FDA Approvals: da Vinci, MicroMed 407C, COBAS AmpliScreen HBV


Yael Waknine

April 29, 2005 - The U.S. Food and Drug Administration (FDA) has approved an in
vitro polymerase chain reaction-based test for use in a minipool format to
directly detect hepatitis B virus in blood donations.
Nucleic Acid Assay (COBAS AmpliScreen HBV) for Use in Screening Blood Donors

On April 21, the FDA approved an in vitro polymerase chain reaction (PCR)-based
assay (COBAS AmpliScreen HBV, made by Roche Diagnostics) for use in a minipool
format as a screening test for the direct detection of hepatitis B virus (HBV)
DNA in donated whole blood and blood components for transfusion and source
plasma, as well as for testing individual plasma samples from other living
donors and organ donors.

Direct detection of infection is achieved using PCR technology that amplifies
minute amounts of viral nucleic acid to detectable levels. In doing so, the
"window of opportunity" for a donation to escape detection is reduced compared
with immunoassay technologies that detect antibodies and antigens produced later
in the infection cycle.

The approval was based in part on the results of a clinical study involving
581,790 individual donations screened at 5 blood centers in the U.S, showing
that use of the DNA assay identified two HBV "window cases" that may have gone
undetected by currently licensed immunoassays for HBV surface antigen (HBsAg).

Two centers elected to continue use of the assay under an investigational new
drug protocol following the conclusion of the study in 2004, leading to the
identification of three additional window cases.

In addition, nonclinical study data demonstrated that use of the DNA assay
reduced the window period by an average of 17 days in 40 seroconversion panels
compared with the HBsAg test.

The HBV DNA assay was previously approved for use in the European Union (EU).
Other COBAS AmpliScreen tests that have been approved for use in the U.S. and
the EU include those for the detection of HIV-1 and hepatitis C virus
infections.

Reviewed by Gary D. Vogin, MD

http://www.medscape.com/viewarticle/504035?src=mp

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[Non-text portions of this message have been removed]

CANADIAN JOURNAL OF GASTROENTEROLOGY
April 2005, Volume 19, Number 4 : 245-249

Cross-sectional study of hepatitis B awareness among Chinese and Southeast
Asian Canadians in the Vancouver-Richmond community

J Cheung, TK Lee, C-Z Teh, CYM Wang, WCP Kwan,
EM Yoshida

BACKGROUND: Hepatitis B (HBV) is endemic and a leading cause of morbidity
and mortality in Asia. British Columbia has the highest proportion of
Chinese and Southeast Asians among all Canadian provinces. The present study
was designed to evaluate the degree of concern for and knowledge of HBV in
this high-risk community.

METHODS: Unselected patrons of two large Asian commercial
centres in Richmond, British Columbia were surveyed. The variables studied
were population demographics, concern for HBV, level of HBV knowledge and
awareness of HBV-related cirrhosis or hepatocellular carcinoma (HCC).
Associations were assessed using c2 testing and multiple logistic regression
analysis.

RESULTS: A total of 1008 individuals participated in the survey. Fifteen
incomplete surveys were excluded. Only 7.7% felt that HBV was not a concern
for the community. Only 13% of respondents felt that HBV education was
adequate in the community. The main sources of community health education
were their doctor? office (56.3%) and media (49.1%). A high number stated
they were ?ware?of HBV (68%) but over 60% were unaware that HBV could cause
HCC or cirrhosis and only 61.3% scored a ?easonable?level of HBV knowledge.
Higher HBV knowledge was significantly associated with increasing age
(P<0.001), higher education (P<0.001) and the use of media for health
education (P<0.001). Awareness that HBV may cause HCC and cirrhosis was
significantly associated with age (P<0.001), education (P=0.006) and
birthplace (P=0.001).

INTERPRETATION: HBV education is necessary in this local Asian community.
Programs should target younger, less educated adults and elaborate on the
potential serious health consequences of HBV. Vehicles for public education
should include the physicians?offices and local media.

CDC HIV/STD/TB Prevention News Update
Friday, April 29, 2005

UNITED KINGDOM:
"Nurses Warn over Teen Group Sex"
BBC News (04.27.05)
      At a conference of the Royal College of Nursing (RCN) in Harrogate,
school nurses said the nature of their work has changed from checking for
lice and administering vaccines to concerns about sex, binge drinking, and
drug abuse. An RCN survey of more than 1,200 school nurses found that 90
percent provided students with sexual health advice and support; two-thirds
dealt with substance abuse problems; and 90 percent handled issues relating
to student obesity.
      At the conference, school nurses from London warned that some teens are
engaging in multiple-partner sexual activity known as "daisy-chaining."
"Colleagues are coming across reports of groups of young people having sex
in large groups," which is "obviously very worrying as far as sexually
transmitted infections and pregnancy" are concerned, said Judy McRae, a
sexual health nurse in London. "As we understand it, it involves groups of
older teenagers going round to each other's homes and having sex in a
similar way as swinging."
      Steve Jamieson, an RCN sexual health adviser, discussed the case of a
14-year-old boy diagnosed with HIV. The youth, who was not involved in
daisy-chaining, was shocked that he had contracted what he perceived to be
an older person's disease.
      Other sexual health nurses cited peer pressure as the cause of young
boys initiating sex at earlier ages. In addition, some children feel
pressure to provide sexual favors because they are part of a gang culture or
are sexually exploited as a result of coercion, violence, trafficking or a
lack of money, said Liz Allen, chairperson of the RCN School Nurse Forum.
      "Risky sexual practices like this are the fastest way to spread
sexually transmitted infections like HIV," said a Terrence Higgins Trust
spokesperson. "Sex and relationship education must improve so that young
people know how to protect themselves and their sexual partners."

THE STANFORD DAILY
Wednesday, April 27, 2005

LIVERight race raises awareness
By Francois Jean-Baptiste
Wednesday, April 27, 2005
last updated April 27, 2005 12:41 AM

Registration for LIVERight, the first annual 5-kilometer run and fundraiser
organized by Stanford's Asian Liver Center and the Answer to Cancer
Foundation, has been extended to Friday, April 29. The run, intended to
raise awareness about hepatitis B and liver cancer, will begin at 8:30 a.m.
Saturday at Golden Gate Park in San Francisco.

According to the LIVERight Web site, as many as one in 10 Asian Americans
are carriers of hepatitis B, and most don't even know they are infected.

Eric Sue, Class of 2004, the outreach coordinator for the Asian Liver
Center, said he hopes the run will shed light on an issue that "hasn't
received much attention in the public eye."

"We're trying to put hepatitis B and liver cancer on the map, much like HIV
/ AIDS and breast cancer," he added. "Stanford students have worked
tirelessly to put on this event, taking care of all the logistical details,
fundraising and advertising."

Liver cancer has received little federal research funding, Sue said.

"The Asian Liver Center's research goals can only be realized with the
generous support of our donors as wel as funds raised through events like
LIVERight," he added.

Stanford-based Asian Liver Center is composed of three branches - liver
cancer research, outreach and education and the clinic.

"The Asian Liver Center research team has identified as potential treatment
and prognostic targets, several highly expressed genes that have biological
functions relating to liver cancer development," Sue said.

Senior Sei-Gyung Kim, an intern at the Asian Liver Center, said money is
being raised from race participants, donations from supporters and corporate
sponsorships. The money will go toward the Asian Liver Center's outreach and
programming efforts.

"I have encountered people who are shocked to hear about the high rate of
hepatitis B in the Asian population," Kim said. "It's easy to think of
cancer as something that only affects the older population, but hepatitis B
and liver cancer have taken the lives of people as early as in their 20s and
30s."

Hepatitis B is a preventable disease that, like other sexually transmitted
diseases, is largely transmitted through unprotected sexual contact, blood
transfusions and from mothers to children. A majority of individuals
inflicted with liver cancer have already been living with hepatitis B,
according to the LIVERight Web site.

"400 million people in the world are chronically infected with hepatitis B,
compared to 47 million people who are living with HIV / AIDS," Sue said.

Seventy Stanford students have already registered for LIVERight, and the
Asian Liver Center has produced jade LIVERight bracelets, which will be sold
at the event for $10 each.

"It is easy to become pigeon-holed in our thinking, like getting absorbed in
our studies and not thinking outside the bubble," Kim said when asked why it
is important for students to attend the event.

"Every time I read the stories on our Web site I am inspired to do something
about the disease that has gone unnoticed for so long," she added. "In
raising awareness about this silent killer, it is critical to start on this
campus - Stanford is building leaders who will undoubtedly influence policy
and education in generations to come."

More information on LIVERight can be found at
http://liver.stanford.edu/liveright.

Wrong, Pamela, there is a cure
(Filed: 28/04/2005)

Lack of public awareness - and funding - is holding back the treatment of
hepatitis C. Barbara Lantin reports on a medical 'timebomb'

Three years ago, when actress Pamela Anderson went public about being
infected with hepatitis C, health education campaigners were delighted that
a celebrity had brought the virus out of the shadows.


Pamela Anderson thought hepatitis C was incurable
But delight turned to dismay, however, when Anderson asserted -
erroneously - that there was no treatment or cure for her condition.

In an interview last week, the former Baywatch star told a newspaper: "The
doctor said 'you have a glitch with your blood.' He told me I had hepatitis
C. I asked how I could get rid of it, and he said, 'Well, you can't'."

As those who work with hepatitis C patients know, that is no longer the
case.

"We have a major problem in this country with very few people being
treated," says Charles Gore, chief executive of the Hepatitis C Trust. "One
of the reasons is that people are not aware that a cure is available. If you
think you may have the disease, but believe there is no cure, you may feel
there is no point in getting a diagnosis."

Of the estimated 200,000 to 500,000 people who are infected with the
hepatitis C virus (HCV) in Britain, only 50,000 have been diagnosed. The
rest are unaware that they are carrying the virus, which can lie apparently
dormant but actually replicating - usually in the liver - for 30 years or
more. By the time symptoms appear, chronic and sometimes fatal liver damage
may have occurred. Last month, an all-party committee of MPs described the
problem as a "time bomb".

HCV is carried in the blood and those most at risk are people who had a
blood transfusion before 1991 - when screening was introduced - and
intravenous drug users. Needles used more than once in tattooing, piercing
and acupuncture can also spread the infection, as can shared razors, even
toothbrushes. Indeed, last week, more than 2,000 women in England and
Scotland were warned that they could have been infected with the virus after
being treated by a gynaecologist with HCV.

"Only a small number of individuals have symptoms at the time of infection,"
says Dr Adrian Hamlyn, a consultant physician and liver specialist at the
Dudley Group of Hospitals in the West Midlands. "Without treatment, a vast
majority will develop chronic infection and about a third will have
cirrhosis of the liver." In a few cases, cancer of the liver can develop.

In up to 15 per cent of patients, the virus clears itself. The rest will
need treatment to eliminate HCV from the blood, ideally before it does
serious damage, which is why early testing is so vital.

Treatment involves a tough regime of weekly interferon injections and daily
anti-viral ribavarin tablets that bring unpleasant side effects. Some
strains of HCV respond to treatment better than others: the overall success
rate is around 60 per cent.

"Even when the virus cannot be eliminated, inflammatory activity in the
liver can sometimes be suppressed," says Dr Hamlyn. "And new drugs are being
developed that stop the virus from replicating. Trials have shown them to be
very effective, but at the moment, they are too toxic for general release."

But the real problem is lack of funds, says Dr Hamlyn. He told the all-party
Parliamentary Group on Hepatology, which reported last month, that he needs
£750,000 worth of drugs a year but receives less than a third of that. "This
under-funding is storing up trouble. Failure to identify and treat those
with hepatitis C will result in thousands requiring expensive treatment for
serious liver disease in the future."

The government action plan and awareness campaign, launched late last year,
was branded as "slow, low-key and under-resourced" by the all-party group,
which pointed out that in Scotland, 40 per cent of HCV patients have been
identified - compared with 10 to 19 per cent in England. In France and
Germany, at least five times as many patients are treated for HCV as in
Britain, despite similar infection rates. According to the group's report:
"An overriding requirement is for the Government to demonstrate greater
urgency in dealing with this coming 'tidal wave' of disease."

For further information, call the Hepatitis Trust helpline, tel: 0870 200
1200, or see www.hepcuk.info. The Department of Health's Face It campaign;
0800 451451, www.hepc.nhs.uk


'I have probably gained 20 years'

When photographer Michele Martinoli began to get drunk after only two
glasses of wine, and suffer from repeated kidney infections, she knew
something was wrong. Swiss-born Martinoli, 55, had taken drugs as a young
woman, but had led a healthy life for the past 30 years.
C was something that happened to other people," she says.

A blood test confirmed hepatitis C, and further tests revealed severe liver
scarring.

"I knew that treatment was really harsh, but no one could tell me how long I
would live without it," she says. "I would probably have gone progressively,
and quite quickly, downhill. With treatment, I had a 70 per cent chance of
being cured after a six-month course."

After each weekly injection, flu-like symptoms would set in. "You get a
fever, your brain feels fogged, and you can't concentrate. Over the course
of the week, you feel better, until the next injection. I lost half my hair,
and the skin on my back was so sensitive it became raw from scratching.

"My energy levels dropped to 40 per cent and I could only walk about 50
metres. I dragged myself around and slowed my life down."

At her last blood test, Martinoli - whose vast pictures of HCV patients were
recently displayed in Leicester Square as part of the Government's Face It
awareness campaign, and will soon tour the country - was clear of the virus.

"Only now, one year after treatment, do I feel I have 100 per cent of my
energy back. But I have probably gained 20 years - no question, it was worth
it."
http://www.telegraph.co.uk/health/main.jhtml?xml=/health/2005/04/28/hhepc28.xml&\
sSheet=/health/2005/04/28/ixhmain.html

N Engl J Med. 2004 Oct 7;351(15):1521-31.

Comment in:
N Engl J Med. 2004 Oct 7;351(15):1567-70.

Lamivudine for patients with chronic hepatitis B and advanced liver disease.

Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM,
Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine
Multicentre Study Group.

Liver Research Unit, Chang Gung Memorial Hospital and University, Taipei,
Taiwan. liveryfl@...

BACKGROUND: The effectiveness of antiviral therapy in preventing disease
progression in patients with chronic hepatitis B and advanced fibrosis or
cirrhosis is unknown. METHODS: Patients with chronic hepatitis B who had
histologically confirmed cirrhosis or advanced fibrosis were randomly
assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo
for a maximum of five years. Of 651 patients, 436 were assigned to receive
lamivudine and 215 to receive placebo. The primary end point was time to
disease progression, defined by hepatic decompensation, hepatocellular
carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal
varices, or death related to liver disease. An independent data and safety
monitoring board monitored the progress of the study and performed interim
analyses of the data. RESULTS: We randomly assigned 651 patients (98 percent
Asian and 85 percent male) to receive lamivudine or placebo. The study was
terminated after a median duration of treatment of 32.4 months (range, 0 to
42) owing to a significant difference between treatment groups in the number
of end points reached. End points were reached by 7.8 percent of the
patients receiving lamivudine and 17.7 percent of those receiving placebo
(hazard ratio for disease progression, 0.45; P=0.001). The Child-Pugh score
increased in 3.4 percent of the patients receiving lamivudine and 8.8
percent of those receiving placebo (hazard ratio, 0.45; P=0.02), whereas
hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine
group and 7.4 percent of those in the placebo group (hazard ratio, 0.49;
P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of the
patients treated with lamivudine, and the Child-Pugh score was more likely
to increase in patients with these mutations than in the other patients
treated with lamivudine (7 percent vs. <1 percent). Overall, 12 percent of
the patients in the lamivudine group and 18 percent of the patients in the
placebo group reported serious adverse events. CONCLUSIONS: Continuous
treatment with lamivudine delays clinical progression in patients with
chronic hepatitis B and advanced fibrosis or cirrhosis by significantly
reducing the incidence of hepatic decompensation and the risk of
hepatocellular carcinoma. Copyright 2004 Massachusetts Medical Society.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 15470215 [PubMed - indexed for MEDLINE]

DGNews

Peginterferon Alfa-2b May be Effective As Monotherapy In the Treatment of
Chronic Hepatitis B

Study is First to Show Importance of HBV Genotype as Predictor of Treatment
Response


ROTTERDAM, THE NETHERLANDS -- January 6, 2005 -- Results from a large
international clinical study reported in this week's issue of The Lancet1
showed that peginterferon alfa-2b produced sustained responses in patients
with chronic hepatitis B. The investigator-initiated study is the largest
clinical trial to date with peginterferon alfa-2b therapy for chronic
hepatitis B.

"Our study showed that patients with chronic hepatitis B responded to
peginterferon alfa-2b, and achieved higher sustained response rates than is
typically seen with any other antiviral treatment," said lead investigator
Harry Janssen, M.D., Ph.D., from the Erasmus Medical Center in Rotterdam,
The Netherlands, where the international study was coordinated. "Based on
our findings with peginterferon alfa-2b, it is appropriate to consider this
therapy as a first-line treatment for HBeAg-positive chronic hepatitis B,"
he said.

The findings of this study are important because chronic hepatitis B
currently affects an estimated 400 million people worldwide, making it one
of the most common infectious diseases and one of the 10 leading causes of
death. Chronic hepatitis B is the single most common cause of liver
cirrhosis and liver cancer. Current antiviral therapies, such as the
nucleoside analogues lamivudine and adefovir, do not achieve a durable
response and probably are not effective long-term treatment options due to
the inevitable emergence of drug resistance.

Dr. Janssen also explained the importance of hepatitis B virus genotype as a
predictor for response to peginterferon alfa-2b treatment. "Just like in
chronic hepatitis C, the genotype of the hepatitis B virus (HBV) will tell
us what the likelihood of response is. It will become our best tool towards
individualized treatment for patients with HBeAg-positive chronic hepatitis
B," he said.

The study, organized and sponsored by the Foundation for Liver Research
(SLO), is the first to assess whether prolonged treatment with peginterferon
alfa-2b, alone or in combination with lamivudine improves sustained
treatment response in patients with HBeAg-positive chronic hepatitis B.
HBeAg indicates that the virus is actively replicating and the infected
person is highly infectious. In the study, more patients in the lamivudine
combination group had a response to therapy at the end of treatment, but the
response was not sustained during the follow-up period. There is growing
evidence that only a complete and vigorous HBV-specific immune response is
capable of achieving control and elimination of the virus, preventing
disease progression.

"This suggests that induction of a host immune response is necessary for
sustained response to hepatitis B treatment, which can only be reached by
immunomodulatory therapy, such as peginterferon alfa-2b," Janssen said.

The study was a multicentre, randomized, double-blind controlled trial
conducted at 42 centres in 15 countries (in Europe, East Asia and North
America). The study compared the efficacy and safety of peginterferon
alfa-2b (PegIntron®, 100 ug/week through 32 weeks; 50 ug/week 33-52 weeks)
with or without lamivudine (Zeffix®) in 307 patients positive for HBeAg
(final modified intent-to-treat analysis n=266). Treatment outcomes were
assessed at the end of treatment (EOT) (52 weeks) and again after a 26-week
treatment-free follow-up period (78 weeks).

The primary endpoint was the percent of patients who achieved a sustained
viral response (SVR) (undetectable levels of serum HBeAg) at the end of
follow-up. Secondary endpoints were the reduction of HBV DNA levels below
200,000 copies/ml or below the level of detection (400 copies/ml); ALT
normalization and HBsAg response.

SVR rates were comparable between the peginterferon alfa-2b monotherapy and
combination therapy groups, 36% and 35%, respectively. HBV DNA levels at the
end of follow-up were suppressed to below 200,000 copies/ml in 32% of
patients in the combination therapy arm and 27% of patients in the
monotherapy arm. Similarly, there was no difference at the end of follow-up
in undetectable levels of HBV DNA, 9% and 7%, respectively; ALT
normalization, 35% and 32%, respectively; or in HBsAg loss, 7% in both
groups.

Importantly, there was a significant difference in sustained response rate
according to HBV genotype (p=0.01), with HBV genotypes A (47%) and B (44%)
more responsive to therapy than genotypes C (28%) and D (25%). There was no
difference in HBeAg loss according to HBV genotype between the two treatment
groups.

Safety and tolerability were similar for patients treated with peginterferon
alfa-2b alone and those treated with lamivudine combination therapy. The
side effect profile of peginterferon alfa-2b was similar to that seen with
standard interferons and there were no new side effects that could be
attributable to peginterferon alfa-2b. Overall, the incidence and severity
of adverse events were comparable between the treatment groups. Common side
effects included flu-like symptoms, headache, fatigue and local reaction at
the injection site. There were serious adverse events in 12% of patients
that were reversible after treatment stopped. At the end of treatment, 91%
of patients remained on treatment and 69% remained on full-dose treatment.


Reference:

1 Pegylated interferon alfa-2b alone or in combination with lamivudine as
the treatment for HBeAg-positive chronic hepatitis B; Harry L.A. Janssen,
Monika van Zonneveld, Hakan Senturk, Stefan Zeuzem, Ulus S. Akarca, Yilmaz
Cakaloglu, Christopher Simon, Thomas M.K. So, Guido Gerken, Robert A. de
Man, Hubert G.M. Niesters, Pieter Zondervan, Bettina Hansen, Solko W.
Schalm, for the HBV 99-01 Study Group; The Lancet 2005;365:123-29.


SOURCE: The Chandler Chicco Agency

DGNews

Multiferon (Natural Human Alpha Interferon) Approved for Sale in the
Philippines

PLANTATION, FL -- April 25, 2005 -- Viragen, Inc. (Amex: VRA) and its
majority-owned subsidiary, Viragen International, Inc. (OTC Bulletin Board:
VGNI), today announced the approval of Multiferon®, natural human alpha
interferon, for sale in the Philippines.

Multiferon was approved in the Philippines for the second-line treatment of
any and all diseases in which recombinant interferon therapy failed or the
patient was unable to tolerate the regimen. As an alternative to
single-subtype, recombinant alpha interferons, Multiferon is primarily
marketed for the treatment of hepatitis B, hepatitis C, chronic myelogenous
leukemia, hairy cell leukemia, renal cell carcinoma and malignant melanoma.

Viragen's President and CEO, Mr. Charles A. Rice, commented, "One of our
stated priority goals for 2005 is to initiate sales of Multiferon in new
markets, and we are pending approvals in parts of Europe, South America and
Asia. The Philippines adds value as part of this international expansion and
is expected to contribute to sales growth as we continue to strive to make
Multiferon the most widely prescribed natural interferon in the world."


SOURCE: Viragen, Inc

http://www.docguide.com/news/content.nsf/news/8525697700573E1885256FEE004A8960?O\
penDocument&id=061C33FC2A7F39888525689900589BFE&c=Hepatitis%20Other&count=10

Doctors mindful of patients' out-of-pocket drug costs

A study shows that physicians prescribe generic drugs, offer free samples
and split high-dose tablets to help patients afford their prescription
medications.
By Andis Robeznieks, AMNews staff. May 2, 2005.


Although a recent study found more than one-third of physicians did not
discuss out-of-pocket costs of prescription drugs with patients, the
report's lead author agrees with others who say there is a growing awareness
and that change already is taking place among doctors.

According to the study, published in the March 28 Archives of Internal
Medicine, nearly 93% of the 519 internists and cardiologists who responded
to a survey said that they know prescription costs can be a financial
hardship for some patients.

Only slightly more than a third were aware of the extent of the hardship.
But the report indicated there was potential that more doctors will become
cognizant of their patients' economic challenges, with 75.2% of the
responding physicians saying they believed they had an obligation to
initiate conversations on drug costs.

"The most important finding is that a considerable proportion of physicians
are entirely engaged in this issue," said the study's lead author G. Caleb
Alexander, MD, an instructor in medicine and affiliate faculty member of the
MacLean Center for Medical Ethics at the University of Chicago.

"I believe increasing awareness of the burden that many patients face will
create a 'tension for change' that will, ultimately, facilitate doctors and
patients working together to address these issues," he said.

American Medical Association Trustee Edward L. Langston, MD, said that
prescription drug costs get addressed every day at his practice in
Lafayette, Ind.

93% of internists and cardiologists in a survey know drug costs can cause
patient hardships.
Dr. Langston, a family physician, keeps a list on his handheld computer of
which health plans cover which drugs. After writing a prescription, he
doesn't hesitate to ask the patient "Are you going to be able to get this?"

Bruce Bagley, MD, medical director for quality improvement at the American
Academy of Family Physicians, said doctors are recognizing that prescription
drug costs have become a "side effect" of the medications they prescribe.
"Cost is just as powerful as any other side effect, maybe more so in some
cases," he said. "If you can't afford it, you aren't going to take it."

Once costs are addressed, Dr. Bagley said patients become relieved and are
better able to focus on what he's telling them about their health and
treatment options.

"Sometimes the cost of the medicine is so much on their minds that they
don't hear the message about how important it is to take it," Dr. Bagley
said.

If physicians are too uncomfortable in bringing up the subject, Dr. Bagley
suggested hanging a sign that reads: "I'm open to discussing the cost of
your medication" and that helps empower patients to start the conversation
themselves.

"Usually, they are thankful to have the discussion because they're
embarrassed," he said.

75% of physicians in a survey feel an obligation to discuss drug costs with
patients.
"Who wants to bring it up that they don't have $10 to pay the co-pay?"

Doctors who took part in the Archives of Internal Medicine study cited a
lack of time, patient discomfort, a lack of being able to offer a solution,
and their own discomfort as barriers to discussing the issue.

But once physicians broach the sensitive issue, the study found that several
strategies are used in attempts to lower a patient's out-of-pocket costs.
Cost-cutting strategies included using generic drugs, offering free samples,
splitting high-dose tablets and evaluating whether some prescriptions can be
discontinued.

"I was somewhat surprised that the second-most common strategy physicians
reported using was giving office samples," Dr. Alexander said. "There is
considerable debate about the practice. It's a complicated issue, and people
will argue about it until the cows come home

Drs. Bagley and Langston are split on the issue.

"Samples, in the big picture, make things worse," Dr. Bagley said. But Dr.
Langston said that if he has samples of a drug that a patient needs but
can't afford, he doesn't hesitate to offer them.

"The criticism for sampling is that, if you only use samples, are you
overlooking other alternatives?" Dr. Langston said. "I use a lot of samples
and I use a lot of generic medicines. You just try to get what your patients
need in any way feasible."

Jettison the unnecessary
All three doctors agreed that doing away with what patients don't need may
be the best strategy for addressing physical and financial health.

"There are few better ways [to reduce out-of-pocket expenses] than to stop a
medication that is not needed," Dr. Alexander said.

Dr. Bagley said patients also are more open to discussing changes in diet
and lifestyle if it may make some of their prescriptions unnecessary.

"That's when you can tell them 'If you stop drinking coffee, smoking
cigarettes and eating buffalo wings, you'll probably be OK,' " he said. "But
we should be doing that with everybody -- not just people who can't afford
prescriptions, and not just for cost, but for side effects and interactions,
too."

The three also agreed that most drug company assistance programs are not
that useful because there are too many "hurdles and hassles" for their
patients to navigate.

"They can be very cumbersome, but if I can plug someone into one, I
certainly will," said Dr. Langston, who added that drugmakers will sometimes
listen to constructive criticism. "I told one company 'You've created a
barrier to access. These people have enough problems, and I'm just telling
you your program is not that helpful,' " he said. "And they changed their
program."
------------------------------------------------------------------------------

  ADDITIONAL INFORMATION:
Strategies for prescription savings
Researchers recently asked physicians to list the ways they help patients
burdened by out-of-pocket prescription costs to afford the medication. Using
a 1-5 scale, doctors then ranked how often they would use the strategy with
1 indicating "not at all likely" and 5 being "extremely likely."

Strategy Mean score
Switch from brand-name to generic drug 4.34
Give the patient office samples 4.16
Review patient medications and
discontinue those deemed nonessential 4.03
Switch to less expensive brand name
drug within the same drug class 3.96
Prescribe a higher dose and tell
patient to split the tablet 3.58
Refer patient to drug company
assistance program 3.57
Recommend over-the-counter substitute 3.21
Refer patient to public aid agency
or social worker 3.15
Encourage patient to address concern
with a different doctor involved in their care 1.86
Do nothing 1.47

Source: Archives of Internal Medicine
http://www.ama-assn.org/amednews/2005/05/02/prsa0502.htm

Keyboards latest culprit in hospital infections

Experts say physicians are not cleaning their hands as often as they should.
By Damon Adams, AMNews staff. May 2, 2005.

First it was neckties. Now it's computer keyboards that have been identified
as nesting grounds for germs that could be spread to patients.

A new study says potentially harmful bacteria can survive on computer
keyboards and keyboard covers up to 24 hours, a threat to hospital patients
as more institutions implement electronic systems and bring technology to
patients' bedsides.

The findings come on top of research showing that white coats, stethoscopes,
pens and even neckties are among germ carriers in a doctor's everyday world.

Physicians say the computer keyboard discoveries are another reminder that
doctors should be mindful of what they might take with them when they see
their next patient.

"We touch a lot of things and don't consciously think about the effect of
touching things and what we carry around," said Lawrence Brandt, MD, chief
of gastroenterology at Montefiore Medical Center in Bronx, N.Y.

In the new study, Gary A. Noskin, MD, and his colleagues studied three types
of bacteria commonly found in hospital environments: vancomycin-resistant
Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and
Pseudomonas aeruginosa. They contaminated computer keyboards and keyboard
covers with the bacteria and examined the germs' ability to survive on both
surfaces.

2 million Americans are infected in hospitals each year.

Researchers found that VRE and MRSA could survive up to 24 hours after being
put on keyboards and covers. PSAE was found to live up to an hour on
keyboards and up to five minutes on covers, according to study findings
presented at the annual meeting of the Society for Healthcare Epidemiology
of America held in Los Angeles in April.

The research also showed that after any contact with the keyboards, gloved
and ungloved hands frequently became contaminated. Not surprisingly, the
more contact hands made with contaminated keyboards, the more likely
bacteria were transmitted.

Disinfectants can help prevent germs from spreading. A disinfectant that
remained on a keyboard for 10 minutes before cleaning was more effective
than one that was supposed to be removed after five minutes, according to
the study.

But old-fashioned hand washing is still seen as one of the best defenses
against spreading germs.

"The key message is that after contact with the computer keyboard, you must
wash your hands. The simple measure of hand washing is the single most
effective way to prevent transmission of bacteria in the hospital," said Dr.
Noskin, medical director of health care epidemiology and quality at
Northwestern Memorial Hospital in Chicago.

Hand washing often neglected

Sounds simple, but infectious disease experts say many physicians do a poor
job of cleaning their hands often enough. A study in the July 6, 2004,
Annals of Internal Medicine found that doctors at a hospital in Switzerland
cleaned their hands 57% of the times they should have.

Lax hand washing among doctors has prompted some groups to encourage better
cleaning.

In October 2002, the Centers for Disease Control and Prevention released new
hand hygiene guidelines that advised using alcohol-based hand rubs to
protect patients. The CDC stressed the guidelines as it found that each year
about 2 million U.S. patients are infected in hospitals and about 90,000 die
as a result.

In addition, the AMA endorses four principles of hand awareness for all
people: Wash your hands when they are dirty and before eating; don't cough
into your hands; don't sneeze into your hands; and don't put your fingers
into your eyes, nose or mouth.

Raising awareness
Philip Tierno, PhD, author of The Secret Life of Germs, has looked at
computer keyboards and found that they can be home to bacteria. He said
doctors need to be more aware that keyboards, neckties and stethoscopes can
be launching pads for bacteria to go from doctors to patients.

"People just don't stop and think of the mechanisms involved in transferring
organisms," said Dr. Tierno, director of clinical microbiology and
diagnostic immunology at New York University Medical Center.

Only 57% of doctors at a Swiss hospital cleaned their hands as often as they
should.
Leonard Mermel, DO, president of the Society for Healthcare Epidemiology of
America, said computer keyboards in office practices also could harbor
bacteria. With keyboard use increasing in health care settings, he said,
hospitals and practices should review keyboard cleaning policies.

"Bugs are becoming more and more resistant. We are running out of antibiotic
options for some germs. As our options become more limited, prevention of
transmission becomes more and more important," said Dr. Mermel, professor of
medicine at Brown Medical School and medical director of the Dept. of
Infection Control at Rhode Island Hospital.

At least one physician wonders if some researchers have gone too far in
culturing bacteria on everything from pens to handhelds.

James J. Rahal, MD, was co-author of a Queens, N.Y., study on bacteria and
neckties, but he said the bacteria were common and not considered dangerous.

"It's being overdone, frankly. Everybody seems to be culturing everything,"
said Dr. Rahal, director of the infectious diseases section at New York
Hospital Medical Center of Queens. "You can find bacteria everywhere. We
don't have a sterile environment. We never will."

But most physicians see the studies as providing useful information that
should nudge physicians to take more notice of what they touch and greater
care of cleansing their hands.

"[Doctors should] realize that we may infect other things," said Matthew
Hall, MD, a staff physician and an infectious disease specialist at
Marshfield (Wis.) Clinic.
http://www.ama-assn.org/amednews/2005/05/02/prl20502.htm

Liver International
OnlineEarly
doi:10.1111/j.1478-3231.2005.01110.x


Non-interferon-based therapy: an option for amelioration of
necro-inflammation in hepatitis C patients who cannot afford interferon
therapy

Abdel-Rahman El-Zayadi1, Mohy Attia2, Hanaa M. Badran3, Ahmed El-Tawil4,
Khaled Zalata5, Eman Barakat1, Osaima Selim6, Adham El-Nakeeb7, and Ahmed
Saied7
  Abstract:

Objectives: Interferon (IFN) therapy is not affordable by the majority of
Egyptian patients. Our aim was to tailor an effective and inexpensive
regimen that ameliorates hepatic necro-inflammatory activity among chronic
hepatitis C (CHC) patients.

Methods: One hundred and seventy naïve CHC patients with elevated alanine
aminotransferase (ALT) (>1.5-fold) and detectable hepatitis C virus
(HCV)-RNA by polymerase chain reaction, who cannot afford IFN-based therapy
were randomly allocated either to non-interferon-based therapy (N-IFN-BT)
(group I) or silymarin therapy (group II). Group I comprised 87 patients
(biopsy proved chronic hepatitis in 62 patients) who were administered a
daily combination of ribavirin (600800 mg) plus amantadine (200 mg) and
ursodeoxycholic acid (UDCA) (500 mg) for 24 weeks. Group II comprised 83
patients who were administered Silymarin 450 mg/day for 24 weeks.

Results: Statistical evaluation was conducted on 82 patients from group I
and 72 from group II because of the withdrawal of five and 11 patients from
Groups I and II, respectively. Age, sex, social status and biochemical
parameters were comparable in both groups. Normalization of ALT at the end
of treatment was achieved in 58.5% and 15.3% (P<0.001), whereas end of
treatment virologic response (ETVR) was achieved in 2.4% and 0% of Groups I
and II, respectively. Twenty-four weeks after cessation of therapy,
sustained biochemical response (SBR) was achieved in 28% and 2.8% (P<0.001),
while sustained virologic response (SVR) was maintained in 2.4% and 0% of
the patients in Groups I and II, respectively. In Group I, histopathological
examination revealed a decreased activity index by an average score of 1.5
points among 38/62 of the rebiopsied patients.

Conclusion: Twenty-four weeks N-IFN-BT achieved a fourfold-higher ETBR and a
tenfold-higher SBR compared with silymarin therapy, which reflects an
improvement of necroinflammatory activity as proven by repeat
histopathology.

Journal of Endocrinology (2005) 185, 345-352    DOI: 10.1677/joe.1.06007

Sexual dysfunction in males with chronic hepatitis C and antiviral therapy:
interferon-induced functional androgen deficiency or depression?

M R Kraus, A Schäfer, T Bentink, M Scheurlen, B Weissbrich2, O Al-Taie and J
Seufert1
Department of Gastroenterology and Hepatology, Medizinische Poliklinik,
University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
1 Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische
Poliklinik, University of Würzburg, Würzburg, Germany
2 Institute for Virology and Immunobiology, University of Würzburg,
Versbacher Strasse 7, D-97078 Würzburg, Germany


(Requests for offprints should be addressed to M R Kraus; Email:
Kraus_m@...)

Decrease of libido and erectile dysfunction are reported by male patients
during antiviral therapy of chronic hepatitis C, but therapy-associated
underlying factors for sexual dysfunction are not well defined. To assess
putative contributions of interferon-induced sex hormone changes to sexual
dysfunction, we prospectively investigated changes in free testosterone,
total testosterone, dehydroepiandrosterone sulfate, prolactin, sex
hormone-binding globulin, FSH and LH levels and psychometric self-assessment
scores in 34 male patients treated with interferon alfa-2b (5 MIU three
times weekly) (n=19)+ ribavirin (n=15) for 6-12 months. Depression was
measured by the Hospital Anxiety and Depression Scale. Sexual dysfunction
was evaluated by the Symptom Checklist 90 Item Revised and a five-point
rating scale assessing sexual arousal disorder. Free and total testosterone
decreased significantly during antiviral therapy in close correlation with
libido/sexual function. Depression scores increased during therapy and were
also significantly associated with sexual dysfunction. However, androgen
levels displayed no significant correlation with depression. These results
suggest that interferon-induced decrease in sexual function is associated -
but not causally related -with both androgen reduction and increased
depressive symptoms. These findings may affect care for male hepatitis C
patients during interferon therapy.

Arch Virol. 2005 Apr 21; [Epub ahead of print]

Mutation analysis of hepatitis B virus promoters in chronically infected
children.

Sohn JW, Lee CW, Lee JH, Lee KC, Son CS, Lee JW, Ha-Lee YM.

Department of Biochemistry, School of Medicine, Korea University, Seoul,
Korea.

Hepatitis B viral (HBV) infection in early childhood is one of the leading
causes of chronic hepatitis and liver cirrhosis that eventually lead to
hepatic carcinoma. Despite the nationwide immunization programs to curtail
the vertical transmission of HBV, childhood HBV infection through mothers is
still occurring in Korea. As one of the efforts to understand the childhood
HBV infection in Korea, four HBV promoter sequences in the sera of the
chronically infected children were analyzed. Children harbored diverse viral
variants as most of the chronically infected adult patients, but the
deletion mutations were rare. The dominant viral sequences in the children
were highly similar to the ones in the respective mothers, indicating that
the maternal viruses were most likely transmitted to the children. The
mutations in X, S1, S2/S promoters did not seem to show any correlation to
the severity of the disease nor ages of the children. The mutations that
showed some correlation to the severity of the disease were the mutations in
C promoter, but the mutations did not seem to be vertically transmitted.
Finally, the children with the elevated ALT/AST levels tended to have more
child-specific variants suggesting that the accumulation of host-specific
mutations might be associated with the development of clinical symptoms.

PMID: 15841341 [PubMed - as supplied by publisher]

World J Gastroenterol 2005 March;11(9):1356-1360

High relative fat-free mass is important for maintaining serum albumin
levels in patients with compensated liver cirrhosis

Kotoh K, Nakamuta M, Fukushima M, Matsuzaki C, Enjoji M, Sakai H, Nawata H.

Department of Medicine and Bioregulatory Science, Graduate School of Medical
Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582,
Japan. nakamuta@...

AIM: In patients with liver cirrhosis, hypoalbuminemia causes edema and
ascites, and a reduction in the quality of life. Since musculature is
catabolized to supply amino acids for albumin synthesis in malnutritional
cirrhotic patients, muscular volume is hypothesized to play an important
role in albumin production. Therefore, we investigated the correlation
between serum albumin levels and the fat-free mass (FFM) in cirrhotic
patients. METHODS: Fifty-seven patients (26 males and 31 females) with
compensated liver cirrhosis were evaluated. Patients with edema or ascites
were excluded from the study. Healthy volunteers (n = 104; 48 males and 56
females) were also evaluated as controls. FFM was measured using 5-500 kHz
multifrequency bioelectric impedance analysis. To minimize the difference in
FFM distribution between males and females, we introduced a new marker,
relative FFM (rFFM), which represents the ratio of FFM in a patient relative
to that in a volunteer of the same height. Following FFM measurement, the
serum albumin levels of patients were assayed monthly. RESULTS: In patients
with active cirrhosis (alanine aminotransaminase (ALT) >50 U/L), both
albumin (the difference between maximum and minimum levels) and the standard
deviation of albumin levels (SD-albumin) during the observation period
showed a significant correlation with rFFM. Multiple linear regression
analysis using variables such as rFFM, platelet number, and serum
cholesterol levels, choline esterase, albumin, bilirubin, and ALT revealed
that rFFM and ALT were significant and independent factors that influenced
albumin or SD-albumin in cirrhotic patients. CONCLUSION: Our results
indicate that cirrhotic patients with high rFFM showed less of a decrease in
albumin levels, and that the muscle volume is one of the most important
factors for maintaining serum albumins level in active cirrhosis. Exercise
and protein-rich nutrition at the early stage of liver cirrhosis may be
advisable for maintaining or increasing muscular volume.

Transfusion
Volume 45 Issue 5 Page 807  - May 2005
doi:10.1111/j.1537-2995.2005.04317.x


The significance of transfusion in the past as a risk for current hepatitis
B and hepatitis C infection: a study in endoscopy patients

Hani M. Tawk1, Karen Vickery1, Linda Bisset1, Sing Kai Lo1, Yvonne E.
Cossart1, and the Infection in Endoscopy Study Group1

BACKGROUND: The objective was to determine the contribution of transfusion
in the past to the risk of current infection with hepatitis B or C among
patients attending a large hospital for endoscopic procedures.

STUDY DESIGN AND METHODS: Blood samples had been tested for hepatitis
markers by routine methods. Patients completed a comprehensive risk factor
questionnaire and results were analyzed using computer software.

RESULTS: Twenty-seven percent of the 2120 participants in the study received
transfusions in the past. There was no increase in prevalence of hepatitis B
among those transfused. Compared with nontransfused participants, recipients
of blood before the implementation of hepatitis C virus (HCV) screening in
1990 had a 4.6-fold increased risk of HCV infection, whereas those
transfused with screened blood had a 3-fold increased risk. The difference
between the odds ratios for patients before and after screening was not
significant.

CONCLUSIONS: Because screening has almost completely eliminated HCV from the
blood supply, our finding of a continuing association of HCV infection with
transfusion was unexpected. It implies that there are significant other
nosocomial risks for hepatitis C transmission associated with the clinical
situations where patients received blood. These should be actively
investigated.

From The Cochrane Library, Issue 2, 2005. Chichester, UK: John Wiley & Sons,
http://www.update-software.com/abstracts/AB003620.htmLtd. All rights
reserved.

Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases
(Cochrane Review)
Rambaldi A, Jacobs BP, Iaquinto G, Gluud C


ABSTRACT
  ---------------------------------------------------------

A substantive amendment to this systematic review was last made on 14
January 2005. Cochrane reviews are regularly checked and updated if
necessary.

Background: Alcohol and hepatotoxic viruses cause the majority of liver
diseases. Randomised clinical trials have assessed whether extracts of milk
thistle, Silybum marianum (L) Gaertneri, have any effect in patients with
alcoholic and/or hepatitis B or C virus liver diseases.

Objectives: To assess the beneficial and harmful effects of milk thistle or
milk thistle constituents versus placebo or no intervention in patients with
alcoholic liver disease and/or viral liver diseases (hepatitis B and
hepatitis C).

Search strategy: TheCochrane Hepato-Biliary Group Controlled Trials
Register, The Cochrane Central Register of Controlled Trials, MEDLINE,
EMBASE, and full text searches were combined (December 2003). Manufacturers
and researchers in the field were contacted.

Selection criteria: Only randomised clinical trials in patients with
alcoholic and/or hepatitis B or C virus liver diseases (acute and chronic)
were included. Interventions encompassed milk thistle at any dose or
duration versus placebo or no intervention. The trials could be double
blind, single blind, or unblinded. The trials could be unpublished or
published and no language limitations were applied.

Data collection and analysis: The primary outcome measure was mortality.
Binary outcomes are reported as relative risks (RR) with 95% confidence
interval (CI). Subgroup analyses were performed with regard to
methodological quality.

Main results: Thirteen randomised clinical trials assessed milk thistle in
915 patients with alcoholic and/or hepatitis B or C virus liver diseases.
The methodological quality was low: only 23% of the trials reported adequate
allocation concealment and only 46% were considered adequately
double-blinded. Milk thistle versus placebo or no intervention had no
significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15),
complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver
histology. Liver-related mortality was significantly reduced by milk thistle
in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials
(RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a
significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to
1.50).

Authors' conclusions: Our results question the beneficial effects of milk
thistle for patients with alcoholic and/or hepatitis B or C virus liver
diseases and highlight the lack of high-quality evidence to support this
intervention. Adequately conducted and reported randomised clinical trials
on milk thistle versus placebo are needed.

Citation: Rambaldi A, Jacobs BP, Iaquinto G, Gluud C. Milk thistle for
alcoholic and/or hepatitis B or C virus liver diseases. The Cochrane
Database of Systematic Reviews 2005, Issue 2. Art. No.: CD003620.pub2. DOI:
10.1002/14651858.CD003620.pub2.



--------------------------------------------------------------------------------

This is an abstract of a regularly updated, systematic review prepared and
maintained by the Cochrane Collaboration. The full text of the review is
available in The Cochrane Library (ISSN 1465-1858).


Abstracts of Cochrane Reviews are compiled and produced by Update Software
Ltd on behalf of the publisher, John Wiley & Sons Ltd.

Replicative Homeostasis: A New Hypothesis to Explain How Viruses Such as
HIV, HCV and HBV Persist and Escape Immune Controls

This article offers a new hypothesis concerning the persistence of certain
viruses such as HIV, HCV and HBV and how they escape control by the immune
system. In 40 days it has become the most downloaded article ever published
by Virology Journal, an "Open Access" journal published by BioMed Central.
This means that anyone can read, without charge, the articles appearing in
it as soon as they are published.

The article explains why RNA viruses like Hepatitis C, HIV, West Nile /
Yellow Fever / SARS / Ebola, etc persist, and demonstrates a mechanism of
genotype/species maintenance, and of generating escape mutants in response
to immune and other pressures. It explains why interferon may fail in some
cases of hepatitis C and also explains the mechanism of antibody mediated
disease enhancement. It also implies novel treatments for West Nile / HCV
(and HIV, HBV, etc) might be possible, and describes what form they might
take.

Hepatitis C (HCV), hepatitis B (HBV), the human immunodeficiency viruses
(HIV), and other viruses that replicate via RNA intermediaries, cause an
enormous burden of disease and premature death worldwide.

These viruses circulate within infected hosts as vast populations of closely
related, but genetically diverse, molecules known as "quasispecies". The
mechanism(s) by which this extreme genetic and antigenic diversity is stably
maintained are unclear, but are fundamental to understanding viral
persistence and pathobiology. The persistence of HCV, an RNA virus, is
especially problematic and HCV stability, maintained despite rapid genomic
mutation, is highly paradoxical.

This paper presents the hypothesis, and evidence, that viruses capable of
persistent infection autoregulate replication and the likely mechanism
mediating autoregulation--Replicative Homeostasis--is described.

Replicative homeostasis causes formation of stable, but highly reactive,
equilibria that drive quasispecies expansion and generates escape mutation.
Replicative homeostasis explains both viral kinetics and the enigma of RNA
quasispecies stability and provides a rational, mechanistic basis for all
observed viral behaviours and host responses.

More importantly, this paradigm has specific therapeutic implication and
defines, precisely, new approaches to antiviral therapy. Replicative
homeostasis may also modulate cellular gene expression.

   Note: This article uses highly technical language that many readers will
find difficult to follow at times. Although the language is challenging for
non scientists, it is worth the effort to read through the entire article,
which offers compelling insights into the possible mechanisms of how HIV,
HCV and HBV, among other viruses, persist.

Link to complete text online

This is an Open Access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly
cited.

Reference
R Sallie. Replicative Homeostasis: A fundamental mechanism mediating
selective viral replication and escape mutation. Virology Journal 2(1):10.
February 11, 2005.

http://www.hivandhepatitis.com/recent/immunology/042505_fea.html

Medscape Alert
FDA Issues Betaseron Hepatotoxicity Reminder

April 22, 2005 - The U.S. Food and Drug Administration (FDA) and Berlex,
Inc., have reminded healthcare professionals via letter of the risk of
hepatotoxicity associated with use of interferon beta-1b (Betaseron),
according to an alert sent today from MedWatch, the FDA's safety information
and adverse event reporting program. Monitoring of liver function at regular
intervals is recommended.

The FDA has received rare postmarketing reports of serious hepatic injury in
patients receiving beta-interferon therapy, including autoimmune hepatitis
and severe liver damage leading to hepatic failure and transplant. In some
cases, hepatotoxicity occurred with coadministration of other medications
and/or in the presence of comorbid medical illnesses associated with hepatic
injury.

As noted in the prescribing information for interferon beta-1b since its
approval in 1993, liver function testing is recommended at regular intervals
(one, three, and six months) after therapy initiation, and periodically
thereafter in the absence of clinical symptoms.

Interferon beta-1b is indicated for the treatment of relapsing forms of
multiple sclerosis to reduce the frequency of clinical exacerbations.

The most frequently reported adverse events associated with use of
interferon beta-1b include lymphopenia, injection-site reaction, asthenia,
flu-like symptom complex, headache, and pain. Cases of anaphylaxis have been
reported rarely.

In controlled clinical trials, injection-site necrosis occurred in 5% of
patients. Patients should be advised of the importance of injection-site
rotation to minimize this risk.

The FDA notes that beta-interferon therapy should be used with caution in
patients with depression, and that female patients be warned about the
potential risk to pregnancy.

More information can be obtained by contacting Berlex Medical and Product
Services at 1-888-BERLEX4, option 4 (1-888-237-5394, option 4) or online at
http://www.berlex.com (select "Products").

Healthcare professionals are encouraged to report adverse events related to
the use of interferon beta-1b to the FDA MedWatch program, by phone at
1-800-FDA-1088, by fax at 1-800-FDA-0178, by mail to MedWatch, HF-2, FDA,
5600 Fishers Lane, Rockville, MD 20857, or online at
https://www.accessdata.fda.gov/scripts/medwatch.

Reviewed by Gary D. Vogin, MD

http://www.medscape.com/viewarticle/503781?src=mp

http://www.hbvadvocate.org/news/reports/EASL_2005/EASL2005_HBVIndex.htm

OCCULT HEPATITIS B VIRUS INFECTION IN A COHORT OF HIV POSITIVE PATIENTS
N. Marino1, S. Lo Caputo1, P. Pierotti1, C. Blé1, M.P. Riccardi2, M.
Trezzi2, M. Toti2, M. De Gennaro3, A. Scasso3, A. Vivarelli4, D. Dionisio4

1Division of Infectious Diseases,S.M.Annunziata Hospital, Florence, Italy
2Division of Infectious Diseases, Misericordia Hospital, Grosseto, Italy
3Division of Infectious Diseases, Campo Di Marte Hospital, Lucca, Italy
4Division of Infectious Diseases, Del Ceppo Hospital, Pistoia, Italy



Background

70-90% of HIV-infected patients have evidence of infection with Hepatitis B
virus. Most individuals develop anti-HBs and anti-HBc; 10-18% develop
anti-HBc in absence of detectable anti-HBs and may reflect latent HBV
infection.



Methods

HIV+ consecutive patients in the year 2003 were chequed in 4 Infectious
Disease Units in Tuscany (Italy) in order to assess parameters HIV-related
(CD4 count, HIV-RNA), serological markers for HBV (HBsAg, anti-HBs, anti-HBc
, HBeAg, anti-HBe) and HCV (anti-HCV, HCV-RNA ). Polymerase chain reaction
(PCR) for HBV-DNA (Cobas Amplicor HBV Monitor ) was performed in patients
who showed only anti-HBc reactivity. Clinical and therapeutical data were
collected. T.Student test was employed.



Results

955 HIV+ patients ( 71,3% males, median age 42,3 years, eterosexual
transmission 26,7%, omosexual 30,2%, IVD 59,4%) were evaluated for HBV
infection. 581 patients (60,8%) were anti-HBc+, 64 (6,7%) were HbsAg+, 361
(37,8%) were anti-HBs+, 190 (19,9%) were anti-HBc+ alone. 402 patients
(42,1%) were coinfected with HCV. Isolated antiHBc+ was not related to sex,
age, immunological status and HIV-viremia. Patients with isolated anti-HBc
were more likely than patients anti-HBc - to be HCV seropositive ( 71% vs
17,3% p<0,0001) . Patients HCV+ were more likely to have isolated anti-HBc
than were subjects with HIV alone ( 33,6% vs. 9,9% p<0,0001). HBV-DNA was
positive in 6,9% of anti-HBc + patients. with low level of replication (
from 102 to 103 copies/mL). Patients HBV-DNA positive didn't show either
clinical or laboratory abnormalities, no evidence of relation with CD4
count, HIV-RNA, HAART, or HCV coinfection. Data on the follow-up of the HBV
viraemic patients report that viraemia in occult Hepatitis B is not
persistent. Liver cirrhosis was observed only in HCV+ patients and does not
relate to HBV-DNA; prevalence was higher in anti-HBc+ 15,8% vs. anti-HBc-
1,5% (p<0,0001).



Conclusions

These findings suggest that occult HBV infection is frequent in patients
HIV+, occurs more frequently in patients with chronic hepatitis C and
enhances the severity of liver disease. HBV-DNA positive in 6,9% was not
related to clinical or laboratoriy. Longitudinal evaluation of HBV-DNA is
necessary for correct etiologic diagnosis of occult HBV infection.

http://www.hbvadvocate.org/news/reports/EASL_2005/EASL2005_HBVIndex.htm

OCCULT HBV INFECTION IN PATIENTS WITH CHRONIC HEPATITIS C AND IN HCV/HIV
COINFECTED PATIENTS

P. Fabris1, M.R. Biasin2, M.T. Giordani1, L. Berardo2, D. Infantolino2, V.
Menin2, E. Conti1, C. Stecca1, F. de Lalla1

1Department of Infectious Diseases and Tropical Medicine, S. Bortolo
Hospital, Vicenza, Italy  2Department of Pathology, Hospital of Castelfranco
Veneto, Treviso, Italy



Background

The frequency and the impact of occult HBV infection in patients with
chronic hepatitis C are  still under discussion.



Aims

To evaluate the prevalence of  occult  HBV infection and to assess  its
impact on HCV viral titre, and  liver histology in patients with chronic
hepatitis C and in HIV/HCV coinfected patients..



Methods

One-hundred and sixty-one  frozen liver biopsies from patients (74% IVDUs)
with chronic hepatitis C (Group A), 26 liver biopsies from HIV/HCV
coinfected patients (Group B) and 32 biopsies from a control group (25
HBsAg+, 4 autoimmune hepatitis and 3 cryptogenic chronic hepatitis) were
studied. DNA was extracted with QIAGEN kit method and amplified with nested
PCR by using  primers for S, Core and X genes. Liver histology was evaluated
using the Ishak' s modified HAI.



Results

The overall HBV-DNA frequency was  14.2% (23/161) in specimens from Group A,
and  in 11.5%  (3/26) specimens from Group B (p=ns). In both groups, HBV-DNA
positivity was unrelated to HCV genotype, while a significant (p<0.01)
association with  serological markers of previous exposure to HBV infection
was found. In Group A, HCV viral titre was lower in HBV-DNA positive than in
HBV-DNA negative patients    (0.4 x 106 UI/ml vs 1.4 x 106,
p=0.06).Furthermore, grading (but not staging) was significantly higher in
HBV-DNA positive than in HBV-DNA negative patients (mean score 7.0 vs 5.2,
p=0.03). Among HCV mono-infected, 5 samples were positive for S gene, 11 for
Core gene, 5 for both S gene and Core gene, and 2 for X gene. Similar figure
was observed in liver tissue from  HCV/HIV co-infected patients.



Conclusions

In our study the prevalence of occult HBV infection appears to be lower than
previously reported, with a  similar  figure   in HCV mono-infected and in
HCV/HIV co-infected patients. The inverse correlation between the HBV-DNA
positivity in liver tissue and HCV viral titre seems to support an
interference of occult HBV infection on HCV replication. Although HBV-DNA
positivity  appears associated with more severe liver inflammation,
prospective studies should be designed to evaluate the impact of occult HBV
infection on liver disease progression.

http://www.hbvadvocate.org/news/reports/EASL_2005/EASL2005_HBVIndex.htm

FACTORS ASSOCIATED WITH THE SEVERITY OF HBV-RELATED CHRONIC HEPATITIS IN
HIV-INFECTED PATIENTS

J.B. Trabut1, B. Nalpas1, M.L. Chaix2, V. Verkarre3, J. Serpaggi1, H.
Fontaine1, S. Pol1

1Unité D'Hépatologie-INSERM U 370, CHU Necker Enfants-Malades, Paris, France
2Laboratoire De Virologie-EA 3620, Université René Descartes- CHU Necker
Enfants-Malades, Paris, France  3Laboratoire D'Anatomo-Pathologie, CHU
Necker Enfants-Malades, Paris, France

Background

HBV infection is a frequent cause of morbidity and mortality in HIV-infected
patients.



Aim

The aim of our study was to analyse the factors associated with the severity
of their liver disease.



Patients and methods

A cohort of 110 patients HBV/HIV co-infected (110 sexual contaminations and
10 unknown). Analysis of : 1. parameters significantly associated with
fibrosis score and mortality ; 2. the impact of'interferon and lamivudine
therapies.



Results

Cirrhosis was present in 25.5% of the patients. Among the 85 patients
without any anti-HBV therapies, fibrosis with the Metavir scoring system
(F3-4 vs. F0-2) was significantly more severe in the older patients (p=
0.004), in those with the longer duration of HBV infection (p=0.006), with a
CD4+ lymphocytes count < 250/mm3 (p=0.03) and those with antiretroviral
therapy (53 vs 28%, p=0.02). Necro-inflammation correlated with severity of
fibrosis (p=0.002). In multivariate analysis, antiretroviral therapy  and
the necro-inflammatory activity were significantly associated with fibrosis
(p=0.04, RR=3.1 and 0.001, respectively). Eight patients (8.7%) died (5 F4,
2 F3 and one F1) during the follow-up, including 5 liver-related deaths ;
yearly mortality was 1.7% and was significantly higher in cirrhotics (20% vs
5%, p=0.039) and in patients with with a CD4+< 250/mm3 (26.3 vs 4.5%,
p=0.004). Mortality was reduced in patients under antiretroviral therapy
including lamivudine (p=0.04). Standard Interferon efficacy (HBV DNA<700.000
copies/ml) was poor since only 10.5% of treated patients had sustained
virosuppression (> 6 months) and only one (2.8%) had HBe/antiHBe
seroconversion. Lamivudine, given to 51 patients, resulted in HBeAg loss in
44.8% and a primary control of HBV replication in 95% of patients ; 52.6%
developped resistance after a mean of 23 months. Lamivudine therapy was
associated with less severe liver lesions, reduction of fibrosis progression
and a lower mortality.



Conclusion

Our study establishes that in HBV/HIV co-infection :1. cirrhosis is frequent
(25%) and severe  (20% of deaths) ; 2. antiretroviral therapies (and
CD4<250/mm3) enhance liver lesions; 3. lamivudine provides a benefit in
reducing liver-related morbidity and mortality.

HEPATIC FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B VIRUS INFECTION CAN BE
PARTIALLY REVERSED BY IFN-GAMMA

S. Dooley1, B-E. Wang3, J-D. Jia3, W-F. Wu4, J-Z. Xiang4, P.R. Mertens5,
W-M. Cai2, H-L. Weng2

1Medical Clinic II, University-Hospital Mannheim, University of Heidelberg,
Heidelberg, Germany 2Institute of Infectious Diseases, First Affiliated
Hospital, Medical School, Zhejiang University, Hangzhou, China  3Liver
Research Center, Beijing Friendship Hospital, Capital University of Medical
Science, Beijing, China  4Eighth Hospital of Guangzhou, Guangzhou, China
5Department of Nephrology and Immunology, University Hospital, RWTH, Aachen,
Germany



Background

Hepatic fibrosis due to chronic hepatitis B virus (HBV) infection has an
enormous socio-economic impact.  Besides strategies aiming at virus
elimination, prevention or reversal of liver fibrosis is amenible. Given the
antifibrotic activity of IFN-?, a randomized open-labeled multicenter trial
was initiated to test IFN-? in HBV infection.



Methods

HBs-antigen positive patients with biopsy proven hepatic fibrosis (n=99,
stages 2-4 according to Scheuer criterion) were treated with diammone
glycyrrhizinate and potassium magnesium aspartate. Treatment with 50 mg
IFN-? i.m. on a daily basis for three months and on alternate days the
subsequent six months was performed in 66 randomly assigned patients.
Efficacy was evaluated by liver biopsy and serologic markers.



Results

54 patients in the IFN-? group and 29 patients in the control group
completed the study protocol. The hepatic fibrosis score was significantly
reduced in 63 percent of IFN-? treated patients compared to 24.1 percent in
the control group as assessed by a semiquantitative scoring system
evaluating both liver architecture and fibrotic deposits. Mean values for
total fibrosis score decreased from 13.8 ± 5.8 to 10.1 ± 5.1 in the IFN-?
group, whereas they were unchanged in controls (13.2 ± 6.8 versus 12.6 ± 4.8
after 9 months). The Scheuer fibrosis scoring system revealed 12 out of 54
patients improved ? 1 stage(s) in the IFN-? compared to 1/29 in the control
group. Antifibrotic activity may be attributed to decreased TGF-? signaling
via phospho-Smad2 and reduced number of activated, ? smooth muscle actin
positive hepatic stellate cells.

Journal of Viral Hepatitis
Volume 12 Issue 3 Page 300  - May 2005
doi:10.1111/j.1365-2893.2005.00633.x


The efficacy and safety of thymosin alpha-1 in Japanese patients with
chronic hepatitis B; results from a randomized clinical trial

S. Iino1,2, J. Toyota3, H. Kumada4, K. Kiyosawa5, S. Kakumu6, M. Sata7, H.
Suzuki8 and E. B. Martins9
Summary. Thymalfasin (thymosin alpha-1; T1) is a 28-amino acid polypeptide
that has shown efficacy in the treatment of chronic hepatitis B virus (HBV)
infection. The objective of this study was to evaluate the long-term,
dose-related efficacy and safety of T1 treatment in chronic hepatitis B
patients with positive HBV-DNA and abnormally high alanine aminotransferase
(ALT) levels. A total of 316 patients were randomized to receive either 0.8
or 1.6 mg of T1 monotherapy for 24 weeks. At the end of the 72-week
observation period (12 months after cessation of therapy), 36.4% of patients
in the 1.6-mg treatment group achieved normalization of ALT, 30% achieved
clearance of HBV-DNA by branched DNA vs 15% by transcription-mediated
amplification, and 22.8% achieved clearance of HBe-antigen. Patients in the
0.8-mg treatment group achieved similar efficacy rates, although patients
with advanced fibrosis demonstrated a significantly better response rate
when treated with 1.6 mg of T1 monotherapy vs 0.8 mg (as determined by
intragroup analysis; patients were not stratified by liver biopsy). All
adverse drug reactions were mild and most involved the fluctuation of liver
enzymes, which was most likely related to the positive immune effects caused
by the response to T1 treatment. Adverse event incidence was similar in the
1.6- and 0.8-mg treatment groups. In conclusion, T1 at doses of 0.8 and 1.6
mg exhibits long-term efficacy against hepatitis B with a good safety
profile.

Alimentary Pharmacology & Therapeutics
Volume 21 Issue 9 Page 1163  - May 2005
doi:10.1111/j.1365-2036.2005.02453.x


The safety of pegylated interferon alpha-2b in the treatment of chronic
hepatitis B: predictive factors for dose reduction and treatment
discontinuation
M. van Zonneveld*, H. J. Flink*, E. Verhey*, H. Senturk, S. Zeuzem, U. S.
Akarca§, Y. Cakaloglu¶, C. Simon**, T. M. K. So, G. Gerken, R. A. de Man*,
B. E. Hansen*§§, S. W. Schalm* & H. L. A. Janssen* for The HBV 99-01 Study
Group1
  Summary

Background: Treatment with interferon-alpha has been shown to be effective
in one-third of hepatitis B e antigen-positive chronic hepatitis B patients,
but is clinically associated with relevant adverse events.

Aim: To investigate the safety of pegylated interferon alpha-2b in 300
hepatitis B e antigen-positive patients with compensated liver disease.

Methods: Patients were treated with pegylated interferon alpha-2b for 52
weeks combined with either lamivudine 100 mg/day or placebo. Pegylated
interferon alpha-2b was administered for 100 g once a week for 32 weeks;
thereafter, the dose was reduced to 50 g once a week. Adverse events and
their effect on study medication were reported at monthly visits in a
standardized way.

Results: The most frequently reported side-effects were flu-like syndrome
(68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at
the injection site (29%). These symptoms typically occurred within the first
month of therapy and subsided during the course of therapy. Neutropenia and
thrombocytopenia induced by pegylated interferon alpha-2b increased the risk
of infections and bleeding complications, but these complications were rare
and mild. The frequency of all side-effects was not different between
patients treated with pegylated interferon alpha-2b combined with lamivudine
or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b
was reduced prematurely. Of these dose reductions, 36 (52%) were because of
neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent
reasons for early discontinuation were psychiatric side-effects (depression,
psychosis) and flu-like symptoms. Multivariate Cox regression analysis
showed that low neutrophil count at baseline and cirrhosis were independent
predictors of dose reduction or therapy discontinuation.

Conclusion: We conclude that in patients with chronic hepatitis B and
compensated liver disease prolonged pegylated interferon alpha-2b therapy is
safe, and that pre-existent cirrhosis and neutropenia are the most important
predictors of dose reduction or early treatment discontinuation.

THYMITAQ(R) Completes Enrollment in Pivotal Phase III Liver Cancer Study


    THYMITAQ(R) (nolatrexed dihydrochloride) May Offer Treatment Option for
                 Patients with Inoperable Primary Liver Cancer

     BERWYN, Pa., April 19 /PRNewswire/ -- Eximias Pharmaceutical Corporation
(Eximias) announced today that it has completed enrollment in its pivotal
Phase III clinical study with THYMITAQ in patients with inoperable primary
liver cancer (hepatoma, hepatocellular carcinoma or HCC). The Phase III
study,
coined the ETHECC(C) trial (Evaluation of THYMITAQ in Unresectable
Hepatocellular Carcinoma), is comparing survival in a randomized trial of
patients with inoperable primary liver cancer treated with THYMITAQ, an
investigational product, to patients treated with doxorubicin. There is no
treatment approved by the United States Food & Drug Administration (FDA) or
the European Agency for the Evaluation of Medicinal Products (EMEA) for
hepatocellular carcinoma. The company believes this is the largest Phase III
trial completed with unresectable liver cancer patients.
     Dr. Robert Gish, Medical Director of the Liver Disease Management &
Transplant Program at California Pacific Medical Center in San Francisco,
and
Dr. Yehuda Patt, Professor of Medicine and Chief of GI Oncology at the
University of New Mexico Cancer Center in Albuquerque, are the co-Principal
Investigators for the ETHECC trial.
     "Cirrhosis precedes HCC in about 60-80% of all patients diagnosed with
this cancer in the US. This coexisting cirrhosis makes treating liver cancer
a
major challenge for oncologists, hepatologists and liver surgeons," said Dr.
Gish. "Efforts have focused on the identification of chemotherapy agents
that
can be tolerated even by patients with compromised liver function."
     "We are eagerly awaiting the results of this randomized study," said Dr.
Patt. "There is a need for treatments in patients with HCC."
     "Primary liver cancer has no approved treatment in the United States,
and
patients who are unable to receive surgical treatment for this rapidly fatal
disease are in need of a viable treatment option. Now that enrollment in the
ETHECC trial is complete, we will conclude the required monitoring of the
patients and then carry out the analysis," said President and Chief
Executive
Officer Gail Schulze. "This also marks a significant milestone for the
company. This milestone is made possible due to the commitment of the
patients, the dedicated work of our investigators and their staffs, and our
employees."
     Eximias initiated the ETHECC trial in late 2000. Approximately 60
centers
in the United States, Canada, Europe and South Africa have participated in
the
study. THYMITAQ has been granted both Fast-Track and Orphan Drug status for
HCC in the United States and Orphan Medicinal Product status in the European
Union.

     About THYMITAQ (nolatrexed dihydrochloride)
     THYMITAQ, an investigational product, is a novel, non-competitive, high-
affinity antifolate that inhibits Thymidylate Synthase (TS) and disrupts DNA
replication, thereby killing tumor cells. THYMITAQ is one of the first
molecularly targeted products, using a high-resolution crystal structure of
the TS target and molecular modeling techniques to design a product that may
overcome some of the known resistance mechanisms of classical antifolates
and
multi-targeted antifolates. THYMITAQ is a registered trademark of Eximias
Pharmaceutical Corporation.

     About Hepatocellular Carcinoma (also known as HCC or primary liver
cancer)
     According to the American Cancer Society, nearly 18,000 Americans will
be
diagnosed with liver cancer in 2005. The incidence is expected to increase
in
the United States in the next decade due to the evolution of Hepatitis C and
cirrhosis, as well as the increasing prevalence of Hepatitis B, which are
possible contributing factors in patients diagnosed with liver cancer. HCC
is
even more common outside of the United States, with more than 500,000 people
worldwide afflicted with this form of cancer, with Hepatitis B being the
most
common cause of HCC worldwide.

     About Eximias
     Eximias Pharmaceutical Corporation is a privately-held pharmaceutical
company that engages in the acquisition, development and commercialization
of
products for the treatment of cancer and cancer-related disorders. The
company's current portfolio includes two therapeutic products: THYMITAQ
(nolatrexed dihydrochloride) and ORATAQ(TM) (an oral form of nolatrexed
dihydrochloride). For more information about Eximias, visit
http://www.eximiaspharm.com.



SOURCE Eximias Pharmaceutical Corporation
Web Site: http://www.eximiaspharm.com

J Hepatol. 2005 May;42(5):639-45.


Estimating the impact of hepatitis C virus therapy on future liver-related
morbidity, mortality and costs related to chronic hepatitis C.

Buti M, San Miguel R, Brosa M, Cabases JM, Medina M, Angel Casado M,
Fosbrook L, Esteban R.

Department of Hepatology, Hospital Vall d'Hebron, Barcelona, Spain.

BACKGROUND/AIMS: Chronic Hepatitis C virus (HCV) infection is common and
often produces a progressive disease. Some studies suggest that HCV related
complications will increase in the future. Our aim was to estimate the
future morbidity, mortality and costs of chronic HCV infection in a cohort
of patients infected by HCV and to evaluate the impact of HCV therapy.
METHODS: A mathematical model was used to project over the next 30 years,
the HCV related complications and costs in a cohort of 419,895 infected
patients representing the HCV infected population in Spain. The impact of
HCV therapy with peginterferon and ribavirin in this population was also
projected. RESULTS: A gradual decline in the infected population is expected
in the future, however, the proportion of patients with cirrhosis will
increase by up to 14% and morbidity associated with HCV infection by up to
10% by the year 2030 with a subsequent increment in HCV related costs.
However, treating from 10 to 50% of the HCV population will result in a
reduction of 6 and 26% in morbidity and 4 and 20% in mortality,
respectively. The cost per year of life gained ranges from 6078 for a
29-year-old patient to 8911 for a 59-year-old patient. CONCLUSIONS: In the
future, HCV infection mortality, morbidity and associated costs will
increase. Treatment of the chronic HCV infected population can eradicate the
infection, increase patients' survival and reduce the need for liver
transplantation, making this a cost-effective strategy.

PMID: 15826711 [PubMed - in process]

http://www.medscape.com/viewarticle/503672?src=mp

FDA Safety Labeling Changes: Viramune, Copegus

Yael Waknine


April 20, 2005 - The U.S. Food and Drug Administration (FDA) approved in
February revisions to safety labeling to notify healthcare professionals of
the following changes: use of nevirapine tablets and oral suspension may
cause serious hepatotoxicity and skin reactions, and intensive monitoring is
therefore required during early therapy; use of ribavirin plus peginterferon
alfa-2a therapy is contraindicated in patients with decompensated liver
disease; and use of atovaquone plus proguanil HCl tablets has been
associated with rare cases of anaphylaxis.

Nevirapine (Viramune) May Cause Serious Hepatotoxicity, Skin Reactions

On Feb. 24, the FDA approved revisions to the safety labeling for nevirapine
tablets and oral suspension (Viramune, made by Boehringer Ingelheim
Pharmaceuticals, Inc) to warn of the risk of potentially life-threatening
hepatotoxicity and skin reactions associated with their use.

The FDA emphasizes the need for intensive monitoring of patients for signs
and symptoms of these reactions during the first 18 weeks of nevirapine
therapy, particularly during the high-risk initial six-week period.

Liver function tests (LFTs) should be performed immediately in patients who
exhibit signs or symptoms suggestive of hepatitis and/or hypersensitivity
reaction, and in all patients who develop a rash during the first 18 weeks
of treatment.

Symptoms of hepatitis may include fatigue, malaise, anorexia, nausea,
jaundice, bilirubinemia, acholic stools, lever tenderness, or hepatomegaly.
A diagnosis of hepatotoxicity should be considered in this setting even if
LFT results are normal or alternative diagnoses are possible.

In addition, the FDA notes that the 200-mg daily regimen for nevirapine must
be strictly adhered to during the two-week lead-in period.

Nevirapine therapy should be discontinued and not resumed in patients who
experience severe hepatic, skin, or hypersensitivity reactions. According to
the FDA, hepatic injury has progressed in some patients despite
discontinuation of therapy.

Nevirapine is indicated for use in combination with other antiretroviral
agents for the treatment of HIV-1 infection.

Ribavirin/Peginterferon Alfa-2a (Copegus/Pegasys) Contraindicated in
Patients With Decompensated Liver Disease

On Feb. 25, the FDA approved revisions to the safety labeling for ribavirin
tablets (Copegus, made by Hoffmann La-Roche Inc) to advise of
contraindications and warnings associated with its use.

Use of ribavirin plus peginterferon alfa-2a combination therapy is
contraindicated in patients with chronic hepatitis C virus (HCV) infection,
with or without HIV coinfection, who demonstrate hepatic decompensation
(Child-Pugh score > 6; class B and C) prior to or during treatment. Its use
is also contraindicated in patients with autoimmune hepatitis.

The FDA also warns that patients with HCV infection and cirrhosis may be at
risk of hepatic decompensation and death when treated with alpha
interferons, including peginterferon alfa-2a (Pegasys, made by Hoffmann
La-Roche, Inc). This risk may be increased in cirrhotic patients coinfected
with HIV who are receiving highly active antiretroviral therapy.

Ribavirin in combination with peginterferon alfa-2a is indicated for the
treatment of adults with chronic HCV infection who have compensated liver
disease and who have not been previously been treated with alpha
interferons.

The FDA notes that ribavirin monotherapy is not effective for the treatment
of chronic HCV infection and should not be used.

<cut>

http://www.sptimes.com/2005/04/17/Floridian/Out_of_line.shtml

Out of line?
Instead of waiting their turn on a transplant list, some patients are using
Web sites to find willing donors.

By SUSAN ASCHOFF, Times Staff Writer
Published April 17, 2005

With as much dignity as a flimsy purple-and-aqua hospital gown allows,
Dolores Smith patiently waits while a technician looks for a vein in her
hand to insert an IV for yet another test. She is accustomed to being poked
and prodded and hooked to a machine, matter-of-fact about her body's
betrayal.

Even when drama might serve her, the Clearwater grandmother cannot play the
pity card.

As one of more than 100 people who've posted a plea to strangers on
www.MatchingDonors.com to give them an organ, hers is notably stoic:

No kidneys. Need transplant to get off dialysis.

Others are more demonstrative.

A New York man promises immortality in a documentary film he is making on
transplants. Another, from California, says he doesn't want to miss his
5-year-old's soccer games.

Some include a photo. Diana Phillips' glamor shot blows back long brunet
hair. Paul Cardinale stands tall in a tuxedo.

"I am 37 years old. I live alone and have 3 dogs. I want a new kidney before
it is too late," reads a posting by David Kleiner of Boca Raton.

Faced with a widening gap between supply and demand, people desperate for an
organ transplant are increasingly turning to the Internet. A New York woman
launched a cyber campaign for a lung in 2004. In Houston, a 32-year-old
newlywed created www.toddneedsaliver.com and advertised on billboards.

But MatchingDonors.com is the first commercial Web site pairing living organ
donors and recipients. With its first surgery in Denver in October, it
fanned a heated and highly politicized national debate about what is ethical
in the search for an organ.

Critics charge the Web site encourages schemers to prey on the sick, and the
sick to take cuts in line, bypassing a national waiting list.

More than a dozen transplant facilities across the country have since banned
surgeries involving Internet introductions. LifeLink, which coordinates
transplants in 15 west Florida counties, in January told some of its 421
kidney patients that surgeries will not be done at Tampa General, All
Children's in St. Petersburg and Southwest Florida Regional Medical Center
in Fort Myers with donors found on MatchingDonors.com.

The national agency that keeps the waiting list for organs from the deceased
condemned advertising. It is considering whether a cyberspace community is
as valid as one at church or workplace as a source of living donors.

"Access to organ transplantation isn't meant to be a popularity contest. In
living donations, if you have a family member or friend willing to donate,
everyone gets that. If you go trolling on the Internet, there's not the same
emotional pull," says Dr. Mark Fox, a professor at the University of
Oklahoma College of Medicine in Tulsa and co-chairman of a national
committee reviewing public organ solicitations.

Such tough ethical questions would be easier to answer if so many were not
dying for help.

There are almost 88,000 people in the United States on the waiting list for
a transplant.

Each day, 17 die waiting.

Looking for that special someone
While bioethicists, doctors and patients debate whether medical maladies
should read like the personals, pairings from MatchingDonors.com have
resulted in six successful surgeries.

Founded by a doctor and a Web entrepreneur in Massachusetts, the
15-month-old site has more than 1,500 people registered as donors and claims
2-million visits a month.

"We don't pay enough attention to altruistic people in the world," says Dr.
Jeremiah Lowney, an internist in Boston and MatchingDonors.com Inc. medical
director. "The common bond is they want to do good for other people."

Lowney was approached by patient Paul Dooley. Dooley makes his living from
CollegeJobBoard.com, a commercial site linking employers and employees. Why
not use the Web to match organ donors and recipients, Dooley suggested.

Living donor transplants began in the mid 1950s. Today more than 40 percent
of kidney transplants in the United States are from living donors. It is
illegal to pay for an organ. Recipients can cover a donor's travel, sick
leave and other expenses. A recipient's health insurance typically pays
medical bills for both.

When MatchingDonors.com announced its first transplant, it rattled a system
two decades old.

Robert Hickey, a 58-year-old retired health care executive in Colorado,
received a kidney from Robert Smitty, a 32-year-old truck driver from
Tennessee he met on the Web site. The Oct. 20 transplant was delayed two
days when Denver's Presbyterian/St. Luke's Medical Center learned how the
two had been introduced. Some accused Smitty of selling his kidney. He
denied it and invited an examination of his finances. Reporters found Smitty
had served prison time for selling LSD and owed $8,000 in child support.

Hickey, on the waiting list for a transplant for five years, said he wasn't
interested in Smitty's past.

"It felt good to see my name on the front page rather than a jail docket,"
Smitty told the Denver Post.

A National Kidney Foundation survey found nearly 1 in 4 Americans would
consider donating an organ, while alive, to a stranger.

Mary Christensen, a mother of three who lives in a small town in Minnesota,
says she was making supper when she saw a man pleading for a kidney on
television news.

"I thought, "I can do this.' I strongly believe the Lord gave us two kidneys
so we can donate one."

She phoned a hospital to volunteer but kept getting transferred. The easier
way, she decided, was to go online. She typed in a search for "organ
donation" and found www.MatchingDonors.com

Initially, Christensen planned to donate to the young man in the tux, but
his transplant institution would not permit Internet matches, she says. She
then found Jacqueline Stopani, a 64-year-old Arizona woman whose only
kidney, donated by her brother, quit working.

"It's just like it was meant to be," says the 47-year-old Christensen,
speaking by phone from her home last month, where she was recovering from
the March 1 surgery. Mayo Clinic in Scottsdale, Ariz., required that the two
meet in person before medical testing, so in December Christensen traveled
from Winthrop, population 1,400, to spend a weekend with Stopani in Arizona.

"We just talked about everything. We still talk almost every day. It's a
wonderful thing to give someone back their life," Christensen said during
the interview.

A week later, on March 18, a fistula shunt in Stopani's leg used for
dialysis ruptured, causing massive blood loss. She died at a Scottsdale
hospital, said her son Chuck, who posted her profile last fall on
MatchingDonors.com.

Decorous desperation
Every 13 minutes, another name is added to the national waiting list.

Every 90 minutes, on average, someone in the United States dies waiting for
a kidney, liver, lung or heart.

Dolores Smith, 56, chose to put her kidney disease on a mental back shelf
for more than 20 years. "My theory is, I didn't bother them (kidneys) and
they didn't bother me."

She was diagnosed in 1981. Blood showed up in her urine. She has polycystic
kidney disease. Cysts multiply in the kidneys and shut down function. A
Chicago resident, she reared her kids and worked as a word processor and
kept her blood pressure down. She and her husband, Kenneth, moved to
Clearwater three years ago. At Christmas, the faces of their 12
grandchildren march across a bookcase, each in a holiday-themed frame.

In summer 2003, Smith's kidney function plummeted to 15 percent and she
began dialysis. A surgically implanted tube creates a port for the
extra-large, 15-gauge needles which pump out the blood and return it
cleansed of toxins and excess fluids. Her inner right arm is purple and
chartreuse, bruised from four-hour sessions three days a week.

"In the back of my mind I thought, these kidneys will come back. When they
told me there was no hope . . ."

Smith put herself on the LifeLink transplant list. A-positive type blood.
High antibodies. Patients on the list are in end-stage organ failure.

Her daughter Kristin, 23, wrote to Oprah Winfrey:

"My older sister (Kimberly) attempted to donate, but because of her own
health issues, her doctor could not condone the procedure. . . . I would
love nothing else than to donate a kidney for my mother, (but) my brother
(29-year-old Michael) has inherited PKD and I will need to reserve that
sacrifice for when his kidneys eventually fail."

Oprah did not write back.

Smith (her family and friends call her Dolly) signed up with
MatchingDonors.com for $97 a month after a friend showed her a newspaper
article.

"I heard from a guy in India who says he has many friends who would help
me," she says with skepticism. Another wrote: "Hi. I am 42 yr old healthy
male. I am very willing to run what ever test need to be done. I am asking
for all expences(sic) and a gift of 40k."

MatchingDonors.com says it deletes messages it finds seeking compensation.
Clients pay up to $295 a month, or nothing at all if they cannot afford the
fees, Dooley says of the nonprofit, private company.

If a donor and patient connect - exchanging e-mails or phone calls, then
deciding to proceed - medical tests, psychological screening and surgery are
handled by regional transplant centers.

Smith referred several promising responses to LifeLink. Then in January, the
Tampa agency phoned to say it will not perform surgeries with donors found
on www.MatchingDonors.com The Web site charges fees, says LifeLink
spokeswoman Ruth Bell, and has not been endorsed by the United Network for
Organ Sharing, or UNOS, which oversees transplants.

"This is an issue nationally that the transplant community has got to come
to grips with," Bell says. "In most instances, people who go through this
process (living donation) have had a longstanding relationship."

Last year LifeLink handled 67 kidney transplants with living donors. Of
those, 40 were blood relatives. The others were "emotionally related" -
spouses and friends.

"Is it ethical," counters Lowney, "not to allow people to search on their
own?

"We're not subverting the organ donor process by bringing new people into
the system."

Now calling number 24,321
The national transplant community operates in a system established by
Congress in 1984 to find and allocate organs. UNOS is a nonprofit agency
under contract with the federal government to maintain the waiting list and
operate the Organ Procurement and Transplantation Network, or OPTN. OPTN's
membership includes transplant coordinators, hospitals, volunteers and other
groups that act as local links: They find donors and transport organs to
recipients matched by blood type, genetics, organ size, medical urgency,
time on waiting list, and geographic proximity.

The goal is to keep the transplant system fair and fed.

"In the very early days, there was no national organization and there were
very few transplant centers. It was kind of a club. The doctors talked to
each other," says Dr. Richard Howard of Shands at the University of Florida.
He is president of the American Society of Transplant Surgeons.

When surgery centers and patients proliferated, the government set up a
national network. "It's not perfect," says Howard, "but I think it's the
fairest system."

The problem is the gap between viable organs and desperate patients: Despite
a record 27,000 organs transplanted last year, the waiting list increased to
almost 88,000.

"We've noticed this trend," says Fox, who chairs UNOS' ethics committee, "of
people using different media, from a classified ad to chat room, to find an
organ. It has changed the landscape" of organ donation.

Todd Krampitz, who got the liver transplant in Houston Aug. 12 after
advertising on two billboards, did multiple media interviews, often with his
wife, Julie. His Web site includes a Bible verse: "With God all things are
possible."

A family in another state, after seeing the publicity, donated their
deceased loved one's liver specifically to Krampitz. Such directed donations
are permitted. But critics say Krampitz "cut in line." When he got his
liver, there were 17,000 people on the waiting list for one.

The need for kidneys is the most urgent.

Howard, a transplant surgeon for almost three decades, operated on a woman
on dialysis 26 years. Most patients cannot wait that long before their
health deteriorates, he says. Drugs have cut the initial risk that a
patient's body will reject a transplanted organ to less than 20 percent. But
almost half of those transplanted will be dead within 15 years due to loss
of organ function and other complications.

A kidney walks into a bar
If Dolores Smith is almost bashful about asking for a kidney, Alex Crionas
broadcasts for one. A 19-year-old community college student when he was
diagnosed with a progressive kidney disease called focal segmental
glomerulosclerosis, the 29-year-old has been on dialysis 20 months.

He has no siblings to donate and O-type blood.

So he created a Web site, www.selflessact.net - "You only need one," reads
the headline.

He moved to Florida because the wait for a transplant here is one-third as
long as in New York.

He phoned an Orlando radio show granting wishes to announce he wants a
kidney.

And that was before he got a lot of publicity.

In October, Crionas says he met Patrick Garrity at a party. The 23-year-old
offered to be a donor and the two were tested at LifeLink. Then
communication with the transplant coordinator abruptly ceased, says Crionas.
In February, LifeLink told him it would not proceed because he has a Web
site, he says.

Crionas complained.

Loudly.

He's been featured in a dozen Florida newspapers and on CNN. He's received
more than 200 sympathetic e-mails. He threatens to sue.

"I went to the media because I wanted to change LifeLink's mind. I wanted
them to approve me."

LifeLink officials declined to comment on Crionas' case, citing medical
privacy laws.

"Having a Web site in and of itself does not rule out a living donation" at
LifeLink, says Bell.

Crionas, dressed in an orange polo shirt and jeans, stretched out in a
recliner inches from his computer keyboard in a one-bedroom apartment in
Orange City, north of Orlando, says he is being punished for initiative.

"Some ethicists imbue Web sites with some kind of hypnotic power. I think
people want to donate to someone they know. Simply by reading my story,
they've established a relationship with me."

He is what some experts fear: "You can't decry it (the Web) on its face, but
it does give some people a leg up," says Howard of the American Society of
Transplant Surgeons. He and others worry that billboards and Web sites give
the physically attractive, the technologically adept, the financially flush,
dibs on an organ another person needs more.

Garrity, Crionas' friend and would-be donor, says if he needed a kidney,
"not only would I have a Web site but a commercial on the Super Bowl."

He works undercover security at a Winn-Dixie and lives with his grandmother
in Apopka. In March he met with his Army National Guard commander to find
out if he'll have to quit if he's minus a kidney. Maybe, the commander says.
Probably.

But Garrity's real calling is standup comedy. He does the best Christopher
Walken impression, bar none, says Crionas.

"I love being on stage," Garrity says. He jokes about the military, and
dating, and, likely some day, surgery.

"Basic training sucks. You lose all your privacy," he says from the stages
of Orlando improvs and a Holiday Inn in Altamonte Springs. "And why the hell
do people who snore fall asleep first?"

Crionas does comedy bits, too.

"People ask me, what do you want for Christmas? I think I'd want a sharp
knife and a ticket to India."

Rescue me
Dolores Smith remains cautious with her Internet debut. She does not want to
reveal too much to strangers.

"Oh c'mon now," she says. "No one is doing this out of the goodness of their
heart." Yet that is whom she hopes she'll find on www.MatchingDonors.com

After LifeLink said it will not handle the site's matches, Smith moved her
paperwork to Northwestern Memorial Hospital in Chicago. Alex Crionas and
Patrick Garrity are transferring their files to TransLife, the coordinator
for the 10-county Central Florida region.

Still angered by the implication that his efforts are somehow tawdry,
Crionas corrects those who use the word "solicit."

"A kidney," he says, "is not a quarter."

Susan Aschoff can be reached at 727 892-2293 or aschoff@...

THE TORONTO STAR

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ype1&c=Article&cid=1114033811063&call_pageid=968332188774&col=968350116467&DPL=I\
vsNDS%2f7ChAX&tacodalogin=yes

MPs back compensating all hep C victims

Tory's motion wins Liberal support
Could take time to make cash available

SEAN GORDON
OTTAWA BUREAU

OTTAWA - In an abrupt about-face, the Liberal government has supported an
opposition motion to extend the federal compensation package for hepatitis C
sufferers infected through tainted blood.

While Health Minister Ujjal Dosanjh said he is sympathetic to the plight of
tainted-blood victims, he warned money would not flow immediately to those
not originally eligible for compensation because the funds are held in trust
and controlled by the courts.

A total of $1.1 billion in federal compensation has been made available to
those infected between 1986 and 1990, a period for which the government has
admitted liability.

Dosanjh explained the change of heart, saying, "we agree because it supports
what we as a government have already been doing. While we are supporting the
motion, we recognize the limitations and flaws of that motion.

"It must be made clear that compensation can only be made once the
discussions (currently) under way have concluded," Dosanjh told the Commons.

Conservative health critic Steven Fletcher introduced the motion April 4.
After a series of procedural delays, it was passed last evening by a vote of
269-0.

"It is a victory in the sense that there is now, finally, a recognition that
all the victims of hepatitis C deserve and require compensation. The
challenge is going to be to actually get these people the money," Fletcher
said after the vote.

Because fewer compensation claims have been made than originally
anticipated, the fund is believed to have a surplus, the size of which is to
be established by an actuary's report due this June.

Fletcher, who represents Charleswood-St. James-Assiniboia, wanted the
program widened to allow anyone infected by tainted blood transfusions to
seek compensation.

"The fight is not over. The Liberals have really been disingenuous in their
whole approach to this issue....

"The only thing that's changed is we may be on the eve of an election and
that has played heavily on the minds of the Liberals," he said.

Dosanjh said last November he was prepared to entertain changes to the
compensation plan, but that it would be up to the courts to decide whether
some of the unclaimed funds could be redistributed.

He also said the government has been negotiating with lawyers representing
the victims for months.

At least one victim bitterly predicted prolonged delay.

"It looks like it's a continuation of their history of stalling on this
issue and waiting for victims to die," activist Mike McCarthy told Canadian
Press. "I don't see any new compassion here."

McCarthy said there are about 5,000 excluded victims and the government
should be prepared to pay up whether the existing fund has a surplus or not.

http://www.joplinglobe.com/story.php?story_id=182241

In Our View: Regulating tattoos

4/21/05

Oklahoma has the toughest tattoo law  the land. Simply put, it makes
tattooing illegal. A bill appearing before the House Health and Human
Resources Committee would have lifted the ban and imposed sanitary
regulations on those who do the tattooing. Unfortunately, it was never
heard.

The fact is that people will get tattoos, whether they are legal or not, and
body artists will ink those designs even though they could face misdemeanor
charges. What the bill would have done is make it safer for those who get
tattoos by legalizing and regulating the industry.

Supporting the proposal were the Oklahoma Department of Health and
physicians' groups, according to The Associated Press. They fear that using
dirty needles, for instance, could spread life-threatening diseases.

According to the AP, Oklahoma has seen a 78 percent increase in hepatitis C
infections between 2000 and 2003. Thirty-four percent of those infected had
tattoos. A 2004 outbreak of hepatitis B in one Oklahoma county may be linked
to unsanitary home tattooing.

The bill should be taken up and sent to the House for consideration. Maybe
this isn't a major health issue for some legislators. But health
professionals believe that it is.