September 9, 2010

Comparison of ELF, FibroTest and FibroScan for the non-invasive assessment of liver fibrosis

FibroTest (FT) is the most frequently used serum fibrosis marker and consists of an algorithm of five fibrosis markers (alfa2-macroglobulin, apolipoproteinA1, haptoglobin, GGT, bilirubin). The Enhanced Liver Fibrosis (ELF) test consists of an algorithm of three fibrosis markers (hyaluronic acid, amino-terminalpropeptide-of-type-III-collagen, tissue-inhibitor of matrix-metaloproteinase-1).

While a systematic review has shown comparable results for both individual markers, there has been no direct comparison of both markers.

Methods: In the present study, the ELF-test was analyzed retrospectively in patients with chronic liver disease, who received a liver biopsy, transient elastography (TE) and the FibroTest using histology as the reference method. Histology was classified according to METAVIR and the Ludwig's classification (F0-F4) for patients with chronic hepatitis C and B virus (HCV, HBV) infection and primary biliary cirrhosis (PBC), respectively.

Results: Seventy-four patients were analysed: 36 with HCV, 10 with HBV, and 28 with PBC.

The accuracy (AUROC) for the diagnosis of significant fibrosis (F[greater than or equal to]2) for ELF and FibroTest was 0.78 (95%CI:0.67-0.89) and 0.69 (95%-CI:0.57-0.82), respectively (difference not statistically significant, n.s.). The AUROC for the diagnosis of liver cirrhosis was 0.92 (95%CI:0.83-1,00), and 0.91 (95%CI:0.83-0.99), respectively (n.s.).

For 66 patients with reliable TE measurements the AUROC for the diagnosis of significant fibrosis (cirrhosis) for TE, ELF and FT were 0.80 (0.94), 0.76 (0.92), and 0.67 (0.91), respectively (n.s.).

Conclusion: FibroTest and ELF can be performed with comparable diagnostic accuracy for the non-invasive staging of liver fibrosis. Serum tests are informative in a higher proportion of patients than transient elastography.

Author: Mireen Friedrich-RustWilliam RosenbergJulie ParkesEva HerrmannStefan ZeuzemChristoph Sarrazin

Credits/Source: BMC Gastroenterology 2010, 10:103

Published on: 2010-09-09
 
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Bone Loss in HIV-Positive Men Tied to AIDS Diagnosis, Opiate Use and Hep C

September 9, 2010

Heroin and methadone users who’ve ever been diagnosed with AIDS are at dramatically higher risk of bone loss as they get older, according to a study published in the September 24 issue of AIDS.

Potent combination antiretroviral (ARV) therapy has significantly cut the death rate and led to longer life spans in people with HIV. This means that people are now living into older age, when additional health problems typically strike. In fact, experts project that by 2015 more than half of all people with HIV in the United States will be older than 50.

A growing concern is bone mineral loss—called osteopenia when it is mild and osteoporosis when it is more severe. Numerous studies have found higher rates of bone mineral loss among people with HIV than their HIV-negative counterparts. This is particularly true of HIV-positive men.

A further risk factor for decreased bone mineral density (BMD) is use of opiates, including heroin and methadone. Both drugs have been associated with osteopenia and osteoporosis. Since a significant number of people with HIV are current or former drug users, Anjali Sharma, MD, MS, and her colleagues from the State University of New York Downstate Medical Center in Brooklyn set out to measure bone health within this population.

Sharma’s team enrolled 389 men in the Bronx, New York, ages 49 and older who were HIV positive or at risk for infection. In total, 230 were HIV positive, and 159 were HIV negative. The men’s average age was 56, and most were of average height and weight. More than half of the HIV-positive men had been positive for at least 10 years, and 77 percent of them reported using protease inhibitors. More than half were African American, roughly one quarter were Latino, and the remainder were white or another race. The median CD4 count among the HIV-positive men was 398, and 42 percent had a history of an AIDS diagnosis.

All of the men underwent extensive interviews to determine their behavioral and medical histories. Each of them also underwent dual energy X-ray absorptiometry (DEXA) scans to measure their bone health in the thigh, hip and lower back, both at the time they entered the study and roughly three years later.

Risk factors associated with diminished BMD were common: 88 percent had a history of cocaine use, almost all had a history of smoking (64 percent were current smokers), 47 percent had evidence of alcoholism, and 47 percent had low serum testosterone.

At time of first DEXA, 46 percent of the men overall had normal BMD, while 42 percent had osteopenia, and 12 percent had osteoporosis. Of the men who initially had a normal BMD, 14 percent progressed to osteopenia, and 86 percent continued to have healthy bones. The risk for developing osteopenia among this group was nearly three times higher in the HIV-positive men. Of those who were initially diagnosed with osteopenia, roughly 12 percent progressed to osteoporosis. The rate of progression here was the same for HIV-positive men as for HIV-negative men.

Most of the typical factors for reduced BMD were associated with bone loss in this study, including, age, race, use of corticosteroids or testosterone, and hepatitis C virus (HCV) infection.

Sharma’s team, however, found a powerful interaction between use of heroin and a history of an AIDS diagnosis, such that the people with the greatest bone loss were heroin users who’d ever received an AIDS diagnosis. This held up after adjusting for all other risk factors. HCV status and current methadone use were also highly predictive. CD4 count and types of ARVs did not affect BMD.

Oddly, cigarette smoking was not significantly associated with bone loss. However, the authors comment that “the lack of an independent association of BMD loss with cigarette smoking might be due in part to the fact that nearly 90 percent of participants in the cohort were current or former smokers.”

“Taken together, these data suggest that HIV-infected opioid-using men may be at particular risk of bone loss as they age, as a result of comorbid disease such as hepatitis C infection, opioid substitution treatment with methadone, ongoing heroin use, progression to AIDS, or a combination of these factors,” the authors concluded.

“An improved understanding of factors associated with ongoing bone loss and fracture risk is needed,” they continued, “to help guide thresholds for assessment of BMD and for osteopenia treatment in HIV-infected persons and opioid users.”

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New HIV Cases High Among French MSM

By Michael Smith, North American Correspondent, MedPage Today

Published: September 08, 2010
Reviewed by Barry S. Zingman, MD; Professor of Clinical Medicine, Albert Einstein College of Medicine, Bronx, NY and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

HIV appears to be out of control among French men who have sex with men, researchers reported.

Data for 2008 revealed that men who have sex with men (MSM) accounted for 48% of all new HIV infections in France, according to St├ęphane Le Vu, PhD, of the French National Institute for Public Health, and colleagues.

The incidence rate in that population was 1% -- a rate of 1,006 new infections per 100,000 person-years in 2008 -- and 200 times higher than the rate estimated for French heterosexuals, Le Vu and colleagues reported online inThe Lancet Infectious Diseases.

"The HIV epidemic seems to be out of control in the MSM population," the researchers contended.

Over the six years from 2003 through 2008, HIV incidence among MSM was "comparatively high and stable," the researchers reported -- although the overall incidence of HIV in France fell by about 3.7% a year.

The new findings are no surprise to those involved in combating the HIV pandemic, said Robert Hogg, MD, of the British Columbia Centre for Excellence in HIV/AIDS in Vancouver.

"Rates in North America in terms of HIV incidence among MSM have been relatively stable and very high for the last little while," he told MedPage Today, although the reasons for that remain unclear.

Most analyses of HIV rates are based on new diagnoses, but the French study added a new wrinkle. Using an enzyme immunoassay, Le VU and colleagues were able to gauge the proportion of recent infections among the new diagnoses.

After accounting for under-reporting, Le Vu and colleagues estimated that 42,330 people were newly diagnosed with HIV over the study period and that overall HIV incidence decreased significantly from 8,930 new found infections in 2003 to 6,940 in 2008. The decline was significant at P=0.002.

The proportion of recent HIV infections, as determined by the immunoassay, remained stable at about 25% a year, they found.

Among those with recent infection during the study period, MSM led the way with 40%, compared with French-national heterosexual women and men (at 28% and 22%, respectively), heterosexual non-French-national women and men (at 16% and 12%), and injection drug users (at 15%), Le Vu's team reported.

In 2008, however, 48% of some 6,940 new infections were found among MSM, the researchers wrote, with only 1% of new infections seen in injection drug users.

Overall, HIV incidence in 2008 was 17 per 100,000 person-years, they reported, based on rates of:

• Nine per 100,000 person-years among heterosexuals
• 1,006 per 100,000 person-years among MSM
• 86 per 100,000 person-years among injection drug users

In a comment accompanying the French report in The Lancet, Hogg and colleagues at the BC Centre argued that one way to reduce those rates would be to employ a multifaceted approach including both individual and population-based prevention strategies.

As well, they argued, such an approach should take into account the increasing evidence that expanding antiretroviral therapy to all people who meet eligibility criteria would reduce the number of new cases.

"It's not treatment or prevention," Hogg told MedPage Today. "It's both."

Hogg added that any prevention strategy will also have to account for the way sexual transmission occurs among men who have sex with men. The pattern, he said, is "like a series of random forest fires," which can be difficult to extinguish.

That contrasts with injection drug users, where transmission usually occurs within a small circle of people involved in using drugs and prevention efforts can be closely targeted, Hogg said.

The study was supported by the French National Institute for Public Health Surveillance and the French National Agency for Research on AIDS and Viral Hepatitis. The authors declared they had no conflicts.

Hogg reported financial links with GlaxoSmithKline and Merck Frosst Laboratories.

Primary source: The Lancet Infectious Diseases

Source reference:

Le Vu S, et al "Population-based HIV-1 incidence in France, 2003-08: a modelling analysis" Lancet Infect Disease 2010; DOI: 10.1016/S1473-3099(10)70167-5.

Additional source: The Lancet Infections Diseases

Source reference:

Hogg RS, et al "Reduction of HIV incidence in men who have sex with men" Lancet Infect Disease 2010; DOI: 10.1016/S1473-3099(10)70200-0.

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ZymoGenetics Acquisition Highlights Competitive Hepatitis C Treatment Race

Bristol-Myers Squibb Company (BMS) announced Tuesday that it had signed an agreement to acquire biopharmaceutical company ZymoGenetics for $9.75 per share in cash, or approximately $885 million. Under the terms of the agreement, BMS will gain control of ZymoGenetics’ product development pipeline, which includes potential treatments for surgical bleeding, metastatic skin cancer, and atopic dermatitis.

However, perhaps the biggest prize BMS will acquire in the deal is pegylated-interferon lambda, a novel interferon drug candidate for the treatment of hepatitis C, an infectious disease that affects the liver. Approximately 3.2 million people in the U.S. are chronically infected with hepatitis C, according to the U.S. Centers for Disease Control, and ZymoGenetics’ drug candidate has the potential to improve upon the current standard of care, interferon combined with ribavirin. While this drug combination works for many patients, it has to be taken for months and has many potential side effects.

According to a report by market research firm Global Data, the global hepatitis C market was worth $4 billion in 2009 and is projected to grow at a compound annual growth rate of 9.8% to reach $8.5 billion by 2016. ZymoGenetics is competing with Vertex Pharmaceuticals, Merck, Anadys Pharmaceuticals, Idenix Pharmaceuticals, and a number of other companies to be the first to market a hepatitis C drug that outperforms the current standard of care.

Along with ZymoGenetics, Vertex has been drawing a lot of attention; the Cambridge, Mass.-based company released positive late-stage clinical data on Tuesday. In a study of 662 treatment-resistant hepatitis C patients, 65 percent of patients who took Vertex’s telaprevir were cured, compared to 17 percent of patients who were treated with the current standard of care. The news wasn’t as good for Idenix, which halted trials of two of its experimental hepatitis C drugs over safety concerns after liver abnormalities were discovered in three healthy study participants. Other news from the hepatitis C space: PSI-7977, developed by Pharmasset, recently received fast track designation from the FDA. The drug is currently in Phase 2b clinical trials. With such a significant need for effective hepatitis C treatments, and with so many competitors in the field, the race to commercialization continues to be an interesting one.

9 September 2010
 
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A Personal Plea for Better HIV & Hepatitis Prevention Policy

Christopher Kennedy Lawford
Actor, lecturer and author

Posted: September 9, 2010 12:32 PM

"I want to test you for hepatitis C and HIV," my doctor said to me during a routine physical in 2000. I'd been in recovery for 15 years, after battling drug addiction for fifteen years (a too public battle for me and my famed families). In the days before we knew about HIV and hepatitis C, I had shared needles -- it was something some of us did. The last time I had done that was in 1981, just as the first cases of AIDS were being identified in the United States.

I'd avoided getting tested for either HIV or Hep C out of fear that God had saved me from drowning in the disease of addiction only to kick me to death with AIDS or cirrhosis on the beach. It seemed the perfect irony, a final exclamation point on a life of great privilege and promise unappreciated and unfulfilled.

My doctor gave me the good news/bad news: I wasn't infected with HIV, but I was infected with hepatitis C.

I'd heard of hepatitis C -- folks trudging alongside me on the recovery road were getting diagnosed with hep C, and it didn't sound good. My doctor gave me the whole cold truth -- without treatment, I might face liver cancer, liver transplant. Maybe death.

A lot of things came together at that point in my life. I've died many, many times during my addiction, but I've never been confronted with the possibility of really dying in sobriety.

With the support of medical professionals, family and friends -- particularly those in recovery -- I survived hepatitis C and became an author and advocate for drug treatment, hepatitis C and HIV treatment, and better prevention policy.

In the ten years since I was cured, I've met thousands of persons confronting a diagnosis of HIV or hepatitis C, a cruel remnant of not only their past, but also a public policy environment in the United States that differs from the rest of the industrialized world. Most of the world responded to AIDS outbreaks among injection drug users by investing in addiction treatment and making sterile syringes available to those who would not, or could not, stop using drugs immediately. Those policies kept Western Europe from suffering a major outbreak of HIV among injection drug users, and a hepatitis C rate that is lower than the U.S.

There is absolutely no controversy among public health researchers and scientists on syringe access. Over 200 studies from around the world concur that allowing adults to legally access and possess syringes suppresses the spread of these diseases without contributing to any increase in drug use, crime or syringe litter.

It is time for California to catch up with the rest of the world. We have that option through two good bills that Governor Schwarzenegger should sign.

• SB 1029 by Senator Leland Yee would allow pharmacists the discretion to sell a limited number of syringes to adults without a prescription.

• AB 1858 by Assemblymember Bob Blumenfield would allow the state Department of Public Health to authorize syringe exchange programs wherever the conditions exist for the rapid spread of HIV or hep C through syringe sharing.

Neither bill costs much to implement, and will save taxpayers billions, literally billions, by averting costly infections.

In politics, there are always those who propose half-measures, like allowing legal syringe access to be a decision of local government. That makes no sense--communicable diseases don't respect the county line, and Californians deserve equal access to a proven disease prevention strategy, no matter where they live. Furthermore, all state taxpayers pay for the healthcare of a low-income person, no matter where he or she lives.

I trust the Governor will respect the scientific consensus that supports legal syringe access. Those of us strong enough to recover from addiction deserve a chance to get better--all the way better. And the taxpaying public deserves smart prevention policy. Governor, please sign SB 1029 (Yee) and AB 1858 (Blumenfield).

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Patient-to-patient transmission of hepatitis C virus (HCV) during colonoscopy diagnosis

No recognized risk factors can be identified in 10-40% of hepatitis C virus (HCV)-infected patients suggesting that the modes of transmission involved could be underestimated or unidentified. Invasive diagnostic procedures, such as endoscopy, have been considered as a potential HCV transmission route; although the actual extent of transmission in endoscopy procedures remains controversial.

Most reported HCV outbreaks related to nosocomial acquisition have been attributed to unsafe injection practices and use of multi-dose vials. Only a few cases of likely patient-to-patient HCV transmission via a contaminated colonoscope have been reported to date.

Nosocomial HCV infection may have important medical and legal implications and, therefore, possible transmission routes should be investigated. In this study, a case of nosocomial transmission of HCV from a common source to two patients who underwent colonoscopy in an endoscopy unit is reported.

Results: A retrospective epidemiological search after detection of index cases revealed several potentially infective procedures: sample blood collection, use of a peripheral catheter, anesthesia and colonoscopy procedures.

The epidemiological investigation showed breaches in colonoscope reprocessing and deficiencies in the recording of valuable tracing data. Direct sequences from the NS5B region were obtained to determine the extent of the outbreak and cloned sequences from the E1-E2 region were used to establish the relationships among intrapatient viral populations.

Phylogenetic analyses of individual sequences from viral populations infecting the three patients involved in the outbreak confirmed the patient pointed out by the epidemiological search as the source of the outbreak. Furthermore, the sequential order in which the patients underwent colonoscopy correlates with viral genetic variability estimates.

Conclusions: Patient-to-patient transmission of HCV could be demonstrated although the precise route of transmission remained unclear.

Viral genetic variability is proposed as a useful tool for tracing HCV transmission, especially in recent transmissions

Author: Fernando Gonzalez-CandelasSilvia GuiralRosa CarboAna ValeroHermelinda VanaclochaFrancisco GonzalezMaria Bracho

Credits/Source: Virology Journal 2010, 7:217

Published on: 2010-09-08

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Hepatitis C sufferers tell how 'manky' blood devastated their lives

Published Date: 09 September 2010
By Lyndsay Moss
Health Correspondent

SCOTTISH patients infected with hepatitis C or HIV through blood products have revealed the devastating impact on their lives as the first stage of a major inquiry ended.

The victims, who received the contaminated blood or blood products in the 1970s and 1980, told of long delays in getting their diagnosis, the stigma associated with their infection and the terrible symptoms.

Their testimonies came as the Penrose Inquiry into the blood scandal published its preliminary report, setting out the evidence it had gathered so far.

The 600-page report, produced after the inquiry team analysed over 80,000 documents and took more than 100 witness statements, also sets out the next stages of the investigation.

This includes looking at the use of commercial blood products in Scotland and the information given to patients after their diagnosis.

Lord Penrose and his team will also look at the introduction of heat treatment to inactivate hepatitis C in blood products in Scotland in 1987 - two years after it was implemented in England and Wales. But campaigners yesterday called for the inquiry to go even further, to include other possible illnesses spread in blood.

Hundreds of people in Scotland - many with haemophilia as well as other patients - were infected after receiving contaminated blood.

As part of the Penrose Inquiry, patients were asked to come forward to reveal their own experiences. Many patients with haemophilia - which means their blood does not clot - spoke of the positive effects treatment with new blood factor products had had on their lives, with one describing it as a "miracle cure".

But the majority of witnesses said they were not warned about the risks linked to the treatment at a time when less was known about hepatitis C and HIV and testing of products not possible. Elsewhere in the report, witnesses voiced concern that they were not being informed when they were being tested for hepatitis C and HIV.

One witness said he was invited for a hepatitis C test in 1996, but found his own medical records suggested he had been diagnosed in 1992. He claimed he had not been told then.

Patients reported "horrendous" side-effects from treatment for hepatitis C, as well as the stigma associated with their diagnosis.

One patient had to move villages for a "fresh start" after parents stopped inviting their children to play. Others reported problems getting insurance and financial problems caused by not being able to work.

Bruce Norval, a trustee of the Haemophilia Society and a victim of contaminated blood, said the inquiry should be widened to look at what other contaminants victims could have been exposed to through clotting products.

"There was all kinds of crap in that stuff.

This stuff was manky, it was filthy, it was dirty and they knew it, but they still stuck it in the arms of children," he said.

Solicitor Advocate Patrick McGuire, of Thompsons Solicitors, the recognised legal representative of families and sufferers, said the report was "a milestone" for families after their struggle for answers.

CASE STUDY

Philip Dolan is not sure when he was infected with hepatitis C during his treatment for haemophilia.

While he may have been diagnosed as early as 1978, he was not informed until 1991 when he asked a consultant.

The Haemophilia Society trustee from Glasgow said: "That is the same for a lot of people - they did not know until years later."

Mr Dolan said he had suffered fatigue due to his condition, while getting insurance was also a problem.
 
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Two Hepatitis C Drug Candidates on Hold Because of Adverse Events

Robert Lowes

September 8, 2010 — The US Food and Drug Administration (FDA) has ordered drug maker Idenix to suspend development of 2 candidate drugs to treat hepatitis C virus after 3 individuals treated with a combination of these drugs in a clinical trial experienced liver function abnormalities, the company announced yesterday.

The 2 investigational drugs are a nucleoside polymerase inhibitor called IDX184 and a protease inhibitor called IDX320.

The FDA verbally notified Idenix on September 3 that the agency had placed IDX184 and IDX320 programs on clinical hold, pending a review of all clinical and preclinical data for the programs, according to the company. An Idenix press release quoted Chief Executive Officer and Chairman Jean-Pierre Sommadossi, PhD, as saying that the company had not yet received a formal letter from the FDA.

A clinical hold means that a study sponsor must delay a proposed investigation or suspend an ongoing one. When an ongoing study is on clinical hold, no new participants may be recruited or given an investigational medication, and patients already enrolled should stop receiving the treatment unless the FDA specifically authorizes it.

Idenix has completed its planned studies of IDX184 and IDX320, and no healthy trial participants or patients are receiving either experimental drug, the company stated.

In a 2-week phase 1 randomized, double-blind, placebo-controlled trial, 16 of 20 healthy individuals were randomly assigned to receive a combination of IDX184 and IDX320. Half of them received IDX184 plus placebo for the 2 full weeks and IDX320 just for the last week, and the other half received IDX320 for 2 weeks and IDX184 for the last week.

Although the drug duo was generally safe and tolerated, elevated liver function tests (LFTs) in 3 participants were deemed serious adverse events, according to Idenix, which reported these findings to the FDA. During follow-up, LFTs in these 3 participants returned to nearly normal.

In a conference call with stock analysts yesterday, Idenix Chief Medical Officer Douglas Mayers, MD, said that the 3 participants with elevated LFTs were later evaluated by liver specialists and screened for hepatitis, drugs and alcohol, and any potentially confounding medications. The elevated LFT in 1 patient, he said, appeared to be related to gallstones. No explanation has yet emerged for the adverse events experienced by the other 2 participants.

Idenix will investigate the adverse events and provide the FDA with the information it needs, said Dr. Sommadossi. "We remain committed to the future potential of these drug candidates."

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Medivir Presenting at the National Swedish Hepatitis Meeting - Clinical Update on TMC435 HCV-Protease Inhibitor

Sept. 9, 2010, 3:41 a.m. EDT

STOCKHOLM, Sep 09, 2010 (BUSINESS WIRE) -- Medivir AB (STO:MVIRB), the biopharmaceutical company focused on infectious diseases caused by viruses, will today present a clinical update on its key drug, TMC435, a potential blockbuster therapy against Hepatitis C which is partnered with Tibotec, at the National Swedish Hepatitis Meeting.

Medivir's CSO, Prof Bertil Samuelsson, will give a presentation entitled 'Clinical update of TMC435 HCV-protease inhibitor' at 12:30 CEST on 9 September 2010 at the Nordic Sea Hotel in Stockholm. A copy of the presentation will be available on Medivir's website (http://www.medivir.se/) after the meeting.

About Medivir

Medivir is an established biopharmaceutical company focused on the development of high-value treatments mainly in infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development. Medivir has a strong R&D portfolio and has recently launched its first product, an innovative treatment for cold sores.

Xerese(TM)/Xerclear(TM) is a treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GSK to be sold OTC in Europe and Russia and by Meda in North America. Medivir have retained the Rx rights for Xerclear(TM) in Sweden and Finland.

Medivir's key pipeline asset, TMC435, a protease inhibitor, is in Phase IIb clinical development for Hepatitis C and is partnered with Tibotec.

For more information on Medivir, please see the company website: http://www.medivir.se/

This information was brought to you by Cision http://www.cisionwire.com/

SOURCE: Medivir

Medivir
Rein Piir, CFO & VP Investor Relations
Office: +46 8 546 831 23
Mobile: +46 708 537 292

or

M:Communications
Mary-Jane Elliott / Emma Thompson
Medivir@mcomgroup.com
+44(0)20 7920 2345

Copyright Business Wire 2010

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