Research & Treatment News
September 19, 2007
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Revealing new potential for future vaccine possibilities, University of Illinois professors have unlocked one of Hepatitis C's propagation mysteries. By using biochemical dye technology, their research demonstrates how the virus gathers enough energy to dismantle RNA and DNA to create new genetic material.
Hepatitis-promoting protein caught in the act
By Greg Kline
Sunday, September 16, 2007 10:29 AM CDT
www.news-gazette.com
When your body, or a nasty virus invading it, cooks up a batch of genes, helicases – an enzyme, or type of catalyzing protein molecule – appear to be bigger than Betty Crocker in the kitchen.
The tasks performed by the proteins apparently include the unwinding of the tightly coiled ribbonlike DNA and RNA molecules containing the instructions for gene making.
Those chains of nucleic acids – the "N" and "A" in DNA and RNA and the basic building blocks of life – are then read by another type of protein molecule, called a polymerase.
But the genetic cookbook has to be cracked open by helicases first, and scientists have been of two minds on how that happens.
Some structural studies of helicases frozen in place seemed to suggest they work one page – or base pair, the basic unit of DNA and RNA strands – at a time.
Meanwhile, biochemical studies indicated that helicases sometimes work over three base pairs at once.
University of Illinois Professors Sua Myong and Taekjip Ha might have resolved the conflict. Their theory, backed by research using a technique developed by Ha to capture the movement of single molecules, is that it's both.
Helicases have three domains, or legs, as Myong described it recently. Two of those legs step along the acid chains, a base pair at a time during the unwinding process. The third leg remains anchored behind and gets stretched out until enough tension builds that it snaps lose and ahead three pairs. Ha, a UI physics professor, likened its movement to a spring.
"When we saw it, it made a lot of sense," said Myong, a professor at the UI Institute for Genomic Biology and the lead author of a paper on the study in the journal Science.
While interesting biologically, the information also has the potential to play into medical breakthroughs.
The UI researchers and collaborators at Yale University and the Maryland-based Howard Hughes Medical Institute looked at a helicase from the hepatitis C virus, which affects hundreds of millions of people worldwide – and for which there is no vaccine.
The helicase and its unwinding job are necessary for the virus to replicate, which makes the protein a potential target for new hepatitis C treatments.
That is undoubtedly a ways off and presents some challenges. For one thing, it appears that many helicases, including those of benefit in the human body, might function in a similar manner. A treatment would need to hone in on the hepatitis C helicase while leaving others alone, said Ha, a biological physicist who's also an affiliate of the Institute for Genomic Biology and of the Hughes Institute.
Besides their role in hepatitis C propagation, helicases have been implicated in human maladies such as cancers and in premature aging diseases, Ha said.
"If they don't function properly, then you can get into trouble," he said.
In their study of the hepatitis C helicase, the researchers found that the protein is powered by a lot of energy – and plenty of a cellular fuel called adenosine triphosphate, or ATP, to generate it. Ha said that makes a helicase more like an SUV than an economy car in this instance.
But gas guzzling could be a good thing here, Ha and Myong said. The nucleic acid chain road is a rough one, full of bumps and twists and turns and possibly obstacles to be cleared, such as other proteins interacting with the DNA or RNA molecules. The helicases might need an SUV's power and off-road capability, a lot more than most SUV owners do, to get their job done.
To track the tiny protein as it moves, Ha's lab uses a method called fluorescence resonance energy transfer, FRET for short, in which the researchers attach, through a biochemical process, fluorescent dye markers at various locations.
The sample is exposed to laser light, which makes the dye glow, and glow in different colors depending on its proximity to another marker.
Those light signals can be captured and interpreted to understand how a helicase is moving, at a resolution that allows not only pictures but animations to be created from the data.
The study was funded by the National Institute of General Medical Sciences at the National Institutes of Health.
Next, the researchers need to look at other helicases in action, Ha said. Myong has a plan to contrast the hepatitis C helicase with a helicase involved in putting the body's immune system on a battle footing in response to invaders like the hepatitis virus.
Posted by Editors at 11:53 AM --- Printer-friendly version
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Pharmasset's nucleoside polymerase inhibitor, R7128, will begin a new round of testing following its positive Phase 1 results. In addition to appearing safe and well-tolerated, R7128 is showing potential to lower Hepatitis C viral load in non-responders.
AFX News Limited
Roche's US partner Pharmasset says hepatitis C trial drug decreases virus level
09.10.07, 10:37 AM ET
www.forbes.com
ZURICH (Thomson Financial) - Roche Holdings AG's US partner Pharmasset Inc said hepatitis C trial drug R7128 successfully lowered the level of the virus in patients who failed to respond to interferon therapy.
The phase I clinical study was carried out for 14 days on 40 patients, with R7128 showing 'potent antiviral activity' as well as being safe and well tolerated, Pharmasset (nasdaq: VRUS - news - people ) said. Dosages used in the study were 750 mg or 1500 mg.
New Jersey based Pharmasset is collaborating with Roche to develop the drug, and based on the results of the trial will start a 28-day study of R7128 in combination with interferon Pegasys plus Copegus.
R7128 is classed as a nucleoside polymerase inhibitor, a new generation of antivirals being developed to treat hepatitis C patients.
sarah.fenwick@thomson.com
Posted by Editors at 9:23 AM --- Printer-friendly version
September 18, 2007
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Body Shop founder Anita Roddick died last week at the age of 64. She had announced to the media earlier this year that she had Hepatitis C, which the disease apparently had led to a previous diagnosis of liver cirrhosis. Ms. Roddick had made new inroads in social and environmental awareness and responsibility in business, while advocating for green cosmetics, animal rights, Community Trade and establishing organizations such as Children on the Edge as well as promoting the work of the Hepatitis C Trust following her diagnosis.
www.cnn.com
(CNN) -- The founder of The Body Shop, which grew from one shop in southern England to an international chain, has died, the chairman of Body Shop International confirmed Monday.
Anita Roddick, 64, died after suffering a major brain hemorrhage, her family said in a statement to the UK Press Association. Her husband, Gordon, and daughters, Sam and Justine, were all with her at St Richard's Hospital in Chichester, England.
Roddick had revealed in February that she contracted hepatitis C through a blood transfusion while giving birth to a daughter in 1971, according to The Associated Press.
Roddick and her husband stepped down as co-chairmen of the company in 2002, according to the AP. Still, she continued to contribute as a consultant.
The Body Shop chain became a massive success selling "green" cosmetics as customers were becoming environmentally aware.
Adrian Bellamy, chairman of Body Shop International, said in a written statement: "All of us in The Body Shop family are deeply shocked and saddened to hear the news of Anita's passing.
"Anita was not only our founder but she was also the heart and passion of The Body Shop and with her we achieved so much, whether on animal rights, human rights, Community Trade, or through the founding of organizations like Children on the Edge.
"It is no exaggeration to say that she changed the world of business with her campaigns for social and environmental responsibility.
"But for everyone who knew Anita, it was about much more than that: you couldn't help but be inspired by her love of life, her vision of the world and her passion for changing it.
"Anita leaves us with an enduring legacy which will long guide the affairs of The Body Shop. Our heartfelt condolences are with the Roddick family at this sad time."
Roddick had said her business ethics were partly inspired by women's beauty rituals that she discovered while traveling in developing countries, and lessons that her mother passed on from life during the hard years of World War II. Watch CNN Boardroom interview with Roddick. Video
Roddick's business opposed product testing on animals and tried to encourage development by purchasing materials from small communities in the Third World. According to AP reports, the Body Shop also invested in a wind farm in Wales as part of its campaign to support renewable energy, and it set up its own human rights award.
The Body Shop has grown into a global phenomenon with nearly 2,000 stores in 50 countries and remains independently run despite being owned by L'Oreal Group.
In recognition of Roddick's contribution to business and charity, Queen Elizabeth II made her a dame, the female equivalent of a knight, in 2003.
Posted by Editors at 9:17 AM --- Printer-friendly version
September 17, 2007
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Infection with Hepatitis C genotype 3 carries a greater chance of a fatty liver than other genotypes. Although this relationship is likely due to the strain's molecular structure, successful treatment can erase this extra burden.
by Nicole Cutler, L.Ac.
All of Hepatitis C’s genotypes are not created equally. Aside from differences in treatment response, one Hepatitis C strain carries a concern above and beyond damage from the virus itself. According to researchers, Hepatitis C genotype 3 (HCV3) is most likely to be accompanied by steatosis, or fatty liver.
Steatosis
As the most common liver disease in the United States, non-alcoholic fatty liver disease often accompanies Hepatitis C infection. Liver steatosis describes the accumulation of fat in liver cells. For those with Hepatitis C, steatosis is associated with more severe fibrosis progression.
Past studies have shown that various Hepatitis C virus (HCV) genotypes are associated with different forms of steatosis. In patients with genotype 1 and 4, steatosis is primarily due to metabolic factors such as obesity and diabetes. For those with genotype 3, the viral strain itself is suspected to cause fat accumulation in the liver cells.
The prevalence of steatosis is reported by a broad range of people, affecting anywhere from 34 to 81 percent of people with HCV. Variables predisposing someone with HCV to develop steatosis include:
· Alcohol consumption
· Obesity
· Diabetes
· Hyperlipidemia (high cholesterol)
· Viral type
Genotype 3 Dominance
By pooling together various bodies of research collectively examining over 6,400 people with HCV, those infected with HCV3 have a much higher chance of developing steatosis. Some statistics relating hepatitis with steatosis include:
· Overall, approximately 56 percent of those with HCV have steatosis.
· Approximately 17 percent of those with autoimmune hepatitis have steatosis.
· Approximately 27 percent of those with Hepatitis B have steatosis.
· Approximately 48 percent of those with HCV of a genotype other than 3 have steatosis.
· Approximately 74 percent of those with HCV3 have steatosis.
In the March 2004 issue of Gut, French researchers reported on the relationship between steatosis and HCV clearance after antiviral treatment. This study examined the liver biopsies before and after antiviral treatment of 151 participants. According to the authors:
· Steatosis improvement was seen significantly more often in patients who achieved HCV clearance from treatment.
· Among those who were successful in eliminating the virus with treatment, steatosis improvement occurred more often in those with HCV3 than those with other genotypes.
· Among those who were not successful in eliminating the virus with treatment, steatosis improvement did not differ by genotype.
Also published in the March 2004 issue of Gut, an internationally-based group of researchers confirmed that Hepatitis C genotype affects steatosis. By analyzing data from 755 people with chronic HCV, the authors advised that those with HCV3 and diagnosed steatosis should receive antiviral treatment.
As published in the March 2004 issue of the Journal of Hepatology, researchers from Scripps Clinic reported on the impact of steatosis on liver disease progression and treatment response in patients with chronic Hepatitis C. The researchers evaluated liver biopsies from 574 patients, and found the following:
· Steatosis severity was associated with body mass index, HCV3, older age and longer duration of infection.
· Among those with genotype 3, higher HCV viral load was associated with more severe steatosis.
· Steatosis improved markedly in genotype 3 patients who achieved viral clearance from treatment.
From a laboratory perspective, scientists agree about the association between HCV3 and liver steatosis. In an in vitro model published in the January 2007 issue of Gut, Hourioux and colleagues compared lipid levels in sections of cells producing genotype 1a or genotype 3 core proteins. They found that the cumulative lipid droplet area was significantly greater in cells producing genotype 3 core proteins; lending this strain more amenable to fat accumulation. Another study comparing HCV proteins found that the genotype 3a core protein induced significantly greater enzyme activity that is required for the development of hepatic steatosis.
To further understand this pathological difference between HCV genotypes, scientists have been closely examining each genotype’s molecular structure variances. One possible explanation may involve HCV3’s obstruction of the liver’s release of very low density lipoprotein (VLDL) particles to the bloodstream. This theory rests on the foundation that dietary fat becomes trapped in the liver of those with HCV3.
When cumulatively examined, the evidence supports the premise that Hepatitis C genotype 3 exerts a specific effect on the genesis of hepatic steatosis independent of metabolic risk factors such as obesity. Although linking steatosis to genotype 3, the evidence also shows that those with this strain who are successful with antiviral treatment have a greater chance of liver recovery. It is clearer now than ever that the divergence between HCV genotypes exert more disparities than previously thought, and is likely due to the virus’ molecular structure.
References:
C Hourioux, et al., The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model, Gut, January 2007.
Hissar SS, et al., Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic liver disease, Journal of Medical Virology, April 2006.
http://clinicaloptions.com, Insulin Resistance and Hepatic Steatosis in Patients With Chronic Hepatitis C, Stephen A. Harrison, MD, LTC, MC, Clinical Care Options LLC, 2007.
J. Westin, et al., Impact of Hepatic Steatosis on Viral Kinetics and Treatment Outcome During Antiviral Treatment of Chronic HCV Infection, Journal of Viral Hepatology, March 2007.
Sharma, Pratina, et al., Hepatic Steatosis in Hepatitis C Virus Genotype 3 Infection: Does It Correlate with Body Mass Index, Fibrosis, and HCV Risk Factors?, Digestive Diseases and Sciences, October 2004.
www.hcvadvocate.org, Liver Steatosis, Liz Highleyman, Hepatitis Journal Review, March 2004.
www.hivandhepatitis.com, Liver Steatosis in Genotype 4 Patients Is Mainly Due to Metabolic Factors, Liz Highleyman, hivandhepatitis.com, 2007.
www.medscape.com, Hepatitis C and Steatosis: A Reappraisal, A. Lonardo, et al, Journal of Viral Hepatology, March 2006.
Posted by Editors at 10:40 AM --- Printer-friendly version
September 14, 2007
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Although re-infection with Hepatitis C usually recurs rapidly following a liver transplant, a Japanese woman has beaten the odds. This 60-year-old with Hepatitis C, cirrhosis, liver cancer and diabetes, is the first reported case where a liver transplant led to a complete recovery from Hepatitis C.
Hepatitis C gone after liver transplant
Posted : Fri, 31 Aug 2007 12:51:49 GMT
Author : Health News Editor
www.earthtimes.org
NAGASAKI, Japan, Aug. 31 A Japanese woman is the first reported case in which a complete recovery from hepatitis C-RNA was achieved after liver transplantation.
The 60-year-old woman with liver cirrhosis and liver cancer caused by hepatitis C had been diagnosed diabetic since 1995; and previous chemotherapies to remove cancer didn't bring any satisfactory result.
Dr. Tatsuki Ichikawa of the Nagasaki University Hospital, in Japan, was hesitant to give the woman a donated piece of the liver offered by her daughter fearing the new liver would get reinfected and progress rapidly to liver cancer. Previous data indicated that complete clearance of hepatitis C is necessary for a good outcome of a liver transplant.
To save the life of the patient, Ichikawa used a more powerful drug -- PEGylated IFN -- before liver transplantation and five weeks after the PEG-IFN treatment, the hepatitis antigen was no longer detectable from the patient but hepatitis-RNA persisted, even after 18 weeks of treatment, so liver transplantation was performed.
Unexpectedly, clearance of hepatitis C-RNA was achieved just one month after the successful liver transplantation and HCV was never detected in this patient thereafter, reported the case study published in the World Journal of Gastroenterology.
Posted by Editors at 9:52 AM --- Printer-friendly version
September 5, 2007
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As reported in the August 21, 2007 edition of the World Journal of Gastroenterology, researchers investigated why some people are able to spontaneously recover from the Hepatitis C virus. This study found the following factors responsible for a person's ability, or inability, to self-recover from the virus - quantity of Hepatitis C antibody, co-infection with Hepatitis B, and the active use of IV drugs.
Source: World Journal of Gastroenterology
Date: August 29, 2007
www.sciencedaily.com
Who Will Recover Spontaneously From Hepatitis C Virus Infection?
Science Daily — More than 3% of world population is infected with hepatitis C virus (HCV). The outcome of HCV infections is either self recovery or chronic hepatitis, and many of the chronic infections will develop into liver cirrhosis or liver cancer. Since there is no cure for chronic hepatitis C, nor is there any approved vaccine for this virus, hepatitis C is currently a major health problem worldwide.
Twenty to fifty percent of HCV infected patients recovers spontaneously. The hepatitis C patients and their relatives like to know if his/her infection would fall into the category for self recovery.
A research article to be published on August 21 in the World Journal of Gastroenterology addresses this question.
The research team led by Dr. Mihm from Georg-August-Universität spent more than 8 years working with a cohort of 67 patients who spontaneously recovered from HCV infection. In addition to these, the researchers included a similar number of patients with chronic HCV infection. Large sample size allowed these investigators to obtain results with great statistical significance, and to draw very reliable conclusions.
One conclusion reported by the investigators is, patients who self recovered usually have lower levels of HCV antibody. Thus patients with lower HCV antibody titer may have a brighter clinical outcome. However, for a practical standard to be established to define a low HCV antibody titer, more effort is needed by investigators in the future.
Another interesting conclusion reached by these investigators is, co-infection by hepatitis B virus (HBV) is associated with a higher possibility of self recovery. The investigators suggested that the infection of HBV interferes with the HCV replication, which would finally lead to virus eradiacation.. HCV patients co-infected by hepatitis A virus also have a better chance of self recovery, possibly by a similar mechanism.
Active iv drug users are less likely to self recover, for a couple of reasons: 1, they have a higher incidence of re-infection; 2, drugs have been shown to inhibit the expression of antiviral cytokines such as IFN-a and IFN-g; 3, HCV replication has been shown to be enhanced both by morphine use and morphine withdrawal.
Several different genotypes of HCV were discovered. The HCV genotype studied by Dr. Milm¡¯s group is type 1b, which is the prevalent genotype in Germany, and in China.
Note: This story has been adapted from a news release issued by World Journal of Gastroenterology.
Posted by Editors at 10:20 AM --- Printer-friendly version
September 4, 2007
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Using inactivated Hepatitis C particles, a Japanese company has successfully suppressed the Hepatitis C virus in mice. This scientific development holds enormous potential as a Hepatitis C vaccine and possibly as a therapeutic medication for those already infected.
Toray develops Hepatitis C vaccine
28 August 2007
www.domain-b.com
The Tokyo-headquartered Toray Industries, Inc, has announced that it has successfully confirmed for the first time in the world that hepatitis C virus (HCV) particles produced using a novel HCV culture system inactivated have the potential for practical use as an HCV vaccine in experiments using mice.
The culture system was established through the company's joint research on the development of an HCV vaccine with the National Institute of Infectious Diseases (NIID) at Shinjuku-ku, in Tokyo and the Tokyo Metropolitan Institute for Neuroscience (TMIN), Tokyo Metropolitan Organization for Medical Research (Fuchu, Tokyo).
Hepatitis C is a refractory viral infection of the liver. It occurs when HCV infects hepatocytes, and can lead to chronic hepatitis, to hepatic cirrhosis, and eventually to hepatocellular carcinoma. According to a WHO survey, it is estimated that 170 million people worldwide were carriers of HCV in 1999 with reportedly 3 to 4 million people being newly infected with HCV every year. Although a combination therapy of interferon and an antiviral drug, ribavirin, is currently used to treat hepatitis C, the development of new vaccines is urgently required to prevent the spread of HCV infection and eradicate the virus.
Vaccines to prevent infection with viruses occasionally contain component protein, part of the viruses, but whole forms of the attenuated viruses are often used successfully in vaccines such as influenza vaccines and polio (poliomyelitis) vaccines. For HCV, however, the inability to grow the virus under in vitro culture conditions has made it difficult to develop a vaccine.
Since its success in the in vitro cultivation of HCV for the first time in the world in 2005 jointly with TMIN, Toray has been seeking the potential of HCV particlest for use as an HCV vaccine in collaboration with NIID. Based on the research it has conducted, the company has successfully increased the efficiency of HCV production by 10,000 times through the research by preparing and using a human liver cell line which produces more HCV particles than conventional cells producing HCV particles.
Moreover, the company confirmed that the HCV infection of cultured human hepatocytes was suppressed by the serum which was obtained from the mice injected with inactivated HCV particles.
Based on the confirmation of the possibility of using these inactivated HCV particles as a HCV vaccine, the company will continue to work with NIID for further research and development to optimize the HCV particles for a vaccine and establish a culture method appropriate for industrial production.
The HCV vaccine is expected to not only become a new prophylactic drug to prevent new HCV infection, but also serve as a therapeutic drug for HCV-infected people. The company hopes that this HCV vaccine will be very good news for millions of patients suffering from hepatitis C worldwide.
Under its corporate slogan "Innovation by Chemistry", Toray is engaged in the expansion of its advanced materials with a focus on the life science field. The company aims for further expansion of its life science business positioned as one of "Strategically Developing Businesses," by promoting innovation of research and development employing its own advanced technologies.
send this article to a friendToray Industries, Inc. is going ahead with this research with the support of the Japan Health Sciences Foundation (Project for the fiscal years 2004 to 2006, "Establishment of hepatitis C virus infection and replication systems to develop effective anti-viral strategies") and the Ministry of Health, Labour and Welfare (Project for the fiscal years 2004 to 2006, "Development of vaccines using hepatitis C virus cell lines which allow infection, replication, and particle formation in cultured cells").
Posted by Editors at 10:26 AM --- Printer-friendly version