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AASLD: Chronic Hepatitis C More Severe, Less
Treated in Elderly
By Jane Salodof MacNeil
BOSTON, MA -- October 31, 2003 -- Chronic
hepatitis C is likely to be more severe in elderly patients, who are also
less likely to be diagnosed or treated.
Dominique Thabut, MD, and her colleagues at
Groupe Hospitalier Pitie-Salpetriere, Paris, France, reported that older
people with chronic hepatitis C were far more likely to be diagnosed as a
result of a major complication, such as bleeding or liver cancer. Their
findings were presented here on October 26th
at the 54th
Annual Meeting of the American Association for the Study of Liver Diseases.
The research team compared 2,241 patients ages
65 and over to more than 10,000 younger patients who had been treated for
hepatitis C at their hospital.Complications prompted the diagnosis of only
2.8% of patients under 65, but 4.3% of patients ages 65 to 80, and 7.2% of
those over 80.
In many patients, the virus had not been
detected for years, despite signs of infection, according to Dr. Thabut, who
heads an intensive-care unit. "Too often we see people [who have had]
elevated alanine aminotransferase (ALT) [for] 10 or 15 years, who were not
treated when they were 60 years old and now come in with complications," she
said.
The older patients typically presented with
lower ALT levels when diagnosed. Normal ALT levels were found in about 40%
of elderly patients but only 31% of younger patients.
Nonetheless, higher stages of fibrosis were
recorded in the elderly. Only 14% of patients younger than 65, but 36% of
patients between 65 and 80, and 70% of those over 80 were diagnosed with
cirrhosis.
Far fewer elderly patients received antiviral
therapy: 19% of patients 65 and over compared to 31% of those under 65.
PEG-interferon plus ribavirin was the most common and most effective
treatment in the elderly; it produced a sustained virological response in
45% of elderly patients, but only 20 people received the therapy.
Dr. Thabut recommended using non-invasive
biomarkers as an alternative to liver biopsy in elderly patients. She also
urged physicians to attempt treatment, starting at low doses in patients who
do not have major contraindications. "I think we should try to treat them,
and stop if it is not possible," she said. "But try at least."
[Study
Title: Hepatitis C in 2,410 Patients 65 Years or Older. A Severe and
Neglected Curable Disease. Abstract 549]
Non-Invasive Technique Measures Liver Elasticity in
Chronic Viral Hepatitis
By Jane Salodof MacNeil
BOSTON, MA -- October 31, 2003 -- A new
non-invasive technique from France shows promise as an alternative to liver
biopsy for assessing fibrosis in patients with chronic viral hepatitis.
Transient elastography clocks the speed of
shock waves traveling through the liver, as measured by ultrasound, to
quantify elasticity. French researchers tested it in 220 patients who had
been hospitalised for liver biopsies.
Only 3 patients could not be assessed with the
device, called the FibroScan; all were too overweight, according to Michel
Beaugrand, MD, Hôpital Jean Verdier, Bondy, who presented the study here on
October 26th
at the 54th
Annual Meeting of the American Association for the Study of Liver Diseases.
"This is the limitation up to now," Dr.
Beaugrand said, predicting the obesity problem could be overcome with
further development by the manufacturer, a Paris-based start-up company
called EchoSens.
In comparison, the liver biopsies were not
interpretable for 45 patients. Dr. Beaugrand said that, in many cases, the
samples were too small to measure firmness of liver tissue.
Comparison of the remaining 172 patients showed
a strong correlation between the measurements of liver elasticity as
expressed in Kpa and the fibrosis grades determined by the biopsies.
Hepatitis C had been diagnosed in 159 of the comparable patients, and
hepatitis B in the remaining 13. Distribution of the patients by fibrosis
grade was: 6 F0, 47 F1, 54 F2, 21 F4, and 44 F4.
Dr. Beaugrand called the results "extremely
good." He predicted the technology could reduce the need for biopsies to
assess fibrosis in low-risk patients and patients being followed for chronic
hepatitis, either treated or untreated.
It also might be used, Dr. Beaugrand suggested,
to detect patients with cirrhosis or advanced fibrosis in the general
population. As the procedure is fast and easy to perform, it could be part
of a check-up, he said.
EchoSens exhibited the device at the Liver
Meeting for clinical investigation purposes only. It is not approved by the
United States Food and Drug Administration.
[Study
Title: Liver Elasticity Measurement by Ultrasonic Transient Elastography: A
New Non-Invasive Method for Assessment of Liver Fibrosis in Chronic Viral
Hepatitis. Abstract
Characteristics of Upper Abdominal
Pain in Those with Chronic Liver Disease
Digestive Diseases and Sciences 48 (10) p.1914-1918 October 2003
Characteristics of Upper Abdominal Pain in Those with Chronic Liver Disease
Riley III Thomas R.1 and Koch Kenneth2
1.The Hershey Medical Center, Pennsylvania College of Medicine, Department
of Medicine, Hershey, Pennsylvania, USA; Triley@psu.edu
2.The Hershey Medical Center, Pennsylvania College of Medicine, Department
of Medicine, Hershey, Pennsylvania, USA
Chronic hepatitis has many causes. Symptoms include upper abdominal pain. To
allow for a better understanding of this pain we compare HCV patients with
other liver diseases and normal controls on their reporting of pain over one
month and describe associations. A cross-sectional, case control study was
performed. Three groups are studied: (1) normal individuals (NC) (N = 64),
(2) patients with chronic liver diseases other than HCV (LD) (N = 53), and
(3) HCV infection (N = 64). A dyspepsia questionnaire was utilized, which
inquired about a one-month symptom presence of upper abdominal pain and
associated symptoms. There was a one-month period prevalence of upper
abdominal pain of 45.3% in the HCV group vs 32% in the LD and 20.3% in the
NC groups (P = 0.01). The LD (22.6%) and HCV (26.6%) groups had markedly
more pain that was worsened by eating compared with NC (1.6%) (P = .003). On
univariate analysis, when comparing those with upper abdominal pain to those
without, there was a lower age (41.3 vs 44.5), a higher BMI (30.3 vs 26),
and more symptoms of fatigue, bloating, and pain worsened by eating and
early satiety. On multivariate analysis, age < 50 (OR 5.1; CI 1.5-17), BMI >
30 (OR 4.1; CI 1.5-10.9), nausea (OR 4.1; CI 1.6-10.4), and pain with eating
(OR 30: CI 6.7-133) predicted upper abdominal pain. In conclusion, upper
abdominal pain is more commonly reported over one month in those with
chronic liver diseases. That the abdominal pain worsened after meals in
liver patients but not in the normal subjects was a surprise. Possible
explanations for this finding are offered.
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Blood ammonia determination in cirrhosis:
Still confusing after all these years?
HEPATOLOGY
November 2003 . Volume 38 . Number 5
Hepatology Elsewhere
Blood ammonia determination in cirrhosis: Still confusing after all these
years?
Cihan Yurdaydin, M.D. [MEDLINE LOOKUP]
Gastroenterology Section, University of Ankara Medical School, Cebeci Tip
Fakultesi Hastanesi, Ankara, Turkey
Abstract
PURPOSE: Because the correlation between ammonia levels and the severity of
hepatic encephalopathy remains controversial, we prospectively evaluated the
correlation in 121 consecutive patients with cirrhosis. METHODS: The
diagnosis of hepatic encephalopathy was based on clinical criteria, and the
severity of hepatic encephalopathy was based on the West Haven Criteria for
grading of mental status. Arterial and venous blood samples were obtained
from each patient. Four types of ammonia measurements were analyzed:
arterial and venous total ammonia, and arterial and venous partial pressure
of ammonia. Spearman rank correlations (rs) were calculated. RESULTS: Of the
121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27
(22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%)
had grade 4 (the most severe signs and symptoms). Each of the four measures
of ammonia increased with the severity of hepatic encephalopathy: arterial
total ammonia (rs = 0.61, P .001), venous total ammonia (rs = 0.56, P
.001), arterial partial pressure of ammonia (rs = 0.55, P .001), and venous
partial pressure of ammonia (rs = 0.52, P .001). CONCLUSION: Ammonia levels
correlate with the severity of hepatic encephalopathy. Venous sampling is
adequate for ammonia measurement. There appears to be no additional
advantage of measuring the partial pressure of ammonia compared with total
ammonia levels.
Background/Aims: To compare venous, arterial and partial pressure of ammonia
(pNH3) in 27 consecutive cirrhotics with hepatic encephalopathy, 15
cirrhotics without hepatic encephalopathy and nine controls; to reevaluate
all parameters after the improvement of encephalopathy.
Methods: Patients were studied by clinical examination and psychometric
testing. pNH3 was calculated from arterial ammonia and pH.
Results: In patients with encephalopathy, each form of ammonia was higher
than in both controls and patients without encephalopathy. The correlation
with the severity of hepatic encephalopathy was similar for venous (r=0.72),
arterial ammonia (r=0.76) and pNH3 (r=0.75). The sensitivity and specificity
of each variable in correctly classifying the patients as having or not
having hepatic encephalopathy was also similar. Each form of ammonia
decreased after the resolution or amelioration of symptoms. However, even in
the 17 patients with complete resolution of hepatic encephalopathy, all
three ammonia determinations resulted unchanged or increased in some
patients.
Conclusions: Despite the significant correlation between pNH3 and hepatic
encephalopathy, our study suggests that neither pNH3 nor arterial ammonia
are, from a clinical point of view, more useful than venous ammonia: all
three determinations being limited both for the diagnosis of hepatic
encephalopathy and for the clinical management of the patients.
Publishing and Reprint Information
(1) Ong JP, Aggarwal A, Krieger D, Easley KA, Karafa MT, Van Lente F,
Arroliga AC, Mullen KD. Correlation between ammonia levels and the severity
of hepatic encephalopathy. Am J Med 2003;114:188-193. (Reprinted with
permission from Excerpta Medica, Inc.)
(2) Nicolao F, Efrati C, Masini A, Merli M, Attili AF, Riggio O. Role of
determination of partial pressure of ammonia in cirrhotic patients with and
without hepatic encephalopathy. J Hepatol 2003;38:441-446. (Reprinted with
permission from the European Association for Study of the Liver.)
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November 12, 2003 03:05 AM US Eastern
Timezone
Maxim Announces Publication of Research Results
Supporting Use of Histamine in Treatment of Hepatitis C
SAN DIEGO--(BUSINESS
WIRE)--Nov. 12, 2003--
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Histamine Protects Immune Cells from
Inactivation by Hepatitis C Virus |
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Maxim Pharmaceuticals (Nasdaq NM: MAXM, SSE: MAXM) today announced
the publication of results from preclinical research suggesting that
histamine, the active agent in its lead drug candidate Ceplene(TM),
protects critical human immune cells from inactivation induced by the
hepatitis C virus. The results were reported at the 6th World Congress
on Inflammation and demonstrate that histamine protects three types of
immune cells critical to the defense against the hepatitis C virus:
T-cells, natural killer (NK) cells, and natural killer/T cells. These
new research results provide additional support for the therapeutic use
of histamine in eradicating virus-infected cells in patients with
chronic hepatitis C.
Summary of New Research
The studies, conducted by Dr. Fredrik Thoren and his associates at
the Faculty of Medicine, University of Goteborg, Sweden, are described
in the publication "Histamine Inhibits Neutrophil NADPH Oxidase Activity
Triggered by the Lipoxin A4 Receptor-Specific Peptide Agonist
Trp-Lys-Tyr-Met-Val-Met," in Scandinavian Journal of Immunology 58(3),
321-326. In chronic hepatitis C, the capacity of the patient's immune
system to destroy virus-infected cells is compromised. This immune
suppression was highlighted by the published results that demonstrated
that human monocytes treated with non-structural protein 3 (NS3), a
protein that is encoded by the hepatitis C virus, induced cell death by
apoptosis in T-cells, natural killer (NK) cells, and natural killer/T
cells. Histamine, however, prevented the NS3-induced apoptosis in all
three types of defense cells, suggesting that histamine has the
potential to improve immunotherapy in the treatment of hepatitis C.
"The results of this new research are encouraging and further support
the proposed use of histamine to prevent immune suppression and improve
immunotherapy for patients with chronic hepatitis C," said Kurt R.
Gehlsen, Ph.D., Maxim's Senior Vice President, Research and Chief
Scientific Officer.
Maxim is currently conducting the MP-8899-0406 Phase 2 trial (M0406)
of Ceplene (histamine dihydrochloride) for the treatment of hepatitis C
nonresponder patients. The randomized, controlled Phase 2 trial is
designed to compare the treatment of nonresponder hepatitis C patients
with a triple-drug combination of Ceplene, Peg-Intron(R) (peginterferon
alfa-2b) and Rebetol(R) (ribavirin, USP) versus treatment with the Peg-Intron
and Rebetol combination. The M0406 trial is one of several efforts Maxim
has underway in parallel to advance the potential use of histamine
therapy in chronic liver disease, including the development of an oral
form of histamine. Maxim expects that an alternative formulation, such
as the oral formulation of histamine currently under development, will
most likely be integrated into further testing of histamine in chronic
liver disease, including hepatitis C.
Maxim Overview
Maxim Pharmaceuticals is a global biopharmaceutical company with a
diverse pipeline of therapeutic candidates for life-threatening cancers
and liver diseases. Maxim's research and development programs are
designed to offer hope to patients by developing safe and effective
therapeutic candidates that have the potential to extend survival while
maintaining quality of life.
Maxim's lead drug candidate Ceplene, based on the naturally occurring
molecule histamine, is designed to prevent or inhibit oxidative stress,
thereby reversing immune suppression and protecting critical immune
cells. Ceplene has been tested in 17 completed or ongoing clinical
trials in 20 countries, including four Phase 3 clinical trials. On
November 7, 2003, Maxim filed an application for market authorization in
Europe for approval to market Ceplene for the treatment of advanced
malignant melanoma. Ceplene is currently being tested in Phase 3 cancer
clinical trials for advanced malignant melanoma with liver metastasis
and acute myeloid leukemia. Phase 2 trials of Ceplene are also underway
for the treatment of hepatitis C and advanced renal cell carcinoma. More
than 2,000 patients have participated in the Company's completed and
ongoing clinical trials.
In addition to Ceplene, Maxim is developing small-molecule inhibitors
and activators of programmed cell death, also known as apoptosis, which
may serve as drug candidates for cancer, cardiovascular disease and
other degenerative diseases. The Company's third technology platform,
the MX8899 topical gel, is being tested in an attempt to help patients
who suffer from oral mucositis and radiation dermatitis, both of which
are debilitating side effects of certain cancer therapies. Ceplene, the
apoptosis inducers, and MX8899 are investigational drugs and have not
been approved by the U.S. Food and Drug Administration (FDA) or any
international regulatory agency.
This news release contains certain forward-looking statements that
involve risks and uncertainties. Such forward-looking statements include
statements regarding the efficacy, safety and intended utilization of
Ceplene, the oral histamine formulation, the apoptosis inducers, and
MX8899, and the conduct, results and timelines associated with the
Company's clinical trials. Such statements are only predictions and the
Company's actual results may differ materially from those anticipated in
these forward-looking statements. Factors that may cause such
differences include the risk that products that appeared promising in
early research and clinical trials do not demonstrate safety or efficacy
in larger-scale clinical trials, and the risk that the Company will not
obtain approval to market its products. These factors and others are
more fully discussed in the Company's periodic reports and other filings
with the Securities and Exchange Commission.
Note: The Maxim logo is a trademark of the Company.
Editor's Note: This release is also available on the Internet at
http://www.maxim.com. |
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Contacts |
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Maxim
Pharmaceuticals, San Diego
Larry G. Stambaugh, Chairman, President and CEO
or
Anthony E. Altig, Chief Financial Officer
858-453-4040
or
Burns McClellan
Aline Schimmel (Investors), 212-213-0006
or
CCG Investor Relations
Sean Collins (Media) or Valerie Bent (Media)
818-789-0100 |
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54th Annual
Meeting of the American Association
for
the Study of Liver Diseases
October
24 - 28, 2003, Boston, MA
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Study Estimates in Year 2030, Deaths from HIV in
the US Will Decline to 4,200 - 6,700, While HCV-related Deaths Will
Peak at 14,000 - 19,000
In the
US, hepatitis C virus (HCV) is perhaps four times more common than
human immunodeficiency virus (HIV). Prior to effective therapy for
HIV, AIDS-related mortality exceeded that from liver disease, but
the advent of highly active anti-retroviral therapy (HAART) has
greatly improved HIV survival and reduced AIDS-related mortality.
Many
HIV-infected individuals have been diagnosed and treated but HCV
remains mostly undiagnosed and untreated. Projecting the future
health burden of these two epidemics may help health policymakers
plan their responses.
The purpose of
this study was to compare the projected future disease burden
(incidence and mortality) related to HCV and to HIV in the US.
Researchers
in Paris, France and Boston, MA , USA applied the back-calculation
method to develop mathematical models of the HIV and the HCV
epidemic in the US and have incorporated antiviral treatment into
these estimates (proportion treated and their likely response; for
HCV these estimates were only up until 1999 and did not consider the
combination of peginterferon and ribavirin).
These models
were based on US epidemiologic data regarding prevalence, incidence
of infection, age and gender of incident cases, AIDS, hepatocellular
mortality and general population mortality from the CDC, WHO and
literature data.
The
investigators first applied the back-calculation method to develop
separate HIV and HCV models. Logistic and time-dependent lognormal
model parameters were adjusted until the models resulted in the best
fit or match to the reported past incidence of these two infections
up to 1998.
They then
projected future HIV and HCV-related mortality until 2070.
In the HIV
model, the time from infection to AIDS (AIDS incubation period) is
assumed to be 8 years in the absence of anti-retroviral treatment or
during the monotherapy period (before 1995), 10 years during
dual-therapy period (1995-96) and 20 years during HAART or
triple-therapy period since 1996. These estimates were based on HIV-seropositive
subjects in French hospitals.
Study Results
Based on the
HCV back-calculation model, the HCV epidemic peaked with a maximum
annual HCV incidence in 1984 at 149,000-224,000 new infections and
then fell to about 33,000-46,000 in 1998.
Based on the
HIV back-calculation model, HIV incidence reached its maximum in
1989 at 132,000-162,000 new infections and then declined to
38,000-49,000 in 1995, before rising again.
Mortality
related to HCV (death from liver failure or hepatocellular
carcinoma) rose from about 3,800-4,200 in 1998 to peak at about
14,000-19,000 in 2030. For comparison, observed HIV-related
mortality was 16,000 in 1998 and projected to be 4,200-6,700
estimated for 2030.
Conclusions
With the
availability of effective HAART for HIV infection, mortality from
HIV appears to have declined substantially. The stability of that
decline will depend on epidemiologic trends and the rate of
development of HAART resistance.
Our model projections for hepatitis C
are consistent with three other US projections that all suggest that
mortality and the public health burden of HCV will rise over the
next 10-30 years.
11/14/03
Reference
S
Deuffic-Burban and others. COMPARING THE PUBLIC HEALTH BURDEN OF
CHRONIC HEPATITIS C AND HIV INFECTION IN UNITED STATES. Abstract 552
(poster).
54th Annual Meeting of the American Association for the
Study of Liver Diseases. October 24-28, 2003. Boston, MA.
www.hivandhepatitis.com
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Flu Vaccination in Transplant
Recipients?
Flu Vaccination in Transplant Recipients?
Question
What are the recommendations for flu vaccination in transplant recipients?
Response from Marc E. Uknis, MD
Assistant Professor of Surgery and Microbiology atUniversity of
Massachusetts Medical School, Worcester, MA and a transplantsurgeon at Umass
Memorial Health Care, Worcester, MA
Influenza vaccination should be given to patients with end-stage organ
failure prior to transplantation if not contraindicated (eg, allergy, etc.).
Also, household contacts should be vaccinated if possible. Most vaccines
have limited efficacy in the first several months after transplantation
because of the patient's decreased level of immunoresponsiveness. However,
it should be safe given that the influenza vaccine is an inactivated
subvirion formulation. On the other hand, commercial nasal preparations are
live-attenuated strains of influenza and probably are not safe for
transplant recipients or their household contacts. In summary, it would be
best to vaccinate pretransplantation with an inactivated subvirion
preparation and, if not possible, then vaccination 6 months (or thereafter)
posttransplantation.
Posted 11/21/2003
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Disclosure: Dr. Uknis has disclosed that he has a clinical grant and speaker
panel pending with Roche. Dr. Uknis has reported that he does not discuss
any investigational or unlabeled uses of commercial products.
Medscape Transplantation 4(2), 2003. © 2003 Medscape
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