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Week Ending: July 9th, 2005
Alan Franciscus
Editor-in-Chief
To download pdf version click here
This Issue:
• The American Liver Foundation Condemns Motion Picture Bewitched for Tasteless Hepatitis C Joke
• Official Donated Blood Despite Having Hepatitis B Antibody
• Pakistan Records a Decline in Hepatitis B, Surge in Hepatitis C
• Drinks Link in Female Liver Cancer
• Hepatitis C 'Time Bomb' Shock
• Dynavax Tests Hepatitis B Vaccine
• Liver Transplant Prognostic Models Have Limited Use
• Insulin Resistance Contributes to Liver Fibrosis in Hep C
• Long-Term Use of Adefovir Dipivoxil Improves Hep B
• Haemophiliacs Infected with HIV, Hepatitis C 'Traced'
• Berg Bill Gets Police Support
• Hep B Transmission with Blood Glucose Monitoring
• Mass Spectrometry for Genotyping Hepatitis C Virus: A Promising New Approach
July 2nd, 2005
The American Liver Foundation Condemns Motion Picture Bewitched for Tasteless Hepatitis C Joke
SourceURL:http://biz.yahoo.com
Comedy Unfairly Stigmatizes, Stereotypes Millions of Sick People in America
NEW YORK, July 2 /PRNewswire/ -- The American Liver Foundation (ALF) today condemned the Nicole Kidman film Bewitched for an insensitive joke regarding people with hepatitis C. In the film, a woman discourages romantic advances from a character played by Michael Caine, by saying she has hepatitis C. Bewitched was written by Nora Ephron and released by Columbia Pictures.
"Tragically, this remarkably tasteless comment plays into the stigma that many people with hepatitis C have to cope with every single day," said Frederick G. Thompson, President and CEO of the American Liver Foundation. "I can't imagine anyone in Hollywood making a joke about HIV infection, for example. But because the public is so uneducated about hepatitis C, it apparently seems acceptable to trivialize the disease in a comedic context, at the expense of millions of hepatitis sufferers. The American Liver Foundation has received hundreds of calls and e-mails from movie-goers expressing outrage and dismay."
There are over 4 million people who are or have been infected with hepatitis C; 2.7 million of whom are chronically infected. Hepatitis C is the major reason for liver transplantation in this country and about 10,000 people die each year from complications of hepatitis C. It is projected that the death rate will triple over the next 10-to-20 years unless something is done.
The symptoms of hepatitis C are often hidden until severe liver damage occurs, which is often too late for effective treatment. Untreated, chronic hepatitis can lead to scarring of the liver (cirrhosis), liver cancer, and liver failure.
The ALF has 26 chapter offices nationwide, with the newest just created in Hawai'i. It provides educational workshops and seminars, runs support groups, works with the media to increase the awareness of hepatitis and other liver diseases, and meets with local, state and federal policy makers to affect positive change. ALF supports research, primarily in two ways: first, by advocating federal policy makers to secure increases in government funding for liver disease; and second, by directly funding young scientists in order to attract them to the lifelong study of liver disease and patient care. ALF sponsors numerous fundraising events and campaigns to support all of these efforts. The toll-free HelpLine, providing information on liver health and disease, is: 1-800-GO LIVER; the Web site is: http://www.liverfoundation.org.
About the American Liver Foundation
The American Liver Foundation (ALF) is the nation's leading nonprofit organization promoting liver health and disease prevention. ALF provides research, education and advocacy on behalf of those affected by hepatitis and other liver-related diseases. The toll-free number is 1-800- GO LIVER, and the Web site is: http://www.liverfoundation.org.
Source: American Liver Foundation
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Official Donated Blood Despite Having Hepatitis B Antibody
SourceURL:http://asia.news.yahoo.com
(Kyodo) _ A blood donation promotion center operated by the Japanese Red Cross Society said Saturday that one of its senior officials, a 51-year-old woman, repeatedly donated blood despite having tested positive for the hepatitis B antibody.
The center in Shiga Prefecture sent the blood to four medical facilities, it said, adding the blood is safe and there are no reports of secondary infection so far.
The official was quoting as saying, "I wanted to cooperate (in collecting blood) because we faced a shortage of blood."
According to the center, she started donating blood in April 1994 but the hepatitis B antibody was detected in June 1997. She resumed blood donations after receiving the hepatitis B vaccine in 2000.
After that, she donated blood six times between August 2001 and December 2004 by using fake names and addresses, the center said.
Fujio Nishizawa, corporate secretary at the center, said, "It's regrettable that we failed and damaged the public trust. We will hold reeducation sessions for our staff so we will not repeat this."
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Pakistan Records a Decline in Hepatitis B, Surge in Hepatitis C
SourceURL:http://www.dailytimes.com.pk
KARACHI: Hematologists have called for an integral approach to address a surge in Hepatitis-C in the country, while a decline has been recorded in the prevalence of Hepatitis-B.
Addressing the continuing medical session on Viral Hepatitis on Friday at the Ziauddin Medical University, Dr M Nasir Laique, a consultant gastroenterologist, emphasised on the twin diseases, chronic hepatitis B and C, and stated them to be part of the global health problems.
He said while the worldwide occurrence of the two is more than 300 million people, its incidence in Pakistan ranges between 6 to 10 percent, adding that public awareness could help combat the ailment effectively.
Regarding medications, he said there was a provision for effective vaccination for Hepatitis-B, but no active immunisation of Hepatitis-C. However, he reiterated that a sustained response rate of up to 80 percent however could be achieved with proper management of Hepatitis-C.
“The scenario remains gloomy for Chronic Hepatitis B patients as its response ratio is not more than 25 percent even with treatment,”he revealed.
Dr I A Khan, a senior consultant gastroenterologist, in his speech highlighted the transmission modes of the Hepatitis B and C virus, including blood transfusion, percutaneous and sexual transmission, transplantation, dental procedures and application of non-sterilised knives and blades by barbers. He also warned of ear piercing that could transmit the H virus if proper precautions are not practiced.
In the given situation, he stressed that the transfusion patients or organ recipients must undergo screening to ensure safety, while those doing health care, emergency, medical and public safety workers after needle-stick injury or mucosal exposure to H positive blood also need to be necessarily screened.
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July 4th, 2005
Drinks Link in Female Liver Cancer
SourceURL:http://dailytelegraph.news.com.au
By ANNA PATTY Political Reporter
AN alarming rise in liver cancer cases among women is being partly blamed on binge drinking.
The number of women diagnosed with liver cancer has doubled in the past decade.
Experts say cirrhosis of the liver, linked to alcohol and hepatitis, is behind the increase.
The latest NSW figures on cancer from 1994 to 2003 show a 97 per cent increase in liver cancer --with a 75 per cent increase in the number of deaths.
Liver cancer rates among men increased by less than 50 per cent.
James Bishop, chief executive officer of the Cancer Institute NSW, which compiled the data, said while the number of people struck with liver cancer was not huge, there had been a notable rise in percentages.
"It is an area of concern there is a higher incidence in females than in males," he said.
"We'd like to understand the reasons.
"We believe the risk factors are prior exposure to hepatitis and alcohol abuse and these would explain the increasing incidences and differential between males and females."
Sydney woman Kylie O'Dwyer said she believed females were drinking more when they were out.
"I see women drinking eight to 10 drinks in a night. I'm not drinking so much at the moment, but was drinking more and partying every night while I was overseas."
Prof Bishop said liver cancer in people of Asian background was 240 per cent higher than other people in NSW.
Alex Wodak, the director of St Vincent's Hospital's Alcohol and Drug Service, said there had been a slight increase in alcohol consumption in younger people between 1995 and 2005.
Hepatitis C was also on a rapid rise, with 220,000 Australians having been exposed to the disease which can lead to liver cancer. In 2001 there were 16,000 new infections compared to 11,000 in 1997.
Increasing rates of intravenous drug use were also linked to the rise in hepatitis cases.
There were 361 new liver cancer cases in NSW in 2003 --244 male and 117 female.
This represented 1.4 per cent of all cancers in males and 0.8 per cent of those in females.
Of the 276 deaths from liver cancer, 193 were males (2.8 per cent of all male cancer deaths) and 83 females (1.5 per cent).
The average age of diagnosis was 69 in males and 74 in females. Men and women in Sydney's southwest had a higher incidence of liver cancer and mortality compared to NSW as a whole. Death rates were much lower in the Hunter and New England areas.
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Hepatitis C 'Time Bomb' Shock
http://www.eadt.co.uk
BY REBECCA SHEPPARD
AN EXPERT in infectious diseases has warned there are an estimated 2,700 undetected carriers of Hepatitis C in Suffolk that could have a potentially fatal "ticking time bomb" in their liver.
Dr Torbjorn Sundkvist, consultant in communicable disease control at the Suffolk Health Protection Unit, has now urged doctors to identify as many carriers of the blood-borne viral infection as possible.
In his latest quarterly newsletter, Germ Warfare, Dr Sundkvist said there are approximately 3,000 carriers in Suffolk and 90% are undetected.
Of those, 300 are not drug-related, 1,500 are among current drug users and 1,200 are former drug users.
This equates to every GP having possibly three undetected carriers on their list from a large group of patients who may have experimented with drugs in their youth, Dr Sundkvist said.
About 30% of those who are Hepatitis C-positive can develop chronic hepatitis, liver cirrhosis and, in some cases, liver cancer. Injected drug users are the highest risk, with the number of cases expected to escalate, as the infection progresses from drug use in the 1970s and 80s.
Dr Sundkvist said: "Our main focus is to find the undetected, previous drug users, who are now unlikely to associate themselves in any way with drug use.
"Some could have experimented with injecting drugs for just a short time, decades ago, but could have a time bomb ticking in their liver which could lead to death."
Statistically, every GP may have one patient who has Hepatitis C from a blood transfusion or haemophilia, which would already be under hospital care and most likely detected, he said.
Dr Sundkvist said the Department of Health should make extra money available for the treatment of Hepatitis C, which is a chronic, or ongoing, illness. The treatment of a patient with the infection can cost about £10,000 a year, but one liver transplant costs £250,000.
He said: "As usual there is no extra money available for this treatment, which has to compete in cash-strapped PCTs [Primary Care Trusts] with cancer treatments and other priorities.
"By not earmarking money for Hepatitis C treatment the UK is in the undignified position of treating 10 times fewer Hepatitis C patients than Germany or France."
However, he said there are public health interventions that can be made that are not costly and could benefit patients, if doctors can identify carriers of the infection.
Although Dr Sundkvist did not advocate the mass screening of patients he said those who had ever injected drugs should be tested.
However, Dr Gareth Richards, president of the Suffolk division of the British Medical Association, which represents GPs, said finding three carriers from their lists would be like searching for a needle in a haystack.
He added: "The only treatment we have for Hepatitis C is expensive and not terribly effective. When the NHS as a whole in Suffolk is overspent you have to ask 'do you want to find people who are going to cost £10-15,000 to treat year after year?'
"There are a lot of priorities. If the Government earmarked money for Hepatitis C we would have to look at it. I think probably there are more important things. Of course, it is very important if you have got Hepatitis C but if you're looking at the amount of money, would you be better off spending it on health education, needle exchanges for drug addicts so they are less likely to pass it around and safe sex messages?
"We still get a lot of people dying from heart disease, which is preventable, and poorly managed diabetes. They cost money to treat but have greater returns in terms of lives saved then Hepatitis C."
A spokeswoman for the Department of Health said: "It is down to the Strategic Health Authority to decide the extent of their budget they spend on specific campaigns or diseases.
"There's an overall NHS budget given to the Strategic Health Authority and then they spend it according to their priorities.
"No money is ring-fenced for anything anymore. Centrally, the Department of Health feels that Hepatitis C is potentially a very big problem.
"The chief medical officer has put together an action plan for Hepatitis C and there is the Face It campaign, which targets people who may have been exposed to Hepatitis C. There is also a helpline and website."
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Dynavax Tests Hepatitis B Vaccine
SourceURL:http://www.bizjournals.com
Susan L. Thomas
Making a play for the potentially lucrative hepatitis B market, Dynavax Technologies Corp. has begun late-stage trials of an experimental vaccine that, if approved, would go head-to-head with vaccines sold by pharmaceutical heavyweights GlaxoSmithKline and Merck & Co. Inc.
The Berkeley company, public for less than two years, says it could file a marketing application for its vaccine in 2007, after finishing a Phase III trial that tests its vaccine against GlaxoSmithKline's Engerix-B.
Dynavax is hoping that by showing it can overcome the shortcomings of existing vaccines, it can squeeze in on GlaxoSmithKline and Merck's duopoly position and potentially expand the $1 billion market for hepatitis B vaccines. The company's strategy is straightforward: Target underserved populations - namely high-risk groups and health care and emergency response workers - in countries where market conditions foster competition among private vaccine makers.
Besides the Phase III trial begun in June to study the vaccine in older adults, Dynavax intends to start a Phase III trial in younger adults in early 2006. The company also plans to conduct additional trials in selected high-risk populations, such as dialysis patients.
"We believe that that product has a very clearly differentiated profile," Dynavax CEO Dino Dina said.
Dina, former head of Chiron Corp.'s vaccine business, said Dynavax was looking for a vaccine that would obviate the need for a course of three shots. One drawback of current vaccines is that many people do not complete the full course. That means they never receive full immunity to the highly contagious disease. Although Dynavax's vaccine is designed to be taken in the traditional three-dose regimen, early trial results showed that it was 79 percent effective after one dose, compared with Engerix-B, which was only 12 percent effective after one dose.
What's more, Dina said, adults with diseases such as kidney disease or HIV require aggressive vaccine regimens, costing in excess of $1,000, and only get about a 50 percent response rate. Early studies, Dina said, show Dynavax's vaccine can give this population 100 percent immunity after three shots, thus substantially cutting the cost - and time - involved with treatment.
Dynavax's vaccine is based on immunostimulatory sequences, or ISS, which are short DNA sequences that are designed to stimulate immune responses. By combining ISS with the HBV surface antigen in a vaccine, Dynavax's vaccine then targets what's called the Toll-Like Receptor 9. TLR-9 acts to enhance the body's immune system response. Dina said the vaccine would be a "first-in-class" technology on the market, which grew out of discoveries made 10 years ago.
The Phase III randomized, double-blind trial will enroll about 400 patients, age 40 to 70, in Singapore, Taiwan, South Korea and the Philippines. The goal is to show protection four weeks after the third vaccination. Dynavax anticipates completing the trial in the second half of 2006.
Dina said its marketing and commercialization strategy will differ, depending on the patient group. The company will look for distribution partners in the countries where it plans to market the vaccine.
Chiron, or other firms that may want to distribute updated vaccines are possible partners. Dynavax also is in the early stages of discussing a commercialization agreement with the Swiss firm Berna Biotech, with which its has a long-term supply contract.
Dynavax, which has posted a $90 million loss since its inception, is studying its technology in early trials for flu and anthrax vaccines.
News of Dynavax's late-stage trial and its potential marketing application bumped up the company's stock on June 24, but questions remain.
Piper Jaffray Co. analyst Mark Karvosky said in a report in June that Dynavax's plans to evaluate the vaccine in high-risk and difficult-to-treat populations are positive because they will help the company define its market opportunity. Although the data looks positive so far, Karvosky said he wanted to learn more about Dynavax's commercialization strategy and is awaiting more detailed information from its midstage trial.
slthomas@bizjournals.com | 925-598-1432
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July 6th, 2005
Liver Transplant Prognostic Models Have Limited Use
SourceURL:http://www.gastrohep.com
The latest issue of Liver Transplantation demonstrates that currently available prognostic models of mortality after liver transplantation have only a limited role in clinical practice.
A model that can accurately predict post-liver transplant mortality would be useful for clinical decision making.
It would also help to provide patients with prognostic information, and would facilitate fair comparisons of surgical performance between transplant units.
Dr van der Meulen and colleagues from England carried out a systematic review of the literature.
5 models were assessed according to statistical validity, model evaluation, and practicality – Liver Transplantation
The research team assessed the quality of the studies that developed and validated prognostic models for mortality after liver transplantation.
The team also validated existing models in a large data set of patients transplanted in the United Kingdom and Ireland between 1994 and 2003.
The team identified 5 prognostic model papers and found that the quality of the development and validation of all prognostic models was suboptimal.
The team obtained this result according to an explicit assessment tool of the internal, external, and statistical validity, model evaluation, and practicality.
The researchers noted that the discriminatory ability of the identified models in the UK and Ireland data set was poor.
Due to the poor quality of the reporting, the team could not always determine the methodology used for the development of the model.
Dr van der Meulen's team concluded, “These findings demonstrate that currently available prognostic models of mortality after liver transplantation can have only a limited role in clinical practice, audit, and research.”
Liver Transpl 2005: 11(7): 814-25
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Insulin Resistance Contributes to Liver Fibrosis in Hep C
SourceURL:http://www.gastrohep.com
This month's issue of American Journal of Gastroenterology reports that insulin resistance contributes to liver fibrosis in chronic Hepatitis C infection, and is a predictor of sustained response to antiviral therapy.
Dr Raymond D'Souza and colleagues from England assessed whether insulin resistance is associated with liver fibrosis in patients with chronic Hepatitis C.
The researchers also assessed whether there were any differences in insulin resistance between Asians and the indigenous Caucasian population.
The research team ascertained whether insulin resistance is associated with sustained virological response to antiviral therapy.
56% completing a course of antiviral treatment had a sustained virological response – American Journal of Gastroenterology
The team determined insulin resistance in 59 patients with Hepatitis C, of which 30 were Caucasian and 29 were Asian, prior to starting antiviral therapy.
The researchers measured insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR).
The relationship between insulin resistance and biochemical, virological, and histological data together with response to antiviral therapy was determined.
The team found, using multivariable analyses, that insulin resistance correlated positively with the stage of fibrosis.
Higher degrees of insulin resistance were found in those with greater degrees of fibrosis.
The team noted that this relationship remained after excluding cirrhotic patients, or after adjusting for other factors associated with fibrosis in univariable analyses.
The researchers observed that insulin resistance was significantly higher in Asians than Caucasians.
The team noted that 56% of patients completing a course of antiviral treatment had a sustained virological response.
Multivariable logistic regression identified Hepatitis C virus genotype 3 as being associated with a higher odds of a sustained virological response.
In addition, the team identified lower fasting glucose levels, and lower aspartate transaminase levels to be associated with a higher sustained virological response.
After adjusting for these variables, Asian ethnicity, and higher fasting insulin levels were associated with a poorer virological response to therapy.
The team noted that poorer virological response to therapy was also associated higher levels of homeostasis model assessment of insulin resistance.
Dr D'Souza's team concludes, “Insulin resistance contributes to liver fibrosis in chronic Hepatitis C infection, and this relationship is not genotypic specific.”
“Asian patients had higher insulin resistance than Caucasians.”
“Insulin resistance is also an important predictor of sustained response to antiviral therapy.”
Am J Gastro 2005: 100(7): 1509
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Long-Term Use of Adefovir Dipivoxil Improves Hep B
SourceURL:http://www.gastrohep.com
In Hep B e antigen-negative chronic Hepatitis B, the benefits achieved from 48 weeks of adefovir dipivoxil are lost when treatment was discontinued, but maintained if treated for 144 weeks, reports this week's New England Journal of Medicine.
Treatment with adefovir dipivoxil for 48 weeks resulted in improvements in patients with Hepatitis B e antigen-negative chronic Hepatitis B.
Treatment showed histologic, virologic, and biochemical improvements.
Dr Stephanos Hadziyannis and colleagues evaluated the effect of continued therapy as compared with cessation of therapy.
Hepatitis B DNA levels were less than 1000 copies per ml in 79% of patients at week 144 – New England Journal of Medicine
The researchers assigned 185 Hepatitis B e antigen-negative patients with chronic Hepatitis B to receive 10 mg of adefovir dipivoxil or placebo.
The treatment was given once daily for 48 weeks at a ratio of 2:1.
After week 48, the team randomly assigned patients receiving adefovir dipivoxil either to receive an additional 48 weeks of the drug or to switch to placebo.
The researchers switched patients originally assigned to placebo to adefovir dipivoxil.
Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy by the researchers.
The primary end points were changes in Hepatitis B virus DNA and alanine aminotransferase levels.
The researchers found that treatment with adefovir dipivoxil resulted in a median decrease in serum Hepatitis B DNA of 3.5 log copies per millilitre at 96 weeks.
The team compared this to 3.6 log copies per ml at 144 weeks.
The researchers observed that Hepatitis B DNA levels were less than 1000 copies per ml in 71% of patients at week 96 and 79% at week 144.
In the majority of patients who were switched from adefovir dipivoxil to placebo, the benefit of treatment was lost.
The team noted that the median change in Hepatitis B DNA levels from baseline, were -1 log copies per ml and only 8% had below 1000 copies per ml at week 96.
The researchers observed that side effects during weeks 49 through 144 were similar to those during the initial 48 weeks.
In addition, resistance mutations rtN236T and rtA181V were identified in 6% of patients after 144 weeks.
Dr Hadziyannis' team concludes, “In patients with Hepatitis B e antigen-negative chronic Hepatitis B, the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued.”
“In patients treated for 144 weeks, benefits were maintained, with infrequent emergence of viral resistance.”
NEJM 2005: 352(26): 2673-81
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July 7th, 2005
Haemophiliacs Infected with HIV, Hepatitis C 'Traced'
SourceURL:http://www.examiner.ie
By Evelyn Ring
EXPERTS believe they have traced every haemophiliac infected with HIV or hepatitis C as a result of receiving contaminated blood products.
A look back programme launched at the end of June did not pick up any more infected haemophiliacs.
Of the 160 haemophiliacs who have been infected with HIV, 64 have died while of the 220 infected with hepatitis C, 20 have died.
All haemophiliacs are treated with a synthetic clotting agent introduced in 1997 to eliminate the infection risk from products made from blood donations.
Before the June programme began, experts believed the number of unidentified haemophiliacs who might have received infected products prior to 1992 would be "significantly" less than 10.
National haemophilia director at the National Centre for Hereditary Coagulation Disorders (NCHCD), Dr Barry White, said the latest campaign was the end of a long process that involved three previous targeted look back programmes, two optional national screening programmes and a long term testing programme Irish Haemophilia Society (IHS) member Brian O'Mahony said three helplines were opened during the week-long campaign.
The NCHCD received 49 telephone calls; the Irish Blood Transfusion Service (IBTS) received 90 and the IHS received seven.
Of the 43 people who called the NCHCD, 34 had received blood transfusions and were referred onto the IBTS. It was later established that none of those who contacted the centre had received the clotting factor concentrates to treat their condition.
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Berg Bill Gets Police Support
SourceURL:http://www.ukiahdailyjournal.com
North Coast Assemblywoman Patty Berg recently gained support for her needle-exchange bill from law enforcement groups working to slow the spread of AIDS and Hepatitis-C.
Berg, D-Eureka, has authored similar bills on the subject of needle-exchange programs for three years and finally gained support from organizations that have traditionally opposed such measures.
The California Peace Officers' Association and the California Narcotic Officers' Association has spent more than two years trying to block Berg's efforts to ease restrictions on clean needle programs, which was eventually vetoed by Gov. Arnold Schwarzenegger last year.
After long negotiations with law enforcement groups, health officers and Schwarzenegger's staff, Berg agreed to make changes to Assembly Bill 547 to satisfy opposition to her measure.
The bill is designed to eliminate a section of state law that requires cities and counties to declare a health emergency every two weeks in order to operate a needle-exchange program, which initially had no periodic review period.
After including a review each year for the measure, opponents of the measure quickly added their names to the list of supporters.
"The amendments remove our opposition and change us to support," said John Lovell, a representative of both law enforcement agencies. "We would be delighted to go on as co-sponsors of this bill."
Mendocino County Undersheriff Gary Hudson said the bill is a public safety issue designed to allow exchange programs to operate more easily while incorporating a local control measure by including the yearly review.
"This is primarily about making government more efficient. Assemblymember Berg's bill eliminates the requirement to pass a declaration for emergency, therefore it eliminates the need to reauthorize the program every two weeks," he said.
"It may not seem like much, but the process of adding an item to the board's agenda every two weeks takes time, and like every other business, time is money."
Much of the opposition was concerned with a part of the bill that would decriminalize the possession of needles by participants in needle-exchange programs, Hudson said, which was removed along with the amendment to establish a yearly review of such programs.
"The reason we have a needle-exchange program is to control the spread of HIV, hepatitis and other blood-borne pathogens. Those problems do not go away every two weeks," he said. "Sheriff Craver and I were in support of the bill even before CPOA changed their stance on the issue because we believe that it is an important public safety issue."
Health experts say providing intravenous drug users with clean needles slows the spread of blood-borne diseases and also serves as a gateway to drug treatment programs.
"The science is clear, this program prevents disease and saves lives," said Bruce Pomer of the Health Officers Association of California, which sponsored the bill.
"This shows once again that there is no limit to what you can do when you are willing to work together and listen to other people's ideas," Berg said. "I believe this will save lives and slow the spread of some terrible diseases, and we can all be very happy about that."
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July 8th, 2005
Hep B Transmission with Blood Glucose Monitoring
SourceURL:http://www.gastrohep.com
Hepatitis in any long-term-care resident should prompt an investigation, and residents with diabetes using fingerstick blood sampling procedures or insulin administration should receive particular scrutiny, finds this week's issue of JAMA.
An estimated 70,000 to 80,000 Hepatitis V infections occur each year in the United States.
Most of these infections occur among young adults with behavioral risk factors, such as sexual contact and injection-drug use.
However, outbreaks of Hepatitis B virus infections are also associated with glucose monitoring.
Hepatitis B outbreaks were due to shared devices related to blood glucose monitoring - Journal of the American Medical Association
Capillary blood is typically sampled with the use of a fingerstick device and tested with a portable glucometer.
Regular monitoring of blood glucose levels is an important component of routine diabetes care.
Therefore, the Centre for Disease Control and the Food and Drug Administration recommended since 1990 that fingerstick devices be restricted to individual use.
Dr Ranck and colleagues from the Centers for Disease Control and Prevention: Morbidity and Mortality describe 3 recent outbreaks of Hepatitis B.
The research team described the outbreak of the infection among residents in long-term-care facilities.
The outbreaks of Hepatitis B described were attributed to shared devices and other breaks in infection-control practices related to blood glucose monitoring.
The researchers found that recommendations concerning standard precautions and the reuse of fingerstick devices have not been adhered to in long-term-care settings.
The team felts that the findings underscore the need for education, training, adherence to standard precautions.
The researchers also highlighted the need for specific infection-control recommendations targeting diabetes-care.
The team observed that initial cases were not identified or investigated in a timely fashion.
The delay in reporting initial cases resulting in missed opportunities to correct deficient practices and interrupt transmission.
Dr Ranck and colleagues on behalf of the Center for Disease Control conclude,”Routine Hepatitis B vaccination or screening of long-term care residents is not recommended”
“Evidence of acute viral hepatitis in any long-term-care resident should prompt a thorough investigation.”
“For a case involving a resident with diabetes, fingerstick blood sampling procedures and insulin administration should receive particular scrutiny.”
“Health departments should encourage reporting of such cases and offer assistance in identifying the source of infection.”
“The Center for Disease Control and Prevention continues to support investigations to improve implementation of the infection-control recommendations described in this report.”
JAMA 2005: 294:35-38
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Mass Spectrometry for Genotyping Hepatitis C Virus: A Promising New Approach
SourceURL:http://www.rednova.com
Hepatitis C virus (HCV) infection is a growing health problem worldwide, with more than 170 million individuals currently infected (1). Because no vaccine is currently available, the mainstay of control is treatment of infected individuals. Although the first attempts at treatment with interferon-a produced sustained responses in only ~25% of patients, more recent combination treatment regimens consisting of pegylated interferon-a plus ribavirin have led to sustained response rates approaching 60% (2, 3). In spite of intense study, the specific HCV gene(s) controlling the response to combination therapy have not been identified. Instead, the best predictor is the HCV genotype of the strain present in the patient (4). HCV is an extremely diverse virus, with 6 major genotypes and more than 60 subtypes identified (5, 6).
Genotype 1 is the most common genotype in the United States and Europe, and genotypes 2 and 3 are also common in these areas. Frequently, the virus within a given infected individual diverges during the course of chronic infection into multiple viral lineages with related sequences (known as quasispecies). Less frequently, an individual may become infected with a mixture of 2 or more genotypes. In spite of the wide sequence variation present in HCV, multiple studies have clearly shown a lower response rate to combination therapy with pegylated interferon-a plus ribavirin for patients who are infected with genotype 1 compared with the other genotypes (7). Thus, 2 therapeutic schemes are used: a 48- week course of therapy for patients infected with genotype-1 HCV and a 24-week course for those infected with other genotypes of the virus (8). The dramatically different response rates place a premium on the accurate assignment of the HCV genotype(s) causing a given patient's infection.
A variety of methods are available to genotype HCV-positive samples. The current gold standard method is direct sequencing of the nonstructural 5, envelope 1, or core (NS5, E1, or C) region. In contrast to these 3 regions, which contain multiple genotype- specific base pair changes over several hundred base pairs of sequence, the 5' untranslated region (5'UTR) has conserved domains and has fewer genotype-specific base pair changes (9). In spite of the lower variability in this region, at present the most commonly used methods in clinical laboratories are based on analysis of the 5'UTR by use of hybridization approaches (such as the line probe assay or melting analysis), direct sequencing of the 5'UTR, or restriction fragment length polymorphism (RFLP) analysis. The 5'UTR- based line probe assay and RFLP methods have been shown to have fair to very good agreement with sequencing of the 5'UTR, ranging from ~84% to 99% for genotype and from 68% to 86% for subtype (10). However, even direct sequencing of the 5'UTR is less informative than sequencing of the NS5, E1, or C region, especially at the subtype level (11), because of the limited variability of the 5'UTR. Nevertheless, the presence of conserved domains within the 5'UTR makes PCR amplification of this region more robust than amplification of the NS5, E1, or C region; thus, the 5'UTR-based methods are more sensitive and are favored by most clinical laboratories.
In this issue, Kim et al. (12) report a promising new approach to determining HCV genotype, which they term restriction fragment mass polymorphism (RFMP) analysis. The technique is based on PCR amplification of the 5'UTR of HCV, using primers that introduce recognition sites for type US restriction enzymes. Type US restriction enzymes have the important characteristic of cleaving DNA strands at points outside their recognition site. Cleavage of the HCV PCR product by such enzymes yields multiple oligonucleotide fragments of defined length representing hypervariable regions of HCV. Kim et al. then use an elegant matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS) approach to identify these hypervariable regions, allowing assignment of HCV genotype.
This novel approach promises several advantages over the current methodologies for HCV genotyping in widespread clinical use. The first is the reported 100% concordance with sequencing of the 5'UTR. Although this rate of concordance is unlikely to hold true for larger studies, and particularly for comparisons with sequencing of the NS5, E1, or C region, it compares favorably with most other methods. Perhaps more provocative is the ability of the RFMP method to detect mixed infections. The authors suggest that this method can detect minor genotypes at concentrations as low as 0.5% of the total HCV burden. Accordingly, the authors report a prevalence of mixed infections (22%) well in excess of the prevalence generally assumed. If mixed infections are truly this frequent, the ability to detect minor populations of treatment-resistant genotypes may have profound implications for HCV management.
However, several aspects of the RFMP method will require further study before this approach is widely adopted for clinical testing. Perhaps the most concerning is the reliance on analysis of the 5'UTR region. Although the RFMP method analyzes 3 different locations within the 5'UTR region, these still represent a relatively small portion of the viral genome. As noted above, analysis of the 5'UTR region rather than the NS5, E1, or C region generally leads to less accurate assignment of viral genotype and subtype, even by direct sequencing. In addition, methods that rely on limited polymorphisms present in a small region of the genome (such as the oligonucleotide fragments analyzed by MALDI-TOF MS) tend to be less informative than methods that analyze many base pair polymorphisms over a larger region of the genome (such as direct sequencing). Thus, the RFMP method may be improved by adding analysis of other regions of the viral genome, especially the NS5, E1, and C regions. Larger sample sizes will be required to determine the precise rate of agreement of the RFMP method with sequencing, particularly for samples with less common genotypes such as 4, 5, and 6.
Second, as noted above, the authors reported a very high rate (22%) of mixed-genotype samples (12). Apparently most (two-thirds) of these were confirmed by direct sequencing, and the remaining one- third were confirmed by clonal sequencing. The high rate of mixtures probably supports the authors' assertion that the RFMP approach is more sensitive for the detection of mixed genotypes, but the rate of mixed infections seems unusually high. The RFMP approach needs to be rigorously compared with other sensitive methods for detecting mixed infections, such as clonal sequencing or heteroduplex mobility analysis, in other patient populations. Furthermore, it will be critical to establish criteria for setting the detection threshold for MS peaks that will accurately distinguish instrument noise from the signal of a minor HCV population.
Third, the authors were unable to determine the genotype of 38 of their 318 samples (12%) because they gave MALDI-TOF MS spectra that did not match any of the predicted mass patterns (12). Analysis of additional samples by RFMP and direct sequencing may identify additional patterns and thus reduce the number of nontyped samples. However, if a large percentage of specimens still cannot be assigned a genotype, clinical laboratories using the RFMP method will need to have a back-up assay for the samples.
Finally, although the authors discuss automation of their method, the method as described uses a manual spin column for isolation of RNA, 2 cycles of nested PCR (reverse transcription-PCR/PCR), and restriction enzyme digestion (12). Thus, as currently embodied, the method requires a fair amount of manual sample handling. However, all of these steps should be amenable to true automation, and if the other caveats prove not to be insurmountable, it is likely that this assay could be performed economically.
In summary, Kim et al. (12) have developed an intriguing new method (RFMP) for genotyping HCV specimens, based on MALDI-TOF MS analysis of PCR product from the 5'UTR. This is a novel approach to the problem of HCV genotyping and promises several potential advantages over current methods, most notably a greatly improved sensitivity for infections with mixed genotypes. Additional studies will be needed to conclusively demonstrate the superiority of this method. However, if the RFMP approach lives up to its promise, the ability to detect minor populations of treatment-resistant genotypes and tailor therapy appropriately may revolutionize the management of HCV infections.
References
1. Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepat 1999;6:35-47.
2. Fried MW, Shiftman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-82.
3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiftman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with Interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-65.
4. Zein NN. Clinical significance of hepatitis C virus genotypes. \Clin Microbiol Rev 2000;13:223-35.
5. Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B, et al. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993;74(Pt 11):2391-9.
6. Pawlotsky JM. Hepatitis C virus genetic variability: pathogenic and clinical implications. Clin Liver Dis 2003;7:45-66.
7. Scott LJ, Perry CM. Interferon-a-2b plus ribavirin: a review of its use in the management of chronic hepatitis C. Drugs 2002;62:507-56.
8. National Institutes of Health Consensus Development Conference Statement. Management of hepatitis C 2002 (June 10-12, 2002). Gastroenterology 2002;123:2082-99.
9. Vizmanos JL, Gonzalez-Navarro CJ, Novo FJ, Civeira MP, Prieto J, Gullon A, et al. Degree and distribution of variability in the 5' untranslated, E1, E2/NS1 and NS5 regions of the hepatitis C virus (HCV). J Viral Hepat 1998;5:227-40.
10. Anderson JC, Simonetti J, Fisher DG, Williams J, Yamamura Y, Rodriguez N, et al. Comparison of different HCV viral load and genotyping assays. J Clin Virol 2003;28:27-37.
11. Laperche S, Lunel F, Izopet J, Alain S, Deny P, Duverlie G, et al. Comparison of hepatitis C virus NSSb and 5' noncoding gene sequencing methods in a multicenter study. J Clin Microbiol 2005;43:733-9.
12. Kim YJ, Kim S-O, Chung HJ, Jee MS, Kim BG, Kim KM, et al. Population genotyping of hepatitis C virus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of short DNA fragments. Clin Chem 2005;51:1123-31.
Linda Cook1,2
Keith R. Jerome1,2*
1 Department of Laboratory Medicine
University of Washington Medical Center
Seattle, WA
2 Program in Infectious Diseases
Fred Hutchinson Cancer Research Center
Seattle, WA
* Address correspondence to this author at: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D3-100, Seattle, WA 98109. Fax 206-667-4411; e-mail kjerome@fhcrc.org.
DOI: 10.1373/clinchem.2005.051706
American Association for Clinical Chemistry Jul 2005
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