitis C. According to IMS data, sales
for Rebetol® for the 12-month period ended March 2003
reached $721 million. Geneva has settled related patent litigation
with Schering-Plough Corporation (Schering-Plough) and has
entered into a non- exclusive license agreement with Schering-Plough
that will enable Geneva to launch its Ribavirin product as
soon as it receives final approval from the Food and Drug
Administration (FDA) of its Abbreviated New Drug Application
(ANDA).
FDA approval of Geneva’s ANDA is pending. Additionally,
the FDA has yet to determine which company or companies will
receive 180 days of marketing exclusivity for the product.
Said John Sedor, Geneva President and Chief Executive Officer,
“We believe Geneva will have an exclusive or shared
exclusive position with respect to the launch of generic Ribavirin.
This could make Geneva the first generic company to launch
a generic version of Ribavirin. This product is being manufactured
in our Broomfield, Colo., facility using isolation suite technology.
We are fully prepared to launch this product and provide a
lower-cost drug alternative for patients. We are working closely
with the FDA in order to make Ribavirin available in the marketplace
as quickly as possible.”
Rebetol® is a registered trademark of Schering-Plough.
This release contains certain “forward-looking statements”
relating to Geneva Pharmaceuticals, an affiliate of Novartis
AG and its business or products, which can be identified by
the use of forward-looking terminology such as “will
be,” “continue to,” or similar expressions,
or by express or implied discussions regarding strategies,
plans and expectations. Such statements reflect the current
plans or views of Geneva with respect to future events and
are subject to certain risks, uncertainties and assumptions.
Management’s expectations and sales of Ribavirin could
be affected by, among other things, ability to obtain or maintain
patent or other proprietary intellectual property, competition
in general, and other risks referred to in Novartis AG’s
Form 20-F on file with the U.S. Securities and Exchange Commission.
Should one or more of these risks or uncertainties materialize,
or should underlying assumptions prove incorrect, actual results
may vary materially from those described herein as anticipated,
believed, estimated or expected.
Geneva Pharmaceuticals, Inc. is one of
the largest prescription generic pharmaceutical companies
in the U.S. Geneva produces more than 200 products each year,
with an annual manufacturing capability exceeding 10 billion
tablets and capsules. Geneva products range across many therapeutic
drug categories including anti-infectives, anti-arthritics,
cardiovasculars, gastrointestinal agents and psychotherapeutics.
Geneva is an affiliate of the Novartis AG (NYSE: NVS) group
of companies (the Group), a world leader in healthcare with
core businesses in pharmaceuticals, consumer health, generics,
eye-care and animal health. Novartis AG (NYSE: NVS) is a world
leader in pharmaceuticals and consumer health. In 2002, the
Group’s businesses achieved sales of CHF 32.4 billion
(USD 20.9 billion) and a net income of CHF 7.3 billion (USD
4.7 billion). The Group invested approximately CHF 4.3 billion
(USD 2.8 billion) in R&D. Headquartered in Basel, Switzerland,
Novartis Group companies employ about 72,900 people and operate
in more than 140 countries around the world. For more information
on Novartis, http://www.novartis.com. For more information
about Geneva Pharmaceuticals, please see our website at genevarx.com
Back to top
August 22nd, 2003
Prevalence of
Hepatitis C Virus Infection in Urban Children in the USA
by gastrohep.com
A study in The Journal of Pediatrics (Journal
of Pediatrics 2003; 143(1): 54-60) reports that only
1 out of 1034 children screened for hepatitis C virus in an
urban hospital in Baltimore, USA, was positive for hepatitis
C virus antibodies.
Dr Samer El-Kamary and colleagues investigated the prevalence
of hepatitis C virus infection in children attending an urban
hospital pediatric primary care clinic in Baltimore, USA.
1034 children were tested for HCV antibodies after excluding
children known to be HIV-positive.
Dr El-Kamary’s team also assessed maternal hepatitis
C virus risk factors through structured interviews with a
sample of mothers and a review of available medical records.
Intravenous drug use was significantly underreported.
Only 1 child (0.1%) tested positive for hepatitis C virus
antibodies.
History of blood transfusion was reported by 7% of mothers
and intravenous drug use by 1.8%.
However, analysis of medical records revealed that intravenous
drug use was significantly underreported.
Dr El-Kamary concludes. “Universal screening of children
for HCV in high-risk urban communities is not warranted.”
“Self-report may not be reliable for identifying mothers
with a history of intravenous drug use.”
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Histoacryl Injection or Beta-Blockers
for the Eradication of Esophogastric Varices
by gastrohep.com
A study in the September issue of Endoscopy (Endoscopy
2003; 729-735) finds that repeated injections of histoacryl
are no more effective than beta-blocker administration in
the eradication of esophagogastric varices, and are associated
with more complications compared with beta-blocker administration.
Histoacryl is highly effective in controlling active bleeding
of esophageal and gastric varices. However, it is not known
whether repeated histaoacryl injections are effective for
long-term eradication of esophagogastric varices.
A team of Belgian doctors compared the efficacy and safety
of endoscopic histoacryl injection with beta-blocker (propranolol)
administration in the secondary prevention of esophagogastric
variceal bleeding.
41 patients with primary bleeding from esophageal or gastric
varices were included in the study.
Primary hemostasis was achieved with histoacryl obliteration
of the varices.
Subsequently, the research team randomised patients to undergo
complete histoacryl obliteration of the remaining varices
with histoacryl or to receive long-term propranolol administration
for the prevention of rebleeding.
There was no significant difference in the incidence of early
rebleeding between the 2 treatment groups. 5 of the 21 patients
who underwent histoacryl injection and 3 of the 20 patients
taking propanolol re-bled within the first 6 weeks.
There was also no significant difference in long-term rebleeding
or mortality between the 2 treatment groups.
Complications, however, were significantly more likely in
patients who underwent histoacryl variceal eradication.
Repeated injections of histoacryl are associated with more
complications compared with beta-blocker administration, with
similar results in terms of rebleeding rate and survival in
the long term.
10 out of 21 patients receiving histoacryl injections suffered
adverse effects, compared with only 2 of the 20 patients receiving
beta-blockers.
Back to top
College Students Ignoring Risks
of Unprotected Sex
by Gary Gately, HealthDay Reporter
An alarming number of American college students engage in
unprotected sex, but most fail to realize the risk of contracting
sexually transmitted diseases, says a new national survey.
Among college students who live away from home, 56 percent
had been sexually active while attending college, and 73 percent
of that group reported having unprotected sex while in college,
says the survey by the Society for Adolescent Medicine.
Underscoring widespread ignorance about sexually transmitted
diseases, the online survey of 516 students found that 68
percent of those who had unprotected sex did not believe they
were at risk of contracting an STD.
And almost half of the sexually active students had never
been tested for an STD, even though one in five college students
knew someone who has contracted a sexually transmitted disease
while in college, according to the survey, which was conducted
last spring by Harris Interactive.
“I’m actually troubled by the findings, particularly
the one about unprotected sex,” says Helen E. Johnson,
co-author of the book Don’t Tell Me What to Do,
Just Send Money: The Essential Parenting Guide to the College
Years.
“I think part of it is people at this age really do
feel immortal; they don’t understand that their behavior
has real consequences,” says Johnson, who contributed
to a free booklet the Society for Adolescent Medicine prepared
for parents on ways to help protect children while they’re
away at school.
Johnson says parents often share much of the blame for their
college-age kids’ risky behavior.
“I think too many parents today want to be their kids’
friends and—sort of by default, not intentionally—they
abrogate that important parental responsibility, which is
making it really clear to your kids what your values are,”
Johnson says.
“Even though they will act like they’re tuning
you out, they hear you, and what I found working with college
students is that they really care what their parents think
about these things, and they generally don’t know,”
she adds.
Charlotte A. Gaydos, an associate professor of medicine at
Johns Hopkins University School of Medicine, says the survey’s
findings came as no surprise.
“Kids are having high-risk sexual behaviors, and they
are not getting screened,” Gaydos says. “One of
the reasons is most of the sexually transmitted diseases are
asymptomatic.” She encourages college students to not
be shy about asking to be screened.
But Gaydos says physicians also could do more to prevent STDs
among young patients.
“Many pediatricians are hesitant to ask whether [their
patients] are sexually active,” she says.
She also believes better high school education about STDs
would help.
The survey also found little awareness among students about
hepatitis B, which can be spread not only through sex but
also through body piercing, tattooing, contact sports and
sharing a razor or toothbrush.
Forty percent of college students either have a tattoo or
body piercing or are likely to get one or the other before
graduating, the survey found, and a third of students admitted
to sharing either a razor or toothbrush with a roommate, partner
or friend. But while almost all students surveyed had heard
of hepatitis B, more than half were not protected by a vaccine
or didn’t know if they were, the survey says.
Hepatitis B—a potentially life-threatening viral liver
disease—is one of the few STDs that can be prevented
by a vaccine, the Society for Adolescent Medicine says.
In its booklet, the society also recommends that parents:
• Review your child’s health history and make
sure all medical information is updated.
• Make sure your child has appropriate medical insurance
and carries a health insurance card. Up to 30 percent of college
students have no health insurance, the society says.
• Check with your doctor about your child’s immunizations
for hepatitis A, hepatitis B, influenza, meningococcal meningitis,
polio (news - web sites), tetanus-diptheria, chickenpox and
measles, mumps and rubella.
• Get a tuberculosis skin test for your child if it’s
required by the college or recommended by a health care provider.
• Have your primary health care provider send the campus
information about care, medications and restrictions on activity
if your child has chronic medical problems. If a disability
requires special accommodations, let the campus disabilities
office know.
• Check into health resources on and near campus so
your child will know about after-hours care, emergency services,
pharmacy services and the location of the nearest hospital.
Back to top
Schering-Plough Slashes Costs. Jobs,
Dividend and Perks Among Cutback Targets
by Ed Silverman, Star-Ledger
Fred Hassan has a dramatic prescription for an ailing Schering-
Plough: Eliminate jobs and bonuses, cut the dividend, close
the executive dining room and sell the company jet.
The eye-popping moves come at a time of turmoil for the Kenilworth-based
drug maker, which is reeling from government probes over its
business practices and a stunning drop in sales of Claritin,
a medicine that was once a franchise product.
The cutbacks, which were announced yesterday after the stock
market closed, are designed to save at least $200 million
and come just one week after the
company disclosed that cash from operations may not be sufficient
to cover expenses this year.
“My review of the situation we inherited
confirmed the need for aggressive measures, including aggressive
cost containment and cost cutting in order to stabilize the
company and to create a realistic base on which to build a
turnaround,” Hassan said in a statement.
The belt-tightening pronouncement, which
includes reducing head count by about 1,000 positions, capped
a “100-day, 360-degree review” of operations by
the new CEO. Hassan, who previously headed Pharmacia, was
billed as a gifted turnaround artist when he was hired by
Schering-Plough in April.
For now, the job cuts will take place through an early retirement
program, but still more jobs will be lost, and a company spokeswoman
said layoffs are possible. Globally, the drug maker employees
about 30,000 people, including 6,900 in New Jersey.
To set the tone, Hassan is foregoing his own bonus this year,
which could have been as much as $2 million, and is eliminating
various perks, such as flying first class and exclusive health
plans for executives.
“We will all be making sacrifices as a result of these
actions,” Hassan’s statement said.
Still, he was criticized last night by Wall Street analysts
for not participating in a conference call with company spokespeople.
“He’s leaving us dangling at 7 o’clock at
night at the end of August,” complained Barbara Ryan,
an analyst at Deutsche Bank Securities, in remarks during
the conference call. “It damages his credibility.”
The most unusual cost-cutting move involves slashing the dividend,
to 5.5 cents per share from 17 cents. It’s a step rarely
taken in the profit-rich pharmaceutical industry, and a further
sign of the company’s breathtaking reversal of fortunes.
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