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Alan Franciscus
Editor-in-Chief
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In This Issue:
• Surprise
Finding Could Lead to Hepatitis C Vaccine
•Immune Patients Inspire Hope of Hepatitis
C Vaccine
•Pegylated Interferon Can Cause Serious
Eye Problems in HIV/HCV Coinfected Patients, Says Study
•Vaccine Boost May Be Needed after Chemotherapy
in Children
•Fighting Fatigue and Depression in Hepatitis
C and HIV Co-Infection
•Organ Shortage a Dire Situation
•Donor Age, Hepatitis C Virus Infection
and 10-Year Liver Graft Histology
•Hep A Crisis Looms: Health Officials
August 23rd, 2004
Surprise
Finding Could Lead to Hepatitis C Vaccine
Source: News-Medical in Medical Research News
http://www.unsw.edu.au
New research from the University of New
South Wales shows some people may repeatedly be able to clear
hepatitis C virus from their bodies, without any biological
traces of the potentially serious infection.
The surprise finding could lead to the
development of a vaccine against the virus, which currently
affects nearly 4 million Americans and 170 million people
worldwide. HCV is responsible for 8,000 to 10,000 deaths per
year in the United States and is the number one cause of liver
transplants. HCV can also lead to cirrhosis, end-stage liver
disease, and liver cancer. Over 30,000 new cases are diagnosed
each year.
The study found some individuals with high-risk
behaviour, involving blood-to-blood contact, appear to develop
"protective immunity" against the virus, thereby
becoming resistant to persistent infection.
The researchers identified 160 prisoners
who were free of the infection and tracked them on a monthly
basis whilst in gaol. This entailed blood collection and recording
episodes likely to put the prisoners at risk for transmission
of hepatitis C, such as injecting drug use or tattooing.
Over the course of the study, four prisoners
became infected with hepatitis C, yet they all went on to
clear the virus without suffering any symptoms or developing
antibodies against the virus. Instead it appeared that another
arm of the immune system based on specialised white blood
cells, or T cells, might be active in fighting the virus.
"It is possible that they had been
infected in the past, perhaps on several occasions and that
may be why they were able to clear the virus efficiently and
without developing antibodies," said UNSW Professor Andrew
Lloyd, who is in the School of Medical Sciences.
This cellular immunity appears similar
to that found in some Kenyan prostitutes who appear to have
protective immunity from HIV. These prostitutes are resistant
to becoming HIV positive, despite repeatedly having unprotected
sex with clients who are infected.
The researchers have found a similar pattern
of cellular immunity to hepatitis C in another high-risk group
- injecting drug users. They ultimately hope to reproduce
a similar pattern of protective immunity with a synthetic
vaccine.
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Immune
Patients Inspire Hope of Hepatitis C Vaccine
Source: Asian News International
Researchers have revealed that a group
of people who appear to be resistant to hepatitis C despite
constant exposure to the virus, may help develop a vaccine
to curb its onset.
The research, published in the Journal
of Infectious Diseases, found that people at high risk
of contracting hepatitis C, which is a virus transmitted via
blood-to-blood contact, had developed protective immunity.
Male prisoners in NSW jails, who were not
infected with hepatitis C, but were at high risk of being
exposed via injecting drug, tattooing, piercing etc, were
the first one to be tested.
"We identified four individuals who,
became infected, then went on to clear the virus and remain
free of persistent infection on follow up, and yet never developed
hepatitis C antibodies," the Sydney Morning Herald quoted
Andrew Lloyd, an infectious diseases physician from the University
of NSW, as saying.
Fifty percent of those tested had developed
T cells i.e. white blood cells that indicate an immune response
to an infection. "It is possible that they had been infected
in the past, perhaps on several occasions, and that may be
why they were able to clear the virus efficiently and without
developing antibodies," said Professor Lloyd.
Around 30 to 40 percent of people who contract
hepatitis C eradicate the virus within six months of infection,
but remain susceptible to re-infection. But the prisoners
didn't get the infection for whole one year despite continuing
exposure.
According to the scientists this cellular
immunity is similar to the sex workers who were repeatedly
exposed to the AIDS virus through unprotected sex with HIV-positive
clients, but remain uninfected.
The researchers have expressed hope that their findings would
allow the reproduction of a similar pattern of protective
immunity with a synthetic vaccine.
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August 26th, 2004
Pegylated
Interferon Can Cause Serious Eye Problems in HIV/HCV Coinfected
Patients, Says Study
Michael Carter
Source: www.aidsmap.com
Treatment with pegylated interferon alpha-2b
(PegIntron) and ribavirin can cause serious eye problems in
individuals coinfected with HIV and hepatitis C virus according
to an article published in the September 3rd edition of AIDS.
The US investigators recommend that patients coinfected with
HIV and hepatitis C and treated with pegylated interferon
and ribavirin receive regular ophthalmic monitoring.
Optic neuropathy, including retinal haemorrhage,
cotton wool spots and decreased colour vision have been reported
in individuals receiving interferon therapy who are monoinfected
with hepatitis B or hepatitis C. However, these are the first
cases to be reported of serious eye problems developing in
HIV and hepatitis C coinfected patients receiving therapy
with pegylated interferon.
A total of 23 patients were included in
the investigators’ analysis. All had received at least
twelve weeks of pegylated interferon alpha-2b and ribavirin
in an open-label, prospective trial at a National Institutes
of Health facility.
Eye examinations included visual acuity,
visual field testing, and a colour vision examination. In
addition, indirect ophthalmoscopy were performed at baseline,
then at least every three months or when the need was suggested
by symptoms.
At baseline the patients had a median CD4
cell count of 553 cells/mm3, a median HIV viral load of below
50 copies/ml and a median hepatitis C viral load of over 1,000,000
copies/ml.
Eight individuals (35% of the study population)
developed ophthalmologic pathology during hepatitis C treatment,
including six patients who developed cotton wool spots, indicate
of retinal haemorrhage. These were detected at the week twelve
ophthalmoscopy, and "waxed and waned while [hepatitis
C] therapy was continued." In addition, two patients
developed cataracts. Hepatitis C treatment was continued in
these individuals and the cataracts remained stable both during
and after therapy.
Decreases in red-green colour vision were
detected in two patients. One patient discontinued hepatitis
C treatment and within ten weeks of its cessation this individual’s
colour vision had returned to normal. Colour vision returned
to normal in the other patient at week 23 of hepatitis C treatment
without any cessation of therapy.
“The rapid development of serious
ocular pathology in our coinfected patients demonstrates a
concerning phenomenon associated with pegylated interferon
and ribavirin therapy for hepatitis C virus” write the
investigators. They add “both cotton wool spots and
cataracts developed in several patients soon after beginning
therapy. These lesions occurred in patients with high CD4
cell counts and in patients with and without comorbidities
such as diabetes and hypertension.”
The investigators cannot say which factors
led to the development of these serious eye problems in their
patients, and note that there were no differences in the CD4
cell count, HIV viral load, or hepatitis C viral load between
the patients who did and did not develop ophthalmologic pathologies.
They note that a much larger cohort of patients would be needed
to determine if any of these factors were significant. They
also speculate that pegylated interferon could induce an immune
response leading to retinal ganglion cell toxicities in susceptible
individuals.
The investigators conclude, “routine
ophthalmologic monitoring in persons receiving pegylated interferon
and ribavirin may be warranted in order to optimize the benefit
from current anti-hepatitis C virus therapy.”
Reference
Farel C et al. Serious ophthalmic pathology compromising
vision in HCV/HIV coinfected patients treated with peginterferon
alpha-2b and ribavirin. AIDS 18: 1805-1809, 2004.
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Vaccine
Boost May Be Needed after Chemotherapy in Children
NEW YORK (Reuters Health) Aug 26 - Children
who have undergone chemotherapy are prone to loss of protective
serum antibody titers acquired from previous vaccinations,
Italian researchers report in the August 1st issue of Cancer.
This finding, Dr. Matteo Zignol and colleagues from the University
of Padua suggest, "may account for the failure of vaccination
programs for patients who have undergone chemotherapy."
The team assessed the persistence of humoral immunity to hepatitis
B, measles, mumps, rubella, tetanus, and polio in 192 children
following chemotherapy for malignancies including acute lymphoblastic
leukemia and Hodgkin's lymphoma.
Overall, 46% of children lacked protective serum antibody
titers to hepatitis B. Corresponding proportions for measles,
mumps, and rubella were 25%, 28%, and 24%. Furthermore, 14%
of children lacked protective titers to tetanus and 7% lacked
protective serum antibody titers to polio.
In children determined to have had immunity before chemotherapy,
rates of loss of protective immunity to hepatitis B, measles,
mumps, rubella, tetanus, and polio were 52%, 25%, 21%, 18%,
13% and 8%.
However, giving a total of 59 booster vaccinations to 51 children
who had lost at least one protective antibody titer led to
an overall response rate of 93%, the team reports.
Thus, they conclude that administering a booster dose 12 months
after chemotherapy ends is a "simple and cost-effective
way to restore humoral immunity against most vaccine-preventable
diseases."
Cancer 2004;101:635-641.
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FightingFatigue
and Depression in Hepatitis C and HIV Co-Infection
Sean Hosein
Source: CATIE News
www.aegis.org
In high-income countries, treatment for
hepatitis C infection (with or without HIV co-infection) consists
of a combination of the drugs ribavirin and a long-lasting
form of interferon called peg-interferon (Pegetron, Pegasys).
This combination's side effects can include fatigue and depression,
particularly in HIV positive people who are co-infected with
hepatitis C virus (HCV).
Fatigue can occur because ribavirin temporarily affects the
bone marrow, reducing its output of red blood cells (RBC).
Since RBCs carry oxygen to tissues and help remove carbon
dioxide, having fewer RBCs can cause feelings of tiredness
and lack of energy.
Interferon can affect the brain and thyroid gland, causing
changes in mood and increasing feelings of anxiety and depression,
which can also cause fatigue.
Because of the fear of becoming depressed while on HCV therapy,
some co-infected people with HIV/AIDS may be reluctant to
receive treatment for HCV infection. Dr. Kristina Jones and
colleagues at the New York-Presbyterian Hospital sought to
study depressive illness in their co-infected patients as
well as ways of managing depression and fatigue associated
with HCV therapy.
Study details
Researchers reported results on 68 men and 20 women, all of
whom were co-infected with HIV and HCV and who were in the
study for 1.5 years. The average CD4+ cell count for all participants
was 457 cells and because they used HAART, 65% of participants
had a viral load below the 50-copy mark. HCV viral load was
detectable in all participants, 56% of whom had high levels-more
than one million copies.
Importantly, researchers also recorded the details of any
history of mental health issues participants may have had
before entering the study. They found the following:
• 17% of participants had depression at some time in
the past
• 6% reported having attempted to commit suicide
• 1% reported thoughts of suicide
During the study, all subjects received standard doses of
interferon and ribavirin for the treatment of HCV infection
for one year. After treatment ended, monitoring continued
for a six more months.
Results - Severe depression
Despite 17% of participants having experienced at least one
prior episode of depression, during the study the following
events occurred:
• No one committed suicide, although one person had
thoughts of this act.
• No one left the study because of fears of committing
suicide.
• No participant developed certain behaviours-mania
and psychosis-associated with depressive illness.
Results - Depression
As much as 35% of PHAs became depressed during the study.
Key findings about depression included the following:
Depression took longer to develop than fatigue; in most cases,
depression occurred four months after participants began therapy
for HCV.
The research team estimated that in 28% of cases depression
occurred because of exposure to interferon, because none of
the participants had prior episodes of depression.
The team noted that despite the many cases of depressive illness
that occurred (and the history of prior depression) there
were no attempts at committing suicide. They attribute this
positive finding to the use of antidepressants and psychiatric
care integrated into regular medical care.
Dealing with depression
Based on their results, the researchers suggest the following
course of action for doctors encountering HCV-therapy-related
depression in their patients:
Assess levels of the thyroid hormones TSH and T4, as well
as hemoglobin and the hormone testosterone, and take appropriate
steps as needed (such as prescribing thyroid or testosterone
supplements).
If hormone and other measurements are within normal ranges,
the research team suggests that doctors consider prescribing
the antidepressants citalopram (Celexa) 20 mg/day, paroxetine
(Paxil) 20 mg/day, or bupropion (Wellbutrin, Zyban) between
150 and 300 mg/day.
Results - Fatigue
The researchers found that fatigue was a common complication
of HCV therapy, with as many as 64% of participants developing
this problem.
According to the researchers, fatigue "developed very
early"; in many PHAs it happened within the first week
of treatment. Yet fatigue was not so severe that participants
had to leave the study prematurely.
Fighting fatigue
Based on the results of their study, the researchers suggest
the following course of action for doctors encountering severe
HCV-therapy-related fatigue in their patients:
Assess levels of the thyroid hormones TSH and T4, as well
as hemoglobin and the hormone testosterone, and take appropriate
steps as needed (such as prescribing thyroid or testosterone
supplements).
If hormone and other measurements are within normal ranges,
the research team suggests that doctors consider the temporary
use of stimulants such as methylphenidate (Ritalin) 10 mg
twice daily.
Because Ritalin is "chemically related" to amphetamine,
some doctors may not wish to prescribe it. As an alternative,
the research team suggested another stimulant that is not
a member of the amphetamine group-modenafil (ProVigil).
These findings and suggestions may help doctors caring for
co-infected PHAs to reduce the distress that sometimes occurs
when patients are treated for HCV infection.
REFERENCE
Jones K, Talal A, Ferrando S, et al. High prevalence of
fatigue and depression in HIV/Hepatitis C co-infected patients
treated with pegylated interferon/ribavirin. XV International
AIDS Conference, July 11-16, Bangkok, 2004. Abstract MoPeB3345.
Back to top
Organ
Shortage a Dire Situation
Peter A. Brown
Detroit Free Press
We'd rather help those we can see and
feel rather than people with whom we lack a personal connection.
It's human nature.
HOW TO GIVE LIFE
If you want to become an organ donor, the most important step
is to talk to family members about it. They will be asked
to give their permission at the time of your death.
To sign up, you can sign one of the new
driver's licenses, or attach a consent sticker to the back
of an older license. Stickers and state donor registry cards
are available at any Secretary of State's office or Gift of
Life, Michigan's nonprofit organ transplantation agency. You
can also register online at www.michigan.gov/sos
or www.giftof
life michigan.org.
For more information, go online to www.organ
donor.gov or www.share
yourlife.org or contact Gift of Life at 1-800-482-4881.
Advertisers, politicians and journalists
have known this for years and produced stories that pull on
our heartstrings.
A Houston man who circumvented the system
to receive a liver transplant taught doctors that lesson this
month.
Many in the medical community were unhappy
that Todd Krampitz launched a media campaign, including buying
billboards, to find a donor.
They rightly worry that, if others bypass
the government-sanctioned, doctor-run allocation of scarce
organs, the system might be endangered.
Even though the medical community's organ-allocation
formula is both equitable and ethically necessary, it makes
many uncomfortable.
Moreover, as Americans we are imbued with
an entrepreneurial spirit and look for a way to circumvent
the existing system, and we applaud those who do. That's why
Krampitz was successful, and others could be.
Yet unless we find a way to increase the
supply of organs -- and that means more than public service
campaigns for donations -- others in Krampitz's situation
will do the same thing.
One answer would be to change the law to
allow families to donate their deceased kin's organs in exchange
for either a payment or funeral-expense reimbursement, a set
amount paid indirectly through a supervised fund. The allocation
of organs would remain based on the existing medical criteria,
and no one could jump to the head of the line by writing a
check.
Also worth considering is changing the
law so donation occurs upon death unless the family specifically
objects. This policy of presumed intent to donate exists in
some European nations and has helped increase the supply of
organs there.
Both changes would increase the number
of available livers, hearts, lungs and kidneys for donation,
but not eliminate the overall shortage.
That's because most deaths do not leave
organs that are suitable for transplant.
In the long-term, stem-cell research might
lead to the production of organs for transplant, and other
scientists are working on creating artificial organs and finding
a way to use animal organs for humans.
But in the short and intermediate term,
we will have many more people needing transplants to live
than we have organs for them.
That's why it is hard to fault either Krampitz,
32, who was taking the only available route to save his life,
or the medical community, which fears the case could open
a Pandora's box of problems.
I underwent a liver transplant in 2002
to replace my cancerous organ. I went through the established
procedures under which patients are evaluated and given a
ranking based on criteria that include one's chances for survival,
overall general health and ability to function post-transplant.
The size of Krampitz's tumor led doctors
to believe his survival chances, even with a new liver, were
limited. Although he was put on the transplant list, his score
made it highly unlikely he would receive one.
U.S. transplants are coordinated by the
United Network For Organ Sharing, which decides, based on
a patient's ranking, who gets an organ when it becomes available.
However, those making an organ donation,
generally the family of a deceased, may designate to whom
it should go.
Such directed donations are quite rare,
roughly 50 in the United States last year. Krampitz was able
to find such a family through his advertising campaign.
The doctors' complaint is easy to understand.
After much refinement, the medical community has created a
workable system that has made the United States by far the
world leader in transplantation.
Our procedure is more equitable than in
many other parts of the world, where money can decide who
lives and who dies.
The Krampitz case, if it is replicated
in sufficient numbers, could undermine the viability of the
U.S. organ-transplant system.
That would be a terrible thing for the
country, yet we as a society are understandably vulnerable
to personal appeals from sympathetic people.
It's one of those times when what's best
for the individual is not necessarily good for society overall.
PETER A. BROWN is an editorial page
columnist for the Orlando Sentinel. Readers may write to him
at the Orlando Sentinel, 633 North Orange Ave., Orlando, Fla.
32801, or at pbrown@orlandosentinel.com.
Back to top
August 27th, 2004
Donor
age, hepatitis C virus infection and 10-year liver graft histology
Source: www.gastrohep.com
Donor age is a strong factor influencing
the long-term histological outcome of liver grafts, find investigators
in the latest issue of the Journal of Hepatology.
Factors influencing the long-term histological outcome of
liver grafts are not known.
In this study, investigators from France
assessed 10-year liver biopsies to identify the main factors
influencing long-term graft histology.
They evaluated 270 of 423 patients who
still had their first functional graft 10 years after liver
transplantation.
All biopsy slides were reviewed by 2 pathologists.
The investigators found fibrosis in 54%
of patients and ductopenia in 29%.
They determined that ductopenia was independently
related to higher donor age. Ductopenia was independently
related to higher donor age.
Journal of Hepatology
The severity of fibrosis was influenced
by hepatitis C virus (HCV) infection, hepatitis B virus (HBV)
recurrence, and higher donor age.
The team found that 30% of biopsies showed
minimal-change lesions which were associated with the absence
of HCV or HBV infection, and lower donor age.
Dr Kinan Rifaia and colleagues concluded,
"Post-transplant infection by HCV or HBV are main factors
influencing the histological course of liver graft".
"Donor age was also a strong factor
in HCV infected patients as well as in HCV-negative patients".
"This variable should be taken into
account, particularly for candidate recipients with long life
expectancy".
J Hepatol 2004; 41(3): 446-53
Back to top
Hep
A Crisis Looms: Health Officials
Wang Hsiao-wen
TaipeiTimes
www.taipeitimes.com
Deputy Director General of the Department
of Health Chang Hung-jen, left, acting Director of the Center
for Disease Control Shih Wen-yi, second right, and National
Taiwan University Hospital physician Dr. Huang Li-min, far
right, smash an ice sculpture of the Hepatitis A virus yesterday.
The DOH is holding an awareness event to help in the prevention
of the virus.
An epidemic of the Hepatitis A virus is
likely to erupt in the nation and leave the country's young
devoid of antibodies against the infectious disease, health
officials and experts warned yesterday.
Statistics from the Center for Disease
control showed that 153 cases of Hepatitis A were reported
by the end of August this year, up an alarming 40.4 percent
compared with statistics from the same time last year.
Improved sanitation and more hygienic eating
habits in the nation over the past two decades helped quell
the liver infection. According to Chang Hong-jen, deputy director-general
of the department of Health, people aged 40 and over were
usually affected during their childhood, and now have received
treatment for the virus.
But now, the Hepatitis A is once again
threatening those aged 30 and under who never experiences
a Hepatitis A epidemic. As an increasing number of Taiwanese
people travel to China and Southeast Asian countries where
the prevalence of Hepatitis A is still high, the virus is
more likely to cross borders and make inroads to Taiwan. According
to Huang Li-min , Chief of the Division of Infectious Diseases
at National Taiwan University Hospital, people traveling to
those countries might unknowingly become virus carriers, since
the disease's incubation period ranges from 14 days to 40
days and early diagnosis is difficult.
"If the virus sneaks into our food
industry, a full-scale epidemic like that in Shanghai in 1988
might hit Taiwan as well," Huang said.
The Hepatitis A outbreak in Shanghai is
a grim reminder of the liver disease's lethal potential. It
claimed 47 lives among the 310,764 patients infected. The
average age of the patients was 27.
"Situations in Taiwan bear resemblances
to those in Shanghai," said Shih Wen-yi , the center's
deputy director-general, "The risk is high when a large
population has no antibodies and lack understanding of the
disease."
The center's latest survey revealed that
public awareness of Hepatitis A is limited. Only 39.2 percent
of the 1,076 interviewees knew that Hepatitis A is transmitted
through intake of contaminated food and water.
The center yesterday called on the public
to wash hands before meals and make sure food is well cooked.
Officials also urged lovers of the nation's night markets
to opt for food stalls with a fixed location and a steady
water supply.
Vaccines for Hepatitis A are available
in hospitals and private clinics. They costs about NT$ 1000,
but are not covered by national health insurance.
Huang suggested that the government
should subsidize the medical costs for foreign spouses and
children who make frequent visits to China and Southeast Asia.
Huang added that chefs and people employed in the food service
industry should also receive the vaccines regularly to fend
off an outbreak of the virus.
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