HCV Research and News

December 5, 2011

Studies of patients with cirrhosis uncover limitations in liver cancer screening

Public release date: 1-Dec-2011

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell

Two studies available in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases, have uncovered limitations in screening for primary liver cancer, also known as hepatocellular carcinoma (HCC). The first study found that, if given the choice during a clinical trial, most patients with cirrhosis prefer surveillance over the possibility of non-screening, therefore making a randomized study of HCC screening not feasible. A second study determined that ultrasonographic screening at three monthly versus six monthly intervals did not improve the detection of small liver cancers.

Medical evidence reports HCC to be the sixth most common cancer and the third most common cause of cancer death worldwide, with 90% of all cases in western countries attributed to chronic liver diseases, typically at the cirrhosis stage. The National Cancer Institute estimates that more than 26,000 cases and close to 20,000 deaths from liver and bile duct cancer occurred in the U.S. in 2011. Clinical guidelines recommend routine screening for HCC, but the efficacy and optimal intervals for testing are strongly debated by experts.

In the first study, researchers led by Professor Jacob George from the University of Sydney and Westmead Hospital in Australia, examined the feasibility of undertaking a randomized controlled trial of HCC surveillance in patients with cirrhosis. The screening program included ultrasonography every six months and alpha-fetoprotein testing every three months. Of the 205 participants with cirrhosis who received information outlining the risks and benefits of surveillance for liver cancer, 99.5% declined randomization, with 88% electing for a non-randomized screening program.

"While a randomized controlled trial is ideal to assess the success of a cancer surveillance program, we found that patients with cirrhosis declined randomization due to possible allocation to a non-screening group," explains Professor George. "Since HCC screening in cirrhotic patients is routine practice for a majority of clinicians, it is impossible to assign patients to a genuine control group. However, further prospective studies that compare individual screening strategies are warranted." In a survey of 40 gastroenterologists of the Sydney Liver Group, the authors found that 74% routinely screen cirrhotic patients despite believing that screening did not increase patient survival (37%) or that the surveillance was cost-effective (66%).

One such liver cancer screening strategy was investigated by a team of French and Belgian researchers led by Professor Jean-Claude Trinchet with the Hôpital Jean Verdier in Bondy, France. The team conducted a multicentre trial with 1278 cirrhotic patients who received ultrasonographic screening at either three-month or six-month intervals. Their results indicated that cirrhosis resulted from excessive alcohol use in 39% of participants, 44% from hepatitis C virus (HCV), and 13% from hepatitis B virus (HBV). During the study period from July 2000 to July 2009, researchers detected at least one focal lesion in 28% of patients, but confirmed small HCC (less than 30 mm) in only 10% of participants.

Dr. Trinchet said, "Our study found that ultrasonographic surveillance performed every three months detects more small focal lesions than screening at six-month intervals. However, more frequent screening did not improve the detection of liver cancer at an earlier stage." The authors note that detection of small tumors were more likely missed in patients with HCV or who abuse alcohol and suggest the limitations of current diagnostic procedures may explain their negative findings. Again, further investigations of screening methods and diagnostic procedures are needed to improve the outcomes in those at risk for developing liver cancer.

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Full Citations: "Feasibility of Conducting a Randomized Control Trial for Liver Cancer Screening: Is a Randomized Controlled Trial for Liver Cancer Screening Feasible or Still Needed?" H. Poustchi, GC Farrell, SI Strasser, AU Lee, GW McCaughan and J George.Hepatology; August 24, 2011 (DOI: 10.1002/hep.24581); Print Issue Date: December 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24581/abstract.

"Ultrasonographic Surveillance of Hepatocellular Carcinoma in Cirrhosis: A Randomized Trial Comparing 3- and 6-month Periodicities." Jean-Claude Trinchet, Cendrine Chaffaut, Valérie Bourcier, Françoise Degos, Jean Henrion, Hélène Fontaine, Dominique Roulot, Ariane Mallat, Sophie Hillaire, Paul Cales, Isabelle Ollivier, Jean-Pierre Vinel, Philippe Mathurin, Jean-Pierre Bronowicki, Valérie Vilgrain, Gisèle N'kontchou, Michel Beaugrand and Sylvie Chevret. Hepatology; September 6, 2011 (DOI: 10.1002/hep.24545); Print Issue Date: December 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24545/abstract.

Author Contact: To arrange an interview with Professor George, please contact Ellie Martel with the University of Sydney at ellie.martel@sydney.edu.au.

These studies are published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.

About the Journal

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Hepatology's current impact factor is 10.885.Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .

About Wiley-Blackwell

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

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Green tea flavonoid may prevent reinfection with hepatitis C virus following liver transplantation

Public release date: 1-Dec-2011

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell

German researchers have determined that epigallocatechin-3-gallate (EGCG)—a flavonoid found in green tea—inhibits the hepatitis C virus (HCV) from entering liver cells. Study findings available in the December issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, suggest that EGCG may offer an antiviral strategy to prevent HCV reinfection following liver transplantation.

HCV infection can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) or primary liver cancer. HCV is one of the most common causes of chronic liver disease and a primary indication for liver transplantation, affecting up to 170 million individuals worldwide according to estimates from the World Health Organization (WHO). Prior studies report that nearly 2% of the world population is infected with chronic HCV and up to 20% of the population in some countries.

While standard treatment with interferon with ribavirin and newer protease inhibitors may clear infection in some individuals, a substantial number of patients still may not respond to these therapies. For individuals receiving liver transplants due to complications from HCV, reinfection of the healthy donor liver remains a significant concern. Antiviral strategies that target HCV in its early stages are urgently needed to prevent graft reinfection and improve long-term outcomes for patients.

To address this critical issue, Dr. Sandra Ciesek and Dr. Eike Steinmann from the Hannover Medical School in Germany investigated the effect of the EGCG molecule, which is a major component of green tea, in preventing HCV from attaching to liver cells. "Green tea catechins such as EGCG and its derivatives epigallocatechin (EGC), epicatechingallate (ECG), and epicatechin (EC) have been shown to exhibit antiviral and anti-oncogenic properties," explains Dr. Ciesek. "Our study further explores the potential effect these flavonoids have in preventing HCV reinfection following liver transplantation."

Results showed that unlike its derivatives, EGCG inhibits entry of HCV into liver cells. The authors suggest that EGCG may impede HCV cell entry by acting on the host cell as the green tea catechin was not found to alter the density of virus particles. Pretreatment of cells with EGCG before HCV inoculation did not reduce the infection; however application during inoculation inhibited the rapid spread of the HCV. Lastly, researchers showed that EGCG inhibits viral attachment—the initial step in the HCV infection process. "The green tea antioxidant EGCG inhibits HCV cell entry by blocking viral attachment and may offer a new approach to prevent HCV infection, particularly reinfection following liver transplantation." concludes Dr. Ciesek.

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Full Citation: The Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) Inhibits Hepatitis C Virus (HCV) Entry." Sandra Ciesek, Thomas von Hahn, Che C. Colpitts, Luis M Schang,Martina Friesland, Jörg Steinmann, Michael P. Manns, Michael Ott, Heiner Wedemeyer, Philip Meuleman, Thomas Pietschmann and Eike Steinmann. Hepatology; Published Online: November 30, 2011 (DOI: 10.1002/hep.24610); Print Issue Date: December 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24610/abstract.

Author Contact: To arrange an interview with Dr. Sandra Ciesek or Dr. Eike Steinmann, please contact Jo Schilling at jo.schilling@twincore.de.

This study is published in Hepatology. Media wishing to receive a PDF of the article may contact healthnews@wiley.com.

About the Journal

About Wiley-Blackwell

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Medivir - TMC435 Will Be Evaluated in a Phase II Combination Study With daclatasvir (BMS 790052) for HCV Genotype-1 Patients

Dec. 2, 2011, 7:30 a.m. EST

HUDDINGE, Sweden, December 2, 2011 /PRNewswire via COMTEX/ -- Medivir AB (omx:MVIR), the research-based speciality pharmaceutical company focused on the development of high-value treatments for infectious diseases, announces that its development partner, Tibotec Pharmaceuticals, has entered into an agreement with Bristol-Myers Squibb Company.

TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection will be investigated in combination with Bristol-Myers Squibb's investigational NS5A replication complex inhibitor, daclatasvir.

Charlotte Edenius, Executive VP Research & Development, of Medivir, commented, "We are very excited to work with Bristol-Myers Squibb to investigate our protease inhibitor, TMC435, in combination with an NS5A replication complex inhibitor to enable the advancement of novel treatment options for people chronically infected with HCV. We believe that an all oral, treatment regimen for HCV would represent a major step towards improved HCV treatments."

Bristol-Myers Squibb released the following statement on 2nd December 2011:

Bristol-Myers Squibb Enters Clinical Collaboration Agreement with Tibotec Pharmaceuticals for Phase II Combination Study in Patients Chronically Infected with Hepatitis C

(NEW YORK, December 2, 2011) - Bristol-Myers Squibb Company /quotes/zigman/220498/quotes/nls/bmy BMY +0.18% announced today that it has entered into a clinical collaboration agreement with Tibotec Pharmaceuticals, one of the Janssen Pharmaceutical Companies, to evaluate the utility of daclatasvir (BMS-790052), Bristol-Myers Squibb's investigational NS5A replication complex inhibitor, in combination with Tibotec Pharmaceuticals' investigational NS3 protease inhibitor, TMC435, for the treatment of chronic hepatitis C virus (HCV).

Under the agreement the companies will evaluate the potential to achieve sustained viral response 12 and 24 weeks post treatment in patients with HCV genotype 1 in a study with three treatment regimens: an oral, once-daily treatment regimen of daclatasvir and TMC435 with pegylated-interferon alpha plus ribavirin; an oral, once-daily treatment regimen of daclatasvir and TMC435 with ribavirin and an oral, once-daily treatment regimen of daclatasvir and TMC435 alone. The study is planned to start in the first half of 2012.

"Bristol-Myers Squibb is dedicated to developing innovative treatment options for patients with serious diseases like HCV," said Brian Daniels, senior vice president, Development. "We are pleased to work with Tibotec to advance the scientific understanding for the potential for an all-oral regimen of direct acting antivirals, which would be an important advancement for patients with HCV. This is a continuation of our leadership in forging partnerships to advance combination antiviral therapy."

About TMC435

TMC435 is a highly potent and selective once-daily (q.d.) investigational drug that is being jointly developed by Tibotec Pharmaceuticals and Medivir to treat chronic hepatitis C virus infections in genotype 1 patients.

TMC435 has received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. TMC435 is currently being developed in three global phase III studies, QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment. In parallel with these trials, phase III studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, are ongoing. These phase III studies are fully recruited.

For additional information from these studies, please see http://www.medivir.com and http://www.clinicaltrials.gov

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The World Health Organization estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.

About Medivir

Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.

In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.

Medivir's first product, the unique cold sore product Xerese®/Xerclear®, was launched on the US market in February 2011. Xerese®/Xerclear®, which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico were sold to Meda AB in June 2011. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.

For more information about Medivir, please visit the Company's website: http://www.medivir.com

For more information about Medivir, please contact:

Medivir ( http://www.medivir.com ): Rein Piir, CFO & VP Investor Relations Mobile: +46-708-537-292 M:Communications Europe: Peter Laing, Amber Bielecka, Hollie Vile Medivir@mcomgroup.com +44(0)20-7920-2330 USA: Roland Tomforde +1-212-232-2356

SOURCE Medivir

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Also See: Bristol-Myers, J&J form hepatitis C partnership

Hepatitis A, B Susceptibility High in Patients on Methadone

Nancy A. Melville

December 2, 2011 (Washington, DC) — Patients in methadone maintenance treatment facilities, known to be at higher risk for hepatitis C virus (HCV) infection than the general population, might also have higher rates of vaccine-preventable hepatitis A (HAV) and B (HBV) infection, according to research presented here at the American Public Health Association 139th Annual Meeting.

HCV, which is often asymptomatic, can be particularly dangerous when patients are coinfected with HAV or HBV, potentially causing more acute liver disease, fulminant hepatitis, hepatocellular carcinoma, and/or death, investigators from the Beth Israel Medical Center in New York City told meeting attendees.

In an effort to determine the prevalence of the diseases at a methadone maintenance treatment program at Beth Israel, the researchers evaluated 8060 patients who were screened from June 2007 to July 2009.

They found that 35% of patients were susceptible to HBV, 15% had isolated HBV core antibody (cAb), 1% were positive for HBV surface antigen, 27% were immune to HBV because of natural disease, 23% were immune to HBV because of vaccination, and 35% were susceptible to HAV.

"Overall, 50% were susceptible to HAV, HBV, or both," the authors write.

In addition, of the 56% of patients who were positive for the HCV antibody, 17% were susceptible to HBV and 22% were susceptible to HAV, representing a very high-risk population.

Overall, 31% who were positive for the HCV antibody were susceptible to HAV and/or HBV.

Of the 1029 patients positive for HBV cAb who were also screened for the HCV antibody, 954 (93%) were positive for the HCV antibody, and 24% of the HCV-positive patients had isolated HBV cAb positivity (24% vs 2%; P < .0001; odds ratio, 12.5; 95% confidence interval, 9.8 to 16.0).

The findings highlight a heightened susceptibility of the substance-abusing generation born before hepatitis A and B vaccines became standard for newborns, said Catherine L. Troisi, PhD, who moderated the session.

"The average age was around 50. What this shows is they were likely not vaccinated at birth and, because of their drug use, there is a heightened risk," said Dr. Troisi, who is from the division of management, policy, and community health at the University of Texas School of Public Health in Houston.

"The fact that so many were hepatitis C–positive, which you cannot vaccinate against, indicates that they should be vaccinated against A and B, because those diseases can place additional assaults on the liver."

Dr. Troisi added that one of the more unusual findings is that 15% were positive for isolated HBV cAb. "It's unclear what that means," she said. "It's higher than you would find normally. It may be that these people had occult hepatitis B [with undetectable hepatitis B antigen]."

Vaccinating populations at methadone maintenance clinics has always been a challenge, but Dr. Troisi noted she had success in one study with an accelerated vaccination schedule, in which patients were vaccinated at 0, 1, and 2 months, instead of the typical 0, 1, and 6 months.

"Using an accelerated schedule is easier because you don't have to find people 6 months later," she said. "But it's hard, especially with hepatitis C, because if they're using needles, they can become positive pretty quickly, and you'd like to vaccinate them against hepatitis A and B before they are infected with C."

The authors and Dr. Troisi have disclosed no relevant financial relationships.

American Public Health Association (APHA) 139th Annual Meeting: Abstract 237717. Presented October 31, 2011.

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Babyboomers Most at Risk for Hepatitis C Virus

Dec. 2, 2011, 8:25 p.m. EST

NEW YORK, Dec. 2, 2011 /PRNewswire via COMTEX/ -- Montefiore Liver Specialists Urge Population to be Tested for This Potentially Deadly Virus

"Twitter Chat" Hosted by @MontefioreNews on December 8, noon, #MonteHepC

Experts at Montefiore Medical Center urge the general public to be tested for the Hepatitis C virus, especially baby boomers, adults born between 1946-1964, who could be most at risk for this disease. Baby boomers are more likely to have been exposed to dangerous risk factors decades ago, such as sharing a drug needle, being tattooed or pierced with unsterilized tools or receiving a tainted blood transfusion. The disease often has no symptoms, and if untreated, can lead to chronic infection that can scar the liver, cause liver failure or cancer and potentially lead to liver transplantation.

Hepatitis C virus (HCV) is the most common chronic blood borne infection in the United States, with 35,000 to 185,000 new cases diagnosed per year. Worldwide, 180 million people are chronically infected with Hepatitis C, with an estimated 3-4 million new cases reported each year. The disease particularly affects minorities, Hispanics, Asian-Americans and African-Americans.

"This disease has grown to epidemic proportions, with 350,000 people around the world dying from Hepatitis C-related liver disease," said Milan Kinkhabwala, MD, Chief, Division of Transplantation at the Montefiore Einstein Center for Transplantation. "But it is called the 'silent killer' because many people don't even know they have it. This condition can be asymptomatic for decades and then present itself when it has already severely damaged the liver."

Individuals at risk can get a simple blood test to detect the virus before chronic infection leads to permanent liver damage. The Montefiore Medical Center Comprehensive Liver Disease Program offers simple and effective screenings. It is recommended that individuals talk to their primary care physician or contact 888-RX-LIVER (888-795-4837) for more information or to set up an appointment for a screening.

"This is a revolutionary time in the treatment of the disease and there is more hope than ever before," said Dr. Kinkhabwala. "The blood test is essential to detecting Hepatitis C, because now there are ways to treat the condition, and even reverse damage to the liver."

Two new anti-viral oral medications, boceprevir and teleprevir, received FDA approval in May 2011. Both drugs work by blocking an enzyme that helps the virus reproduce. The drugs are intended to improve on standard treatments using the injected drug pegylated interferon alpha and the pill rivavrin.

"So far, the new drugs have shown promise in clearing the virus from the body and almost doubling the cure rate of the disease," said Allan Wolkoff, MD, Professor of Medicine and of Anatomy and Structural Biology at Albert Einstein College of Medicine of Yeshiva University and Chief of the Division of Gastroenterology and Liver Diseases at Montefiore and Einstein. "Another key benefit is that they cut treatment time in half, thus reducing the time the patient has to endure the severe side effects, which include anemia, depression and flu-like symptoms like fatigue, fever and headache."

When symptoms do occur after the disease has progressed, they're generally mild and flu-like and may include fatigue, fever, nausea or poor appetite, muscle and joint pain, bruising, abdominal pain, jaundice and itching. At that point, chronic infection can lead to scarring of the liver (fibrosis) and then advanced scarring (cirrhosis). Scarring of the liver makes it difficult for the liver to function properly and can be devastating to the rest of the body, often causing liver failure or liver cancer.

If the liver disease progresses too far and the medications are not effective, then transplantation is the last resort. However, more than 16,000 people in the United States are currently waiting for a liver donor, and in New York State, there are 1,700 patients on the waiting list.

Factors that have been reported to accelerate the rate of HCV disease progression include age, gender (males have more rapid disease progression than females), alcohol consumption, HIV coinfection (approximately 35% of patients) and fatty liver (the presence of fat in liver cells caused by obesity).

Unlike Hepatitis B, there is no vaccine to prevent this disease. While the symptoms are similar, distinct differences exist between the two viruses. Hepatitis B is primarily transmitted through sexual intercourse and is less severe.

Dr. Kinkhabwala will be available for a live twitter chat to answer questions about Hepatitis C and liver disease on December 8, 2011 at noon. Follow @MontefioreNews to discuss #MonteHepC.

About Montefiore Medical CenterAs the University Hospital for Albert Einstein College of Medicine, Montefiore is a premier academic medical center nationally renowned for its clinical excellence, scientific discovery and commitment to its community. Recognized among the top hospitals nationally and ranked sixth out of 184 in the New York metropolitan area by U.S. News & World Report, Montefiore provides compassionate, patient- and family-centered care and educates the healthcare professionals of tomorrow. The Children's Hospital at Montefiore is consistently named in U.S. News' "America's Best Children's Hospitals," and is second among those in the New York metro area. With four hospitals, 1,491 beds and 93,000 annual hospital discharges, Montefiore is an integrated health system seamlessly linked by advanced technology. State-of-the-art primary and specialty care is provided through a network of nearly 100 locations across the region, including the largest school health program in the nation and a home health program. Montefiore's partnership with Einstein advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. The medical center derives its inspiration for excellence from its patients and community, and continues to be on the frontlines of developing innovative approaches to care. For more information please visit www.montefiore.org and www.montekids.org and follow us on Twitter @MontefioreNews.

SOURCE Montefiore Medical Center

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Bristol-Myers, J&J form hepatitis C partnership

The Associated Press December 2, 2011, 11:32AM ET

NEW YORK

Bristol-Myers Squibb Co. said Friday it will collaborate with a unit of Johnson & Johnson to study a potential combination therapy for chronic hepatitis C.

The companies will study a regimen that combines Johnson & Johnson's drug TMC435 with Bristol-Myers Squibb's daclatasvir. The clinical trial of the drug cocktail will begin in the first half of 2012. It will include a combination of the two drugs, the drugs plus pegylated interferon and ribavirin, and the drugs plus ribavirin.

Pegylated interferon and ribavirin have been staples of hepatitis C treatment for decades. Several drugmakers are studying potential treatments that could work without interferon, which is given by IV and is associated with particularly severe side effects. That could allow patients to treat their hepatitis C infections using only pills. Some studies are testing experimental drugs alone and without ribavirin.

Bristol-Myers of New York and Johnson & Johnson, based in New Brunswick, N.J., did not disclose the terms of their partnership.

Tibotec Pharmaceuticals is part of J&J's Janssen Pharmaceuticals business. In July the company announced a partnership with Pharmasset Inc. that will combine TMC435 with Pharmasset's PSI-7977, which is considered one of the most promising of all the current experimental therapies for hepatitis C in part because it's an oral treatment. Bristol-Myers is conducting late-stage trials of daclatasvir.

Shares of Johnson & Johnson fell 36 cents to $64.08 in morning trading, while Bristol-Myers Squibb stock rose 24 cents to $33.14.

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New Book About Hepatitis C and Other Liver Conditions Just Released by Dr. Tuesdae Stainbrook

Dr. Tuesdae Stainbrook is pleased to announce her new book, Hepatitis C: What You Need To Know. From diagnosis to treatment, the book contains important information people need to know about hepatitis C.

Philadelphia, PA, December 04, 2011 --(PR.com)-- "Hepatitis C: What You Need To Know" contains questions and answers about hepatitis C. From diagnosis to treatment and other important information people need to know about hepatitis C.

The book is very straight forward and easy to understand and is intended to help patients and families understand the causes, effects, and health risks of Hepatitus C and other liver conditions.

Facts: Hepatitus C can be cured.

Most people with hepatitis C do not have any symptoms. The two most common symptoms are right upper quadrant pain and fatigue.
Only about 80-85% of individuals exposed to hepatitis C will go on to have chronic hepatitis C. Learn about the new treatments available and their side effects.

Want To Know More? Check Out The New Book, "Hepatitis C: What You Need To Know" By Dr. Tuesdae Stainbrook.

Book Information:
"Hepatitis C: What You Need To Know"
Author: Dr. Tuesdae Stainbrook
Publisher: AuthorHouse
ISBN: 978-1-4634-2854-9
Pages: 37
Published: September 2011

About The Author
Dr. Tuesdae Stainbrook is an infectious disease physician in central Pennsylvania. She is board certified in internal medicine, infectious disease, and HIV. She has also a master's degree in public health. Dr. Stainbrook has a large hepatitis C treatment population and is considered to be one of the largest hepatitis C providers in Pennsylvania.

Dr. Stainbrook has been crucial in bringing community and physician awareness along with free hepatitis C testing in her area. In 2007, she was honored with the Viral Hepatitis Award of Excellence given by the Commonwealth of PA Health Department. Dr. Stainbrook in 2011 received the Outstanding Community Service Award for her exceptional support and dedication to the field of Substance Abuse by the Clearfield-Jefferson Drug and Alcohol Commission.

For more information, review copies, or interviews please contact the author at:

Dr. Tuesdae Stainbrook
Email: trrod203@pol.net
Website: http://www.hepcinfo.com

"Hepatitis C: What You Need To Know" is available for purchase through the author’s website, from the publisher, from Amazon.com, BN.com and other online retailers. Bookstores should contact Ingram for wholesale orders.

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Contact Information

Dr. Tuesdae Stainbrook
419-791-8004
Contact
www.hepcinfo.com

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Achillion Announces Preliminary Phase 1b Proof-of-Concept Data With ACH-2928 NS5A Inhibitor for the Treatment of Hepatitis C

Dec. 5, 2011, 7:00 a.m. EST

Achieves 3.68 Log10 Reduction in HCV RNA After Three Days of Treatment

NEW HAVEN, Conn., Dec 5, 2011 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. /quotes/zigman/100395/quotes/nls/achn ACHN +1.61% , a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today reported proof-of-concept data from its Phase 1b clinical trial of ACH-2928, a first-generation NS5A inhibitor, demonstrating that patients treated with ACH-2928 achieved a mean maximum 3.68 log10 reduction in HCV RNA after three-day monotherapy of 60 mg once daily. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with chronic hepatitis C (HCV).

ACH-2928, Achillion's first generation inhibitor of the NS5A protein, was discovered through the Company's NS5A inhibitor program. Achillion also recently nominated a second-generation NS5A inhibitor, ACH-3102, which is currently undergoing IND-enabling studies and is expected to be advanced into clinical trials during the first half of 2012.

"We believe NS5A inhibitors have emerged as an important component for an all-oral, direct acting antiviral (DAA) regimen," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "Furthermore, NS5A inhibitors, when combined with a protease inhibitor, have achieved sustained viral responses in clinical trials in tough to treat genotype 1 HCV populations. We believe this highlights the potential to form a proprietary interferon-free DAA combination regimen for the treatment of HCV within Achillion's pipeline."

ACH-2928 Phase 1 Program

In July 2011, Achillion initiated dosing in a randomized, double-blind, placebo-controlled phase 1a/1b clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2928. The trial consists of three segments: assessment of single ascending oral doses (SAD) in healthy volunteers, evaluation of 3 days of oral repeat doses in subjects with genotype 1a or 1b HCV, and a 5-day multiple ascending doses segment in healthy volunteers.

During the oral repeat doses segment in subjects infected with HCV, a total of 10 patients were enrolled with 2 patients (genotype 1a) receiving placebo and 8 patients (7 genotype 1a and 1 genotype 1b) treated with 3 doses of 60 mg ACH-2928 administered once daily. No serious adverse events (SAE) were reported and there were no patient discontinuations during treatment. The mean maximum HCV RNA decline during therapy was 3.68 log10 compared to a 0.54 log10 decline for patients receiving placebo. There were no viral breakthroughs observed during ACH-2928 monotherapy.

Preliminary data from the SAD trial segment demonstrated ACH-2928 was well tolerated at all doses evaluated up to and including the maximum dose of 500 mg. There were no serious adverse events, no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations.

All reported adverse events were classified as mild or moderate, and were transient in nature.

Based upon these preliminary results, the ongoing Phase 1 study will continue to evaluate the pharmacokinetic, pharmacodynamic, and antiviral profile of ACH-2928. These Phase 1 results have been submitted for presentation at a medical meeting being held during the second quarter of 2012.

In parallel, Achillion is advancing its second generation NS5A inhibitor ACH-3102 through IND-enabling studies and the Company expects to initiate clinical development during the first half of 2012.

"As we continue to evaluate ACH-2928 in this Phase 1 study, we are also working rapidly to advance ACH-3102, which has shown in preclinical studies to possess the same potent activity against genotype 1a HCV as ACH-2928, as well as enhanced activity against resistant HCV mutants that have been observed in this patient population," stated Milind Deshpande, PhD, President of Research and Development and Chief Scientific Officer. "We believe these results validate our NS5A development program, and look forward to developing an all-oral combination for clinical evaluation that includes one of our protease inhibitors and an NS5A inhibitor next year."

About NS5A Inhibitors

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. Achillion's NS5A inhibitors, including ACH-2928 and ACH-3102, possess potent in vitro activity against all HCV genotypes and demonstrate, in preclinical studies, additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, and ribavirin. In preclinical studies, ACH-2928 and ACH-3102 have demonstrated excellent potency, in the pico-molar range, against HCV RNA replication, including potent activity against genotype 1a while ACH-3102 has been shown to possess enhanced activity against recognized genotype 1 resistant variants.

About HCV

The hepatitis C virus infects the liver and is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80 percent of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors, including statements with respect to the potency, safety and other characteristics of Achillion's NS5A inhibitors, which may not be duplicated in clinical studies, and Achillion's expectations regarding results, timing and duration of clinical trials and reporting of results from clinical trials of Achillion's NS5A inhibitors. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to: Achillion's ability to advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; to obtain patent protection for its drug candidates, and the freedom to operate under third party intellectual property; to establish commercial manufacturing arrangements and to identify, enter into and maintain collaboration agreements with appropriate third-parties; and to raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2010 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Achillion Pharmaceuticals, Inc.

CONTACT:
Glenn Schulman Achillion Pharmaceuticals, Inc.
Tel. (203) 752-5510
gschulman@achillion.com

Investors: Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
mfenton@achillion.com

Media: Christin Culotta Miller
Ogilvy PR
Tel. (212) 880-5264
christin.miller@ogilvy.com

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Poor Liver Transplant Outcomes for HIV/HCV Coinfected Patients

Neil Canavan

December 5, 2011 (San Francisco, California) — Patients coinfected with hepatitis C virus (HCV) and HIV have only a 55% chance of survival 5 years after liver transplantation, according to results from a study performed at a French transplant center and reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting. The study authors concede that improvements in care might depend on the near-term availability of new HCV therapies.

Liver disease progression to cirrhosis is rapid in HIV-infected patients, and liver transplantation is now an accepted therapeutic option for those with end-stage liver disease. "However, everyone knows that the mortality in HIV/HCV coinfected patients is very high," said principal investigator Jean-Charles Duclos-Vallée, MD, Centre Hépato-Biliaire, Hôpital Paul-Brousse, Villejuif, France. "A paper from 2005 puts the figure at just 25% 5 years after the first episode of decompensation, compared with 44% for HCV patients without HIV."

This reference aside, there are limited data overall regarding the survival of coinfected patients who undergo liver transplantation, he said. However, the increasing frequency of HIV-positive patients undergoing transplantation and the severity of recurrence of HCV infection in the liver grafts in transplanted patients is of growing concern.

Dr. Duclos-Valle and colleagues looked at survival rates and the degree of recurrence of HCV infection in 105 transplant patients at their center. The patient cohort was 83% male, 61% had HCV genotype 1, median MELD score was 16.0, and waiting time to transplantation was 4.9 months. All patients were using highly active antiretroviral therapy (HAART) at the time of transplantation. Reasons for transplant included HCV-related cirrhosis (56%), hepatocellular carcinoma (HCC; 19%), hepatitis B virus (HBV)-related cirrhosis (7.6%), HBV/HCV-related cirrhosis (4.7%), and other (14%).

"The overall survival rate for the entire cohort was 55% at 5 years posttransplant," said Dr. Duclos-Valle.

The 5-year survival rate for patients with HCV-related cirrhosis was 45%, with HCC was 49%, and with HBV-related cirrhosis was 100%. Nine patients have undergone retransplantation. Of the 40 deaths, 20 were due to HCV recurrence, 5 were due to HCC, 5 were due to sepsis, and 2 were due to myocardial infarction; the remaining patients died for other reasons.

After transplantation, anti-HCV therapy (pegylated interferon alfa-2a plus ribavirin) was given to 36 of 58 patients who had a recurrence of HCV infection in the new liver graft. The response rates were as follows: no response in 24 patients, partial response in 6, and sustained viral response in 6.

"For response to treatment after recurrence, we had [a sustained viral response] of 16.6%, with 64% nonresponders and 1 relapse," said Dr. Duclos-Valle. Given the dismal survival outcomes 5 years after transplantation and the less-than-optimal response rates to retreatment after HCV recurrence, Dr. Duclos-Valle said he is doubly concerned. Transplant organ resources are already strained, and with the success of HAART treatment, the number of HIV-infected individuals that will require transplantation in the future will only increase.

Race Against Demographics

"We are going to be seeing more of these patients," noted Jay H. Hoofnagle, MD, director of the Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Maryland. "They're living longer so they're going to have other health issues."

Dr. Hoofnagle said he is seeing an increase in complications from chronic conditions such as heart disease. "As HAART therapy extends lives, you're going to see these complications. That is particularly true with hepatitis C because of the common modes of transmission."

Dr. Hoofnagle is optimistic, however, about the overall prognosis for the situation. "The treatments for hepatitis C are improving so fast that what looks bad now is just going to improve with new drugs. This will be particularly helpful for the coinfected group, when you get the chance to get these patients away from interferon, which is very hard to take." Dr. Hoofnagle expects to see critical improvements in HCV treatment within the next 5 years.

Dr. Duclos-Valle and Dr. Hoofnagle have disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 4. Presented November 6, 2011.

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November 24, 2011

Largest Ever Genetic Study of Liver Function Could Point the Way to New Treatments

Published: October 16, 2011. Imperial College London

Researchers have identified a large number of areas in the human genetic code that are involved in regulating the way in which the liver functions, in a new study of over 61,000 people, published today in the journal Nature Genetics.

The work is an international collaboration led by Imperial College London and it identifies 42 genetic regions associated with liver function, 32 of which had not been linked to liver function before. The work should lead to a better understanding of precisely what goes wrong when the liver ceases to work normally. Ultimately, it could point the way to new treatments that can improve the function of the liver and help to prevent liver damage.

The liver is the body's largest internal organ and the British Liver Trust estimates that around two million people in the UK have a liver problem at any one time. The liver carries out hundreds of different tasks, including making proteins and blood clotting factors, and helping with digestion and energy release. It also purifies the blood of bacteria, and of the by-products of digestion, alcohol and drugs.

In the new genome-wide association study, the researchers compared the genetic makeup of over 61,000 people, in order to identify areas of the genetic code that were associated with liver function.

The team assessed the function of the volunteers' livers by looking at the concentrations of liver enzymes in their blood. People who have liver damage have high concentrations of these enzymes, which are associated with an increased risk of conditions such as cirrhosis, type 2 diabetes and cardiovascular disease.

Dr John Chambers, the lead author of the study from the School of Public Health at Imperial College London, said: "The liver is a central hub in the body and because it has so many diverse functions, it is linked to a large number of conditions. Our new study is a big step towards understanding the role that different genes play in keeping the liver working normally, and towards identifying targets for drugs that can help prevent the liver from functioning abnormally or becoming susceptible to disease."

The researchers identified 42 areas on the genetic code associated with liver function and they then went on to pinpoint 69 associated genes within these areas. Some of the genes are known to play a part in other functions in the body, including inflammation and immunity, and metabolising glucose and carbohydrates.

Professor Jaspal S Kooner, the senior author of the study from the National Heart and Lung Institute at Imperial College London, said: "This massive international research effort provides in-depth new knowledge about the genes regulating the liver. We are particularly excited about the genes whose precise role we don't yet know. Investigating these further should help us to fill in the gaps in our understanding about what happens when the liver ceases to function normally and how we might be able to tackle this."

Professor Paul Elliott, also a senior author of the study, from the School of Public Health at Imperial College London, said: "Liver problems affect a huge number of people and they can have a devastating effect on a person's quality of life. This study represents a vast discovery that opens up multiple new avenues for research."

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Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial

HepatologyVolume 54, Issue 5, pages 1527–1537, November 2011

Marc G. Ghany^1,*,§, Hae-Young Kim², Anne Stoddard², Elizabeth C. Wright³, Leonard B. Seeff⁴, Anna S.F. Lok⁵, the HALT-C Trial Group

Article first published online: 28 OCT 2011
DOI: 10.1002/hep.24550
Copyright © 2011 American Association for the Study of Liver Diseases

Abstract

Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the hepatitis C long-term treatment against cirrhosis (HALT-C) trial database to develop two models, using baseline values of routinely available laboratory tests together with changes in these values during follow-up to predict clinical decompensation and liver-related death/liver transplant in patients with advanced hepatitis C. Patients randomized to no treatment and who had ≥2-year follow-up without a clinical outcome were included in the analysis. Four variables (platelet count, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio, total bilirubin, and albumin) with three categories of change (stable, mild, or severe) over 2 years were analyzed. Cumulative incidence of clinical outcome was determined by Kaplan-Meier analysis and Cox regression was used to evaluate predictors of clinical outcome. In all, 470 patients with 60 events were used to develop models to predict clinical decompensation. Baseline values of all four variables were predictive of decompensation. There was a general trend of increasing outcomes with more marked worsening of laboratory values over 2 years, particularly for patients with abnormal baseline values. A model that included baseline platelet count, AST/ALT ratio, bilirubin, and severe worsening of platelet count, bilirubin, and albumin was the best predictor of clinical decompensation. A total of 483 patients with 79 events were used to evaluate predictors of liver-related death or liver transplant. A model that included baseline platelet count and albumin as well as severe worsening of AST/ALT ratio and albumin was the best predictor of liver-related outcomes. Conclusion: Both the baseline value and the rapidity in change of the value of routine laboratory variables were shown to be important in predicting clinical outcomes in patients with advanced chronic hepatitis C. (HEPATOLOGY 2011;)

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Living with chronic illness during the holiday season

by Toni Bernhard, JD
Posted on KevinMD.com

In the U.S., we’re getting ready to celebrate Thanksgiving. Soon, people around the world will turn their attention to the holiday season. Chronic health problems can take a toll on relationships any time of the year. Most people have to experience unrelenting pain or illness themselves before they understand how debilitating it is, physically and mentally. Loved-ones (by whom I mean family and close friends) may be in some form of denial about what’s happened to you, or they may be scared and worried about the future. Bottom line, suffering from a chronic condition can be an ongoing crisis—for you and for those you’re close to.

That crisis can come to a head during the holidays when people’s expectations of one another are high and when stress levels for everyone are likely to be off the charts for any number of reasons—health, financial, relationship issues. If you’re like me, during the rest of the year, you carefully limit interactions with others in order to manage your symptoms; on a typical day, your most complex decision may be to choose between showering and shopping! But when the holidays arrive, you’re suddenly thrust into the middle of a lively and chaotic social scene where you’re expected to participate in a range of activities, often for days in a row. A bit of advance warning to loved-ones can go a long way toward minimizing stress levels over unrealistic expectations.

I know that this piece won’t apply to everyone. One of the heartbreaking consequences of living with chronic pain and illness is that some people are unable to be with loved-ones at all during the holidays, either because people are too disabled by their pain or illness to be able to gather with others, or because family and close friends having drifted out of their lives. I know the pain of that isolation; I’ll be writing about it in my next piece.

For those of you who are able to gather with others, the holidays can be a recipe for double disaster—the increase in activity exacerbates your physical symptoms, while coping with sadness, frustration, and maybe even guilt about your physical limitations gives rise to emotional pain. No wonder many people with health problems dread the approaching holidays.

If you’re one of the many people with chronic health problems who don’t look sick, the initiative is with you to make your condition visible. Here are some suggestions for helping loved-ones understand what your life is like and for giving them a heads-up on what to expect from you during the holidays.

Share information with them from the Internet or from books

Often the best way to educate loved-ones about chronic pain and illness is to use a neutral source because it takes the emotional impact out of the communication. A quick web search will yield a host of organizations devoted to every conceivable medical problem. Print out select pages or forward a few links to family and close friends. Alternatively, if you have a book about your condition, photocopy the pages that cover what you’d like them to know about you. In your accompanying note, keep it “light”—you could joke that “there won’t be a test.” But also make it clear that this favor you’re asking is important to you.

Write a letter

Many years ago, two friends of mine were in couples therapy. They weren’t able to speak to each other about their marital problems without one of them shutting down emotionally and the other reacting by shouting recriminations. Their therapist told them to write letters to each other expressing their feelings and their concerns about the marriage. It turned out to be a major first step in healing their relationship.

If you decide to write a letter, be sure it’s not accusatory. In composing it, use the word “I” more than the word “you.” Without complaining, express how difficult it’s been for you to adjust to this unexpected change in your life and how you wish you could be as active as you once were during the holidays.

You could briefly describe what your day-to-day life is like, including how unpredictable your condition is which means that you can’t know for sure how you’ll feel on the day of the actual gathering no matter how much you rest in advance. (This is the hardest concept for most loved-ones to comprehend—that we can spend weeks before a big event in full “rest mode,” but still feel very sick when the day arrives.)

I would end by telling them what to expect from you during the holidays—that you may have to skip some events, that you may have to excuse yourself right after eating to go lie down, that you may have to come late and leave early. In my experience, spelling out my limitations ahead of time is helpful not just to others, but to me, because I find it much easier to exercise the self-discipline it takes to excuse myself from a room full of people if I know that at least some of them are already expecting it.

P.S. It will be tempting to send an email, and if you have a lot of people you want to communicate with, it may be the most feasible way to reach everyone. But one thing’s for sure: people will read a handwritten letter, antiquated document that it’s become!

Find that ONE ally and enlist his or her help

If you have just one close friend or family member who understands what you’re going through, enlist his or her help in explaining your condition and your limitations. Before the holidays start, you could ask your ally to talk to loved-ones on your behalf or to be present when you talk to them. Ask your ally to be supportive if you have to excuse yourself in the middle of a gathering, or even to let you know if you’re wilting (as we call it in my household). It’s so helpful for me to be “prompted” by my ally because, when I start to overdo things, adrenaline kicks in which fools me into thinking I’m doing fine. But using adrenaline to get by just sets me up for a bad crash later on.

Your ally may be a close friend or family member who’s just waiting for you to enlist his or her help. Think long and hard before you decide there’s no such person in your life.

In the end, you may have to recognize that some loved-ones may never accept your limitations

Some family and close friends may refuse to accept that you’re disabled by pain or illness. I know this from personal experience and it hurts. Try to recognize that this inability is about them, not you. Don’t let their doubt make you doubt yourself. Your medical condition may trigger their own fears about illness and mortality, or they may be so caught up in problems in their own lives that they’re not able to see their way clear to empathize with you.

Just as you can’t force people to love you, you can’t force people to accept you. But getting angry at them just exacerbates your own symptoms. That’s why it’s important to protect yourself from allowing their lack of understanding to continually upset you. Think of it as protecting yourself from another chronic condition: chronic anger.

The physical suffering that accompanies chronic pain and illness is hard enough to endure without adding emotional suffering to it. When I feel let down family or close friends, the first thing I do is acknowledge how much it hurts. Then I reflect on the many possible reasons for their behavior. Finally, I work on genuinely wishing them well. These three steps immediately lessen my emotional suffering.

As you experiment with these suggestions, treat yourself kindly. Don’t blame yourself if one of them doesn’t work out. Instead, give yourself credit for having had the courage to try! My heartfelt wish is that your loved-ones come to understand and accept your limitations, but that if they don’t, you’ll be able to accept them as they are without bitterness.

Toni Bernhard was a law professor at the University of California—Davis, serving six years as the law school’s dean of students. She is the author of How to Be Sick: A Buddhist-Inspired Guide for the Chronically Ill and Their Caregivers and can be found online at HowToBeSick.com.

Submit a guest post and be heard on social media’s leading physician voice.

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November 23, 2011

Are you ready for World AIDS Day, December 1?

November 23, 2011
By Miguel Gomez, AIDS.gov Director

“Leading with Science. United for Action.” is the U.S. Government theme for World AIDS Day 2011. This year, we are thankful for scientific advances in the response to HIV/AIDS, leading Secretary Clinton to call for an “AIDS-free generation.” Creating an AIDS-free generation has never been a policy priority for the U.S. Government until now, because this goal would have been unimaginable just a few years ago. Secretary Clinton’s call echoes the historic charge of the National HIV/AIDS Strategy.

On December 1st, people all around the world will commemorate World AIDS Day. We will think about how far we have come in the last 30 years and we at AIDS.gov want everyone to get involved.

What can you do?

Watch and share Secretary Hillary Clinton’s historic speech on HIV/AIDS which calls for an “AIDS Free Generation.”
Plan a community event and/or take a photo for Facing AIDS. Share your message of why we all need to step up and face AIDS together.
Print posters and tools from our World AIDS Day resources and use them at your events. Many are customizable and in English and Spanish.
Locate HIV testing and other HIV services: Use and share the HIV/AIDS Prevention & Service Providers Locator and add the widget to your website or blog.
Learn about and share the National HIV/AIDS Strategy. Read about agencies who are putting the strategy in action and talk about it with your colleagues — what would it take to make the goals of the Strategy real in your community?
Follow our AIDS.gov blogs and tweets from guest blogs from the CDC and other Federal partners.
Use the hashtag #WAD11 when sharing your thoughts on Twitter or Facebook.

We are all united together to take at least one small action to commemorate World AIDS Day. What are you doing in your community?

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Researchers determine how antibody recognizes key sugars on HIV surface

November 23, 2011

HIV is coated in sugars that usually hide the virus from the immune system. Newly published research reveals how one broadly neutralizing HIV antibody actually uses part of the sugary cloak to help bind to the virus. The antibody binding site, called the V1/V2 region, represents a suitable HIV vaccine target, according to the scientists who conducted the study. In addition, their research reveals the detailed structure of the V1/V2 region, the last part of the virus surface to be visualized at the atomic level.

The study was led by Peter D. Kwong, Ph.D., chief of the Structural Biology Section of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Some people who have been infected with HIV for several years begin to make antibodies that can neutralize a wide range of virus strains. These broadly neutralizing antibodies bind to one of four sites on the virus. One site involves a sugar at a spot called amino acid residue 160. (Amino acids are the building blocks of proteins.) The sugar is located on the protein-based spikes that jut out of the surface of HIV.

The new study demonstrates how a broadly neutralizing HIV antibody called PG9 disarms the virus by grabbing hold of the sugar at residue 160, along with part of a second sugar and a short string of amino acid residues in the V1/V2 region of an HIV spike.

Similarly, a separate, recently published report* from the IAVI Neutralizing Antibody Center at The Scripps Research Institute showed how a different broadly neutralizing HIV antibody also binds to the virus via two sugars and a string of amino acid residues. Taken together, these two studies indicate that in some cases, the combination of viral sugars and amino acids can form the binding site for broadly neutralizing HIV antibodies.

The new study may also help scientists who are examining data from the clinical trial of the first HIV vaccine to demonstrate effectiveness in people (http://www.physorg.com/news172992753.html).

Recent analyses of blood samples from that trial showed that study participants who were vaccinated and then developed antibodies to the V1/V2 region were less likely to become infected. Although the role of those antibodies in protection against HIV is unknown, this finding underscores how understanding antibody-V1/V2 binding could aid the design of a more effective HIV vaccine.

More information: JS McLellan et al., Structure of HIV-1 gp120 V1V2 domain with broadly neutralizing antibody PG9. Nature DOI: 10.1038/nature10696 (2011).

*R Pejchal et al., A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science DOI: 10.1126/science.1213256 (2011).
Provided by National Institutes of Health

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Video: Mount Sinai Medical Center Launches Initiative to Erase the Stigma of Hepatitis C

Along with shattering the stigma surrounding the Hepatitis C virus, Dr. Dieterich wants patients to understand that testing positive for the virus is not a death sentence if caught early.

Also See: The Mount Sinai Medical Center Launches Initiative to Erase the Stigma of Hepatitis C and Encourage Everyone to Get Tested

Acetaminophen: Repeated Use of Slightly Too Much Can Be Fatal

Laurie Barclay, MD

November 22, 2011 — Repeated doses of slightly too much acetaminophen (known as paracetamol in the United Kingdom and elsewhere in Europe) can be fatal, according to the results of a large, single-center cohort study published online November 22 in the British Journal of Clinical Pharmacology.

"On admission, these staggered overdose patients were more likely to have liver and brain problems, require kidney dialysis or help with breathing and were at a greater risk of dying than people who had taken single overdoses," senior author Kenneth J. Simpson, MBChB (Hons), MD, FRCP (Edin), from the University of Edinburgh and Scottish Liver Transplant Unit in the United Kingdom, said in a news release.

"They haven't taken the sort of single-moment, one-off massive overdoses taken by people who try to commit suicide, but over time the damage builds up, and the effect can be fatal," he adds.

In the United Kingdom, acetaminophen hepatotoxicity is the leading cause of acute liver failure (ALF). However, the effect of a staggered overdose pattern or delayed hospital presentation on mortality or need for emergency liver transplantation was previously unknown.

Of 663 patients admitted with acetaminophen-induced severe liver injury between 1992 and 2008, 161 (24.3%) had taken a staggered overdose. Compared with patients who took an overdose at a single time, patients with staggered overdose were significantly older and more likely to abuse alcohol.

When asked why they repeatedly ingested more than the recommended dose of acetaminophen, patients with staggered overdose most often cited pain relief as their rationale (58.2%).
Compared with patients who took an overdose at a single time, those who took staggered overdoses had lower total ingested doses and lower serum alanine aminotransferase (ALT) levels on admission. Nonetheless, they were more likely to be encephalopathic and to require renal replacement therapy or mechanical ventilation.

Although mortality was higher in staggered overdoses than in single-time overdoses (37.3% vs 27.8%; P = .025), the staggered overdose pattern was not an independent predictor of mortality. For staggered overdoses, sensitivity of the King's College poor prognostic criteria was reduced (77.6%; 95% confidence interval [CI], 70.8% - 81.5%).

Delayed presentation to medical services more than 24 hours after single-time overdose occurred in 44.9% of those in whom accurate timings could be determined, and was independently associated with death or liver transplantation (odds ratio [OR], 2.25; 95% CI, 1.23 - 4.12; P = .009).

In their logistic regression analysis, the investigators controlled for signs and symptoms, such as hepatic encephalopathy and prothrombin time, as well as various demographic factors.

"Staggered overdoses or patients presenting late after an overdose need to be closely monitored and considered for the paracetamol antidote, N-acetylcysteine [NAC], irrespective of the concentration of paracetamol in their blood," Dr. Simpson said.

Because both these groups are at increased risk of developing multiorgan failure, they should be considered for early transfer to specialist liver centers.

Limitations of this study include reliance on patient recall regarding the time of last ingestion, total paracetamol dose, and suicidal intent; limited data regarding the use of concomitant P450 enzyme inducers or recent fasting; and selection bias for the more severe cases of acetaminophen toxicity in Scotland.

"[T]his large cohort study demonstrates the deleterious effects of delayed presentation and staggered overdose pattern upon outcome following paracetamol-induced acute liver injury," the study authors conclude. "Both delayed presentation > 24 hours and staggered overdoses are strongly associated with multiorgan injury and the need for [liver transplantation]. Patients presenting with these overdose patterns should be treated as high risk for progression to ALF, and should receive NAC in their presenting hospital whilst awaiting serial ALT and PT levels."

This study received no external funding. The authors have disclosed no relevant financial relationships.

Br J Clin Pharmacol. Published online November 22, 2011.

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New HCV Drugs at AASLD