Plenty Of Room For Everyone In The Race To FDA Approval For New Hepatitis C Therapies

Jul 23 2013, 12:32 by: Three Knights Capital  |  includes: ABBV, BMY, ENTA, GILD, JNJ

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours

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The United States Preventive Services Task Force, or USPSTF, reversed its stance late on June 25 to conclude that all baby boomers - those people born between 1945 and 1965 - should be tested for hepatitis C. The USPSTF is an influential medical guidelines organization that advises Congress and, as its website reads, "makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms."

The recommendation of the USPSTF could lead to health insurance companies having to pay for screening under the revamped U.S. healthcare laws that start next year. It also could also lead to a lot more diagnoses of hepatitis C infections and a boon in sales for pharmaceutical companies. According to the Centers for Disease Control and Prevention, about 3.2 million Americans have the chronic version of the hepatitis C virus (HCV). Worldwide, it's estimated that more than 150 million people are infected with HCV, according to the World Health Organization.

HCV is a viral infection that can lead to swelling of the liver, cirrhosis, the need for transplant, and possibly even liver cancer. Today's standard of care is the injectable interferon, which is well documented to cause flu-like side effects. Because of the side effects and the method of delivery, new therapies that treat HCV more quickly are in great demand. Demand and potentially changing guidelines have planted several companies firmly on investors' radar.

A definite leader in the treatment of HCV is Gilead Sciences, Inc. (NASDAQ: GILD), with shares rising about 45 percent in 2013 as optimism for its oral HCV medication, sofosbuvir, are soaring. The drug is meant for use in combination with pegylated interferon and/or ribavirin, and represents what most consider the next generation of HPV therapies as an all-oral regime. Gilead's interferon-free ELECTRON trial of sofosbuvir demonstrated a strong response rate in patients with HCV genotypes 2 and 3 treated only with sofosbuvir and ribavirin.

Gilead, the world's biggest maker of HIV drugs, diversified into the HCV market by snagging the promising drug - and two other HCV drug candidates - in its $11.1-billion acquisition of Pharmasset, Inc. in November 2011. On June 10, the U.S. Food and Drug Administration granted Gilead priority review, following completion of Phase III clinical trials for the drug. Gilead is hoping for approval no later than early in December this year. S&P Capital IQ maintains a 5-STAR "Strong Buy" recommendation for Gilead.

Gilead may be leading the pack, but it is not alone in a race that will likely deliver billions of dollars in sales to the first to market. AbbVie (NYSE: ABBV) is nipping at Gilead's heels with its own all-oral, interferon-free treatment for HCV, with and without ribavirin. Much like sofosbuvir, AbbVie's HCV protease inhibitor ABT-450, in combination with other AbbVie drugs, produced strong response rates of greater than 90 percent in only a few months. ABT-450 was developed in a joint effort with Enanta Pharmaceuticals, Inc. (NASDAQ: ENTA).

AbbVie's drugs, ABT-450/r, ABT-267 and ABT-333, have received the vaunted "Breakthrough Therapy" designation from the FDA. A "Breakthrough Therapy" designation from the FDA, a relatively new category from the FDA (initiated in 2012), is meant to expedite the regulatory process for drug candidates that may meet great areas of unmet medical need. To date, the FDA has received over 60 applications for "Breakthrough Therapy" designation, but only 15 have been awarded, with AbbVie commanding three of them with its HCV treatments.

Shares of ABBV have also lofted higher, rising about 27 percent in 2013, on bets that they can catch Gilead in the quest for FDA approval to market a new HCV treatment. The Breakthrough designation gives AbbVie an outside shot, but Gilead appears to still be out front in a very close contest.

Even if one or both win the thumbs-up from the FDA, there are a host of other companies running the regulatory gamut with HCV drugs that can certainly still benefit in the future. It's also notable that both AbbVie's and Gilead's treatments would likely include ribavirin, a drug that many patients have difficulty tolerating. Bristol-Myers Squibb (NYSE: BMY), developing a ribavirin- and interferon-free treatment, is certainly in the hunt. BMS already has Baraclude approved for the treatment of chronic hepatitis B and several ongoing clinical trials testing its antiviral cocktails. In May, the company completed a Phase III trial of BMS-790052 and BMS-650032 in Japanese HCV patients. Japan has recently unveiled plans under Prime Minister Shinzo Abe that are meant to raise the number of clinical applications by consolidating management of research money. To that end, it will be interesting to see where BMS goes with this research moving forward.

Shares of BMY have risen about 23 percent so far in 2013.

Johnson & Johnson's (NYSE: JNJ) oral HCV drug, simeprevir, received priority review from the FDA in May and has also delivered very promising clinical data. It's noteworthy that research has been conducted combining simeprevir with Gilead's sofosbuvir with compelling results. That's another point in recognizing that there can be more than one blockbuster drug in the massive HCV industry. Several of the drugs in development could eventually receive FDA approval and potentially be used together to treat patients.

Shares of JNJ are up about 29 percent in 2013.

This also means considering medical device manufacturers in the HCV business. Late in June, Aethlon Medical, Inc. (AEMD.OB), a maker of medical devices targeting unmet medical needs in cancer, infectious disease and more, got the green light from the FDA to commence a clinical trial evaluating its Hemopurifier® in end-stage renal disease patients (ESRD) infected with HCV.

The Hemopurifier is a first-in-class "blood filter" that targets the rapid elimination of infectious disease and cancer glycophathogens, removing the pathogen from the bloodstream. It allows for extracorporeal therapeutic delivery on standard CRRT and dialysis equipment currently used in hospitals and clinics globally. Specific to HCV, the Hemopurifier potentially could be used as an adjuvant to any type of therapy, whether it is interferon-based or the aforementioned oral antiviral regimes. Further, for patients that develop a drug resistance to any or all HCV treatments, the Hemopurifier could work independently to reduce viral load.

Trials conducted in India showed the Hemopurifier to be well tolerated in naïve HIV and HCV-infected ESRD patients while reducing viral loads in excess of 50 percent in both disease conditions. Follow-on studies in non-ESRD HCV patients treated with the Hemopurifier and interferon demonstrated an undetectable viral load in as little as seven days in genotype-1 patients, the hardest-to-treat patient population.

Successful completion of the 10-patient clinical trial could pave the way to a pivotal trial necessary for marketing clearance of the Hemopurifier as a new HCV treatment.

Shares of AEMD.OB are ahead 71 percent so far in 2013.

There has certainly been no shortage of buzz surrounding potential "cures" for hepatitis C, qualified by no detectable HCV viral load. Investors have been jumping into the companies mentioned based upon the lucrative revenue stream potential that surrounds the disease, helping drive valuations for each upward. Regardless of who garners approval from the FDA first, each company is bringing something substantial to the table that could provide an invaluable benefit to patients, giving each one significant headroom for growth.

Source

Splitting Donated Livers Shown to be Safe, Allowing Doctors to Save Two Lives from Single Organ

Donor organ allocation policy could be changed to nearly eliminate waitlist mortality for children —without additional risk to adult recipients.

BOSTON, July 17, 2013 /PRNewswire-USNewswire/ -- Split liver transplantation carries no increased risk of failure in either recipient, allowing surgeons to safely save two lives from a single donated organ (graft), according to new research from Boston Children's Hospital published online in the Journal of the American College of Surgeons. 

Due to their regenerative nature, livers donated by a deceased adult or adolescent can be surgically split into two unequally sized portions; the smaller segment is allocated to a young child awaiting transplant and the larger portion to an adult.

"Infants waiting for a donor liver have the highest waitlist mortality of all liver transplant candidates, and dozens of children die each year waiting for size-appropriate organs to become available," says Heung Bae Kim, MD, director of Boston Children's Hospital's Pediatric Transplant Center and lead author on the study. "If we can increase the number of split livers to just 200 a year, which would still affect less than four percent of the total number of livers transplanted each year, it would save virtually every small child waiting for a new liver."

Based on his recent findings, (which includes research on how well children function with split livers) Kim is advocating for changes in how donor livers are allocated—automatically placing infants and small children at the top of the liver waitlist, thereby giving pediatric transplant surgeons the option to split the first graft to become available. Once the liver has been split, the smaller portion is transplanted into a child and the larger portion is transplanted into the next appropriate adult on the list.

Analyzing United Network for Organ Sharing (UNOS) records, Boston Children's researchers looked at data compiled over a fifteen year period (1995-2010), studying the graft survival rates of 62,190 first-time adult deceased-donor liver transplant recipients, 889 of whom received partial grafts from a split liver transplant. The research shows that from 2002 forward the vast majority of adults who received a split graft experienced a risk of graft failure comparable to those who received a whole graft.

"After an extensive review of the data, it's clear that in the current era, with the exception of a small, very sick population of patients, adults who receive a split graft can expect to fare as well as those who received a whole organ," says Ryan Cauley, MD, MPH, first author on the paper. "Because risks once associated with this technique are now negligible, if a center has a patient waiting for a liver and it has access to a split graft, there's no reason not to accept it."

In addition to saving young patients, Kim's proposed amendments to the allocation process could take place without sweeping change, affecting only an extremely small portion of available grafts. "There are around 500 to 600 pediatric liver transplants done each year in the United States, with split liver transplant only accounting for 120 of the total number," Kim says. "By splitting just 80 more livers a year, it would make grafts available to virtually every small child on the waitlist. Given the current national debate on maximizing access to organs for children, it's my hope that implementing changes that would benefit children without harming adults would be considered favorably."

Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 13 members of the Institute of Medicine and 14 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 395 bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Boston Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Boston Children's, visit: http://vectorblog.org.

Contact:
Erin Tornatore
617-919-3110
erin.tornatore@childrens.harvard.edu

SOURCE Boston Children's Hospital

RELATED LINKS
http://www.childrenshospital.org/

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Hepatitis is a silent epidemic that kills two people per minute throughout the world

PAHO/WHO urges everyone to become better informed about hepatitis, to get screened for the disease and to seek treatment, if needed

Washington, D.C., 23 July 2013 (PAHO/WHO) - Viral hepatitis affects some 424 million people throughout the world, killing 1.4 million per year as a result of complications such as acute liver failure, cirrhosis, or liver cancer. The disease is sometimes called a "silent epidemic" because most people who are infected are unaware of their status.

The theme of this year's World Hepatitis Day, July 28, is "This is the hepatitis. Know It. Confront it."  This year the Pan American Health Organization/World Health Organization (PAHO/WHO) is marking the day by calling on everyone to become better informed about hepatitis, to get screened for the disease and to seek treatment, if needed.

"People know very little about hepatitis, its potential severity, and its serious consequences for health and quality of life," said PAHO Director Carissa F. Etienne. "We therefore need to intensify our information, education and communication initiatives around this disease and take action to promote prevention and early detection so people can get the treatment they need."

Hepatitis is an inflammation of the liver generally caused by a viral infection. Five principal types of hepatitis virus are known: A, B, C, D and E, which can be transmitted through a variety of routes including unprotected sexual intercourse, unsafe injecting and piercing practices and through contaminated water or food. These cause infection and severe and chronic inflammation of the liver, which in turn can lead to cirrhosis and liver cancer. In the Americas, between 8 million and 11 million people suffer from chronic hepatitis B infection, and 7 million have chronic hepatitis C.

This disease puts a heavy burden on health-care systems because of the high cost of treatment. In many countries it is the main cause for liver transplants.

The fact that most people do not have symptoms-and tend not to have them for decades until they develop chronic liver disease-has contributed to the problem of poor diagnosis and inadequate treatment.

"The number of deaths throughout the world each year from causes associated with hepatitis is about equal to the number of traffic deaths, that is, more than two deaths every minute," said Rafael Mazin, PAHO/WHO senior advisor on HIV, sexually transmitted diseases, and hepatitis.

Hepatitis can be controlled with simple measures such as good hygiene, avoiding consumption of contaminated food and water, getting vaccinated for hepatitis B, practicing safe sex, and not sharing injection or piercing equipment.

PAHO/WHO has been collaborating with its Member States on strategies to prevent and control viral hepatitis. All the countries of Latin America and the Caribbean have officially introduced the hepatitis B vaccine into their child immunization programs, and more than 99% of donated blood units are screened for hepatitis B and C viruses

The Pan American Health Organization is also promoting hepatitis B vaccination of health workers and the expanded use of sterilized, disposable injecting, cutting and piercing tools and instruments to prevent cross infections (this includes needles used both in health facilities and in cosmetic procedures, such as tattooing).

WHO to launch global policy report

WHO will launch a new global policy report on prevention and control of viral hepatitis on July 24. The report presents the results of a survey examining the response of WHO Member States to the disease and provides information from 27 countries in the Americas.

The report's launch will take place at 6.30am (Washington DC time) at WHO headquarters in Geneva, Switzerland. Health authorities from Brazil will participate in the event and describe their country's efforts to increase access to treatment for hepatitis. Join the launch live via webinar. The report and other information can be found on the web.

PAHO is the oldest international public health organization in the world. It works with its Member States to improve the health and the quality of life of the people of the Americas. It also serves as the Regional Office for the Americas of WHO.

More information on hepatitis:

• Fact sheet
• Frequently asked questions
• Infographic
• WHO Global policy report on the prevention and control of viral hepatitis in WHO Member States

Links:

• PAHO/Hepatitis
• WHO/World Hepatitis Day
• World Hepatitis Alliance

Last Updated on Tuesday, 23 July 2013 13:52

Source

How to Save $200 Billion and Cure Hepatitis C

Peter Kolchinsky 7/22/13

Wall Street is buzzing with anticipation about the first new all-oral drugs for hepatitis C approaching the market. The high rate of HCV infection and dissatisfaction with current treatments have created a potential multi-billion dollar bonanza for drug companies. It’s estimated that Gilead, the frontrunner in this race, will charge as much as $90,000 per patient. With roughly 3 million infected patients currently in the U.S., that’s about $270 billion to cure everyone.

Is this necessary? Or even advisable? Particularly in the case of hepatitis C, payers, physicians, and patients can collaborate to extract huge price concessions from pharmaceutical companies, netting more than $200 billion in savings. All they have to do is acknowledge that sometimes “good enough” is better than “best.” I’m wagering they will, and that’s why my firm, RA Capital, has invested in Achillion Pharmaceuticals, which we believe will compete quite aggressively and effectively on price once they launch their HCV therapy in 2016.

Price competition is going to play a bigger and bigger role in containing healthcare cost, and HCV treatment is one area where such competition won’t have to come at the expense of patient welfare.

An estimated 150 million people are infected with hepatitis C worldwide. All current treatment regimens require long-term, weekly interferon injections with significant side effects. Many patients can’t tolerate those or just don’t want to bother with them. Because the disease progresses slowly, patients can and do wait for years for better treatment choices. Hence the mounting anticipation for the all-oral treatments.

Clearly, being first to market will be a plus. Both Gilead and AbbVie are likely to get approvals around the same time towards the fall of 2014. Gilead’s treatment also appears to deliver the highest cure rate (about 95 percent) and will comprise just a single pill daily for eight to twelve weeks. Abbvie’s regimen has a similar cure rate but requires taking a number of pills twice a day. By 2016, several other all-oral treatments are expected to be approved, including one from Bristol-Myers Squibb and another from Achillion, a small biotech.

Analysts are buzzing about the various characteristics of the new drugs and trying to determine which company has the advantage. All of these combo drug regimens are expected to provide cure rates of 85 percent or better, but there are slight differences in their side-effect profiles, pills per day, treatment duration and cure rates. By most accounts, Gilead offers the “best” treatment and is therefore expected to both charge top dollar and win a majority market share. Its stock has more than doubled in the last year to a $90 billion valuation on high expectations for hepatitis C drug sales.

In business-as-usual mode, U.S. payers would just throw open their wallets and pay whatever it costs to provide the “best” therapy to all the patients who could benefit. But once they start receiving the bills, payers and providers may begin singing a different tune.

Certainly, some patients with advanced disease will immediately require treatment with the “best” drug available. But many patients are still in the early stages of Hepatitis C and will feel no sense of urgency. With at least four competitive “good-enough” all-oral regimens on the market by 2016, payers could negotiate dramatically reduced prices, awarding the lowest bidder the privilege of selling the first line treatment. The small percent of patients who fail that regimen could then cycle onto the best and presumably most expensive one.

This approach is extremely simple and convenient for patients, compared to today’s regimens that can take up to a year and require injections with many side effects. Indeed, this is similar to the way doctors usually prescribe antibiotics, moving to the more expensive options only after the cheaper ones have been exhausted.

After all, every one of these drugs represents a huge improvement over current therapy. They are all “good enough” to cure most patients. And, assuming that the first-line drug could be negotiated down to as low as $10,000, each patient who responds to the cheapest drug (most will) would save the system as much as $80,000 compared to using the best drug first. By our calculations, the cumulative savings nationwide would be as much as $200 billion in the U.S. alone over the next decade. Similar savings await other nations.

Certainly companies deserve to be rewarded for tremendous breakthroughs like the new hepatitis C drugs. And many on Wall Street are incredulous that drug companies will lower their prices. Indeed, large pharmaceuticals companies don’t have a strong track record of offering deep discounts even in the face of significant competition. For example, there are many drugs approved for multiple sclerosis yet the prices for these only go up each year.

But hepatitis C is a big market and a certain type of company could still do quite well charging even $10,000 per patient. The 3 million patients in the U.S. alone could net $30 billion of sales, which might be modest for Gilead shareholders but would be a windfall for a company as small as Achillion, whose market capitalization is less than 1 percent of Gilead’s valuation. So even if having Gilead, AbbVie, and Bristol-Myers on the market is not enough to spark a price war by 2015, payers will likely get a discounted offer they can’t refuse from Achillion in early 2016.

To some, the idea of using merely “good enough” drugs will seem offensive. It’s a point of pride for Americans that patients come first and doctors have the freedom to prescribe the best regardless of cost. Even if this American healthcare fantasy were true, when the most expensive route to a cure is merely more convenient than the least expensive drug regimen, are those extra billions of dollars worth it? My bet is that private and public insurers will both be taking a much closer look at scenarios like this one, cutting wherever they can reap huge savings without harming patients.

Besides, if $90,000 were offered directly to patients, what would they chose? My guess is that most would buy the cheaper drugs, get cured for less, and put the massive savings towards countless other necessities.

If only reimbursement worked that way.

Hepatitis C has proven to be surprisingly easy to cure and we will soon see multiple “good enough” drugs on the market, which makes it easy for payers and providers to negotiate down prices on behalf of patients, employers, and taxpayers. Just as oncologists have started to push back against high drug prices, others will begin taking a stance against exorbitant spending, especially for mere convenience.

After all, our definition of “best” has left us with the priciest healthcare system in the world, but not always the best outcomes. HCV treatment is one textbook example of how mindlessly sticking to our old ways will have spectacularly expensive consequences.

Source

World Hepatitis Day 2013: Know it, Confront it

The Lancet Global Health, Early Online Publication, 22 July 2013

doi:10.1016/S2214-109X(13)70038-X Cite or Link Using DOI

Copyright © 2013 2013 Lazarus et al. Open Access article distributed under the terms of CC BY World Hepatitis Alliance Published by Elsevier Ltd. All rights reserved.

Jeffrey V Lazarus a, Charles Gore b, Tim Nguyen c, Kelly Safreed-Harmon a, Ida Sperle a, Raquel JJ Peck b, Hande Harmanci c, Stefan Wiktor c

Viral hepatitis has not received the level of attention that it warrants. However, the global picture began to change in May, 2010, when the World Health Assembly adopted its first resolution on viral hepatitis.1

Recent data clearly show the magnitude of the challenge. Hepatitis A and E together caused more than 34 million cases of illness in 2005.2 According to Global Burden of Disease3 estimates, 1·3 million deaths occurred in 2010 from diseases related to hepatitis B and C. To put this finding into context, malaria and HIV caused about 1·2 million and 1·5 million deaths in 2010, respectively.3 Much of the suffering caused by hepatitis is unnecessary. Safe and effective vaccines for hepatitis A and B are available. Hepatitis C is curable, and hepatitis B treatable. Improvements in sanitation, hygiene, and blood and injection safety can reduce the spread of viral hepatitis and many other diseases.

In 2012 WHO, in collaboration with the World Hepatitis Alliance, did the first worldwide survey to investigate how governments are addressing viral hepatitis.4 The findings will be released on July 28, 2013—World Hepatitis Day.1 126 of WHO's 194 member states submitted answers to the survey—a response rate of 64·9%. Slightly more than a third of the countries reported the existence of a national hepatitis strategy or plan. Less than half of respondents reported holding events for World Hepatitis Day 2012, and less than a third had funded any other type of hepatitis public awareness campaign in recent months. The survey also asked questions about surveillance, disease prevention measures, and policies and practices for screening, care, and treatment.4

The findings provide a crucial baseline against which progress can be measured in coming years. We hope that the report will also stimulate dialogue with respect to the roles of all stakeholders in forging a cohesive and effective response to viral hepatitis. For example, civil society organisations can help to strengthen and call attention to governmental responses to hepatitis, in line with their involvement in many other pressing health issues. The relatively high response rate for the survey is an affirmation of the global community's concern about viral hepatitis.

However, low response rates from the WHO African Region and Western Pacific Region suggest that some of those member states do not see viral hepatitis as a priority disease. Further, the fact that so few survey respondents reported having a national strategy or plan for viral hepatitis is alarming. Such documents provide foundations for strong national leadership to address the complex array of issues to improve prevention, treatment, and care.

Another component of an effective public health response is to raise awareness of hepatitis among the general public, policy makers, and health-care workers. Governments should commemorate World Hepatitis Day and promote other awareness-raising activities. The World Hepatitis Alliance has adopted the three wise monkeys motif (figure) for World Hepatitis Day to call attention to the widespread public ignorance surrounding viral hepatitis, which will not end unless policy makers show better leadership on this issue. The World Hepatitis Day slogan is: “This is hepatitis…Know it. Confront it.” We invite readers to ask themselves why, given its burden, viral hepatitis is absent from major global health initiatives.

Figure Full-size image (76K) World Hepatitis Alliance

The three wise monkeys call attention to how people block out the reality of viral hepatitis

TN, HH, and SW are staff members of WHO. The authors alone are responsible for the views expressed in this publication, and they do not necessarily represent the decisions or policies of WHO. We declare that we have no conflicts of interest.

References

1 WHO. Sixty-third World Health Assembly. WHA63.18 Viral hepatitis. Geneva: World Health Organization, 2010.

2 WHO. Prevention and control of viral hepatitis infection: framework for global action. Geneva: World Health Organization, 2012.

3 Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2095-2128. Summary | Full Text | PDF(1201KB) | CrossRef | PubMed

4 WHO. Global report on the prevention and control of viral hepatitis in WHO member states. http://apps.who.int/iris/bitstream/10665/85397/1/9789241564632_eng.pdf. (available July 22, 2013).

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a Copenhagen HIV Programme, Copenhagen University, Copenhagen, DK-2100, Denmark

b World Hepatitis Alliance, London, UK

c World Health Organization, Geneva, Switzerland

Source

Sixth Annual World Hepatitis Day Takes Place on July 28

BOSTON, Mass.—Sunday, July 28 will mark the sixth annual World Hepatitis Day sponsored by the World Hepatitis Alliance in collaboration with the World Health Organization.

Local, national, and international organizations will hold events this week to raise awareness of viral hepatitis. AIDS Action Committee of Massachusetts will offer confidential information, referrals, and support about hepatitis from 9 a.m.-8 p.m. Monday through Thursday and from 9am-5pm on Friday. Call 800-235-2331 or email hotline@aac.org for more information.

“People can live with hepatitis for a decade or more before learning they have the disease, which greatly complicates their eventual treatment and increases the costs of care,” said Rebecca Haag, President & CEO of AIDS Action Committee of Massachusetts, a convening member of the Massachusetts Viral Hepatitis Coalition. “If we don’t slow the infection rate and improve treatment outcomes, the state’s costs for treating people with hepatitis—which is often called the ‘silent epidemic’ because people can live with hepatitis for more than a decade without symptoms—will continue to increase. One of the first things we need to do is to raise awareness of what viral hepatitis is and the devastating impact it is having on the public’s health.” 

“People can live with hepatitis for a decade or more before learning they have the disease, which greatly complicates their eventual treatment and increases the costs of care,” said Rebecca Haag, President & CEO of AIDS Action Committee.

A new report released this year by the State Healthcare Access Research Project (SHARP) and prepared by The Center for Health Law and Policy Innovation of Harvard Law School, the Treatment Access Expansion Project, and the Massachusetts Viral Hepatitis Coalition found the average age of death between 1992 and 2009 of those in Massachusetts who had been previously diagnosed with hepatitis C was 53 with the cause of death being either hepatitis C or other causes. Seventy-three percent died within five years of receiving their diagnosis of hepatitis C. During the same period, the average age of death from all causes of those who were not infected with hepatitis C was 75. The report concludes that “many people with [hepatitis C] may be getting diagnosed and entering care late in their illness.”

Facts About Viral Hepatitis

• Viral hepatitis causes inflammation of the liver which can lead to cirrhosis and increased risk of liver cancer.
• There are an estimated 110,000 people living with viral hepatitis in Massachusetts today with between 7,000 to 10,000 new diagnoses annually.
• 14 percent of those living with HIV/AIDS are co-infected with hepatitis C.
• Viral hepatitis is spread in the same manner as HIV, but is much more highly infectious and easily transmitted from one person to another.
• Between 2002 and 2009, the rate of infection among teens and young adults age 15-24 increased 74%, largely driven by the shared use of injection drug equipment.
• In 2008, the number of US deaths attributed to hepatitis (15,768) surpassed, for the first time, the number of deaths due to HIV/AIDS (11,924).

AIDS Action provides on-going outreach, education, and prevention services to those living with viral hepatitis and at risk of contracting hepatitis C in several critical ways:

• Running a monthly support group for people living with hepatitis C
• Providing easy access to PharmaHealth, a hepatitis C specialty pharmacy located in our Jamaica Plain office;
• Providing one-on-one education at our drop-in centers in Jamaica Plain, Cambridge, and Lynn to those at-risk and infected with hepatitis C;
• Operating two needle and sterile injection equipment exchanges, one in Boston and one in Cambridge;
• Making information about hepatitis freely available to providers, researchers, policy analysts, lawmakers, and the general public via the Health Library and a telephone hotline (888-443-HEPC (4372);
• Referring those newly diagnosed with hepatitis C to medical care and providing the support necessary to keep them connected with care
• Advocating for increased public funding to conduct outreach, education, and prevention to those vulnerable to infection with viral hepatitis, and encouraging those born between 1945 and 1965 to get tested for hepatitis C;
• Convening the Massachusetts Viral Hepatitis Coalition

About AIDS Action Committee of Massachusetts

AIDS Action Committee of Massachusetts is the state’s leading provider of prevention and wellness services for people vulnerable to HIV infection. It provides services to one in six people in Massachusetts living with an HIV diagnosis. These services include HIV counseling and testing; needle exchange; mental health counseling; housing assistance; and legal services. AIDS Action works to prevent new HIV infections, support those affected by HIV, and tackle the root causes of HIV/AIDS by educating the public and health professionals about HIV prevention and care; and advocating for fair and effective HIV/AIDS policy at the city, state, and federal levels. Founded in 1983, AIDS Action Committee of Massachusetts is New England’s first and largest AIDS service organization. Learn more at www.aac.org.

[From a News Release]

Source

World Hepatitis Day, 28 July 2013

This is hepatitis. Know it. Confront it

Every year on 28 July, WHO and partners mark World Hepatitis Day to increase the awareness and understanding of viral hepatitis and the diseases that it causes.

Hepatitis viruses A, B, C, D and E can cause acute and chronic infection and inflammation of the liver that can lead to cirrhosis and liver cancer. These viruses constitute a major global health risk with around 240 million people being chronically infected with hepatitis B and around 150 million people chronically infected with hepatitis C.

For 2013, the overall theme continues to be "This is hepatitis. Know it. Confront it." The campaign emphasizes the fact that hepatitis remains largely unknown as a health threat in much of the world.

Goal: moving from awareness to commitment and action to address the "silent epidemic" of viral hepatitis

Millions of people are living with viral hepatitis and millions more are at risk of becoming infected. Most people with chronic infection with hepatitis B or C are unaware that they continue to carry the virus. They are therefore at high risk of developing severe chronic liver disease and can unknowingly transmit the virus to other people. Approximately one million people die each year from causes related to viral hepatitis, most commonly cirrhosis and liver cancer.

World Hepatitis Day provides an opportunity to focus on specific actions, such as:

• strengthening prevention, screening and control of viral hepatitis and its related diseases;
• increasing hepatitis B vaccine coverage and integration of the vaccine into national immunization programmes;
• coordinating a global response to viral hepatitis.

Although the burden of disease related to hepatitis infection is very high, in most countries, the problem has not been addressed in a comprehensive way for many reasons. These include the fact that most people do not develop any symptoms when they become infected and that they remain free of symptoms often for decades until they develop chronic liver disease. This has largely resulted in "the silent epidemic" we are experiencing today.

Viral hepatitis also places a heavy burden on the health-care system because of the high costs of treatment of liver cancer and liver failure from cirrhosis. In many countries, liver failure from viral hepatitis is the leading reason for liver transplants. Such end-stage treatments are expensive, easily costing up to hundreds of thousands of dollars per person.

The date of 28 July was chosen for World Hepatitis Day in honour of the birthday of Nobel Laureate Professor Baruch Samuel Blumberg, discoverer of the hepatitis B virus.

Related links

• Fact sheets on hepatitis
• WHO's work on hepatitis
• More on hepatitis

Source

Proof of Principle shown in liver disease vaccine program

ASX Announcement

Highlights

• BioDiem's vaccine program targeting liver disease underway at the University of Canberra
• Researchers successfully establish new system designed to deliver drugs specifically to the liver
• Treatments for viral hepatitis and liver cancer represent large markets where new effective therapies are required.

Melbourne, 22 July 2013: Australian infectious disease therapy and vaccine development company BioDiem Ltd (ASX: BDM) has announced that its hepatitis vaccine program has successfully achieved an important milestone towards developing treatments for liver diseases.

Researchers at the University of Canberra have developed a system designed to target the liver specifically to deliver therapies directly there. This would be relevant for hepatitis and liver cancer, for example. Due to this targeting, smaller dosages of currently used therapies could be given to liver disease patients. This could result in higher cure rates and/or fewer dose-related side effects.

The groundbreaking work done recently has shown that the hepatitis D virus, which has been used as the basis for the technology, can be engineered into a stable and replication-competent virus (called a vector).

"This is an important breakthrough, which shows promise to support an array of new therapies targeting liver disease," said BioDiem CEO Julie Phillips. "We have filed international patents for this new vector technology and we envisage further development for specific treatments targeting viral hepatitis and liver cancer. This opens opportunities for vaccine manufacturers to design vaccines to target the liver selectively."

"The work conducted by the team at the University of Canberra has allowed us to file the patents necessary to protect the inventions associated with the development of this novel vector."

Professor Ian Ramshaw from the University of Canberra said it was a significant development in the science supporting treatment of serious human disease affecting the liver. Currently treatments are rarely curative and often are associated with side effects which can cause patients to cease treatment. A targeted approach would open the possibility of better results for patients.

An estimated 4.4 million Americans are living with chronic hepatitis, most of whom do not know they are infected. Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation. Liver cancer in men is the fifth most frequently diagnosed cancer worldwide and is the second leading cause of cancer-related death in the world. The global hepatitis market was estimated to be $3.2bn in 2009, representing a compound annual growth rate (CAGR) of 3.1% between 2001 and 2009. The market is anticipated to reach revenues of approximately US$5.9bn by 2016, growing at a CAGR of 9% between 2009 and 2016. The chief reason for its growth is the large chronic carrier hepatitis population, primarily Hepatitis B and C.

BioDiem Ltd has a worldwide exclusive license to the technology from the University of Canberra.

ENDS

About BioDiem Ltd
BioDiem (ASX: BDM) is an ASX-listed biopharmaceutical company developing vaccines and antimicrobials targeting treatment and prevention of infectious diseases and related cancers. The lead technology is the LAIV (Live Attenuated Influenza Virus) used for seasonal and pandemic influenza vaccines and is given intranasally. A therapeutic hepatitis vaccine project targeting hepatitis D and B is underway at the University of Canberra. BioDiem's antimicrobial, BDM-I, is in preclinical development for fungal and bacterial diseases, also schistosomiasis, tuberculosis and protozoal infections. The SAVINE (scrambled antigen) technology is in development for tuberculosis and also EBV-related disease including nasopharyngeal cancer. BioDiem's retinal product, BDM-E, in development for retinitis pigmentosa is available for outlicence.

About BioDiem's Liver-Targeted Technology
The vector is based on the Hepatitis D virus (HDV) which is a small, enveloped RNA virus requiring the envelope proteins of a helper virus, Hepatitis B virus (HBV), for further particle formation. HDV can only infect liver cells and produce virus particles in cells that are also infected with HBV. Based on this natural tropism for the liver and the successful generation of replication-competent recombinants this technologically has the potential to deliver biologically active therapies to the liver.
For additional information, please visit www.biodiem.com

About University of Canberra
The University of Canberra is Canberra's own university. It has a dynamic, innovative and collaborative research culture with a focus on applied research in areas aligned with the needs of our local community as well as national and international research priorities. The University of Canberra's researchers deliver breakthroughs that help solve real-world problems, particularly in the areas of governance, environment, communication, education and health.

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Does Successful Hepatitis C Treatment Eliminate Liver Cancer Risk?

July 11, 2013

Abigail Zuger, MD reviewing Aleman S et al. Clin Infect Dis 2013 Jul 15. Pereira OC and Feld JJ. Clin Infect Dis 2013 Jul 15.

Not in patients with cirrhosis, who still risk both decompensated cirrhosis and hepatocellular carcinoma.

Although eradication of hepatitis C virus (HCV) infection with combined antiviral therapy generally will halt or even reverse liver pathology, risk for bad outcomes such as decompensated cirrhosis or hepatocellular carcinoma (HCC) is not eliminated. But exactly how common are these life-threatening complications of HCV in patients with sustained virologic responses (SVRs) to HCV treatment?

Swedish researchers prospectively followed 351 patients with HCV-related cirrhosis for a mean 5.3 years. Among 110 patients with SVRs to interferon-based treatment, HCC incidence was 5%, compared with 13% among 198 treated patients without SVRs and 29% among 48 untreated patients. Risks for any clinical decompensation (i.e., ascites, variceal bleeding, or encephalopathy), liver-related mortality, and all-cause mortality all followed the same pattern: highest among the untreated, lower among the unsuccessfully treated, and lowest (but not zero) among the successfully treated.

Comment

Sweden's comprehensive national health registries make these data among the most precise available on the long-term outcomes of HCV treatment started after a patient already has progressed to cirrhosis. Editorialists note that risk for hepatocellular carcinoma in successfully treated cirrhotic patients is low enough that routine sonographic screening generally would not be considered cost-effective, but they endorse ongoing screening of these patients nonetheless.

Disclosures for Abigail Zuger, MD at time of publication Editorial boards Journal Watch AIDS Clinical Care; Clinical Infectious Diseases Other New York Times medical writer

Citation(s):

Aleman S et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C–associated liver cirrhosis. Clin Infect Dis 2013 Jul 15; 57:230. (http://dx.doi.org/10.1093/cid/cit234)

Abstract/FREE Full Text

Pereira OC and Feld JJ. Sustained virologic response for patients with hepatitis C–related cirrhosis: A major milestone, but not quite a cure. Clin Infect Dis 2013 Jul 15; 57:237. (http://dx.doi.org/10.1093/cid/cit237)

FREE Full Text

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Simeprevir Shines in Hep C Trial

Gastroenterology and Endoscopy News

In the News

ISSUE: JULY 2013 | VOLUME: 64:7

by David Wild

Orlando, Fla.—Of patients who relapsed following treatment with peginterferon (PEG-IFN)-based therapy for chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, 80% experienced rapid and sustained virologic response with triple therapy including PEG-IFN-2a, ribavirin (RBV) and simeprevir, an experimental oral, once-daily HCV NS3/4A protease inhibitor (PI). Results from the Phase III PROMISE study were presented at the 2013 Digestive Disease Week meeting (abstract 869b).

The findings led Gregory Gores, MD, executive dean for research at Mayo Clinic, Rochester, Minn., to speculate that simeprevir will soon be added to the clinician’s HCV treatment toolbox.

“The surprising efficacy of simeprevir triple therapy in patients who had relapsed after prior RBV plus PEG-IFN therapy, and in patients with advanced liver fibrosis, along with its once-daily dosing, minimal drug–drug interactions and good safety profile, make it likely the drug will be approved by the FDA for use in HCV patients,” said Dr. Gores, who was not involved in the research.

Eric Lawitz, MD, professor of medicine at the University of Texas Health Science Center and vice president of scientific and research development at the Texas Liver Institute in San Antonio, and his colleagues randomized 260 patients with HCV GT1 to receive the triple therapy and 133 similar patients to receive an oral placebo with PEG-IFN/RBV, both for 12 weeks, in a double-blind fashion. Simeprevir recipients who experienced a drop in HCV RNA below 25 IU/mL after four weeks of treatment and who had undetectable HCV RNA at 12 weeks received an additional 12 weeks of PEG-IFN/RBV alone, whereas those who did not meet these criteria received an additional 36 weeks of PEG-IFN/RBV treatment, for a total of 48 weeks. All placebo recipients received 36 weeks of PEG-IFN/RBV after the initial 12 weeks of placebo plus PEG-IFN/RBV treatment.

Dr. Lawitz reported that 77% of patients who received simeprevir experienced a rapid virologic response (RVR), and 79% had a sustained virologic response 12 weeks after treatment completion (SVR12). In contrast, 3% of placebo recipients achieved RVR, and 37% achieved SVR12 (P<0.001 for simeprevir vs. placebo).

SVR12 rates among various patient subgroups were higher in the simeprevir arm compared with the placebo arm, Dr. Lawitz reported. These included patients with METAVIR scores of F0-F2 (82% vs. 41%), METAVIR scores of F3 (73% vs. 20%), METAVIR scores of F4 (74% vs. 26%), HCV GT1a (70% vs. 28%), HCV GT1b (86% vs. 43%), interleukin-28 B (IL28B) genotype CC (89% vs. 53%), IL28B genotype GT CT (78% vs. 33%) and IL28B genotype GT TT (65% vs. 19%; P<0.001 for all).

Only 7% of simeprevir recipients required 48 weeks of treatment, and rates of on-treatment failure and post-treatment relapse with the drug were 3% and 19%, respectively, compared with 27% and 48% with placebo.

There were no differences in serious adverse events in the simeprevir and placebo groups.

Dr. Lawitz said the study participants were a difficult-to-treat population and included those with prior treatment failure and compensated and fibrotic liver disease.

“Hepatitis C is a complex disease, and we need multiple treatment options in order to provide our patients with the best possible chance of successful therapy,” he concluded.

---

Dr. Lawitz has received research support from Abbott Laboratories, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Intercept Pharmaceuticals, Janssen Pharmaceuticals, Medtronic, Merck & Co., Novartis, Presidio, Roche, Santaris Pharmaceuticals, Scynexis and Vertex Pharmaceuticals. Dr. Gores has no conflicts of interest.

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Interferon-free Regimen for Hepatitis C Advances

Medscape Medical News > Conference News

Neil Canavan

Jul 11, 2013

KUALA LUMPUR, Malaysia — A new interferon-free drug regimen for the treatment of hepatitis C is safe and effective in treatment-naïve patients and in those who previously had a poor response to treatment, according to the phase 2b AVIATOR trial.

The direct-acting antiviral combination, manufactured by AbbVie Pharmaceuticals, consists of the protease inhibitor ABT-450, the non-nucleoside NS5B polymerase inhibitor ABT-333, and the novel NS5A inhibitor ABT-267. When used in combination with ribavirin, it reportedly produces sustained virologic response rates of up to 99% in patients with hepatitis C.

Barry Bernstein, MD, vice president of infectious disease at AbbVie, and his team evaluated the safety and efficacy of this interferon-free regimen in combination with ribavirin to determine whether toxic events would lead to dose reductions in ribavirin and whether that would have any effect on treatment outcome.

Ribavirin is a key component of effective hepatitis C treatment, but often it cannot be used at optimum therapeutic levels when combined with interferon — the current standard of care.

Dr. Bernstein presented the results here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

“These results, if they hold up, will be very significant for people coinfected with HIV and hepatitis C.”

In the AVIATOR trial, first presented last year at the annual meeting of the American Association for the Study of the Liver Diseases, patients were treated with the interferon-free combination with or without ribavirin for 12 or 24 weeks.

In the study cohort, 159 patients were treatment-naïve and 88 were previous nonresponders to ribavirin. Median age was 50 years, and was 86% of the cohort was white. All patients had chronic infection with hepatitis C genotype 1 and plasma HCV RNA levels above 50,000 IU/mL.

The primary end points were safety and sustained virologic response at 24 weeks.

Four patients (1.6%) discontinued treatment because of adverse events, 1 patient experienced a serious adverse event (arthralgia), and 16 patients (6.5%) had hemoglobin levels below 10 g/dL.

In 24 of the 247 (10%) patients, the dose of ribavirin was reduced because of adverse events. Of these, 20 were treatment-naïve and 4 were previous nonresponders.

The incidence of ribavirin dose reductions was similar in the 12- and 24-week treatment groups.

The most common adverse events were anemia, with 10 events reported, and fatigue, with 3 events reported. Other events, with 2 reports each, were diarrhea, dizziness, and pruritus.

There were more adverse events in treatment-naïve patients than in nonresponders.

All 24 patients whose dose of ribavirin was reduced achieved a sustained virologic response at 24 weeks. For those without a dose reduction, 92.1% of the treatment-naïve patients and 94.0% of the nonresponders achieved a sustained virologic response at 24 weeks

"Significantly, ribavirin dose reduction occurred less frequently than in previous studies of peg-interferon-containing regimens," said Dr. Bernstein. As important, he noted, is the fact that when dose reductions did occur, response rates were not negatively affected.

Toward Interferon-free Treatment

Preliminary trials to determine drug–drug interactions with HIV medications are near completion, and a trial of this drug combination in patients coinfected with HIV and hepatitis C will start soon, Dr. Bernstein said.

These results, if they hold up, will be very significant for people coinfected with HIV and hepatitis C, said Tom Campbell, MD, a principal investigator of the Colorado AIDS Clinical Trial Unit. "The exciting thing is that they don't require the use of interferon, which is very poorly tolerated, particularly in people with coinfection."

The need for interferon-free regimens is clear. "We have patients who are waiting for new drugs before they are willing to be treated, particularly those who have less advanced hepatitis C infection who don't need immediate treatment," Dr. Campbell explained. He acknowledged that "it will be a few years before these drugs are approved for HIV and hepatitis C coinfection, so it is a bit of a gamble to wait."

However, he understands the reluctance of these patients to be treated now. "It's a decision that the patient should make in consultation with their care provider."

Dr. Bernstein is an employee of AbbVie Pharmaceuticals. Dr. Campbell has disclosed no relevant financial relationships.

7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract TUAB0103. Presented July 2, 2013.

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Hepatitis C Reinfection Rising Among HIV Patients

Medscape Medical News > Conference News

Neil Canavan

Jul 11, 2013

KUALA LUMPUR, Malaysia — Nearly 25% of HIV patients infected with and subsequently cured of the hepatitis C virus went on to acquire a second or even third infection within 24 months at one hospital in the United Kingdom.

"Liver disease is one of the leading non-AIDS causes of death in HIV-infected individuals," said lead investigator Thomas Martin, from the Chelsea and Westminster Hospital in London, United Kingdom. In fact, hepatitis C accounted for "roughly two thirds of those cases."

These results suggest that much better educational initiatives related to coinfection with HIV and hepatitis C are needed, he noted.

It has previously been shown that coinfection with HIV reduces the spontaneous clearance of hepatitis C infection, reduces the rate of successful treatment, and can lead to a 3-fold increase in the rate of progression to cirrhosis.

However, the extent to which HIV patients are reinfected with hepatitis C has not been established.

To look at this issue, Dr. Martin and his team analyzed reinfection rates in 191 HIV patients with a primary hepatitis C infection treated at the Chelsea and Westminster Hospital.

Dr. Martin presented the results here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

“Liver disease is one of the leading non-AIDS causes of death in HIV-infected individuals.”

The researchers defined reinfection as any newly positive hepatitis C virus RNA polymerase chain reaction result 24 weeks or more after the end of hepatitis C treatment, spontaneous clearance of the virus, or the emergence of a different hepatitis C genotype in a 24-month period.

In the study cohort, the rate of hepatitis C reinfection was 7.8 per 100 patient-years (95% confidence interval, 5.8 - 10.5). "That's approximately 5 to 10 times the baseline primary infection incidence of hepatitis C in this population," Dr. Martin explained.

Of the 32 reinfected patients, the hepatitis C infection was cleared with treatment or spontaneous remission in 17 patients. Of those, 8 went on to acquire a third hepatitis C infection, resulting in an infection rate of 23.2 per 100 patient-years.

Overall, the second and third reinfections cleared spontaneously in 20% of patients, and a complete viral clearance was achieved with standard-of-care treatment in 80%.

"We saw no evidence of protective immunity from the initial hepatitis C infection," said Dr. Martin. "In fact, these individuals remain at high risk for reinfection."

Coinfection Education Needed

"We're becoming increasingly aware that gay men have this elevated risk of sexual acquisition of hepatitis C," said Charles Hicks, MD, professor of medicine at Duke University in Durham, North Carolina.

However, the high frequency of reinfection over a fairly short period after the initial hepatitis C diagnosis is "striking," Dr. Hicks told Medscape Medical News. "That was alarming to me. It means we need to do a better job of counseling gay men who have hepatitis C that just because their first infection has been managed successfully, it doesn't mean they are no longer at risk." Prevention here is key.

It also has implications for future monitoring of patients. Typically, an active hepatitis C infection is detected with an antibody test, he explained. "But in cases of previous viral clearance, you're going to have to use an RNA viral load test to find cases of reinfection."

Dr. Marin and Dr. Hicks have disclosed no relevant financial relationships.

7th International AIDS Society (IAS) Conference on HIV Pathogenesis: Abstract TUAB0101. Presented July 2, 2013.

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Renal impairment common with telaprevir, boceprevir therapy for HCV

Provided by Healio

Mauss S. Hepatology. 2013;doi:10.1002/hep.26602.

July 11, 2013

Patients with chronic hepatitis C treated with pegylated interferon, ribavirin and either telaprevir or boceprevir frequently experienced renal impairment that typically resolved after switching to dual therapy in a recent study.

As part of the noninterventional PAN study — which includes patients with HCV treated with peginterferon alfa-2a and ribavirin with or without telaprevir or boceprevir — researchers evaluated the estimated glomerular filtration rate (eGFR) of 895 patients with HCV genotype 1 who received at least 12 weeks of therapy and 591 who received 24 weeks or more. Five hundred seventy-five telaprevir patients, 211 taking boceprevir and 109 on dual therapy were in the 12-week group.The 24-week arm had 398 patients on telaprevir, 113 on boceprevir and 80 on dual therapy.

The 12-week analysis measured the impact of treatment on eGFR; the 24-week review determined whether this effect could be reversed after discontinuing telaprevir or boceprevir.

All participants had an eGFR above 60 mL/min at baseline. In the 12-week cohort, 5.5% of patients experienced an eGFR decrease to below 60 mL/min, which was more common among telaprevir (6.6%) and boceprevir (4.7%) recipients than those who received peginterferon/ribavirin alone (0.9%) (P<.05). Multivariate analysis indicated associations between this decrease and advanced age (P<.001), high baseline creatinine levels (P<.001), receipt of telaprevir or boceprevir (P<.01) and arterial hypertension (P<.05).

In the 24-week analysis, 8.3% of telaprevir and 3.5% of boceprevir recipients experienced eGFR decreases to below 60 mL/min after 12 weeks, compared with 1.3% of dual therapy recipients (P<.05). After telaprevir discontinuation at 12 weeks, eGFR below 60 mL/min was observed in 1.3% of those who had received telaprevir, compared with 4.4% of boceprevir recipients and 1.3% of dual therapy recipients (P<.05 for boceprevir vs. dual therapy).

“Renal impairment has not been an issue with dual therapy [interferon and ribavirin],” researcher Stefan Mauss, MD, Center for HIV and Hepatogastroenterology in Dusseldorf, Germany, told Healio.com. “[However,] with the current triple therapy, it has to be added to the adverse event list. Include creatinine in your checklist, and keep an eye in particular on patients with additional risk factors for renal impairment, [such as] older age, arterial hypertension [or] diabetes mellitus.”

Disclosure: See the study for a full list of relevant disclosures.

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Tenofovir Lowers HIV Risk in Drug Abusers by Half

Medscape Medical News > Conference News

Neil Canavan

Jul 11, 2013

KUALA LUMPUR, Malaysia — A large study of intravenous drug users has found a surprisingly high rate of adherence to pre-exposure prophylaxis with tenofovir, resulting in a marked reduction in new HIV infections.

"The study tells us that pre-exposure prophylaxis can work for all populations at risk for HIV, including people who inject drugs," said study investigator Michael Martin, MD, from the Centers for Disease Control and Prevention in Atlanta, Georgia.

Dr. Martin presented findings here at the 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.

The double-blind placebo-controlled Bangkok Tenofovir Study involved 2413 intravenous drug users. The cohort was 80% male, and the average age was 31 years.

Investigators randomized participants to receive daily oral tenofovir 300 mg or placebo. "We provided monthly HIV testing, participant-centered risk-reduction and adherence counseling, blood safety testing every 3 months, condoms, and methadone treatment," said Dr. Martin.

Participants were asked to record their medication use in an adherence diary or were directly observed taking the study drug. At monthly visits, the staff and the participant reviewed the adherence diary and did a pill count.

Results showed that participants took the drug 84% of the time, which translated into a substantial reduction in the rate of HIV infection. "We had 17 new infections in the tenofovir group and 33 in the placebo group," Dr. Martin reported. "This translates into a 49% reduction in risk (P = .01)."

Adherence did not differ by treatment group (P = .16). However, older participants were more adherent than younger participants (P < .001), and women were more adherent than men (P = .04).

"Needle sharing and sexual risk were similar in the 2 study arms," Dr. Martin explained. However, participants reported that these behaviors declined substantially during the trial. "This was true for both treatment groups."

Despite the positive data that continue to emerge for pre-exposure prophylaxis, real-world use remains limited. Antiretroviral medications for pre-exposure prophylaxis are "not flying off the shelf," Robert Grant, MD, lead investigator of the landmark Pre-Exposure Prophylaxis Initiative (iPrEx) trial, told reporters attending a news conference.

Perceptions From the iPrEx Trial

"We're finding that demand for such services and people interested in providing pre-exposure prophylaxis to their clients remain relatively low. We think that part of this is that it takes time for people to get their heads around new ideas, but part of it is that we really do need to learn more about how best to provide pre-exposure prophylaxis and how best to promote it's effective use."

At the IAS meeting, Dr. Grant reported recent findings from an open-label extension of the iPrEx trial, in which 65% of the original 2340 patients participated. Of the 1451 participants who were not infected with HIV at the time of enrollment in the extension study, 1038 chose to receive pre-exposure prophylaxis.

"We were impressed that 72% of those offered pre-exposure prophylaxis chose to participate, and of those who did, 72% had detectable drug levels," he reported.

That said, it's obvious that pre-exposure prophylaxis is not for everyone, Dr. Grant noted. "It's for people who perceive themselves to be at risk. If roughly half of iPrEx participants are able to appropriately use pre-exposure prophylaxis, that's a substantial number."

Dr. Martin has disclosed no relevant financial relationships. Dr. Grant reports serving as an advisor and consultant for Siemens AG.

The 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstracts WELBC05 and WELBC02. Presented July 3, 2013.

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New Insights Into Genetic Basis Of Deadly Liver Cancer

Health & Medicine
July 12, 2013

Researchers have tracked down recurrent genetic abnormalities in hepatocellular carcinoma, a deadly form of liver cancer

Asian Scientist (Jul. 12, 2013) - An international team of researchers has used whole-genome sequencing to track down recurrent genetic abnormalities in hepatocellular carcinoma (HCC), a deadly form of liver cancer.

HCC is more common in parts of Africa and Asia, where the patients with hepatitis B or C have a higher risk of developing liver cancer.

In their study, published online in Genome Research, the researchers found that the tumor suppressor gene TP53 was mutated in more than one-third of tumors when they sequenced tumor and normal tissue samples from 88 HCC patients in Hong Kong.

Patients with tumors containing TP53 mutations were also less likely to survive.

An oncogene called beta-catenin was often altered, too, they found, as were other components of the beta-catenin pathway and a signaling pathway that includes JAK1 and STAT gene products.

“Liver cancer is intractable to nearly all currently available anti-cancer targeted therapies. Our findings in this study provide a better understanding of molecular basis of hepatocarcinogenesis and provide new clues to improving the diagnosis and treatment of liver cancer in the future,” said Hancheng Zheng, a leader of the project.

The researchers are hopeful that existing drugs targeting these key genes in HCC, particularly JAK1, can be tested for the treatment of HCC in the near future.

The article can be found at: Kan et al. (2013) Whole Genome Sequencing Identifies Recurrent Mutations In Hepatocellular Carcinoma.

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Use redistricting maps to make organ allocation more equitable, researchers advocate

Provided by Medical Xpress

July 11, 2013

Using the same type of mathematical formulas used to draw political redistricting maps, Johns Hopkins researchers say they have developed a model that would allow for the more equitable allocation of livers from deceased donors for transplantation.

Currently, in the United States, where you live dictates the availability of a liver transplant. Studies show that geography can mean the difference between a 10 percent chance of dying while on the waiting list for a donor liver, and a 90 percent chance, the researchers say. The new model depends not on the longstanding relationships among medical centers used to create the current unbalanced system, but on making the distribution of organs as equitable as possible, they say.

"This is gerrymandering for the public good," says study leader Dorry L. Segev, M.D., Ph.D., an associate professor of surgery and epidemiology at the Johns Hopkins University School of Medicine. "We have applied to transplantation the same math used for political redistricting, school assignments, wildlife preservation and zoning issues." A report on the research is published in online in the American Journal of Transplantation.

"Some geographic areas have very good access to donated organs and some have desperate gaps between organ supply and organ demand," says co-author Sommer Gentry, Ph.D., a research associate in the department of surgery at Johns Hopkins and an associate professor of mathematics at the U.S. Naval Academy. "Our model helps decrease geographic disparity. It's not fair that where you live so vastly affects your ability to get a transplant. We want to fix that."

Currently, patients with the most severe disease go to the top of the liver transplant waiting list. But the list isn't a single national list; instead, it is subdivided according to location. Thus, the sickest person in one region may be much sicker than the person in a nearby region who gets a new liver, simply because the second region has a greater supply—or smaller demand—for organs.

In 2009, the late Apple founder Steve Jobs, who lived in Northern California, famously underwent a liver transplant in Memphis, Tenn. There, he had put himself on one of the shortest waiting lists in the country. In Tennessee in 2006, it took 48 days to receive a liver transplant, compared with 306 days nationally. Jobs was able to do this because he had the financial resources to immediately fly to Tennessee when the liver became available. His situation brought national attention to the large geographic disparities in liver transplantation.

Segev, a transplant surgeon, says that if a patient from San Francisco or New York City needed a liver transplant, it would be difficult to recommend one of the great transplant centers in those cities because the wait is so long.

In developing their new allocation model, the Johns Hopkins researchers essentially redistricted the regions by analyzing supply, demand and access factors for 6,700 deceased donors, 28,063 liver transplant candidates and 242,727 changes in 2010 to what is known as MELD (Model for End-Stage Liver Disease), a score that categorizes the sickest patients on the list at any given time.

The optimal regional sharing map they created would reduce geographic disparity by half, while significantly reducing waitlist deaths.

Segev, the director of clinical research for transplant surgery at Johns Hopkins, says that the geographic disparity in the current allocation system violates government rules that say geography shouldn't affect organ supply.

He says he hopes the United Network for Organ Sharing, the private, nonprofit organization that manages the nation's organ transplant system under contract with the federal government, will act on this new model.

Explore further: Most liver transplant candidates receive donation offers

Journal reference: American Journal of Transplantation

Provided by Johns Hopkins University School of Medicine

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Outcomes for Indigenous and non-Indigenous patients who access treatment for hepatitis C in the Top End of the Northern Territory

The Medical Journal of Australia

Letters

Joshua S Davis, Anuja C Kulatunga and Krispin Hajkowicz

Med J Aust 2013; 199 (1): 23. doi: 10.5694/mja13.10083

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Authors    References

To the Editor: Chronic hepatitis C virus (HCV) infection affects over 225 000 Australians1 and is a leading cause of the need for liver transplantation and of liver-related death, but curative treatments are available. Ethnicity is a major determinant of treatment responsiveness, with the lowest sustained virological response (SVR) rates reported in African patients, and the highest in Asian patients.2 Much of this difference is accounted for by racial differences in polymorphisms in the interleukin-28B (IL28B) gene;3 however, it is unknown how common these polymorphisms are in Indigenous Australians, and no studies have been published about hepatitis C treatment outcomes among Indigenous Australians.

The hepatitis C treatment service for the Top End of the Northern Territory is run from a community-based sexual health clinic in Darwin. As clinicians working at this service, our perception was that Indigenous people rarely accessed the service or received treatment for HCV infection. Further, we were concerned that — due to social, cultural and linguistic barriers — Indigenous people who accessed the service may be less likely to commence treatment and to successfully complete treatment and achieve an SVR. Following ethics approval from the Human Research Ethics Committee of the Northern Territory Department of Health and Families, we performed a retrospective case-note audit to determine the number of Indigenous people accessing the hepatitis C treatment service and their characteristics and treatment outcomes.

During the period 1 January 2006 to 31 December 2010, 243 patients were seen on at least two occasions for assessment of HCV infection; all were adults and 22 (9%) were Indigenous. During the audit period, HCV infection was treated with pegylated interferon-α plus ribavirin for 24–48 weeks. There were no significant differences in the proportion of patients who went on to commence and complete treatment, and to achieve an SVR, between Indigenous and non-Indigenous patients (Box). Of five Indigenous patients tested for IL28B genotype, all had the favourable CC polymorphism at the rs12979860 locus. Compared with the unfavourable TT and CT polymorphisms, the CC polymorphism at this locus is associated with at least a twofold higher chance of achieving a cure of HCV with interferon treatment, due to enhanced host immune responsiveness to interferon.3

In conclusion, Indigenous people in the NT who access hepatitis C treatment services have a similar chance of achieving a cure (SVR) to non-Indigenous people. This may be partly because they are likely to carry the favourable CC polymorphism at the IL28B gene.

Box  – Indigenous compared with non-Indigenous patients who attended a hepatitis C treatment service on at least two occasions for assessment of HCV infection*

	Indigenous (n = 22)	Non-Indigenous (n = 221)	P
Age, median (interquartile range)	41.0 (36.2–45.0)	47.3 (39.3–52.1)	0.14
Men	15/22 (68% [45%–86%])	144/221 (65% [58%–71%])	0.78
HCV genotype 1	10/18 (56% [31%–78%])	87/173 (50% [43%–58%])	0.67
Commenced HCV treatment	11/22 (50% [28%–72%])	99/221 (45% [38%–52%])	0.58
Completed HCV treatment	9/11 (82% [48%–98%])	80/99 (81% [72%–88%])	0.94
Achieved sustained virological response†	4/8 (50% [16%–84%])	54/88 (61% [50%–72%])	0.53
HCV = hepatitis C virus. * Data are number/denominator (% [95% CI]) unless otherwise indicated. † Denominators represent those patients for whom 6-month post-treatment blood test results were available.

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The threat of a new epidemic

by John Coulter | Coulter is vice president, Molecular Diagnostics, at Abbott.

Tuesday, July 9, 2013

A public health problem decades in the making, hepatitis C (HCV) has become a leading viral killer in the U.S., slyly growing in prevalence under the radar of both patients and the American public.

A disease that once may have been scarcely thought of, HCV is now commonplace and costs the U.S. more than 15,000 lives and nearly $11 billion each year. In recent years, government agencies such as the Centers for Disease Control and Prevention and nonprofit groups have been working overtime to alert the public through events such as World Hepatitis Day, which is held annually on July 28.

In Roanoke, the New River Valley and throughout Southwest Virginia, demographic trends reflecting an aging population put residents of the state at risk. With as many as one in 30 U.S. baby boomers (adults born 1945-1965) infected with HCV and at least 800,000 of these unaware they’ve contracted the virus, it’s no surprise the CDC now recommends HCV screening for baby boomers.

More recently, the U.S. Preventive Services Task Force recommended all baby boomers get tested for HCV, sending a clear signal to health care professionals, policy makers and the public that screening for HCV is beneficial for both patients and the public health.

Increasingly, conversations about a variety of medical concerns — cancer, diabetes and mental health, for example — are driven by deeper understandings of the genetic structures of illnesses.

Less frequently talked about among stories of amazing science and revolutionary care, however, is how molecular testing is helping the U.S. face one of its biggest infectious disease challenges.

As our nation battles a burgeoning HCV epidemic, it’s important to recognize the everyday significance molecular testing plays in battling this long-silent killer. Molecular testing enables a more clearly mapped battleground on an individualized basis, and that’s just a part of how diagnostics is reshaping the health community’s approach to HCV.

Health experts fighting HCV have identified six major genetic variations, or genotypes, and more than 50 subtypes of HCV.

The genetic spectrum of HCV is as diverse as the boomer generation itself, but make no mistake about it, anyone of any age, race or gender can contract any genotype or subtype of HCV. With the same DNA sequencing principles used to determine hereditary predisposition for some types of cancers, companies like mine have pioneered systems that provide physicians with HCV genotype identification for each patient.

This information is vital in determining how to treat each patient individually, since each genotype of the virus responds to treatment differently. A recent article in the New England Journal of Medicine illuminated this fact by mapping genotype-specific responses to current and developing therapies. Armed with genotyping data for each patient, doctors can prescribe the treatment that is most likely to be successful and help avoid side effects from less targeted, less effective treatments.

From the early 1990s, when we introduced a pioneering assay to protect our nation’s blood supply from hepatitis, to today’s technology that helps identify genotypes faster, diagnostics have helped offset the global HCV burden and create early warning systems for both patients and doctors. Getting tested for HCV is critical for adults, especially those who fall within the CDC’s recommended guidelines.

However, the journey to wellness in battling HCV goes beyond just getting tested. Our ability to understand the genetic makeup of the virus — thanks to advanced diagnostics — and to respond with appropriate treatment options brings new empowerment to the fight against the HCV epidemic. Molecular diagnostics allow us to zoom in on HCV and, in doing so, make this public health challenge an increasingly personal one.

Source

Half a Diagnosis: Gap in Confirming Infection among Hepatitis C Antibody-positive Patients

The American Journal of Medicine

Article in Press

Emily McGibbon, MPH, Katherine Bornschlegel, MPH, Sharon Balter, MD

New York City Department of Health and Mental Hygiene, Long Island City, NY

published online 19 June 2013.
Corrected Proof

Abstract

Background

Recent guidelines recommend testing all individuals born during 1945-1965 for hepatitis C virus (HCV) antibody. For antibody-positive patients, subsequent RNA testing is necessary to determine current infection status. This study aimed to assess whether clinicians order HCV RNA tests as recommended for antibody-positive patients and to identify barriers to such testing.

Methods

We sampled individuals newly reported to the New York City Department of Health and Mental Hygiene's HCV surveillance system and collected information from clinicians. For patients without RNA test results, we asked the reason an RNA test was not ordered and requested that the clinician order the test.

Results

Of 245 antibody-positive patients, 67% were tested for HCV RNA (for 21% of these, the test was ordered only after our request); 33% had no RNA testing despite our request. Patients without RNA testing were seen in medical facilities (47%), detox facilities (30%), and jail/prison (15%). Reasons RNA testing was not done were that the patient did not return for follow-up (35%), the facility does not do RNA testing (22%), and the patient was tested in jail (15%).

Conclusions

In our study, one third of patients did not get complete testing for accurate diagnosis of HCV, which is essential for medical management. Additional education for clinicians about the importance of RNA testing may help. However, with improved antiviral treatments now available for HCV, it is time for reflex HCV RNA testing for positive antibody tests to become routine, just as reflex Western blot testing is standard for human immunodeficiency virus.

Keywords: Hepatitis C, Surveillance, Testing

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