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Week Ending: September 3rd, 2005
Alan Franciscus
Editor-in-Chief
To download pdf version click here
This Issue:
• Hepatitis Remains an Uncontrolled Disease in Pakistan
• Doc Shares the Straight Ink on Self-Tattooing Perils
• Dirty Needles 'Spreading Hep C in Jail'
• Predicting Renal Function after Orthotopic Liver Transplant
• Very Low Rate of Liver Problems Seen with Kaletra
• 13C-Caffeine Breath Test Distinguishes Fibrosis in Hep B
• Governor Gets Needle Exchange Legislation
• S.T.O.P. Hep C Task Force 2nd Annual Hepatitis C Awareness Day
• A New Player in the Battle against Hepatitis Prevents Inflammation and the Death of Liver Cells
• Most Chronic Hepatitis C Sufferers Will Develop Cirrhosis in Later Life
• Metal-Based Medicine Could Treat Diseases in the Body
• Potent Drug vs Hepatitis B Introduced
• HIV Viral Load, not CD4 Cell Count, Predicts Protective Response to Hepatitis B Vaccine
August 28th, 2005
Hepatitis Remains an Uncontrolled Disease in Pakistan
http://www.dailytimes.com.pk
Shahzad Raza
ISLAMABAD: One out of every 10 Pakistanis suffers from either Hepatitis B or C. Almost 15 million patients infected with the disease have waited for several years for a campaign against the deadly disease.
Unsafe drinking water, unscreened blood transfusions and used syringes have made Hepatitis one of Pakistan’s greatest health concerns.
Health professionals and the government are making conflicting statistics on Hepatitis B prevalence in the country. According to these statements, the rate may vary from 4.8 to 5.8 percent.
The Extended Programme of Immunisation (EPI) launched an anti-hepatitis campaign in the country and set out to immunise 80 percent of all children. This, however, did not improve conditions significantly.
The programme has been facing problems in the rural areas of the country where parents are not cooperative on the immunisation of children under the age of one.
Although millions of Pakistanis are infected with the deadly Hepatitis virus, no concerned public department or agency has accurate statistical information. The 5.8 percent prevalence rate suggests that there may be around 8 million patients in the country.
The virus has five types, A, B, C, D and E. Hepatitis A and E are caused by oral infection, contaminated water and unhygienic food. Hepatitis B, C and D are caused by un-sterilised syringes, sexual intercourse, blood transfusion, and from mother to infant.
Hepatitis B and C are global health problems. There are 350 million Hepatitis B carriers worldwide. Medical experts associate the fast increase in Hepatitis B cases to ignorance and a lack of appropriate preventive measures.
The efforts against Hepatitis in Pakistan are being supported by the Global Alliance for Vaccines and Immunisation (GAVI), which is financially supported by the Bill and Melinda Gates Foundation. Pakistan is expected to receive 81.093 million medicinal doses from GAVI to immunise more than 21 million children by the end of the year 2005.
It is claimed that the hepatitis B virus is 100 times more concentrated in the blood than the HIV, virus making it much easier to be transmitted through bodily fluids such as blood, semen, saliva and vaginal secretions.
Hepatitis C is often called the ‘silent epidemic.’ The virus can live in the body for decades, often with no symptoms, continuously damaging the liver. The long-term consequences of hepatitis C include liver diseases such as liver cancer, and may even cause death. There is also neither a cure nor a vaccine for hepatitis C.
The federal government is set to launch the first ever “National Programme for Prevention and Control of Hepatitis in Pakistan” today (Monday). An official of the National Institute of Health estimates that the five-year programme will cost Rs 2.59 billion.
The major goals of the programme include ensuring safe drinking water, safe blood transfusions, the safe disposal of injection and invasive devices, capacity building, vaccination of high risk groups, and the free treatment of over 5,000 patients annually.
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Doc Shares the Straight Ink on Self-Tattooing Perils
By Nicola Hassap/ Teen correspondent
http://theedge.bostonherald.com
It's not just celebs and rockers who get tattoos - now everyone is doing it, including teens.
But Dr. Roy Geronemus, member of the American Society for Dermatologic Surgery, says the recent trend for tattoos and piercings has set a dangerous precedent.
An increasing number of teens are piercing and tattooing themselves - a practice that can lead to serious infection and even death.
Earlier this month, The Associated Press reported a 13-year-old Bostonian tried to pierce her own navel and ended up being hospitalized with a near-fatal infection that remained untreated for almost a month and damaged several internal organs.
“Many teens do not understand the potential risks of self-piercing, which would include excessive bleeding, scarring and transmission of infection,'' Geronemus said.
As for self-tattooing, the India ink most commonly used has been known to induce allergic reactions. In addition, using nonsterile needles, sharing needles and double-dipping into the ink are all likely to cause infection.
“The potential for complications is great,'' Geronemus said. Some who attempted self-piercing or -tattooing contracted HIV and Hepatitis C.
His advice to those getting tattooed or pierced? “Make sure you go to a reputable facility that uses a sterile technique.''
Think before you ink: Tattoo removal facts
- Black tattoos are much easier to remove than those done with colored inks.
- The darker your skin color, the more complicated the tattoo-removal process.
- Tattoos are meant to be permanent; the ink is inserted about 3 millimeters into the skin with a specialized tattoo gun.
Nicola Hassapis, 17, is a high school senior from Surrey, England. Hassapis is staying with American relatives for the summer.
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August 29th, 2005
Dirty Needles 'Spreading Hep C in Jail'
http://news.ninemsn.com.au
AAP
Thousands of prisoners are exposing themselves to hepatitis C infection by using dirty, resharpened needles, prisoners' advocates say.
In its latest prison newspaper, Just Us, Justice Action is calling for a regulated needle syringe program across all Australian prisons to stem the "rampant" tide of hepatitis C infections.
More than one third of the country's 23,000 prisoners are infected with the disease that affects the liver and causes nausea, fatigue and lethargy, abdominal and back pain, and flu-like symptoms, Justice Action researcher Michael Strutt says in this month's Just Us.
In NSW, it is estimated 68 per cent of women and 40 per cent of men would test positive for hepatitis C, while it is thought half of all prisoners in that state have a history of injecting drug use.
In comparison, just one per cent of the general Australian population carries the disease.
"Almost all of those prisoners will eventually be released to carry the virus back to their communities," Mr Strutt said.
"Around a quarter of prisoners continue in their furtive injecting and hasty cleaning of the hundreds of reused, resharpened, dirty, pitted needles that circulate around the prisons."
Justice Action argues an official needle syringe program is the best and most cost-effective way of combating the problem.
According to the Australian National Council on Drugs, there are 19 official prison needle and syringe programs operating overseas and not one has reported needles being used as a weapon.
Around 18,000 copies of Just Us are being distributed to prisoners across Australia and New Zealand over the next week.
Despite various hurdles to distributing the paper, including initial reluctance from various state corrective services departments to allow the paper into prisons, Justice Action estimates around half of the prison population in the two countries will read it.
The paper carries a mix of articles, letters, poetry by prisoners and a lonely hearts column requesting letters from readers.
Justice Action plans to host the 11th International Conference on Penal Abolition in Tasmania in February next year.
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August 30th, 2005
Predicting Renal Function after Orthotopic Liver Transplant
www.gastrohep.com
Duration of pretransplantation creatinine elevation, but not cause of renal dysfunction predicts renal outcome in orthotopic liver transplantation alone recipients, finds the most recent issue of Liver Transplantation.
In patients with recent onset renal insufficiency, the decision to perform combined kidney/liver transplantation vs orthotopic liver transplantation alone can be difficult.
Dr Rajender Reddy and colleagues hypothesized that duration of renal dysfunction may correlate with creatinine elevation after liver transplantation.
The researchers retrospectively identified 69 liver transplantation patients with pretransplantation creatinine 1.5 mg/dL.
The team included 53 patients with orthotopic liver transplantation alone, and 13 combined kidney/liver transplantation.
Variables analyzed were presence of hepatorenal syndrome, creatinine, Model for End-Stage Liver Disease score, and albumin levels.
The researchers also analyzed age, race, gender, cause of liver disease, diabetes mellitus, hypertension, history of ascites, and spontaneous bacterial peritonitis.
Creatinine levels in the orthotopic liver transplantation alone group were 2 mg/L – Liver Transplantation
In addition, variceal bleeding, hepatic encephalopathy, renal replacement therapy, and transjugular intrahepatic portosystemic shunting were assessed.
The team reported that duration of pretransplantation renal dysfunction was predictive of 6- and 12-month creatinine post- orthotopic liver transplantation alone.
The researchers found that area under the receiver operating characteristic curve for prediction of 12-month renal insufficiency by renal dysfunction duration was 0.7.
The team noted that optimal duration cutoff was 4 weeks.
A multivariable model was derived from patients with orthotopic liver transplantation alone.
The team applied this model to combined kidney/liver transplantation subjects with definite or possible hepatorenal syndrome.
The research team observed that predicted 12-month creatinine without renal transplantation was more than 2 mg/dL for each patient.
Combined kidney/liver transplantation patients as opposed to orthotopic liver transplantation alone patients had longer duration of renal dysfunction of 18 vs 3 weeks.
The team found that patients with combined kidney/liver transplantation had higher creatinine levels of 4 mg/dL vs 2 mg/dL in the orthotopic liver transplantation alone group.
Patients with combined kidney/liver transplantation had a higher rate of pretransplantation renal replacement therapy, of 62% vs 7%.
Combined kidney/liver transplantation patients had lower creatinine than orthotopic liver transplantation alone patients at 6 months and 12 months after transplantation.
Dr Rajender Reddy's team concluded, “Duration, but not cause, of renal dysfunction predicts renal outcome in orthotopic liver transplantation alone recipients.”
“Prospective studies may use duration of renal dysfunction to help identify combined kidney/liver transplantation candidates.”
Liv Transplant 2005: 11(9): 1048-55
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Very Low Rate of Liver Problems Seen with Kaletra
Michael Carter
http://www.aidsmap.com
Treatment with Kaletra (lopinavir/ritonavir) does not involve a high rate of major liver side-effects, according to an Italian study published in the September 2nd edition of AIDS. The investigators found that, even though over 40% of the patients enrolled in their study were coinfected with hepatitis B or C virus, the incidence of a grade III or IV liver abnormality was less than one per 100 person years of follow-up.
Since effective antiretroviral therapy became available, liver-related illness has emerged as a major cause of illness and death amongst HIV-positive individuals. This is because of the high rate of viral hepatitis coinfection amongst HIV-positive patients and the hepatotoxicity which some drugs in each of the three main classes of antiretrovirals can cause.
Studies suggest that between 2 - 11% of patients taking Kaletra will develop severe hepatotoxicity. Italian investigators used data obtained from an online reporting system for severe side-effects caused by antiretrovirals (the SCOLTA project) to determine the incidence of severe (grade III and IV) liver-related side-effects in 755 patients treated with Kaletra.
A total of 44% of patients were coinfected with hepatitis B or C virus and the mean period of observation was 17 months. The total incidence of severe adverse events was 11 per 100 patient years of follow-up. There was a lower incidence of severe side-effects amongst treatment-naive patients (7 per 100 person years) compared to treatment- experienced patients (12 per 100 person years). The most common side-effects were metabolic-related events (5 per 100 person years).
The investigators then examined liver-related side effects. They observed that “hepatic toxicity was not frequent”, with an overall incidence of 0.59 per 100 person years. There was a marginally higher incidence in treatment-naive patients (0.54 per 100 person years) compared to treatment-experienced individuals (0.48 per 100 person years).
One treatment-naive and four treatment-experienced patients experienced severe liver-related events. Four of these patients were coinfected with hepatitis C virus. Two cases developed shortly after treatment was initiated, the other three after a year of therapy. In all five cases treatment had to be stopped.
“This study comprises the biggest series to date of patients treated with Kaletra and followed prospectively outside clinical trials...this HIV-positive population had a high prevalence of coinfection with hepatitis viruses”, comment the investigators. They suggest that the retrospective design of other studies could explain the apparently higher rate of hepatotoxicity they found.
Reference
Bonfanti P et al. Low incidence of hepatotoxicity in a cohort of HIV patients treated with lopinavir/ritonavir. AIDS 19: 1433 - 1434, 2005.
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August 31st, 2005
13C-Caffeine Breath Test Distinguishes Fibrosis in Hep B
www.gastrohep.com
The 13C-caffeine breath test distinguishes chronic Hep B virus-related fibrosis and detects improvement in liver function in response to long-term lamivudine, reports September's Alimentary Pharmacology & Therapeutics.
The 13C-caffeine breath test is a non-invasive, quantitative test of liver function.
Dr Park and colleagues from Australia determined the utility of the 13C-caffeine breath test in chronic Hepatitis B virus.
The research team also determined the ability of the 13C-caffeine breath test to monitor response to lamivudine.
The team reported that 48 chronic Hepatitis B virus patients and 24 controls underwent the 13C-caffeine breath test.
The 13C-caffeine breath tests were performed at 1 week in 12 of the 28 patients commenced on lamivudine and after 1 year of therapy.
The researchers found that patients with Metavir F0 to F1 fibrosis had a 13C-caffeine breath test similar to controls.
However, patients with F2 to F3 fibrosis and cirrhotic patients had a decreased 13C-caffeine breath test.
13C -caffeine improved by 61% in responders to long-term lamivudine –Alimentary Pharmacology & Therapeutics
The research team noted that fibrosis correlated best with the 13C-caffeine breath test.
The 13C-caffeine breath test independently predicted significant, or F2, and advanced, F3, fibrosis.
The team observed that 13C-caffeine breath test predicted the greatest area under the receiver operating characteristic curve for predicting advanced fibrosis.
The test was unaltered by 1 week of lamivudine but improved by 61% in responders to long-term lamivudine.
However, the researchers noted that in those with viraemia and elevated alanine aminotransferase, values remained stable or deteriorated.
Dr Park's team commented, “The 13C-caffeine breath test distinguishes chronic Hepatitis B virus-related fibrosis and detects improvement in liver function in response to long-term lamivudine.”
Aliment Pharmacol & Ther 2005: 22(5): 395
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Governor Gets Needle Exchange Legislation
http://www.ukiahdailyjournal.com
The Daily Journal
SACRAMENTO Gov. Arnold Schwarzenegger has until Oct. 9 to consider a bill authored by Assemblywoman Patty Berg that would make it easier for cities and counties to maintain needle-exchange programs that help control the spread of AIDS and Hepatitis-C.
The measure, which was approved by the Assembly floor Monday and sent to the governor, would eliminate a section of state law that requires cities and counties to declare a health emergency every two weeks in order to continue operating a needle-exchange program.
The Mendocino County AIDS Volunteer Network currently operates a local exchange program and several county health officers have said they would be more likely to initiate needle-exchange programs if AB 547 became law, according to Berg's office.
MCAVN distributed some 76,000 clean syringes in the county last year on a mostly one-to-one exchange for used needles.
Needle-exchange programs help fight the spread of blood-borne diseases that not only threaten intravenous drug users, but people who are knowingly or unknowingly linked to them.
The governor vetoed a similar bill authored by Berg last year, but the measure that passed the Assembly Monday carries the support of multiple law enforcement agencies. This is the third year Berg has presented legislation regarding needle-exchange programs, but the first time she has garnered support from law enforcement groups.
"We have built a very impressive coalition of support," Berg, D-Eureka said. "So I hope we are sending the governor a bill that he can sign."
Gov. Schwarzenegger has not taken a position on the pending legislation, according to a spokesperson from the governor's office. As of Monday, the governor has until Oct. 9 to sign or veto any legislation received from the Legislature.
The measure is backed by California's public health officers as well as the California Peace Officer's Association and the California Narcotic Officer's Association.
Health officers, who are responsible for protecting Californians from the spread of illness, have long argued that existing law places a wasteful burden on local government by requiring supervisors or council members to declare a health emergency every two weeks in order to continue operating exchange programs, according to Berg.
In California, more than 1,800 people die of AIDS each year and 1,500 new infections occur through syringe sharing among intravenous drug users. Another 5,000 people become infected with Hepatitis-C through needle sharing.
Injection drug users are the second-largest group at risk of HIV infection and are the primary source of heterosexual, female and perinatal transmission, according to Berg's office.
According to MCAVN records, there are some 150 AIDS-positive individuals living in Mendocino County and about 5,000 cases of Hepatitis-C. MCAVN regularly works with about 500 needle users out of an estimated 2,500 syringe users in the county, exchanging anywhere from one to 200 needles at a time.
There are 14 cities and counties that currently operate needle-exchange programs, including Alameda, Humboldt, Marin and Sonoma counties. Health officers from Butte, Inyo, Riverside, Sacramento, Siskyou, Solano and Yolo counties have expressed interest in operating exchange programs if AB 547 becomes law, according to Berg's office.
AB 547 had 32 co-authors and passed on a bipartisan 46-29 vote.
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September 1st, 2005
S.T.O.P. Hep C Task Force 2nd Annual Hepatitis C Awareness Day
Press Contact: Leslie Benson Chair S.T.O.P. Hep C
916.454.5431 or mobile 916.717.5722
FOR IMMEDIATE RELEASE: September 1, 2005
Over 26,000 Sacramento and Yolo County residents are infected with Hepatitis C yet approximately 18,400 do not know they are infected. To help raise awareness about the hepatitis C epidemic, The S.T.O.P. Hep C Task Force will be conducting its 2nd Annual Hepatitis C Awareness Day on Wednesday September 14, 2005 from 10am to 2pm at eight area Rite Aid locations:
Rite-Aid – Alhambra & L Streets
Rite-Aid – Florin Rd & Franklin
Rite-Aid - Jefferson & W. Capitol West Sacramento
Rite-Aid – 215 California Street Woodland
Rite-Aid - Fruitridge & Stockton
Rite-Aid - Del Paso & El Camino
Rite-Aid - K Street Mall at 9th
Rite Aid – Norwood & Jesse
S.T.O.P. Hep C Task Force volunteers and Vital Volunteers from Golden State Donor Services will be distributing literature on risk factors for hepatitis C, information on HCV disease management and treatment as well as information on becoming an organ donor.
The S.T.O.P. Hep C Awareness Day will culminate in a rally on the west steps of the California State Capitol at 3:30pm. Hundreds of yellow-shirted volunteers and other concerned citizens will come to hear local officials urge support of measures that will slow the spread of hepatitis C including the implementation of SB1159 in Sacramento County. The Center for Health Improvement will present two major policy papers concerning the hepatitis C epidemic.
The Center for Health Improvement (CHI) and Education for Healthy Choices (EHC) have joined the Sacramento Area STOP Hep C Task Force in sponsoring the Capitol rally. Stop Hep C is a partnership between HCV advocates, community-based organizations and county health departments in Sacramento and Yolo Counties. CHI is a national, independent, nonprofit health policy center dedicated to improving population health and encouraging healthy behaviors. EHC is a Sacramento-based non-profit organization that provides comprehensive hepatitis education to people at risk for hepatitis C infection.
Hepatitis C is a communicable disease transferred through blood contact. According to the Center for Disease Control it is estimated that 1.9% of the U.S. population is infected with Hepatitis C, which is roughly 4 times the infection rate of HIV/AIDS. Because the symptoms of hepatitis C are often slow to progress and frequently mistaken for other medical conditions, as many of 70% of those infected do not know they are HCV positive. Until the late 1980’s Hepatitis C was known as Non-A/Non B Hepatitis. The majority of new infections are due to sharing injection equipment among IV drug users. Persons who received blood transfusions, blood products or organ transplants prior 1992 may be infected and should be tested.
The S.T.O.P. Hep C Task Force was formed in January 2003 to help prevent new HCV infections, raise awareness in the community about HCV and assist those who are HCV positive to find appropriate health care. The task force is represented by local health officials in Sacramento and Yolo counties, management and staff of community based organizations and interested members of the community.
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A New Player in the Battle against Hepatitis Prevents Inflammation and the Death of Liver Cells
www.eurekalert.com
A new player in the battle against hepatitis prevents inflammation and the death of liver cells
Ghent, Belgium -- Scientists from the Flanders Interuniversity Institute for Biotechnology (VIB) have again achieved a breakthrough in research on hepatitis. The researchers, connected to Ghent University, have discovered the function of one of the most important proteins involved in hepatitis. Using a mouse model, they have shown that the protein prevents inflammation of the liver as well as the death of liver cells. This discovery can form the basis for the development of a new therapy in the battle against hepatitis in humans.
Hepatitis, a liver disorder
Hepatitis is a collective term for a number of inflammations of the liver whose symptoms strongly resemble each other. These inflammations can have a wide variety of causes, such as alcohol abuse or infection by a hepatitis virus. Hepatitis B and C, for example, are caused by a virus through contact with the blood or other bodily fluids of infected persons. In some cases, the person remains a carrier of the virus, and chronic hepatitis and even cancer of the liver can develop.
In Belgium, at least 700,000 people have had hepatitis B, and 5%-10% of these persons are still chronic carriers of the virus. Each year, there are about 6000 new infections. The number of people with hepatitis C comes to 80,000-100,000 - and 60%-80% of these persons develop chronic hepatitis. There is a vaccination against hepatitis B, but none against hepatitis C.
A new role for the protein ABIN-1
TNF (Tumor Necrosis Factor) is produced by our body, normally in small quantities. In inflammations of the liver, excessive TNF production activates the mechanisms that lead to inflammation and the death of liver cells and liver tissue. In addition, excessive TNF in liver cells stimulates the protein NF-ƒÛB, which is also responsible for the inflammation of the liver. This makes NF-ƒÛB an attractive target for a therapy that would neutralize the inflammation. However, an ideal therapy also needs to prevent the death of the liver cells.
The new player that this research brings a step closer to the realization of such a therapy is the protein ABIN-1. From previous research by the VIB research group - led by Rudi Beyaert - it turns out that ABIN-1 inhibits the action of NF-ƒÛB. Now, Andy Wullaert and several colleagues from this team have shown that an extra dose of ABIN-1 provides a double protection to liver cells in mice. With an elevated production of ABIN-1, this protein will neutralize the inflammation caused by NF-ƒÛB and also prevent the complete death of liver cells after induction by TNF.
ABIN-1 in the treatment of liver disorders
This research discloses the double protective action of ABIN-1 in liver disorders. NF-ƒÛB, also responsible for inflammations, is inhibited by an elevated presence of ABIN-1. In addition, ABIN-1 also counteracts the death of liver cells. Further research can lead to new therapies in the battle against hepatitis, through which - by increasing the presence of ABIN-1 in the liver - one can inhibit the inflammation and prevent dell death.
Contact: Ann Van Gysel
info@vib.be
32-9-244-66-11
VIB, Flanders Interuniversity Institute of Biotechnology
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Most Chronic Hepatitis C Sufferers Will Develop Cirrhosis in Later Life
http://www.medicalnewstoday.com
Nearly 80 percent of chronic hepatitis C sufferers who have the disease for several decades will develop cirrhosis or end-stage liver disease later in life, according to a study published today in the American Gastroenterological Association (AGA) journal Clinical Gastroenterology and Hepatology. Researchers found that it is highly likely that people who are infected with hepatitis C (HCV) for more than 60 years will develop cirrhosis--the highest rate of hepatitis C-associated cirrhosis reported to date.
Hepatitis C is a virus that affects the liver and is spread primarily by contact with blood and blood products in transfusions and among drug users who share needles. Other common routes of transmission are infants born to HCV-infected mothers, tattoos and body piercings and risky sexual behavior. Of those who are infected, more than 80 percent will be chronic carriers of the disease. HCV can cause long-term scarring of the liver and usually presents with mild and non-specific symptoms, if any. They include fatigue, nausea, poor appetite and muscle and joint pain. It is estimated that more than 4 million Americans are now infected with HCV (more than 170 million people worldwide) and nearly 10,000 Americans die from the disease each year.
"Hepatitis C begins generally as a silent acute infection, with a fraction of the patients developing cirrhosis, end-stage liver disease or liver cancer," according to an editorial appearing in this month's journal. "Although this is a generally accepted scenario in persons infected with HCV, there remains uncertainty about the true frequency of evolution of liver disease and its rate of progression."
According to results of the study from researchers at the Queen Mary's School of Medicine and Dentistry in London, the prevalence of cirrhosis in patients with chronic HCV increases with the duration of the disease. Nearly 80 percent of Asian patients who were infected at birth and lived with the disease for 60 years or more developed cirrhosis--a finding that researchers say can be applied to the general population because of the similarity in the way the disease progresses in all ethnic groups.
"This study suggests that prolonged infection with hepatitis C leads to cirrhosis in the majority of those who are infected," said Graham R. Foster, PhD, FRCP, study author and professor of hepatology at Queen Mary's School of Medicine and Dentistry in London. "While previous studies have found differences in disease progression in various ethnic groups, our findings confirm that fibrosis progression is the same across these groups and leads to development of cirrhosis and liver disease at the same rate in everyone."
Researchers conducted retrospective analyses of 382 patients diagnosed with hepatitis C at three hospitals in northeast London between 1992 and 2003. Study participants were divided into two groups: Asian patients presumably infected in childhood and Caucasian patients. While the prevalence of cirrhosis in Caucasian patients was similar to the findings of previous studies, the statistics in Asians were markedly higher than previously found. The higher prevalence was partially attributed to the longer duration of HCV in the Asian patient population, those patients having suffered with the disease nearly 30 years more than the Caucasian subjects.
This study was funded by local investigators and an unrestricted research grant from Roche Pharmaceuticals.
For more information on hepatitis C, visit http://www.gastro.org.
About the AGA
The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is the oldest medical-specialty society in the United States. The AGA's 14,500 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. On a monthly basis, the AGA publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The AGA's annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
About Clinical Gastroenterology and Hepatology
The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org.
Kimberly Wise
media@gastro.org
301-941-2620
American Gastroenterological Association
http://www.gastro.org
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Metal-Based Medicine Could Treat Diseases in the Body
http://www.sciencedaily.com
Washington, DC – Designer molecules that combine metals such as copper with natural organic materials could one day attack viruses in the body and treat a wide range of diseases.
That's the finding of chemists at Ohio State University, who have successfully tested such molecules against portions of HIV and Hepatitis C virus RNA in the laboratory. They've also created molecules that act like ACE, or angiotensin-converting enzyme, inhibitors – drugs that are used to lower blood pressure.
At the American Chemical Society national meeting in Washington, DC, project leader James Cowan described how the same patent-pending technology could one day produce novel anti-tumor agents.
Drugs based on these molecules could produce fewer side effects compared to some of today's treatments, and they could also combat drug resistance, said Cowan, professor of chemistry at Ohio State.
Pharmaceutical companies tend to make drugs from the same limited set of ingredients, drawing upon only about a half-dozen of the more than 100 known chemical elements, Cowan explained. At the same time, drug-resistant bacteria and viruses are emerging.
“Faced with a problem like that, you can't ignore 95 percent of the periodic table,” he said. “We have to start broadening the landscape of drug design.”
His new molecules, called metal coordination complexes, mimic the activity of natural enzymes that break apart DNA, RNA, and proteins in the body.
Cowan and his colleagues have tailor-made different complexes to break apart portions of RNA that enable HIV and Hepatitis C viruses to function, as well as the ACE enzyme that constricts blood vessels in the body. In test tubes and in cell cultures of E. coli, the complexes targeted these particular RNA structures and enzymes and destroyed them.
The complexes work in one of two ways. Some use a process called redox chemistry to steal electrons from the bonds holding the target molecule together. Others use hydrolysis, meaning that they break down the target's chemical waterproofing, so that the water that is naturally present in a cell dissolves the target.
That's what makes these complexes different from most drugs.
“Most drugs are designed to inhibit – that is, they will bind to a protein molecule and just block its function,” Cowan said. “But with metals you have the option of completely destroying the target.”
He hopes that with proper tailoring to certain metabolic enzymes, these strategies could work against cancer. He also sees applications in homeland security, such as complexes that destroy the anthrax bacterium.
Even though these new complexes are partly made of metal, drugs based on them could potentially be less toxic to the body than conventional treatments.
Metals can be toxic, but so can some organic molecules that are used as drugs, Cowan pointed out.
One of these complexes could destroy a target, and then move on to another, eventually destroying many targets. So a smaller dose of a metal complex could do the work of a larger dose of a traditional drug.
Completely destroying the target molecule also lowers the chance that a virus will develop a drug-resistant strain.
The chemists are also working on metal-free versions of their molecules that will assemble themselves on site, by harvesting the metal that is naturally present in cells. It's a matter of designing an organic molecule that will have a natural affinity for the small amounts of iron or copper that are already inside the body – one that will then target the right viral RNA once it's assembled.
One of the potential obstacles to using metals as drugs is that the Food and Drug Administration doesn't yet have streamlined procedures for approving the compounds. But Cowan is confident that the situation will soon change, given the need for alternatives to traditional drugs.
He feels that these metal complexes represent a good first step toward the development of multi-functional drugs called dual-activity agents.
“What the industry really needs for the next generation are compounds that work on more than one target, because this will really accelerate progress against disease,” he said.
He offered heart disease as an example. Today, people often must take several drugs to combat different cardiovascular enzymes. One dual-activity drug could do the work of two, by lowering blood pressure and simultaneously reducing the formation of arterial plaque.
This work was funded by the National Institutes of Health.
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September 2nd, 2005
Potent Drug vs Hepatitis B Introduced
By Cesar Mangawang
http://news.inq7.net
Editor's Note: Published on page B6 of the September 3, 2005 issue of the Philippine Daily Inquirer
DOCTORS now have an important new medication to treat chronic hepatitis B by suppressing viral replication and the risk of developing liver disease. This latest treatment option is entecavir, which is considered the most potent oral antiviral drug for hepatitis to date.
The new treatment was made known in Bali, Indonesia, where a distinguished group of medical experts strengthened the fight against one of Asia Pacific region’s most threatening chronic disease.
This is good news for the 300 million people living in the region and infected with hepatitis B, a potentially life-threatening viral infection that may lead to liver disease.
Another encouraging news is that the new effective treatment would be soon available in the region.
Other approved drugs
This brings to five the number of approved drugs doctors can prescribe for their patients who have chronic hepatitis B.
These drugs include lamivudine and adefovir dipivoxil, both are pills taken once a day. The primary concern of lamivudine is the possible development of hepatitis B virus mutants during and after treatment. Adefovir dipivosil is primarily concerned with kidney toxicity occurring while taking the drug.
The two other treatments are inteferon-alpha and pegylated interferon, both given by injection but vary on the number of times they are administered in a week. The side effects of these drugs include flu-like symptoms and depression.
Entecavir efficacy
Based on data from three studies presented at the Bali meeting, entecavir was found to be superior or comparable to lamivudine in a wide variety of patients chronically infected with hepatitis B virus (HBV).
Included in the study are patients with compensated liver disease who were starting antiviral treatment for the first time (nucleoside-naive); had received prior antiviral treatment (other than entecavir); and those who were refractory to lamivudine (defined as nonresponsive, relapsed or resistant).
Another study found that after one year of treatment, there was no evidence of resistance to entecavir in the nucleoside-naive hepatitis B patient group.
Phase 3 studies analyzed the efficacy of entecavir in treating a variety of patients with chronic hepatitis B infection. Among them were both hepatitis B e-antigen (HBeAg)-positive and HBeAg-negative nucleoside-naive patients and lamivudine-refractory patients.
Patients who are HBeAg-positive show deterioration of liver function, cirrhosis and liver cancer and account for 25-40 percent of patients who are chronically infected. Patients who are HBeAg-negative have disease characterized by a progressive course of severe liver damage with a poor long-term prognosis and frequent progression to cirrhosis and liver cancer.
In a statement on the management of chronic hepatitis B, Asia Pacific liver experts clarified that “sustained viral suppression is the key to reduction or prevention of hepatic injury and disease progression. Therefore, the primary goal of treatment for chronic hepatitis B is to eliminate of permanently suppress HBV.”
First in Asia Pacific
It was also during the Bali meeting of liver experts that Bristol-Myers Squibb Co. announced that Indonesia has approved Baraclude (entecavir) for the treatment of chronic hepatitis B virus infection.
An oral antiviral therapy specifically designed to block the replication of hepatitis B virus in the liver, Baraclude will be available in Indonesia in the last quarter of this year.
More than half a million people worldwide die each year from primary liver cancer, and up to 80 percent of primary liver cancers are caused by hepatitis B.
Viral load is a key predictor of progression to serious liver diseases and hepatocellular carcinoma (HCC or liver cancer). The higher the viral load the greater the risk of developing cirrhosis and HCC.
The US Food and Drug Adminstration approved Baraclude for the treatment of chronic hepatitis B infection in adults in March this year.
FAST FACTS
Worldwide, more than two billion people (one out of three people) have been infected with hepatitis B. About 350 to 400 million people worldwide are chronically infected with hepatitis B, out of which 75 percent reside in Asia.
More than half a million people die each year from liver cancer and 80 percent of liver cancers are caused by hepatitis B. This is equivalent to 2,700 deaths/day, 114 deaths/hour, and 2 deaths/minute due to hepatitis B.
In China, some 120 million people are infected with chronic hepatitis B. Of these people, about 600,000 people die of liver cancer each year.
China accounts for 50 percent of the liver cancer deaths worldwide.
Each year, 380,000 deaths are from countries in Eastern Asia (China, Hong Kong, Japan and Korea).
In India, it is estimated that one in 20 people is chronically infected with hepatitis B virus, with one percent of total deaths in adults in India due to hepatitis B virus.
An estimated 6 percent of the Singaporean population, or approximately 250,000 people, are chronically infected with hepatitis B virus.
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HIV Viral Load, not CD4 Cell Count, Predicts Protective Response to Hepatitis B Vaccine
http://www.aidsmap.com
Edwin J. Bernard
Only one out of every six vaccinations in HIV-positive individuals against hepatitis B (HBV) produced an antibody response strong enough to protect them from infection, according to data due to appear in the October 1st issue of Clinical Infectious Diseases, and now available online in CID's Electronic Edition. The only factor associated with a protective antibody response was an HIV viral load below 400 copies/ml at the time of vaccination, which contradicts a previous study which found both nadir and current CD4 cell count to be correlated with HBV vaccine response.
UK treatment guidelines recommend that all HIV-positive patients who lack immunity to hepatitis B are vaccinated against HBV, which is many times more infectious than HIV, and is usually transmitted through contact with blood, semen, vaginal fluids or saliva of an HBV-infected person.
Recent studies have found that HBV coinfection significantly increases the risk of death in people with HIV (Rockstroh 2004). A study of patients in the Multicenter AIDS Cohort found that men who were hepatitis B surface antigen-positive were eight times more likely to die of liver-related causes when compared to men with HIV who did not have hepatitis B (Thio 2002).
In order to characterise clinical factors that contribute to HBV vaccine response, investigators from St. Louis and New York in the United States, and Dublin, Ireland, conducted a retrospective cohort study, reviewing 920 medical records at a tertiary care HIV clinic.
Of the 920 records reviewed, 813 patients had complete HBV serologic data. Previous HBV infection was found in 255 (31.4%) and 166 (20.4%) had not received any dose of the HBV vaccine.
The vaccine used at the clinic is the three-dose GlaxoSmithKline (GSK) recombinant hepatitis B vaccine, Engerix-B, given over six months. This is one of two HBV preventative vaccines currently available in the United Kingdom, the other being Aventis Pasteur's HBvaxPRO. In the United States, Merck's Recombivax is the alternative to Engerix-B, although GSK's combination hepatitis A and B preventative vaccine, Twinrix is also approved there. There are no studies comparing the effectiveness of these various vaccines in HIV coinfected individuals.
Of the remaining 392 patients with complete HBV serologic data, 354 completed all three vaccinations. However, 160 did not have follow-up surface antibody tests in order to determine whether the vaccine was, in fact, protective, leaving 194 (just 35% of all eligible vaccine recipients with complete HBV serologic data) to be included in the analysis.
Of the 194 vaccinated individuals who had follow-up testing, 192 (99%) received a 10mg dose for doses 1 and 2, and two (1%) received a 20mg dose. For dose 3, 188 (97%) received a further 10mg dose, five received a 2mg dose, and one received a 40mg dose. The median interval between doses 1 and 3 was seven months (interquartile range [IQR], 6-9 months).
Protective vaccination was defined as hepatitis B surface antibody titre of 10mIU/ml or greater, measured after all three doses had been administered. Just 34 (17.5%) of the 194 reached this level. Last year, the US HIV Outpatients Study (HOPS) found that 19 (37%) out of the 51 who had post-vaccination testing for HBV surface antigen were protected (Tedaldi 2004). However, the criteria in the HOPS paper was merely a positive surface antigen result; without quantification this may have overestimated how many were truly protected.
Univariate analysis found that male gender (p=0.006) and HIV viral load below 400 copies/ml at the time of the first (p<0.001) and third (p=0.004) dose administrations were found to be predictors of successful vaccination. In addition there was a significant correlation between HIV viral load and hepatitis B surface antibody titre: the higher the viral load, the lower the titre (p=0.027).
Length of treatment with antiretroviral therapy also correlated with vaccine response: responders received highly active anti-HIV therapy (HAART) for a median of 13.5 months (IQR, 6.1-19.4 months), whereas non-responders received HAART for a median of 3.7 months (IQR, 1.3-15.5; p=0.005).
No significant difference in either the nadir CD4 cell count or in the CD4 cell count at time of vaccination was found, in contrast to the HOPS study which found that the majority of responders had a nadir CD4 cell count above 200 cells/mm3 and higher median CD4 cell counts (584 cells/mm3 vs. 384 cells/mm3, p=0.08) at time of vaccination, as well as an undetectable baseline viral load (63.2% vs. 33.3%, p=0.04) (Tedaldi 2004). In the current study, poor response was seen across the spectrum of CD4 counts.
On multivariate analysis, only an HIV viral load below 400 copies/ml at first dose administration was found to predict success (Odds Ratio [OR], 3.47; 95% CI, 1.5-7.6).
During subsequent 24-month follow-up, no vaccine responder developed HBV infection, compared with 16 (10%) of the non-responders, two of whom developed chronic active hepatitis B and five of whom developed natural immunity.
"Although the overall proportion of patients who developed protection was very poor at 17.5%, responders were truly protected from subsequent infection," write the investigators.
They also comment on the "concordance of missed opportunities" to provide the vaccine to those who need it, and for the low rates of follow-up measurements of hepatitis B surface antibody titre. With success rates this low, they conclude, clinicians should "consider booster vaccinations for patients who do not develop protective antibodies."
References
Overton ET et al. Undetectable plasma HIV RNA load predicts success after hepatitis B vaccination in HIV-infected persons. Clinical Infectious Diseases 41, electronic edition, 2005.
Rockstroh J et al. Hepatitis B and hepatitis C in the EuroSIDA Cohort: prevalence and effect on mortality, AIDS progression and response to HAART. Eleventh Conference on Retroviruses and Opportunistic Infections San Francisco, abstract 799, 2004.
Tedaldi EM et al. Hepatitis A and B vaccination practices for ambulatory patients infected with HIV. Clinical Infectious Diseases 38: 1483-1489, 2004.
Thio CL et al. Liver disease mortality in HIV-HBV co-infected persons. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 656, 2002
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