June 3, 2013

Provided by Healio

June 3, 2013

ORLANDO, Fla. — The presence of metabolic syndrome post-liver transplantation increased the risk for infection and cardiovascular disease, according to data presented at Digestive Disease Week.

In a retrospective cohort study, researchers evaluated 158 patients who underwent liver transplantation between 2002 and 2007 at a single medical facility, with follow-up through September 2012. The presence of metabolic syndrome (MetS) before transplant and at 6 and 12 months post-transplant was determined in each case.

Before transplantation, 25% of the cohort had MetS, which increased at 6 months (51% of cases) and 12 months post-transplant (61%). Thirty-one percent of participants who did not have prior MetS developed it de novo at 6 months, while 54% developed it by 12 months.

Investigators observed a significant association between MetS at 6 months and infection-related hospitalizations within the first post-transplant year (53% of those with compared with 31% of those without MetS; P=.005). Hospitalizations due to cardiovascular disease (CVD) also were more common among those with post-transplant MetS (26% of cases at 5 years post-transplant vs. 13%; P=.05).

Patients with MetS and nonalcoholic fatty liver disease (NAFLD) were not at increased risk for either infection- or cardiovascular-related hospitalization compared with those with MetS alone. NAFLD, however, significantly increased the risk for CVD among patients without MetS (14% vs. 0% of those without NAFLD; P=.03). Neither MetS nor NAFLD significantly impacted post-transplant survival, according to Kaplan-Meier analysis.

“We were able to show there was a statistically significant association with early infectious morbidity, as well as later cardiovascular morbidity, if you have symptoms of [MetS],” researcher Nicholas Kim, MD, an internal medicine resident at the University of Wisconsin, told Healio.com. “Our data suggest that it’s important to prevent metabolic syndrome from developing post-liver transplant. It’s a very common complication due to a variety of reasons, but if we are able to prevent it, we might be able to reduce the amount of early infectious complications and later cardiovascular complications after liver transplant.”

For more information:

Kim N. Tu1019: Development of the Metabolic Syndrome and Its Outcomes After Liver Transplantation. Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.

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Blood Tests OK for Fibrosis Dx in Hep C

By Salynn Boyles, Contributing Writer, MedPage Today

Published: June 03, 2013

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Action Points

  • While liver biopsy remains the gold standard for predicting disease progression in people with HCV infection, it is no longer recommended as necessary in all patients before the initiation of antiviral therapy with newer medications.
  • This study suggests that blood tests can help to identify HCV-infected patients with clinically significant fibrosis, with somewhat greater accuracy for identifying cirrhosis than for less advanced fibrosis.

Blood testing can accurately identify clinically significant fibrosis and cirrhosis in people with hepatitis C virus (HCV) infection and may be an alternative to liver biopsy in some patients, a new study found.

The analysis of 172 studies comparing various blood tests to biopsy in HCV patients revealed that some of the simplest, cheapest blood tests performed as well as more expensive, complex tests, reported Roger Chou, MD, and Ngoc Wasson, MPH, from the Evidence-Based Practice Center at Oregon Health and Science University in Portland.

Six tests identified clinically meaningful fibrosis with a median positive likelihood ratio of 5 to 10 at commonly used cutoffs and areas under the receiver-operating characteristic curve (AUROCs) of 0.70 or greater (range 0.71 to 0.86), they wrote in the June 4 issue of the Annals of Internal Medicine.

The tests were the platelet count, age-platelet index, aspartate aminotransferase-platelet ratio index (APRI), FibroIndex, FibroTest, and Forns index.

In addition, three of those tests, platelet count, age-platelet index, APRI, plus Hepascore, all identified cirrhosis with median positive likelihood ratios of 5 to 10 and AUROCs of 0.80 or greater (range 0.80 to 0.91).

"Our results suggest that blood tests can help to identify HCV-infected patients with clinically significant fibrosis, with somewhat greater accuracy for identifying cirrhosis than for less advanced fibrosis," the researchers wrote.

Liver biopsy remains the gold standard for predicting disease progression in people with HCV infection, but it is no longer recommended in all patients before the initiation of antiviral therapy. Drawbacks of liver biopsy include the potential for sampling error and risk for complications such as bleeding, severe pain, and infection,

Blood tests have been proposed as a less invasive alternative to liver biopsy, and more than two dozen tests have been studied for this purpose.

"We expect to see all-oral, interferon-free HCV treatment regimens in a few years, and that means many more people are likely to begin antiviral therapies," they wrote. "Having blood tests to help identify patients who can benefit from these treatments will be increasingly important."

Using MEDLINE, the Cochrane Library database, and other reference lists, the authors identified studies that compared blood tests to liver biopsy for diagnosing fibrosis or cirrhosis in HCV-infected people.

Most of the studies included in the analysis were conducted in the U.S., Europe, Asia and northern Africa, and 15 were rated as good quality studies, while five were rated poor quality. The remainder were considered fair quality.

Chou said one of the most surprising findings was that the simple APRI blood test performed as well or better than more complex and expensive tests.

"This test provided useful information about the severity of underlying liver disease," he told MedPage Today. "For patients trying to decide if they should begin antiviral therapy, this and other blood tests may be an alternative to biopsy."

In a subanalysis in which APRI was compared to FibroTest (known as FibroSure in the U.S.), the predictive value of the two tests was very similar, Chou said.

FibroTest is a patented, six blood serum test for liver damage marketed by French company BioPredictive.

APRI was associated with a slightly lower AUROC than the FibroTest for fibrosis (18 studies: median difference, -0.03; range, minus 0.10-0.07), but there was no difference for cirrhosis (seven studies; median difference, 0.0; range, minus 0.04 to 0.06).

Chou and Wasson noted several limitations to their analysis, including the fact that only English-language studies were included and that most trials failed to describe blinded interpretation of liver biopsy specimens. Many also included inadequate descriptions of enrollment methods.

The added that the results may not apply to populations excluded from the review, including patients coinfected with hepatitis B virus, HIV, and those receiving hemodialysis.

The study was funded by a grant from the Agency for Healthcare Research and Quality.

Primary source: Annals of Internal Medicine
Source reference:
Chou R, et al "Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis c virus infection" Ann Intern Med 2013; 158.

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WHO: Improving the health of patients with viral hepatitis

World Health Organization

EXECUTIVE BOARD EB133/17
133rd session 29 May 2013
Agenda item 6.5

Report by the Secretariat

1. Viral hepatitis is caused by five distinct viruses (hepatitis A, B, C, D, and E), each of which has a distinct transmission route, and consequent disease course. Hepatitis A and E viruses are spread through fecal–oral contamination and hepatitis E virus is also transmitted by consumption of meat from infected animals. The disease caused by hepatitis A and E viruses is usually self-limiting, but can cause death due to acute liver failure. In addition, infection with hepatitis E virus results in high mortality among pregnant women. Hepatitis B and C viruses are spread through bloodborne transmission (e.g. blood transfusion, contaminated injections); through sexual intercourse; and from mother to child. Although these viruses cause some cases of acute disease, their greatest damage is caused decades after infection, as most deaths result from liver cancer and cirrhosis. For this reason, viral hepatitis is called the “silent epidemic”.

2. Viral hepatitis causes a significant burden of disease. Estimates vary, but approximately 240 million persons are chronically infected with hepatitis B virus and 150 million with hepatitis C virus. These viruses are also responsible for significant mortality. Annually, some 500 000 persons die from diseases related to hepatitis B and some 350 000 from hepatitis-C-related diseases. The most notable new piece of evidence that catalogues the burden of hepatitis-related disease comes from the Global Burden of Disease 2010 study: the estimate is that, annually, a total of 1.4 million deaths are due to acute and chronic hepatitis infections (hepatitis A–E). This is similar to the number of deaths attributable to HIV infection, and makes viral hepatitis the eighth leading cause of death globally.

3. In view of the different routes of transmission, effective prevention requires a comprehensive approach that includes a number of interventions. To reduce infection with hepatitis A and E viruses, improved sanitation and access to clean water are a priority. The improvement in living standards in many countries has resulted in a documented reduction in incidence of hepatitis A disease. Vaccination is also an effective preventive strategy. Several countries have adopted universal vaccination of infants against hepatitis A infection, further reducing the incidence of hepatitis A disease.

4. An effective vaccine also exists against hepatitis B infection. Over the past two decades, countries have adopted universal vaccination for children, and by 2011, 180 countries had included universal vaccination against hepatitis B for infants as well. Globally, coverage with hepatitis B vaccine is estimated at 75% and is as high as 91% in the Western Pacific Region, and 90% in the Region of the Americas. Vaccination against hepatitis B in the South-East Asia Region reached 56% in 2011. The current emphasis is on raising the universal coverage of vaccination of infants at birth against hepatitis B (i.e. within 24 hours of birth). Thanks to these interventions, the Western Pacific Region was the first WHO region to achieve the goal of controlling hepatitis B (the prevalence of hepatitis B surface antigen is less than 2% among five-year-olds). According to a WHO analysis, through continued investments in hepatitis B vaccination, an estimated 3.4 million hepatitis B-related deaths due to liver cancer and cirrhosis will be prevented. In fact, vaccination coverage against hepatitis B virus is one of the 25 indicators of the draft action plan for the prevention and control of noncommunicable diseases 2013–2020.1

5. Progress is also noted in the prevention of bloodborne transmission of hepatitis B and C. Among countries that provide reports, 90% indicate that all blood donations are screened for hepatitis B and C viruses. Regarding injection safety, continued efforts both to improve access to disposable syringes and needles, and to train health care workers in universal precautions have decreased the rate of unsafe injections.

6. The most significant advances regarding hepatitis control are in the area of treatment. Treatment experts predict that in the next two to five years, 90% of hepatitis C infections will be curable with an all-oral, once-daily,12-week regimen of safe medicines (as compared to the current regimen that requires 24 to 48 weeks of weekly injections and that has a cure rate of between 45% and 80%). The new medicines have the potential to cure millions of persons who have chronic infection and thereby prevent deaths from cancer and cirrhosis. Therapy to treat chronic hepatitis B infection is also improving; new medicine regimens are being developed that are more potent and are easier to administer. The complexity and toxicity of existing regimens have deterred advocacy for making these medicines available in low-income countries. Few national governments have plans for scaling up hepatitis therapy. However, with the arrival of the new medicines in the next few years, Member States, WHO and other international organizations can expect patients’ advocacy groups to exert significant pressure in pursuit of lower prices and greater access to the medicines. Currently, some groups are advocating for WHO to include pegylated interferon in the WHO Model List of Essential Medicines, to prequalify diagnostic tests and medicines for hepatitis, and to negotiate with industry for lower medicine prices.

PREVIOUS HEALTH ASSEMBLY ACTION AND SECRETARIAT ONGOING RESPONSE

7. The Health Assembly has previously considered specific aspects of hepatitis. In 2010, the Health Assembly adopted resolution WHA63.18, in which, inter alia, it urged Member States to support or enable an integrated and cost-effective approach to the prevention, control and management of viral hepatitis, recognizing the scale of the disease burden attributable to viral hepatitis. To facilitate implementation of the resolution, the Secretariat established the global hepatitis programme in December 2011. In 2012 the Sixty-fifth World Health Assembly noted a progress report on implementation of the resolution.2

8. Resolution WHA63.18 requests the Director-General, inter alia, to establish in collaboration with Member States the necessary guidelines, strategies, time-bound goals and tools for the surveillance, prevention and control of viral hepatitis. The framework for global action responds to this request, with work aligned along four strategic axes:

1 See document A66/9, Appendix 2.

2 Document A65/26, section G, and document WHA65/2012/REC/3, summary record of the sixth meeting of Committee B.

  • Strategic axis 1: raising awareness and mobilizing resources. Activities focus on increasing awareness about viral hepatitis among policy-makers, health professionals and the public; strengthening prevention and control measures; and removing discrimination against those who are infected. Priority activities include working with Member States to commemorate World Hepatitis Day (July 28) more visibly.
  • Strategic axis 2: data for policy and action. The Secretariat is updating estimates of the global prevalence and burden of viral hepatitis. Guidelines and standards for disease surveillance are being finalized so that countries can better prioritize resources and select appropriate interventions. The Secretariat is developing approaches that will allow countries to better assess the cost-effectiveness of various hepatitis interventions, including expanding therapy. The next step is to create a comprehensive approach to the development of national hepatitis control plans and programmes.
  • Strategic axis 3: prevention of transmission. Successful prevention efforts are being adapted in response to growing populations, changing epidemiology and new economic constraints. WHO is re-examining policies on immunization such as those relating to immunization schedules, the protection of neonates and health care workers (especially against infection with hepatitis B virus), expanded roles for existing hepatitis A vaccines and new hepatitis E vaccines, and innovative approaches for the future. WHO continues to work with partners to enhance the screening of blood for bloodborne pathogens including hepatitis B and C viruses and to reduce unnecessary and unsafe injections.
  • Strategic axis 4: screening, care and treatment. The Secretariat is developing guidelines for treatment of infection with hepatitis B and C viruses. WHO is also assessing whether pegylated interferon should be included in the WHO List of Essential Medicines and is initiating discussions with global partners to advocate for increased access to medicines to treat hepatitis.

ACTION BY THE EXECUTIVE BOARD

9. The Executive Board is invited to take note of the report and provide further strategic guidance.

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Drugs Go From Hit to Dud in $15 Billion Hepatitis Race: Health

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A research scientist for Gilead Sciences Inc., works on the synthesis of a potential hepatitis C virus drug candidate at the company's lab in Foster City, California. Photographer: David Paul Morris/Bloomberg

By Simeon Bennett June 02, 2013

Jean-Michel Pawlotsky has déjà vu.

The doctor in the town of Creteil, just outside Paris, is telling hepatitis C patients to delay treatment until later this year, when two new drugs that may boost their chances of defeating the lethal liver infection hit the market.

It’s the same advice he offered two years ago, when earlier medicines developed by Vertex Pharmaceuticals Inc. (VRTX) and Merck & Co. (MRK) were poised for approval. Now he says those drugs, hailed as breakthroughs in 2011, will soon be superseded by products fromGilead Sciences Inc. (GILD) and Johnson & Johnson. (JNJ)

The pace of innovation, spurred by drugmakers jostling for a slice of a market that may reach $15 billion by 2018, has turned hepatitis C research into one of the fastest-developing areas of medicine. That boosted Gilead’s shares to a record last month, and left others like Vertex facing dwindling sales as their products quickly go from revolutionary to outdated.

“Things are moving very fast,” Pawlotsky, who teaches medicine at the University of Paris-Est, said by phone. “People are frustrated, they want more, better.”

Hepatitis C, an infectious disease that can scar the liver and afflicts about 170 million people worldwide, is still treated largely with injections that can take six months to clear the virus, sometimes don’t work, and cause side effects ranging from flu-like symptoms to depression. If untreated for longer periods, hepatitis C can cause cancer.

Gilead, a newcomer to the field, in April applied for regulatory clearance of a drug known as sofosbuvir. The pill may become the Foster City, California-based company’s top-selling product by 2015, and reach sales of $6.3 billion by 2016, according to the average of nine analyst estimates (GILD) compiled by Bloomberg. The stock has more than doubled in the past year on optimism about the pill.

Drug Deluge

Until 2011, there was only one standard treatment: the generic antiviral ribavirin, together with a weekly injection called pegylated interferon, sold by Roche Holding AG and Merck.

Two years ago, doctors and patients embraced the new drugs from Vertex and Merck because they boosted cure rates to about 80 percent from 50 percent. But they came with more side effects, including skin rashes and the risk of birth defects.

In clinical studies, newer formulations from Gilead and J&J show similar or better results in ridding patients of the disease, and fewer risks. Both may win regulatory approval this year. Johnson & Johnson’s Janssen unit applied in March for clearance of its product, simeprevir, which was developed by Medivir AB. (MVIRB) Other drugs from AbbVie Inc. (ABBV) and Bristol-Myers Squibb Co. (BMY) are in late-stage trials.

Much Promise

“It’s not often you’re in a field that moves so fast and offers so much promise,” said Graham Cooke, a clinician at Imperial College London. “We’ve had very difficult treatments for so long, and we’re now in this era of incredible throughput from the pipeline.”

Vertex, of Cambridge, Massachusetts, gets 76 percent of its revenue from Incivek, the hepatitis drug it developed with Janssen, which markets the treatment as Incivo in Europe. The drug won U.S. regulatory approval in May 2011 and prescriptions and sales reached a peak in the fourth quarter of that year, but have declined since. The drug may only garner sales of $669 million this year, the average of 12 analyst estimates (VRTX) compiled by Bloomberg.

“We recognize that fewer patients are starting treatment for hepatitis C, however there are still patients who want or need to be treated now,” Erin Emlock, a spokeswoman for Vertex, said by e-mail. “Three of four people who start treatment today get Incivek, a number that’s unchanged since launch.”

‘Almost Unethical’

To stoke demand, Incivo’s booth at a meeting of the European Association For the Study of the Liver in Amsterdam in April featured a video with the message, “Treat now to take your patient’s life off hold.”

Some doctors agree. The practice of delaying treatment to wait for better drugs, known as warehousing, is “irrational, and almost unethical,” said Mitchell Shiffman, a clinician who sees about 1,000 new hepatitis C patients a year at the Liver Institute of Virginia. “If a patient can be cured now, why do you want to tell them to wait?”

French doctor Pawlotsky says people with mild disease aren’t harmed by a short delay. Most of his patients want to try the new drugs by participating in clinical trials, he says.

“Obviously if we thought that the new treatments would come in something like five or six years, we would not warehouse,” he said. “But it’s a matter of months.”

Mark Thursz, the secretary-general of the European Association for the Study of the Liver, says many people he has put on experimental drugs are faring better than those using treatments now on the market.

$100,000 Treatment

“Our patients are struggling with the current regimes,”Thursz said. “The sooner we can get the new drugs licensed and in the clinic for our patients, the better.”

Gilead may charge up to $100,000 per patient for a course of sofosbuvir, according to ISI Group in New York. The drugmaker says it doesn’t comment on drug prices before they’re approved, but says the medicine can shorten treatment times to as little as 12 weeks, from as long as a year now.

Even as doctors disagree on whether to delay treatment, they’ve got one eye on the next wave of drugs. At least three are in the final stage of clinical trials and may become available within two years.

‘Therapeutic Jacuzzi’

Gilead is testing a combination of sofosbuvir with an experimental drug called ledipasvir in a cocktail that cured 100 percent of patients in a mid-stage trial presented in Amsterdam in April. AbbVie’s three-in-one combo won designation as a“breakthrough therapy” from the U.S. Food and Drug Administration on May 6, meaning it may be reviewed more quickly, after a study showed it cured 96 percent of patients after 24 weeks. Bristol-Myers Squibb’s three-in-one experimental combo won the same accelerated status just weeks earlier.

That means yet more difficult decisions about whether to treat or wait, said Dominique Larrey, a doctor at Saint-Eloi Hospital in Montpellier, France.

“I tell my students it’s like we’re in a therapeutic jacuzzi,” he said. “Each bubble is a new drug.”

To contact the reporter on this story: Simeon Bennett in Geneva at sbennett9@bloomberg.net 

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net 

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gI_83052_Avail%20CLinical%20Research

Avail is conducting a 12-week, Phase 2, Randomized Study to Evaluate the Safety and Efficacy of a new drug in Subjects with Chronic Hepatitis C Infection.

DeLand, Florida (PRWEB) June 03, 2013

*To see if you qualify for this Hepatitis C Clinical Trial, visit Avail Clinical Research on the web or contact us directly at (386) 785-2404.

BACKGROUND

The Hepatitis C virus (HCV) infection is a global public health problem. The global prevalence of hepatitis C infection is estimated to average 3% resulting in approximately 170 million HCV-infected persons worldwide. Most of those infected develop persistent, chronic infection. An estimated 20-50% of patients with chronic HCV infection are at risk for developing such long-term complications as cirrhosis and hepatocellular carcinoma (HCC).

PRIMARY OBJECTIVES

The primary objectives of this Hep C Clinical Study are to evaluate the:

Safety and tolerability of a new Hep C drug and simeprevir when given in combination with RBV for up to 12 weeks.

Efficacy of a new Hep C drug and simeprevir when given in combination with RBV for up to 12 weeks.

SECONDARY OBJECTIVES

The secondary objectives are to evaluate the:

1. Pharmacokinetics (PK) of a new Hepatitic C drug and simeprevir when given in combination with RBV.

2. PK/Pharmacodynamics (PK/PD) of a new Hepatitic C drug and simeprevir when given in combination with RBV.

3. Emergence of resistance mutations over 12-weeks of combination treatment of a new Hepatitic C drug, simeprevir and RBV and in the post-treatment follow-up period.

INCLUSION CRITERIA

1. 18 (or the legal age of consent per local regulations, if greater than 18 years) to 65 years of age, inclusive.

2. Female subjects of both childbearing potential and non-childbearing potential may be included, unless the local regulatory authority requires that only females of non-childbearing potential be included. Non-childbearing potential is defined as one of the following:

Postmenopausal, defined as amenorrheic for at least 2 years and serum follicle stimulating hormone (FSH) level consistent with postmenopausal status at Screening, OR

A documented hysterectomy, bilateral oophorectomy or bilateral tubal ligation at least 6 months prior to study initiation.
3. All female subjects must have a negative serum beta-human chorionic gonadotropin (β-HCG) at Screening and a negative urine pregnancy test prior to the first dose of study medication on Day 1.

4. Women of childbearing potential and men must have agreed to use an acceptable double method of birth control (one of which must be a barrier method) from Screening through at least 6 months after the last dose of study drugs.

5. Male subjects must have agreed not to donate sperm from the first dose through at least 6 months after the last dose of study drugs.

6. QTcF interval ≤ _450 ms at Screening and prior to dosing on Day 1.

7. Documented clinical history compatible with chronic hepatitis C, including any one of the following:

a) anti- HCV antibody positive at least 6 months prior to Screening or dosing, OR

b) HCV RNA present in plasma by a sensitive and specific assay at least 6 months prior to Screening or dosing, OR

c) HCV genotype at least 6 months prior to Screening or dosing, OR

d) histologic evidence of chronic hepatitis C infection.

8. Must not have received prior antiviral treatment for HCV infection.

9. Plasma HCV RNA positive at Screening with minimal viral load according to genotype:

a) Genotype 1b HCV RNA ≥5 log10 IU/mL

b) Genotype 4 HCV RNA ≥ _4 log10 IU/mL

10. HCV genotype 1b or 4 by HCV genotyping performed at Screening (Note: mixed subtypes are not acceptable).

11. Documented absence of cirrhosis within 36 months of Screening or dosing (histology or non-invasive equivalent, according to local standard of care).

12. Subject is, in the opinion of the investigator, willing and able to comply with the protocol and all other study requirements.

13. Subject has provided written informed consent to participate in the study.

BENEFITS OF PARTICIPATION

  • Receive medical care at No Cost
  • Health Insurance is not required
  • Receive Compensation for time & travel
  • Help Advance medical research

*Achieve Clinical Research conducts Clinical Research Trials in Florida. For more information about participating in a Hep C Clinical Study, please visit our website or contact us directly at (386) 785-2404.

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