Cancer biggest killer of Hispanic Texans

Cancers more common among Hispanics were stomach and liver cancer in men and stomach, liver and cervical cancer in women. Such cancers can arise from untreated infections.

Overall mortality from all cancer was lower among Hispanics with the exception of stomach and liver cancer


Cancer biggest killer of Hispanic Texans

More Hispanic Texans die from cancer than any other cause, according to a new report by the Comparative Effectiveness Research on Cancer in Texas research group.

The report documents cancer as the leading cause of death among Hispanic Texans under the age of 76. Only three percent of Hispanic Texans are older than 75.

Texas's Hispanic population has more than doubled since 1990. Texans of Hispanic ethnicity now comprise 38 percent of the state's population.

The findings are published in a September 2013 special issue of the Texas Public Health Journal, available online at http://txcercit.org/.

Based on data from the Texas Cancer Registry, Medicare claims records and state vital statistics, researchers compared rates and trends for cancer in Hispanics to those for non-Hispanic whites in Texas.

Key findings include:

Hispanic Texans are less likely to be screened for breast or colon cancer.

Hispanics have lower rates of new cancer diagnoses for breast, colon and lung cancer.

Of the cancers diagnosed in Hispanics, fewer were in the earliest, most treatable stages – those typically detected through screening. Breast cancer at the most advanced stage was diagnosed at a 12 percent higher rate.

Cancers more common among Hispanics were stomach and liver cancer in men and stomach, liver and cervical cancer in women. Such cancers can arise from untreated infections.

Overall mortality from all cancer was lower among Hispanics with the exception of stomach and liver cancer.

Survival after a diagnosis of cancer is superior for Hispanics compared to non-Hispanic whites.

These findings were based on 10 years of data about the diagnoses of new cancer cases and 21 years of data about cancer deaths.

The CERCIT researchers noted one puzzling contradiction. Even though cancers tend to be more advanced when diagnosed in Hispanics, death rates were lower than in the white population. This phenomenon, known as the Hispanic Paradox, has been noted before by other researchers looking at disease and survival rates across the spectrum. Hispanic Americans tend to survive illness and live longer than white Americans with the same diseases even though the Hispanics have less education, income and access to health care.

Foreign-born Hispanics had lower mortality rates than those born in the United States, according to analyses of regional differences within the state.

The multidisciplinary consortium of CERCIT investigators works on issues related to cancer screening, cancer treatment, post-treatment surveillance and supportive care for cancer patients and survivors. CERCIT is funded by the Cancer Prevention and Research Institute of Texas.

The CERCIT project is led by principal investigator Dr. James S. Goodwin of University of Texas Medical Branch at Galveston and co-principal investigator Dr. Linda S. Elting of the University of Texas MD Anderson Cancer Center. Other project and core lead investigators include Drs. Catherine D. Cooksley, Anthony DiNuzzo, Karl Eschbach, Jean Freeman and Taylor S. Riall of UTMB; Dr. Sharon H. Giordano of MDA; Dr. Vivian Ho of Rice University and Dr. Melanie Williams of the Texas Cancer Registry.

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The University of Texas Medical Branch
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Galveston, Texas 77555-0144
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ABOUT UTMB HEALTH: Texas' first academic health center opened its doors in 1891 and today comprises four health sciences schools, three institutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, and a health system offering a full range of primary and specialized medical services throughout Galveston County and the Texas Gulf Coast region. UTMB Health is a component of the University of Texas System and a member of the Texas Medical Center.

National screening strategy for hepatitis C urged for Canada

National screening strategy for hepatitis C urged for Canada

(TORONTO, Canada; Sept. 30, 2013) – Canada should begin screening 'Baby Boomers' for the hepatitis C virus infection, since this age group is likely the largest group to have the illness, and most don't know they have it, say a group of liver specialists in the Toronto Western Hospital Francis Family Liver Clinic.

Unlike many other chronic viral infections, early treatment makes hepatitis C curable.

Photo: Dr. Feld

(TORONTO, Canada; Sept. 30, 2013) – Canada should begin screening 'Baby Boomers' for the hepatitis C virus infection, since this age group is likely the largest group to have the illness, and most don't know they have it, say a group of liver specialists in the Toronto Western Hospital Francis Family Liver Clinic. Unlike many other chronic viral infections, early treatment makes hepatitis C curable.

In an article entitled, A Canadian Screening Program for hepatitis C – is Now the Time? published in the Canadian Medical Association Journal (CMAJ) Sept. 30, 2013, by Drs. Hemant Shah, Jenny Heathcote and Jordan Feld, the authors present arguments and data in favour of developing and implementing a national screening program for hepatitis C in Canada.

"Baby boomers are much more likely to be infected with hepatitis C than other age groups. Most people who have the infection have no or very few symptoms even if they've been infected for decades. Without symptoms, many infected people have no idea they have the disease until it's too late," says Dr. Jordan Feld, Toronto Western Hospital liver specialist and one of the authors of the article.

"Hepatitis C has the greatest impact of all infectious disease in Ontario, even more so than HIV, influenza virus or human papillomavirus," says Dr. Hemant Shah, Clinic and Education Director of the Francis Family Liver Clinic, Toronto Western Hospital. "It's a life-changing diagnosis, yet there is a huge gap in public and healthcare provider awareness about the disease, it's implications and the treatment options for patients."

Hepatitis C causes more years of life lost than any other infectious disease in Ontario, and likely in Canada, and is the leading indication for liver transplantation. The virus slowly destroys the liver over many years of infection eventually leading to cirrhosis and ultimately liver failure or liver cancer.

However, if hepatitis C is diagnosed early, it is curable. Once liver disease is very advanced, treatment is much less effective and may not be possible, so the goal is to find people with hepatitis C before the virus has caused liver damage. Screening for hepatitis C involves a simple blood test which is covered by all provincial health care plans.

Currently, the recommended Canadian approach is to test based on risk factors. These include: injection drug use (even once), receiving blood transfusions or blood products before 1992, piercings or tattoos done in an unclean environment with unsterile equipment, exposure to infected blood through sharing personal care items such as razors, toothbrushes, or even being immunized or receiving a medical procedure in countries where hepatitis C is common.

In contrast, the Centers for Disease Control and Prevention (CDC) in the U.S. has recently recommended screening all individuals born between 1945 and 1965 for hepatitis C virus (HCV). Even though most Baby Boomers do not have the infection, the CDC adopted the policy because they have shown that identifying infected people and treating them early will save lives and money by avoiding the costs associated with complications of liver disease.

The Canadian Liver Foundation has recently advocated that all those born between 1945 and 1975 get a test for HCV, basing their recommendations on the prevalence of the illness in Canada, and on the immigration into Canada from areas where hepatitis C is very common, such as Africa (particularly Egypt), southern Italy, Eastern Europe, and Central and Southeast Asia

The authors state that HCV meets all the criteria for a condition where wider screening, particularly among Baby Boomers, would be useful, namely:
 

1. HCV is a major cause of morbidity and mortality
2. Prevalence is increased in Baby Boomers
3. Many individuals are unaware they are infected with HCV
4. HCV is curable with early treatment.  

Photo: Dr. Shah

"There is a great deal of misinformation about the illness in the public domain, causing patients to feel fear, shame and stigmatized," says Dr. Shah, who is also an Assistant Professor in Medicine, University of Toronto. "An education campaign can help these patients feel more hopeful, and impress on everyone that early diagnosis and intervention can prevent much of the damage of the illness."

Two of the authors report receiving consulting or speaking fees from: Achillon, Abbott, Boehringer Ingeliheim, Gilead Sciences, Janssen, Merck. Hoffman, La-Roche, Vertex. 

About Toronto Western Hospital:
Toronto Western Hospital is a member of the University Health Network, along with Toronto General and Princess Margaret Hospitals and the Toronto Rehabilitation Institute. It is a teaching and research hospital affiliated with the University of Toronto. Toronto Western Hospital is a world leader in neuroscience, advanced liver disease, musculoskeletal health and arthritis, orthopaedics, the hand program, rheumatology and complex care.   

Key Facts about hepatitis C:

Burden of hepatitis C is high 

HCV is a major public health problem in Canada and world-wide; infection rates and diagnosis rates are often underestimated

HCV infection causes more years of life lost and illness than any other infectious disease in Ontario, and likely Canada

HCV is the leading indication for liver transplantation and the leading cause of liver cancer

The prevalence in Canada is estimated at about 250,000, but the authors state that this number is likely too low; they suggest that the number is closer to 400,000

Because it may take decades for any symptoms to appear, most people who have HCV are unaware that they have it

CDC in the U.S. estimates that Baby Boomers account for three fourths of all HCV infections and that anywhere from 45 % - 85 % of those living with HCV infection are unaware that they have it

Liver cancer rates are on the rise because the major causes of primary liver cancer – hepatitis B and C – are not being identified and treated early enough

An estimated 20% of infected persons will progress to cirrhosis 20 years after infection, which can then lead to liver failure and/or liver cancer

By 2022, the number of hepatitis C-related deaths will increase by one third How is it spread?

Hepatitis C virus is spread by blood-to-blood contact meaning that blood infected with the virus must get into a person's blood stream

Once infected with the virus, nearly 8 in 10 people remain infected for life

Chronic hepatitis C is often called a "silent" disease because no symptoms appear until the liver has been severely damaged; people can live from 20-30 years without feeling ill

Treatment

There is no vaccine for Hepatitis C

Treatment with a combination of antiviral medications can cure the body of the virus with prevention of liver-related complications and death

Many direct–acting, anti-viral agents are being tested so that within the next five years, there will be improved and better-tolerated treatments with over 90% cure rates

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Cocaine use may increase HIV vulnerability

Cocaine use may increase HIV vulnerability

New research published in the Journal of Leukocyte Biology suggests that cocaine makes quiescent CD4 T cells susceptible to HIV resulting in significant infection and new virus production

Bethesda, MD -- Cocaine use may increase one's vulnerability to HIV infection, according to a new research report published in the Journal of Leukocyte Biology. In the report, scientists show that cocaine alters immune cells, called "quiescent CD4 T cells," to render them more susceptible to the virus, and at the same time, to allow for increased proliferation of the virus.

"We ultimately hope that our studies will provide a better understanding of how drugs of abuse impact how our body defends itself against disease," said Dimitrios N. Vatakis, Ph.D., the study's senior author and a scientist with UCLA's Department of Medicine, Division of Hematology-Oncology and the UCLA AIDS Institute. "Such discovery can significantly improve the quality of life of drug users."

To make this discovery, scientists collected blood from healthy human donors and isolated quiescent CD4 T cells, and exposed them to cocaine and subsequently infected them with HIV. Following infection, researchers monitored the progression of HIV's life cycle and compared this progression against that of untreated cells. They found that cocaine rendered this subset of CD4 T cells susceptible to HIV, resulting in significant infection and new virus production.

"The co-epidemics of elicit drug use and infectious disease are well documented, though typically this connection is thought to occur through lifestyle choices and increased exposure," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "What often does not come to mind is that drugs such as cocaine may be helping to fuel infections in this high-risk population by altering the immune system. These new studies are an important advance documenting how cocaine use may increase a person's vulnerability to HIV and further highlighting the need for improved education for both HIV prevention and drug abstinence."

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The Journal of Leukocyte Biology publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.

Details: Sohn G. Kim, James B. Jung, Dhaval Dixit, Robert Rovner, Jr., Jerome A. Zack, Gayle C. Baldwin, and Dimitrios N. Vatakis. Cocaine exposure enhances permissiveness of quiescent T cells to HIV infection. J Leukoc Biol, October 2013 94:835-843; doi:10.1189/jlb.1112566 ; http://www.jleukbio.org/content/94/4/835.abstract

Transplant - Laparoscopic Living Donor Liver Retrieval (removal of a portion of the liver)

Surgeons at NewYork-Presbyterian/Columbia University Medical Center Report Successful Laparoscopic Living Donor Liver Retrieval for Adult Recipients
NEW YORK (Sep 26, 2013)

A team of surgeons at NewYork-Presbyterian/Columbia University Medical Center is the first in the country to report a fully laparoscopic hepatectomy — the removal of a portion of the liver — from a living adult donor for adult and teenage recipients. The procedure advances transplant surgery and offers hope for addressing the significant shortage of liver donors.

In the September issue of the American Journal of Transplantation, the team, led by Dr. Benjamin Samstein, surgical director of the Living Donor Liver Transplant Program at NewYork-Presbyterian/Columbia and assistant professor of surgery at Columbia University Medical Center, reports on two of the center's five successful fully laparoscopic hepatectomies from living adult donors for adult and teenage recipients. The group is one of three teams in the world, and the only in the United States, reporting the successful procedure.

"This is a small step, but I think a useful one," says Dr. Samstein. "We're at the forefront of perhaps a new era for living-donor liver transplants."

Despite public awareness campaigns and other efforts aimed at raising the availability of donor organs, there is a nationwide shortage of deceased organ donations. Thus, living donors are an important source of organs to aid patients living with end-stage organ disease, particularly of the liver and kidneys.

The first successful living-donor liver transplant was performed in children in 1989 and subsequently extended to adults. Yet only about four percent of liver transplants are done with a living donor, compared with nearly 50 percent of kidney transplants, Dr. Samstein says. "Even though there is a tremendous need, we're not seeing the same use of living-donor livers as we are of living-donor kidneys," he says.

More than 90 percent of living-donor kidney transplants are done laparoscopically, explains Dr. Samstein, which results in reduced morbidity, scarring, and pain, as well as a quicker return to normal activities. Laparoscopic living-donor kidney removal has replaced the open approach in many centers around the world. Most liver donor surgeries, however, are still done through complex open surgery, leaving the donor with a greater risk of postoperative mortality, morbidity, and pain, as well as a recovery period that lasts, on average, eight to 12 weeks — two to three times longer than the recovery period for a laparoscopic kidney donor. Dr. Samstein says these factors may contribute to potential donors' hesitation or ineligibility.

While open hepatectomy remains the standard procedure for adult living-donor liver transplantation at most centers, a few strategies over the past several years have made the surgery less invasive. Researchers have succeeded in reducing the incision needed to remove a portion of the liver; they have also developed a hybrid technique that uses both open surgery and laparoscopy. This model has reduced postoperative pain for the donor.

In 2009, NewYork-Presbyterian/Columbia surgeons began doing fully laparoscopic hepatectomies on adult donors for transplantation into children. Pediatric recipients require only about 15 to 20 percent of a healthy adult liver for transplant. The liver has the unique ability to regenerate in both the donor and the recipient, growing and remodeling to form a complete, functioning organ. But adult recipients require a much larger portion of liver for successful transplant — about 30 to 35 percent — necessitating a more central cut through the donor liver. With three years of experience with hybrid and full laparoscopic techniques with more than 50 minimally invasive donor hepatectomies, the team was ready to expand laparoscopy to full left hepatectomies for adult recipients.

The current publication presents the details of two living adult donors who donated, through laparoscopic surgery, portions of their livers to others — the first, a 47-year-old man who donated to his young teenage daughter and the second a 28-year-old woman who donated to her mother-in-law.

While the recipient operation still requires an open procedure, the surgeons found the donor recovery in these cases to be half that of traditional open-surgery donation — from eight to four weeks — and substantially reduced even from the hybrid technique, with no additional postoperative donor complications. The donors also appeared to have less pain and lower risk of postsurgical hernia.

The authors caution that this procedure should be performed only in select cases and only by teams with significant experience in both living-donor procedures and laparoscopic liver surgery, as laparoscopic hepatectomies require specific training. "While donor comfort and recovery are extremely important issues, donor safety continues to be paramount and the adoption of new surgical techniques ultimately needs to demonstrate that it meets the standard of safety of old techniques before adopted," they write.

NewYork-Presbyterian/Columbia remains the only center in the country currently performing fully laparoscopic living-donor hepatectomies for transplant into both pediatric and adult recipients.

"Clinical innovation and scientific progress constitute the core of the Center for Liver Disease and Transplantation's mission," says Dr. Jean C. Emond, chief of transplantation at NewYork-Presbyterian/Columbia and the Thomas S. Zimmer Professor of Reconstructive Surgery (in Pediatrics) at Columbia University Medical Center. "While this fully laparoscopic approach is still new and in its infancy, this is an important step in furthering the goal of successful liver transplantation from generous living donors." Dr. Emond was a member of the team that pioneered living donor liver transplantation, which is now considered one of the most important advances in the treatment of severe liver disease.

About the Living Donor Liver Transplant Program at the Center for Liver Disease and Transplantation

The Living Donor Liver Transplant Program at NewYork-Presbyterian/Columbia University Medical Center is one of the largest living-donor liver programs in North America. The program has performed more than 220 living-donor liver transplants since its inception. The team has also performed more left lobe donations than any other living-donor liver program in North America and introduced fully laparoscopic donation for all pediatric living-donor liver transplants in 2009.

NewYork-Presbyterian Hospital/Columbia University Medical Center

NewYork-Presbyterian Hospital/Columbia University Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and its academic partner, Columbia University College of Physicians and Surgeons.

NewYork-Presbyterian/Columbia provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian Hospital/Westchester Division, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian/Lower Manhattan Hospital. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report.

http://nyp.org/news/hospital/2013-Laparoscopic-Retrieval%20.html

Watch: Alcohol, Acetaminophen, Liver, Cirrhosis and Transplant

Alcohol, Liver, Cirrhosis and Transplant
by Joe Galati, M.D    on 09/26/2013

A segment that I recorded for this weeks Your Health First was with Dr. Howard Monsour who’s the Chief of hepatology at Houston Methodist. In this two-part interview, we discussed various aspects of alcoholic liver disease, effects of acetaminophen on the liver, and the difference between men and women in their alcohol consumption. As noted in prior posts, the issue of liver transplant in patients with alcoholism and alcoholic cirrhosis is controversial, but when carefully reviewed, their outcomes following transplant are equal or better than other diseases we transplant livers for.



The Blog of Dr. Joseph S. Galati

AASLD an IDSA to develop updated recommendations for the management of hepatitis C

Leading Liver and ID Experts to Develop Hepatitis C Practice Recommendations

Recognizing the rapid development of hepatitis C medications coupled with increasing numbers of people being identified with hepatitis C virus (HCV) infection, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) are collaborating to develop clinical recommendations for the management of hepatitis C.

New medications approved by the Food and Drug Administration in recent years have increased HCV cure rates, and several additional medications are expected to be approved in the next three to five years. At the same time, new HCV testing guidelines are expected to increase the number of patients diagnosed with hepatitis C, many of whom currently are HCV-infected but unaware of their status. Ensuring that patients receive the new, effective treatment will be critical in increasing cure rates for hepatitis C. "We can finally say that cure of HCV infection has become a real possibility for the majority of individuals infected with this deadly virus," said Gary Davis, MD, of AASLD.

"Members of AASLD and IDSA are committed to ensuring that patient care keeps pace with rapidly advancing science," said David Relman, MD, president of IDSA. "This effort is an important step toward advancing that goal and comes at an important time as we all work to raise awareness of hepatitis virus infections on World Hepatitis Day on July 28."

Through this collaboration, the societies will review current treatment recommendations and use evidence-based, consensus guidance to develop updated recommendations for managing patients. Recommendations will be updated regularly and made available online. "A web-based system of new recommendations coupled with a published annual update will afford the greatest opportunity for both rapid and comprehensive output," said Donald M. Jensen, MD, of AASLD.

About Hepatitis C

Hepatitis C is a liver disease resulting from chronic infection with the hepatitis C virus (HCV). It is estimated that between 3 million and 4 million Americans are infected with HCV and have chronic liver disease as a result. Because symptoms of HCV infection may not appear for many years, more than 70 percent are unaware they are infected.

Earlier this year, the Centers for Disease Control and Prevention recommended an age-based screening strategy consisting of a one-time test for HCV for those at highest risk, including everyone born between 1945 and 1965. This recommendation was endorsed by the U.S. Preventive Services Task Force in June 2013. The broader testing recommendations likely will detect a substantial number of people who are unaware they are infected.

According to a July 10, 2013 article published in The Journal of The American Medical Association (JAMA), deaths from liver disease increased from 1990 to 2010. HCV is the most likely cause of the emergence of liver disease as a growing threat to Americans. Early testing enables people who are infected to receive treatment as soon as possible, and prevent progression to more serious disease, such as cirrhosis and liver cancer.

Currently available drugs and the next generation of direct-acting antivirals that will likely be available later this year offer the potential to treat and cure most patients with HCV infection. Therefore, up-to-date recommendations for the medical management of these patients and their treatment are critically important.

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About the AASLD

AASLD is a medical subspecialty society representing clinicians and researchers in liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with viral hepatitis. Access to care and support of liver disease research are at the center of AASLD’s advocacy efforts.

AASLD is the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease. AASLD was founded in 1950 by a small group of leading liver specialists and has grown to an international society responsible for all aspects of hepatology.

Press releases and additional information about AASLD are available online at www.aasld.org.

About IDSA

The Infectious Diseases Society of America (IDSA) is an organization of physicians, scientists, and other health care professionals dedicated to promoting health through excellence in infectious diseases research, education, prevention, and patient care. The Society, which has nearly 10,000 members, was founded in 1963 and is based in Arlington, VA. For more information, see www.idsociety.org.

Visit www.idsociety.org/Hepatitis_C  to access IDSA’s extensive collection of resources on hepatitis C, including the Society’s Core Curriculum for HPV at www.idsociety.org/HCV_Curriculum/#Introduction .

Achillion Pipeline Update:Hepatitis C Drug Still on Hold by U.S. FDA

Updated-
June 10 2014
FDA lifts clinical hold on Achillion's HCV drug sovaprevir, shares jump

NEW HAVEN, Conn., Sept. 27, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today provided an update on development of compounds in its pipeline of therapies for the treatment of chronic hepatitis C virus, or HCV. Achillion today received a response from the U. S. Food and Drug Administration, or FDA, on the clinical hold related to sovaprevir, Achillion's NS3 protease inhibitor. The FDA response indicated that, while Achillion's submission addressed all issues noted in the FDA's June 29, 2013 letter, the FDA concluded that the removal of the clinical hold is not warranted.

"While we are disappointed that we were not able to resolve the clinical hold at this time despite having addressed all the issues, we believe the breadth of our portfolio allows us to quickly advance other all oral combination regimens for the treatment of HCV," stated Milind Deshpande, President and Chief Executive Officer of Achillion. "With our Phase 2 NS5A inhibitor, ACH-3102, we are in a position to rapidly initiate combination studies with ACH-2684, our protease inhibitor, with results expected in 2014. Further, we continue to advance our uridine-analog nucleotide, ACH-3422, with which we anticipate initiating clinical trials in the first half of 2014."

ACH-2684 has completed all of the necessary preclinical and clinical trials necessary to support advancement into Phase 2 combination development. Achillion previously reported robust anti-viral activity with ACH-2684 as monotherapy including Phase 1b data in both non-cirrhotic and cirrhotic treatment-naïve HCV genotype (GT) 1 patients. In addition, Achillion will continue to work to resolve the clinical hold related to sovaprevir.

Phase 2 -007 Trial of Sovaprevir and ACH-3102 with Ribavirin

Achillion also announced interim data from the ongoing -007 Phase 2a clinical trial evaluating two doses of sovaprevir, either 200 mg or 400 mg once daily, in combination with 50 mg once daily of ACH-3102 and ribavirin (rbv) twice daily for 12 weeks in patients with treatment-naïve GT 1a or 1b hepatitis HCV.

The Phase 2 trial is a double-blind, placebo-controlled study evaluating the safety, tolerability and efficacy of 12 weeks of sovaprevir, ACH-3102 and rbv in up to 50 treatment-naïve patients with chronic GT 1a or GT 1b HCV. The first segment enrolled 30 patients who were randomized to receive a combination of either 200 mg or 400 mg sovaprevir once daily in combination with a 150 mg loading dose followed by a 50 mg daily dose of ACH-3102, and twice daily doses of rbv, or matching placebos. The primary endpoints for this trial include safety, tolerability, and sustained viral response 4 weeks after the completion of dosing (SVR4). The trial is being conducted at sites in the United States, Canada, New Zealand and Australia.

All patients achieved a very rapid virologic response (vRVR) with HCV RNA less than 25 IU/ml by week 2. Potent efficacy was observed against GT 1b HCV with 100% of patients achieving rapid viral response, or RVR, with HCV RNA levels less than 10 IU/mL at week 4. RVR was achieved in 79% of GT1 patients overall.

To date, the combination of sovaprevir and ACH-3102 with rbv for up to 12 weeks has been well tolerated with no drug-related serious adverse events, no clinically significant changes in vital signs or electrocardiograms. There have been no graded increases in liver function tests, including ALT or AST, for patients receiving active treatment to date. No other laboratory abnormalities were noted with the exception of decreases in hemoglobin observed and attributed to ribavirin.

Conference Call

The Company will host a conference call and simultaneous webcast on Monday, September 30, 2013 at 8:30 a.m. Eastern time. To participate in the conference call, please dial (877) 266-0482 in the U.S. or (631) 291-4567 for international callers. A live audio webcast of the call will be accessible from the Calendar page in the News Center at www.achillion.com. Please connect to Achillion's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

A replay of the webcast will be available on www.achillion.com. Alternatively, a replay of the conference call will be available starting at 11:30 a.m. Eastern time on September 30, 2013, through 11:59 p.m. Eastern time on October 6, 2013 by dialing (855) 859-2056 or (404) 537-3406. The replay passcode is 73738655.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV 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 that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the safety, efficacy and clinical benefits of the combination of sovaprevir and ACH-3102; Achillion's plans and timing for initiating additional combination trials of ACH-3102 and ACH-2684 and ACH-3422; Achillion's development plan; and Achillion's goals and strategies with respect to addressing all types of HCV patients. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," "estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: satisfactorily respond to regulatory actions with regard to its clinical development programs; replicate in subsequent dose groups and/or later clinical trials positive results observed in the interim data from the -007 combination trial of sovaprevir and ACH-3102, and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and 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 Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2013 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 duty to update any forward-looking statement, except as required by applicable law.

CONTACT:

Company Contact:
Glenn Schulman
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
gschulman@achillion.com

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

Seth Lewis
The Trout Group, LLC
Tel. (646) 378-2952
slewis@troutgroup.com

(Source: PrimeZone )
(Source: Quotemedia)

To read more Press Release articles, click here.

Simeprevir Approved in Japan

Simeprevir Approved in Japan

Medivir AB has reported that Janssen Pharmaceutical R&D Ireland (Janssen) has been informed by the Japanese Ministry of Health, Labour and Welfare (MHLW) that simeprevir has been approved for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection.

"The approval in Japan is a very important step in providing patients with new treatment options. It is the first approval based on the series of global filings that our partner initiated during 2013. Japan is commercially a very exciting market with a huge unmet medical need among hepatitis C patients", says Maris Hartmanis, CEO of Medivir.

The approval in Japan triggers a milestone payment of €5m to Medivir.

Simeprevir, a new direct-acting antiviral agent (DAA), is a protease inhibitor for the treatment of genotype 1 chronic HCV infection. Simeprevir is administered once-daily for 12 weeks as part of a “triple combination” with pegylated interferon and ribavirin followed by an additional 12 or 36 weeks of pegylated interferon and ribavirin alone.

In the CONCERTO clinical trials, simeprevir, as part of a regimen with pegylated interferon and ribavirin, demonstrated strong efficacy, with 89 percent of patients with previously untreated genotype 1 HCV infection achieving a sustained virological response (SVR). The primary endpoint in all clinical studies for simeprevir was a SVR 12 weeks after the last dose of treatment. In studies that included patients who had relapsed after stopping previous HCV treatment, results showed an SVR rate of 96 percent. These results were presented in June at The Japan Society of Hepatology.

http://www.pharmpro.com/news/2013/09/simeprevir-approved-japan

Hepatitis C - ADA Statement on Infection Control in Dental Settings

ADA Statement on Infection Control in Dental Settings

Written by Dentistry Today Thursday, 26 September 2013 07:51

CHICAGO, Sept. 19, 2013 – The American Dental Association (ADA) is deeply concerned about the first confirmed report of patient to patient transmission of hepatitis C in a dental practice setting linked to improper infection control practices. The ADA wishes to assure the public that patient health and safety are top priorities for the Association.

“This is a highly atypical and disconcerting case,” states ADA President Robert A. Faiella, D.M.D., M.M.Sc. “Every day, hundreds of thousands of dental procedures are performed safely and effectively thanks to the diligence of dentists who follow standard infection control precautions developed by the Centers for Disease Control.”

Dr. Faiella added, “While this is an isolated case, it understandably raises questions about infection control in the dental office. The ADA encourages people to talk with their dentists, who will be glad to explain or demonstrate their infection control procedures.”

The statement issued today is part of an interim status report from the Oklahoma State Department of Health and the Tulsa Health Department on the results of their joint investigation of the dental surgical practice with offices in Tulsa and Owasso. The oral surgeon involved in the case voluntarily surrendered his license to practice.

 The investigation began March 28 when public health officials notified the practice’s former patients that they may have been exposed to blood-borne viruses.

 An epidemiological investigation indicated that one case of transmission of the virus occurred in the dental practice. The transmission was described as “patient-to-patient” because improper infection control procedures caused the virus to be passed from one patient to another. Genetic-based testing of patient specimens by the Centers for Disease Control and Prevention (CDC) provided laboratory confirmation of the finding.

 The ADA has long recommended that all practicing dentists, dental team members and dental laboratories use standard precautions as described in the Centers for Disease Control and Prevention’s (CDC) Guidelines for Infection Control in Dental Health Care-Settings.
Standard precautions protect patients and health care workers by preventing the spread of disease. Examples of infection control in the dental office include the use of masks, gloves, surface disinfectants and sterilizing reusable dental devices.

 Before any patient enters the examining room, all surfaces, such as the dental chair, dental light, instrument tray, drawer handles and countertops, have been cleaned and decontaminated. Some offices may cover this equipment with protective covers, which are replaced after each patient.

Non-disposable items like dental instruments are cleaned and sterilized between patient appointments. Disposable dental instruments and needles are never re-used. Infection control precautions also require all dental staff involved in patient care to use appropriate protective garb such as gloves, masks, gowns and eyewear. After each patient, all disposable wear items, such as gloves, are discarded. Before seeing the next patient, the members of the treatment team cleanse their hands and put on new gloves.

 More information on infection control in dental offices is available online on the ADA consumer website Mouthhealthy.org.

Stanford scientists working to develop broad-spectrum antiviral drug

Stanford Report, September 26, 2013

Stanford scientists working to develop broad-spectrum antiviral drug

There are currently no vaccines or antiviral drugs for many of the most troubling viruses, in part because of the traditional one drug/one bug strategy to developing antiviral drugs. Stanford scientists are developing a new approach that could help identify drug pathways that could be effective across entire families of viruses.

By Bjorn Carey

When a virus infects a person, it hijacks the body's natural processes in order to fuel its rampage.

A pair of Stanford scientists aims to turn this strength into a weakness and develop what could become a broad-spectrum antiviral drug.

Most antiviral drugs are concocted to act against a specific viral protein. As such, they usually provide a "one drug/one bug" approach.


Courtesy of Shirit Einav
Shirit Einav

"Penicillin can kill many types of bacteria, but most antiviral drugs work only against one virus, and sometimes a single subtype of a virus," said Shirit Einav, an assistant professor of medicine and of microbiology and immunology at Stanford School of Medicine.

Additionally, targeting viral proteins is problematic; viruses can mutate quickly, and a single change in the viral sequence can render it fully resistant to the drug.

"With the exception of HIV, we still have very few antiviral drugs to offer patients with viral infections, and even those are often quite limited," Einav said. "No approved antiviral drugs or vaccines are available for emerging viruses, such as dengue, which pose major challenges to global health."

Viruses live within our cells and rely upon host cell machineries in order to replicate. Instead of targeting the virus directly, the solution, Einav said, may be to instead interfere with host cell proteins that are utilized by multiple viruses. "We treat diabetes and hypertension by targeting host proteins, so why not viral infections?" Einav said.

With support from Stanford's Bio-X Interdisciplinary Initiatives Program (Bio-X IIP), Einav and Stephen Quake, a professor of bioengineering, have developed a process of identifying human proteins that wide families of viruses depend on for their success.

The initial focus of the work has involved identifying host proteins that, if knocked out, could inhibit both hepatitis C virus and HIV. This requires combing through incredibly large libraries of thousands of proteins, and a careful understanding of their role in both the virus and the host.

Photo - L.A. Cicero

Stephen Quake

To find the needle in the haystack, Quake and Einav have developed a high-fidelity platform that uses microfluidic chips created by Quake to express small amounts of a wide variety of host and viral proteins, and screens for direct interactions between them.

Once the researchers discover a positive protein interaction between virus and host, they knock out the corresponding host gene in an infected cell to determine if the protein plays a vital role in the virus' life cycle. If it does, they then investigate whether other viruses require this protein.

In just a year, the researchers have shown that this approach can accurately identify host proteins or pathways that play critical roles in multiple infections by unrelated viruses. Based primarily on this work, the researchers are building a catalog of such overlapping host proteins that represent potential attractive targets for broad-spectrum antivirals.

The Einav lab has also produced proof-of-concept evidence that repurposing already approved drugs targeting host proteins required by multiple viruses can lead to the development of broad-spectrum host-centered antiviral approaches with activity against hepatitis C virus and HIV, as well as the currently untreatable dengue and ebola viruses.

"We have to make sure that the single targeted protein is absolutely crucial to multiple viruses," Einav said. "At the same time, we need to make sure that the drug that inhibits this host protein is safe. As long as viral replication is inhibited at a drug level that is not toxic and allows the host cell to function as close to normal as possible, this could work.

"This is just the beginning, but the more we look, the more we find."

Since 2000, Bio-X has provided funding for interdisciplinary projects that have the potential to improve human health in innovative ways. Bio-X seed grants have funded 141 research collaborations connecting hundreds of faculty. The proof-of-concept projects have produced hundreds of scientific publications, dozens of patents and more than a tenfold return on research funds to Stanford.

"Bio-X has really made this possible for me," Einav said. "I'm a new assistant professor, and this is essentially defined as discovery-based research, which is very difficult to get funded by conventional funding mechanisms. Many funding agencies want you to catch, prepare and cook the fish, and they will provide you funding just before you take the first bite. So to get early-stage funding for high-risk but high-reward research like this is really quite remarkable."
Media Contact

Shirit Einav, Microbiology and Immunology, Stanford School of Medicine: seinav@stanford.edu

Bjorn Carey, Stanford News Service: (650) 725-1944, bccarey@stanford.edu

http://news.stanford.edu/news/2013/september/einav-quake-antiviral-092613.html

Drug Users and HCV Providers: How Do We Work Together to Achieve HCV Treatment Success?

 

Clinical Thought
Clinical Care Options CCO

 Gregory Dore,  - 9/24/2013  More from this author

Drug Users and HCV Providers: How Do We Work Together to Achieve HCV Treatment Success?

Need and the greater good should drive healthcare decision making. As a consequence, we must never forget that behind a needle and spoon, there is a human being in need. Human frailty, personal choices, and politics aside, people who inject drugs (PWID) represent a segment of the population that, with understanding and the will to act, can be successfully treated for hepatitis C. However, to achieve the goal of successful treatment, healthcare providers must first create a nonjudgmental environment to overcome the reluctance of PWID to report their drug use. By allowing them to open up to us as providers, we establish a foundation of trust and support that will enable them to begin and then remain on treatment.

Engage With Education
Once we know where we stand, both sides of the treatment equation can meet the inevitable challenges together. It is this partnership between provider and patient that creates the foundation of a successful treatment team, especially when those patients are PWID. Once patients have taken the first step to reach out, it is incumbent upon providers to identify and address their needs in order to keep them coming back.

In my experience, developing a program that successfully treats PWID begins with early and ongoing education of providers and staff across the spectrum of specialties. Although the number of studies is limited, the data they present argue in favor of treating PWID for hepatitis C. A recent systematic analysis revealed that PWID—even those who actively use drugs during treatment—have demonstrated acceptable sustained virologic response (SVR) rates of 37% for genotype 1/4 and 67% for genotype 2/3 after peg-IFN/RBV treatment for chronic HCV infection. Another analysis of pooled data found that PWID experience low reinfection rates (1% to 5% per year) following successful treatment. Additional pooled study results have found that PWID demonstrate 80/80/80 adherence rates of 82% (95% CI: 74% to 89%) and discontinuation rates of 22% (95% CI: 16% to 27%), both rates that approximate those for people who do not use drugs. Finally, the Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) study demonstrated that a multidisciplinary team integrating nursing and specialist support into existing community health clinics and opioid substitution treatment centers can successfully assess and engage PWID in HCV treatment. We have promoted these data as widely as possible to bring attention to the possibility of treating PWID successfully. Ongoing initiatives will evaluate strategies to improve HCV treatment uptake among PWID and enhance treatment outcomes, particularly in the context of new direct-acting antiviral (DAA) regimens.

To enhance hepatitis C treatment and care for PWID, there is a need to expand points of assessment. One provider group we should aggressively recruit is addiction specialists. Using their access to and intimate knowledge of these patients enables us to reach these patients on a more personal and immediate level. Reaching this group of providers is especially important when we recognize that many PWID are reluctant to engage in care at large, tertiary care centers. They are often more easily engaged at smaller community clinics and methadone treatment centers. Once engaged in an environment they are comfortable in and by providers they are familiar with, PWID could be either treated within drug and alcohol or community-based settings or referred to more specialized providers at larger secondary or tertiary care centers. The advent of IFN-free all-oral DAA regimens should enhance feasibility of hepatitis C treatment delivery within a broader range of settings.

By reaching out to specialists other than the “usual suspects” of hepatologists and gastroenterologists, we are following the very successful HIV care model. This outreach allows us to create care partners who recognize the real possibility of treating PWID successfully, if not by the individual provider, then by a readily available specialist. Furthermore, in keeping with the HIV model, a multidisciplinary team will enable us to maximize the possibility of successfully treating not only their hepatitis C, but also their common comorbid psychiatric difficulties, social isolation, and other medical issues.

Impacting Care and Treatment
We can affect both the health of our community and PWID by recognizing that they can be treated successfully with careful patient selection. Getting information into the hands of providers who may be more familiar with and trusted by PWID is an important first step. PWID should not be dismissed as “untreatable” but receive individualized assessment for treatment as undertaken for other patients with hepatitis C. A range of disease-based, social, and family factors require evaluation in relation to treatment readiness and potential impact on outcomes.

Rightfully, society at-large has concerns about the enormous expense associated with hepatitis C therapy and the potential for transmitted resistance due to suboptimal adherence in any patient with hepatitis C including PWID. Individualized hepatitis C treatment assessment thus provides the opportunity to optimize uptake and outcomes.

Educate yourself, educate others, and make a positive impact in everyone.

Recently published international recommendations from the International Network on Hepatitis in Substance Users, of which I am a co-author, supplement existing guidelines and address many issues associated with successfully treating HCV in PWID.

Your Thoughts?
I am interested in hearing your thoughts on treating HCV in PWID. Is there an outreach program in your community to engage these patients? What has your experience been in treating PWID for any medical condition? How have you overcome obstacles to treatment in this patient population?

Topics: HCV - Treatment

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Report of a new hepatitis virus was a false alarm

“At first we thought this was a genuine hepatitis virus, but later we found it in data sets from patients with many other diseases and even from animals,” said Charles Chiu, PhD, a professor of laboratory medicine at UCSF.


False Alarm on Hepatitis Virus Highlights Challenges of Pathogen Sleuthing

UCSF Researchers Find Virus from the Ocean That Confounds Lab Analysis

Newswise — The report by scientists of a new hepatitis virus earlier this year was a false alarm, according to UC San Francisco researchers who correctly identified the virus as a contaminant present in a type of glassware used in many research labs. Their finding, they said, highlights both the promise and peril of today’s powerful “next-generation” lab techniques that are used to track down new agents of disease.

In research published online September 11, 2013, in the Journal of Virology, researchers led by Charles Chiu, MD, PhD, director of the UCSF Viral Diagnostics and Discovery Center, traced the source of the contamination back to tiny diatoms, a type of oceanic algae having nothing to do with human disease.

A scientific team led by researchers from the National Institutes of Health (NIH) first identified the virus as a potential cause of hepatitis in their study of blood samples from 92 people from China who had serious cases of hepatitis not caused by any of the five known hepatitis viruses. Chiu and colleagues discovered the same virus, which they called parvovirus-like hybrid virus (PHV), independently, in a different set of hepatitis patients whose disease was not caused by known viruses.

To further investigate the origin of the virus, Chiu’s UCSF team tracked down its true source by applying next-generation DNA sequencing techniques in a set of carefully controlled experiments, and by referencing the ever-expanding scientific databases that spell out and catalog viral genomes.

“At first we thought this was a genuine hepatitis virus, but later we found it in data sets from patients with many other diseases and even from animals,” said Chiu, a professor of laboratory medicine at UCSF.

The researchers also found that the virus sequenced from samples around the world strangely exhibited almost no genomic diversity. The research team strongly suspected that PHV was a laboratory contaminant and began probing other databases in search of the true source of the virus.

“We did some data mining of environmental databases and found matching DNA sequences from viruses originating in coastal waters off California and Oregon, but not elsewhere” Chiu said.

A developer of sampling and testing technologies may have sourced silica from diatoms in the ocean to make a popular glass column used in the studies, Chiu said. The columns are used to centrifugally spin biological samples to extract nucleic acids — DNA and RNA. Viral DNA that may have once infected the diatoms was also likely extracted as a contaminant during the procedure, along with DNA from biological samples, he said.

“The silica used in nearly all commercial spin columns is derived from the cell walls of diatoms,” he said. “We believe that PHV may be a diatom virus that had inadvertently contaminated the silica-based spin columns during manufacture.”

The scientists do not know what caused the cases of hepatitis examined in the studies.

Earlier techniques developed to read out the sequence of DNA building blocks extracted from biological samples permitted the stepwise decoding of genes and eventually the characterization of entire genomes of humans and other organisms.

But in recent years game-changing technological advances referred to as next-generation sequencing have permitted exponentially faster and cheaper sequencing of millions of DNA molecules in a single run through a lab protocol.

These state-of-the-art techniques for piecing together the genomes of organisms from tiny amounts of DNA can be used to efficiently detect pathogens previously unknown to science, but they also are so sensitive that they easily pick up contaminants, Chiu said.

It is not clear why the NIH-led team did not also detect the contaminating DNA in the control samples, Chiu said. Different techniques may have been used in the analysis of control samples in comparison to samples from hepatitis patients, or there may have been lot-to-lot variations in glassware, Chiu speculates.

A similar viral false-alarm scenario unfolded in recent years with a mouse virus called XMRV, first reported in 2006. The virus initially was thought to be associated with human prostate cancer and chronic fatigue syndrome, but last year Chiu and others, including original XMRV co-discoverer Joseph DeRisi, PhD, Howard Hughes Medical Institute Investigator and professor of biochemistry at UCSF, confirmed that XMRV was actually a viral contaminant of laboratory cell cultures and was not present in prostate cancer tissue.

These studies highlight the importance of repeating experiments with good controls to ensure that results are accurate, Chiu said. “Reproducibility is a cornerstone of science, yet far too few studies are validated by follow-up investigation,” he said. Next-generation sequencing is a promising approach to rapidly confirm and validate discoveries of new disease agents, saving investments in time and money that might otherwise be spent pursuing false leads, he added.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital.

Source - Newswise

UPDATE 1-U.S. FDA strengthens hepatitis B warning on 2 cancer drugs

UPDATE 1-U.S. FDA strengthens hepatitis B warning on 2 cancer drugs

Wed Sep 25, 2013 12:23pm EDT 

WASHINGTON, Sept 25 (Reuters) - U.S. health regulators have strengthened the warnings on two blood cancer drugs to reflect the risk that they may reactivate the hepatitis B virus in patients previously infected with the disease.

The warnings affect GlaxoSmithKline Plc's Arzerra, which was approved in the United States in 2009 to treat chronic lymphocytic leukemia (CLL); and Rituxan, a drug made by Roche Holding AG and Biogen Idec Inc that is approved to treat a variety of conditions including CLL, non-Hodgkin's Lymphoma and rheumatoid arthritis.

The U.S. Food and Drug Administration said the risk is already described in the warnings and precautions section of the label for both drugs but that cases of reactivation continue to occur and some patients have died. Now the information will be placed in a black box, indicating the most serious type of risk.

The FDA said it recommends that physicians screen all patients for hepatitis B infection before starting treatment with the drugs, and monitor patients with evidence of prior hepatitis B infection for signs that the virus has been reactivated, including for several months after therapy has stopped.

Both drugs work be suppressing the body's immune system, which is critical in fighting infections. Hepatitis B is a serious liver infection that can become chronic and lead to liver failure, liver cancer or cirrhosis, a condition that causes permanent scarring of the liver. It is spread through contact with blood and body fluids. The best way to prevent the disease is through vaccination.

http://www.reuters.com/article/2013/09/25/cancer-drugs-fda-warning-idUSL2N0HL17I20130925

MRE - Liver Imaging Test Detects Pediatric Liver Disease Without Need for Needle Biopsy

Imaging Technique Detects Pediatric Liver Disease Without Need for Needle Biopsy

Friday, September 20, 2013

A new, non-invasive imaging technique, magnetic resonance elastography (MRE), can now help physicians accurately detect fibrosis (scarring) in children with chronic liver disease – a growing problem due in part to increasing obesity rates.

A new study shows that MRE detects such chronic diseases as non-alcoholic fatty liver disease (NAFLD), which is increasingly common in children and teens, affecting an estimated 13 percent of adolescents. NAFLD can lead to progressive liver disease and liver failure. Obesity is a major risk factor.

“Because many pediatrics patients in the United States with NAFLD are severely obese, MRE is likely to be superior to ultrasound-based elastography in this population, as ultrasound-based methods are less reliable in severely obese patients,” says Stavra Xanthakos, MD, a gastroenterologist at Cincinnati Children’s Hospital Medical Center and lead author of the study.

The study, conducted by physicians at Cincinnati Children’s, is published online in the Journal of Pediatrics. If the findings are validated in larger studies, MRE could reduce dependence on costly and invasive liver biopsies to detect fibrosis.

In 2011 and 2012, the researchers evaluated 35 children and teens between the ages of 4 and 20 for chronic liver disease using both MRE and liver biopsy. The study demonstrated that MRE was highly accurate in detecting more advanced fibrosis in children with chronic liver disease, including severely obese patients.

A needle biopsy is standard practice for evaluating liver fibrosis. This not only has risks for the patient and high expense, but it is often frightening for children and teens. MRE is a way to measure tissue stiffness that uses low frequency sound waves in combination with magnetic resonance, which involves the combination of magnetic fields and radio frequency waves to produce diagnostic images. MRE can be accomplished in just a few minutes using the MR scanner.

“Having the ability to easily and non-invasively assess the degree of fibrosis in a child’s liver could help us identify the issue early and being the right course of treatment in a timely and effective manner,” says Daniel Podberesky, MD, chief of thoracoabdominal imaging at Cincinnati Children’s and a co-author of the study. “An added strength of magnetic resonance technology is the ability to more precisely measure liver fat, which allows us to non-invasively determine changes in liver fat quantity after clinical interventions.”

“Our results show the exciting potential of MRE to improve clinical care and reduce dependence on liver biopsies, but it is not yet ready for primetime clinical use,” adds Dr. Xanthakos. “In addition to validation in larger pediatric cohorts, we still need to determine whether MRE can predict changes in liver disease over time. We hope to study MRE in patients to test how well changes in imaging correlate with changes in liver stiffness after treatment or lifestyle changes.”

Dr. Xanthakos co-directs the Cincinnati Children’s Steatohepatitis Center. Steatohepatitis is an advanced stage of fatty liver disease.

In all, physicians at Cincinnati Children’s have successfully evaluated more than 200 children using liver MRE with no adverse events.

The study was supported by National Institutes of Health (NIH) grants K23DK080888 and K08DK084310 and by the National Center for Research Resources and the National Center for Advancing Translational Sciences (Grant 8 UL1 TR000077-04).
About Cincinnati Children’s

Cincinnati Children’s Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S.News and World Report’s 2013 Best Children’s Hospitals ranking. It is ranked #1 for cancer and in the top 10 for nine of 10 pediatric specialties. Cincinnati Children’s is one of the top two recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org. Connect on the Cincinnati Children’s blog, via Facebook and on Twitter.

Contact Information

Jim Feuer, 513-636-4656, jim.Feuer@cchmc.org

Hepatitis C Survey on Stigma, Lack of Awareness and Not Being Tested

The Centers for Disease Control and Prevention (CDC) and US Preventive Services Task Force recommend that all people born from 1945 through 1965 to be tested for hepatitis C. A serious liver disease which causes cirrhosis, liver cancer and is the leading cause of liver transplants in the United States, killing more than 15,000 Americans each year. More than 75 percent of the estimated 3 million US citizens with HCV are baby boomers. Officials reported the screening strategy will identify over 800,000 people infected with the virus, prevent 100,000 cases of cirrhosis - over 50,000 cases of liver cancer, and save more than 120,000 lives.

A recent survey by Wakefield Research and funded by Roche/Genentech reported on the lack of HCV awareness, stigma, testing and misconceptions about the disease in Miami, Washington DC and Philadelphia. The survey is available online this week at NATAP.

As an example one of the fourteen online questions asked in the survey.

Continue reading @ NATAP

In the spring Jules Levin reported on an interesting study which was presented at the Digestive Disease Week (DDW) this May in Orlando, Florida; Key Drivers and Barriers to Treatment Initiation and Adherence in Individuals with Hepatitis C, also available at NATAP 

As seen below in figure 1, the objective of this study was to understand factors that motivate or provide barriers to individuals initiating and adhering to IFN-based HCV treatment.

View full results of the study provided by NATAP

Related
August 2013
Hey Grandma, Let's Get You Checked for Hep C

July 2013
Reflex RNA testing should follow a positive HCV antibody test

Real-world SVR rate about 33% with hepatitis C triple therapy

Real-world SVR rate about 33% with hepatitis C triple therapy

By: M. ALEXANDER OTTO, Family Practice News Digital Network

DENVER – Only one-third of a group of patients with hepatitis C achieved a sustained virologic response when a protease inhibitor was added to standard ribavirin and interferon dual therapy, a real-world finding that flies in the face of reported response rates closer to 90%, according to Dr. Arpita Sheth who presented a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of 42 patients at the Veterans Affairs hospital in East Orange, N.J., who started on triple therapy with the protease inhibitor boceprevir, 9 had to drop out because of previously recognized adverse events, including thrombocytopenia, neutropenia, anemia, and depression. Five other patients did not comply with treatment, and treatment failed in 10. About half of the patients were new to therapy and the rest either non- responders to dual-therapy or triple-therapy relapsers.

Of the 18 who completed treatment, 9 achieved SVR [sustained virological response] at 3 months and 5 at 6 months. The four remaining patients relapsed.

"The incremental gain of adding protease inhibitors to the traditional regimen of ribavirin and interferon has a potential SVR rate of 33% (14/42) among retreaters and naive-to-treatment patients. Treatment should be evaluated at a more realistic number of 33% success [rather] than the 80%-90% SVR rate so frequently quoted from the FDA registration trials," concluded Dr. Sheth, a fellow at Rutgers New Jersey Medical School in Newark, in her presentation. 

The real-world rate is lower, at least in Newark’s VA population. To avoid disappointment, "we should always make our patients aware of that; we’ve seen a lot of patients get upset that they didn’t really get cured" with triple therapy, she said at the meeting. The findings from the study conducted by Dr. Sheth and her associates was published earlier (N. Engl. J. Med. 2011;364:1207-17).

The results probably had something to do with "the patient population we had. They do have some underlying history that includes depression, alcohol use, drug use, and a lot of other things. Even though [most] said they were compliant, I don’t think [compliance was] what they reported," Dr. Sheth said. 

About a third of patients in the study required erythropoietin to maintain their hemoglobin at 10 g/dL or higher while on triple therapy. 

Dr. Sheth and her team reported that they have no disclosures. 

http://www.familypracticenews.com/news/infectious-diseases/single-article/real-world-svr-rate-about-33-with-hepatitis-c-triple-therapy/e2f64491385001c6ca18670bf0d8636d.html

Gilead's (Sofosbuvir) FDA review could be delayed because of government shutdown?

Adam Feuerstein writes the FDA's October 25th meeting to review Gilead's (GILD) Sofosbuvir may be in jeopardy because of a government shutdown.

U.S. Government Shutdown Could Postpone FDA Advisory Panels

BY Adam Feuerstein | 09/24/13 - 08:04 AM EDT

WASHINGTON D.C. (TheStreet) -- Advisory committee meetings scheduled for October by the U.S. Food and Drug Administration to review drugs from Amarin (AMRN), Johnson & Johnson (JNJ) and Gilead Sciences (GILD) might be postponed or cancelled if the political stalemate over the U.S. budget and debt-ceiling limit leads to a government shutdown. 

Continue reading...

Government shutdown would likely roil FDA's drug-approval process
September 24, 2013 | By John Carroll
 @ FierceBiotech

So what happens at the FDA in the event of a government shutdown next Tuesday? For now, the agency isn't saying, referring reporters to an OMB statement guiding government agencies to prepare to execute "an orderly shutdown."

But the FDA has been here before and agency watchers are referring to some of the old guidelines to prepare for what may--or may not--be about to happen. For drug developers in particular, it seems clear that a government shutdown would delay PDUFA dates for any companies looking to get a near-term approval. FDA panel reviews for drugs under regulatory review are also likely to get pushed back.

A short interruption in government services would not likely have a big impact on the regulatory timelines. But all bets are off if there's a lengthy interruption, which has the potential to roil the arrival of some closely watched therapies. Gilead ($GILD), for example, is looking for an approval by early December for sofosbuvir--with the chance of an early OK for a key breakthrough therapy.

Continue reading @ FierceBiotech

 

Association between vitamin D and hepatitis C virus infection: A meta-analysis

World J Gastroenterol 2013 September 21; 19(35): 5917-5924

Published online 2013 September 21. doi: 10.3748/wjg.v19.i35.5917.

 

Association between vitamin D and hepatitis C virus infection: A meta-analysis

 Livia Melo Villar, José Antonio Del Campo, Isidora Ranchal, Elisabeth Lampe and Manuel Romero-Gomez.

Abstract & Discussion Only
Full Text Available @ World J Gastroenterol

2013 September 21; 19(35): 5917-5924

AIM: To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and sustained virological response (SVR) in hepatitis C virus (HCV) infected individuals.

METHODS: Relevant studies were identified by systematically searching MEDLINE databases up to March 2012 and abstracts of the European and American Congress of Hepatology conducted in 2011. Studies must provide information on SVR and the levels of 25(OH)D3 and/or 25(OH)D2 [henceforth referred to as 25(OH)D] in sera samples from HCV infected individuals. The inclusion criteria were: clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group; provided information on SVR rates; and were reported in the English language as full papers. Due to the heterogeneity of studies in categorizing serum vitamin D levels, a cut-off value of 30 ng/mL of serum 25(OH)D was used. Heterogeneity was assessed using I2 statistics. The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model.

RESULTS: Overall, 11 studies (8 observational and 3 interventional) involving 1575 individuals were included and 1117 HCV infected individuals (71%) showed low vitamin D levels. Most of the studies included mono-infected HCV individuals with the mean age ranging from 38 to 56 years. Four studies were conducted in human immunodeficiency virus/HCV infected individuals. Regarding vitamin D measurement, most of the studies employed radioimmunoassays (n = 5) followed by chemiluminescence (n = 4) and just one study employed high performance/pressure liquid chromatography (HPLC). Basal vitamin D levels varied from 17 to 43 ng/mL in the studies selected, and most of the HCV infected individuals had genotype 1 (1068/1575) with mean viral load varying from log 4.5-5.9 UI/mL. With regard to HCV treatment, most of the studies (n = 8) included HCV individuals without previous treatment, where the pooled SVR rate was 46.4%. High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL (OR = 1.57; 95%CI: 1.12-2.2) and those supplemented with vitamin D (OR = 4.59; 95%CI: 1.67-12.63) regardless of genotype.

CONCLUSION: Our results demonstrated high prevalence of vitamin D deficiency and high SVR in individuals with higher serum vitamin D levels or receiving vitamin D supplementation.

Received December 14, 2012; Revised January 31, 2013; Accepted February 9, 2013;

Published online 2013 September 21. doi: 10.3748/wjg.v19.i35.5917.

Discussion Only

Our review and meta-analysis summarize the results of eleven studies, which included a total of 1575 cases with hepatitis C, where basal 25(OH)D levels and 25(OH)D supplementation were associated with SVR in HCV patients. This updated review confirms and extends earlier results of a systematic review conducted by Cholangitis[6], who reported that vitamin D deficiency is very frequent before liver transplantation and ranges between 51% and 92%, whereas, in the liver transplantation setting, the prevalence of vitamin D deficiency is also high.

Vitamin D is metabolized by the liver and converted to 1,25-dihydroxyvitamin D3, which is the active form of the vitamin[29,30]. Individuals with chronic liver disease may have poor conversion from vitamin D3 or any of its other biologically active metabolites[31]. Severe liver disease may increase the risk of vitamin D deficiency and/or there might be a relationship between vitamin D deficiency and fibrosis. Putz-Bankuti et al[32] and Baur et al[33] also showed that low levels of 25(OH)D are associated with fibrosis and suggested that low 25(OH)D levels may predict hepatic decompensation and mortality in patients with chronic liver failure. More recently, Gal-Tanamy et al[34] showed that vitamin D3 increased the expression of the VDR and inhibited viral replication in cell culture.

Due to the observation of vitamin D deficiency in chronic liver disease patients, some studies have been conducted to evaluate vitamin D supplementation in these patients[20,26,27]. In some of these studies, it is reported that higher sunlight exposure or vitamin D supplementation should be recommended in patients with CHC[20,26,27]. In the present meta-analysis, vitamin D supplementation was related to higher SVR rates in HCV infected individuals, where the highest level was observed among genotype 1 HCV infected individuals. Although only a few studies regarding vitamin D supplementation fulfilled the eligibility criteria, different patterns were observed. The first study included only genotypes 2 and 3, the second included only genotype 1 and the third study involved genotypes 1, 2 and 3. Moreover, two of these studies were prospective and one was retrospective. Some limitations of these studies included the small number of patients, lack of vitamin D level assessment during therapy in the treatment and control groups, the design of prospective and randomized studies which were not placebo-controlled in one study[27], and the retrospective design of the study where immunocompromised HCV patients were supplemented with low-dose vitamin D (800 IU/d) after liver transplantation and most of the HCV patients (75%) had low vitamin D levels despite treatment[20].

In this meta-analysis, the levels of vitamin D were also associated with SVR, although different methods of vitamin D determination were used. Lai et al[8] demonstrated bias and variability in 25(OH)D measurements between laboratories and between different assays [quimioluminescence and liquid chromatography-tandem mass spectrometry (LC-MS/MS)] which can significantly affect clinical decision-making. In this situation, the adoption of common standards to allow assay calibration is urgently required.

Our study is the first meta-analysis of serum 25(OH)D levels and HCV infection in observational and interventional studies. Given the very small numbers of studies available to date, additional studies, ideally from different countries and populations are needed to assess potential differences in the associations between 25(OH)D and SVR for HCV. Large differences can be observed in different populations, depending on exposure to sunlight or vitamin D supplementation, and genetic differences[23]. Moreover, patients of African and Hispanic descent are less likely to respond to standard therapy[23] probably due to polymorphisms of the interleukin (IL)-28B gene, polymorphism of the VDR or vitamin D deficiency[17,35,36]. In this meta-analysis, all the individuals were Caucasian and most lived in Europe, which could explain vitamin D deficiency in this population resulting from possible low exposure to sunlight.

Meta-analysis is an important tool for revealing trends that may not be apparent in a single study. Pooling of independent, but similar studies increases precision and therefore the confidence level of the findings. A particular strength of our study is the application of advanced statistical techniques which allowed a summary of adjusted associations across studies and over the entire range of serum 25(OH)D values, despite the very heterogeneous categorization of 25(OH)D levels in the individual studies. Our study also has important limitations. First, as data on serum 25(OH)D in individuals were not available in each study, median, midpoints and mean of the groups were used for pooling. As a result, estimates of risk may have been less accurate than if data points on each individual had been used. Second, our meta-analysis was limited by the data provided in the individual studies, and although the authors tried to obtain the raw data from the articles, not all were available. Finally, although our review searched the MEDLINE database, recent Congress of Hepatology and Gastroenterology articles, and extensive checks for completeness by cross-referencing were employed, we cannot exclude the possibility that relevant studies may have been missed.
Despite its limitations, our review and meta-analysis support previous suggestions and provide the most comprehensive empirical evidence to date that basal serum 25(OH)D levels and vitamin D supplementation improves SVR in HCV infected individuals. However, available data are still sparse and in-depth analyses of these associations, in the context of additional longitudinal and prospective studies, are highly desirable to enable more precise estimates and a better understanding of the role of vitamin D in HCV infection.

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