Monday Hepatitis News Ticker

Hepatitis C-Interferon-Free Trial of PSI-7977 and PSI-938 for All HCV Genotypes Initiated
PRINCETON, N.J., Sept. 13, 2011 /PRNewswire via COMTEX/ -- Pharmasset, Inc. announced today that screening has begun in a Phase 2b, international study of PSI-7977 and PSI-938, two nucleotide analog polymerase inhibitors for the treatment of chronic hepatitis C (HCV). The QUANTUM trial will evaluate interferon-free regimens of PSI-7977 400mg QD and PSI-938 300mg QD with and without ribavirin over 12 or 24 weeks in patients with HCV who have not been treated previously. The trial will also evaluate the use of PSI-938 monotherapy."We are encouraged by the early efficacy and safety data being generated with our nucleotide analogs, PSI-7977 and PSI-938," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "The QUANTUM trial is the first interferon-free, all-nucleotide study with an SVR endpoint. The ability to include all HCV genotypes was supported by data from the NUCLEAR study and the interferon free arms of the ELECTRON trial. Data from ELECTRON are expected later this year.".....

Hep C weaknesses could lead to vaccine
Australian researchers have discovered two "Achilles heels" in the hepatitis C virus that could help protect people against infection.

A team from the University of New South Wales says the discovery of these weaknesses could lead to the creation of an effective vaccine.
More than 200,000 Australians are known to have hepatitis C, while over 120 million people are affected worldwide.

Hepatitis C is transmitted through blood-to-blood contact and causes chronic infection and liver disease that in many cases can lead to death.

Study leader Professor Andrew Lloyd said the discoveries were significant because of their potential to overcome the barriers that have slowed development of an effective hepatitis C vaccine.

"Hepatitis C is very difficult to target because there are many different strains of the virus," he said.
"Hepatitis C replicates faster than HIV and it's very variable, meaning that if it mutates too much the immune system has no defence against it."
The study found that there are two points or "bottlenecks" where the virus is weakened.
"These Achilles heels are like having whole forests suddenly narrow down to where you can make out a few remaining trees individually.

"These moments mean that the virus is vulnerable," Professor Lloyd said.
Dr Fabio Luciani of UNSW's Inflammation and Infection Research Centre, and the team's biostatistician, holds high hopes for the research.
"If we can help the immune system to attack the virus at these weak points early on, then we could eliminate the infection in the body completely," he said.
The research is reported in the scientific journal, PLoS Pathogens.

Future of hepatitis C therapy: development of direct-acting antivirals.
Curr Opin HIV AIDS. 2011 Sep 3. [Epub ahead of print]
Dore GJ, Matthews GV, Rockstroh J.
Source
aViral Hepatitis Clinical Research Program, The Kirby Institute, The University of New South Wales bHIV, Immunology, Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, New South Wales, Australia cDepartment of Medicine I, University of Bonn, Bonn, Germany.

Abstract
PURPOSE OF REVIEW:
The landscape of hepatitis C virus (HCV) therapy will change considerably over the next decade with the probable licensure of many HCV direct-acting antiviral (DAA) therapy agents. This review will outline the data on the initial two DAA agents licensed (protease inhibitors telaprevir and boceprevir) and cover potential future therapeutic strategies and challenges for DAA-based therapy, including in the context of HIV/HCV coinfection.

RECENT FINDINGS:
Phase III trials evaluating the addition of telaprevir or boceprevir to pegylated interferon and ribavirin in both HCV treatment naïve and experienced populations with chronic HCV genotype 1 have demonstrated considerable improvements in sustained virological response, with many patients able to shorten total treatment duration from 48 to 24-36 weeks. Although these initial DAA-based treatment results are encouraging, additional toxicity, problematic dosing schedules, and potential drug-drug interactions pose challenges for clinical management, particularly in HIV/HCV coinfection. Phase II trials with telaprevir and boceprevir in HIV/HCV populations are underway. Subsequent DAA agents appear to have improved tolerability and dosing schedules and open the door for interferon (IFN)-free DAA-based combination therapy.

SUMMARY:
Development of DAA therapy will lead to a major shift in HCV clinical management, particularly with the potential for IFN-free combination therapy.

Long-term follow-up among Danish transfusion recipients identified in the national hepatitis C lookback.
Just SA, Grau K, Georgsen J, Weis N, Cowan S, Groenbaek K, Krarup H, Christensen PB; The Danish HCV Lookback Group.

Transfusion. 2011 Aug 29. doi: 10.1111/j.1537-2995.2011.03309.x.

Source
From the Department of Clinical Immunology and the and Department of Infectious Diseases, Odense University Hospital, Odense; the Department of Internal Medicine, OUH Svendborg Hospital, Svendborg; the Department of Epidemiology Research, Statens Serum Institut, Copenhagen; the Department of Infectious Diseases and the Department of Gastroenterology, Copenhagen University Hospital, Hvidovre; the Faculty of Health Science, University of Copenhagen, Copenhagen; the Department of Epidemiology, Statens Serum Institut, Copenhagen; and the Department of Medical Gastroenterology and Department of Clinical Biochemistry, Aalborg Hospital, Aalborg, Denmark.

Abstract

BACKGROUND:
In 1996, a national lookback study was performed in Denmark identifying 1018 patients exposed to hepatitis C virus (HCV) by transfusion before 1991. The objective of this study was to describe morbidity and mortality during extended follow-up among patients in the Danish HCV lookback cohort alive in 1996.

STUDY DESIGN AND METHODS:
In a retrospective cohort study of 230 patients exposed to HCV by blood transfusion and alive in 1996 we extracted data from national registers and compared these with a matched group of unexposed transfusion recipients.

RESULTS:
Among 230 HCV-exposed recipients alive in 1996, 124 (53.9%) had chronic hepatitis C, 43 (18.7%) were not infected, and 63 (27.4%) had incomplete HCV data. In 2009, 121 (52.6%) were still alive a median of 21.8 years after transfusion. The mortality rate among the HCV-exposed recipients followed from 1996 was 4.9 per 100 person-years (PY). The incidence of liver cirrhosis and decompensated cirrhosis was 1.0 per 100 PY and 0.4 per 100 PY, respectively; 16.5% had cirrhosis at death. Among HCV-exposed recipients, no difference in all-cause or liver-related mortality was observed between HCV-infected and HCV-uninfected recipients. Further, there was no difference in mortality between HCV-exposed and -unexposed transfusion recipients (mortality rate ratio [MRR], 1.06; 95% confidence interval [CI], 0.96-1.17; p = 0.47), but liver-related mortality was significantly higher among HCV-exposed patients (MRR, 10.0; 95% CI, 7.20-17.7; p < 0.001).

CONCLUSION:
Two decades after exposure to blood products from HCV-infected donors, only 121(11.8%) of 1018 recipients remained alive. For HCV-exposed recipients no excess all-cause mortality was observed, but liver-related mortality was significantly increased.

From Medscape

Early IL-10 Responses and HCV in Injecting Drug Users
Do injection drug users have a different cellular response to recent hepatitis C infection than non users?
Journal of Viral Hepatitis, September 2011

AIDS

From Bloomberg

Ending AIDS Pricetag Starts at $6 Billion as Donors Pull Back Amid Slump
Michel Kazatchkine and Eric Goosby may be able to halt the spread of HIV. They just need the money.
The two men control the funds that buy drugs for most of the world’s AIDS patients. Studies in July provided the strongest evidence yet that medicines used since 1994 to treat HIV can almost eliminate the chance an infected person will pass the virus to a sex partner. Given to healthy people, the treatments can also protect against infection, offering the potential to end a pandemic that has killed 30 million people in 30 years.........

From The New England Journal Of Medicine

HIV Vaccine Development — Improving on Natural Immunity
M.I. Johnston and A.S. Fauci
Free Full Text
Since our natural immune response to HIV infection is ineffective, a key goal for an HIV vaccine is to induce a response different from that induced by natural infection — an “unnatural immunity,” involving production of broadly neutralizing antibodies.

HBV

Cancer, rheumatism drugs tied to hep B deaths
A number of people who had recovered from past hepatitis B infections died due to a sudden and acute reactivation of the virus in their bodies after taking newly introduced drugs to treat such conditions as rheumatism and blood cancer, according to health ministry research.The people who died from fulminant hepatitis had weakened immune systems as a result of using new drugs to treat other conditions, according to a research team at the ministry and other sources......

Diabetes

Developing risk prediction models for type 2 diabetes: a systematic review of methodology and reporting
Gary S Collins , Susan Mallett , Omar Omar and Ly-Mee Yu
BMC Medicine 2011, 9:103doi:10.1186/1741-7015-9-103
Published:
8 September 2011 Abstract (provisional)

Background
The World Health Organisation estimates that by 2030 there will be approximately 350 million people with type 2 diabetes. Associated with renal complications, heart disease, stroke and peripheral vascular disease, early identification of patients with undiagnosed type 2 diabetes or those at an increased risk of developing type 2 diabetes is an important challenge. We sought to systematically review and critically assess the conduct and reporting of methods used to develop risk prediction models for predicting the risk of having undiagnosed (prevalent) or future risk of developing (incident) type 2 diabetes in adults.

Methods
We conducted a systematic search of PubMed and EMBASE databases to identify studies published before May 2011 that describe the development of models combining two or more variables to predict the risk of prevalent or incident type 2 diabetes. We extracted key information that describes aspects of developing a prediction model including study design, sample size and number of events, outcome definition, risk predictor selection and coding, missing data, model-building strategies and aspects of performance.

Results
Thirty-nine studies comprising 43 risk prediction models were included. Seventeen studies (44%) reported the development of models to predict incident type 2 diabetes, whilst 15 studies (38%) described the derivation of models to predict prevalent type 2 diabetes. In nine studies (23%), the number of events per variable was less than ten, whilst in fourteen studies there was insufficient information reported for this measure to be calculated. The number of candidate risk predictors ranged from four to sixty-four, and in seven studies it was unclear how many risk predictors were considered. A method, not recommended to select risk predictors for inclusion in the multivariate model, using statistical significance from univariate screening was carried out in eight studies (21%), whilst the selection procedure was unclear in ten studies (26%). Twenty-one risk prediction models (49%) were developed by categorising all continuous risk predictors. The treatment and handling of missing data were not reported in 16 studies (41%).

Conclusions
We found widespread use of poor methods that could jeopardise model development, including univariate pre-screening of variables, categorisation of continuous risk predictors and poor handling of missing data. The use of poor methods affects the reliability of the prediction model and ultimately compromises the accuracy of the probability estimates of having undiagnosed type 2 diabetes or the predicted risk of developing type 2 diabetes. In addition, many studies were characterised by a generally poor level of reporting, with many key details to objectively judge the usefulness of the models often omitted.
The complete article is available as a provisional PDF.

Pharmaceuticals

From The Yorkshire Post

Stolen medicines found in pharmacist’s warehouse in Wakefield
A MAN who stored stolen medication worth more than £1 million in a warehouse in Wakefield was jailed for four years today.
Hafiz Noorullah, 45, was asked to keep more than two million Contam, Lopresor and Femara pills.

The medication, used to treat Parkinson’s, high blood pressure and breast cancer, was stolen in 2005 while en route from the Swiss headquarters of pharmaceutical giant Novartis to a distribution depot in Thatcham, Berkshire.

Today at Southwark Crown Court, Noorullah was told he would spend half the four year sentence for one count of handling stolen goods in custody.

The court heard that the medication was being transported in a lorry from Switzerland to Berkshire in March 2005, where the trailer was stolen overnight.

More than two years later, investigators found the pills being sold on the internet and were invited to Noorullah’s warehouse in Wakefield to view them.

Another man, Mahmoud Aziz, allegedly showed them the merchandise. He later fled to Canada and UK authorities are currently trying to extradite him to face trial here.

Noorullah, who had previously trained as a pharmacist and was a licensed wholesale pharmaceutical dealer, denied knowing that the pills were stolen.

But prosecutors said he would have realised they were not legitimate.

Today Andrew Bird, prosecuting, said: “Mr Noorullah was not only the responsible person under the licence but he had also qualified as a pharmacist and he would know these sort of products, if legitimate, would be accompanied by paperwork.”

The value of the drugs to Novartis was £1.1 million, and Mr Aziz was seeking a price of 3.6 million dollars, the court heard.

They were marketed as being within their sell-by date but in fact were not.
Noorullah was last month found guilty of one count of handling stolen goods.
He was previously acquitted of breaching his dealer’s licence.

Passing sentence, Judge David Higgins said: “One way or another you met a man called Mahmoud Aziz who made it plain to you from the outset that he was in possession of a large quantity of drugs which had been stolen from Novartis, the large Swiss pharmaceutical company.”

While the value of the medicine in the EU would be diminished because it was past its sell-by-date, it could still attract a seven-figure sum outside the region, he said.

“The drugs were in fact, and you knew this, intended for sale outside the EU and by necessary implication to the sort of people who for one reason or another would not be bothered by such matters and therefore would still be willing to pay a seven-figure sum for the drugs,” the judge said.

He accused Noorullah of showing “indifference” to any health hazard that might be faced by those who took the medication, and said he had responded “with enthusiasm” when approached by Aziz.

Aziz marketed the drugs as being stored in a licensed warehouse, and Noorullah “facilitated in a fundamental way the attempted sale of the stolen goods” by allowing his premises to be used, Judge Higgins said.

He called the crime “a highly organised, professional commercial operation”.

Referring to Noorullah’s previous convictions, which include violence and fraud, he said: “You have regularly been involved in the most deplorable and deeply anti-social conduct, the offence currently before the court being particularly serious.”

Judge Higgins went on: “You are entirely devoid of remorse. You continue to be a man of great moral turpitude.”

The father of two, whose parents are from Pakistan but was born in the UK, remained impassive as he was sentenced.

He was also ordered to pay £15,000 costs.

Clinical Trials

From Nature

Proposed centralization of trial oversight stirs mixed reaction
Posted: 2011-09-08 10:51
By Meredith Wadman
Over the last two decades, scientists have increasingly followed the mantra that “bigger is better” when planning drug trials. Large, multisite trials have become staples of clinical investigation, enabling wider enrollment and more statistically meaningful research results.
But, as the number of participating sites per study has grown, so has the administrative red tape. And, nowadays, dozens of local ethics committees—known as institutional review boards (IRBs)—are commonly involved in approving multisite studies, routinely suggesting changes to protocols and consent forms that then need to be reapproved by all the other parties involved. As a result, trials can take months to launch, delaying progress, and meaning that study participants don't benefit from the oversight of one central committee with ultimate responsibility for the research.....

Off The Cuff

From Medpage

22 Things Amiss in Medicine Today
By George Lundberg, MD, Editor-at-Large, MedPage Today





Warning: Reality TV Shows Can Be Hazardous to Health
By: Michele R. Berman, MD

Semi-starvation, Infectious Disease & Exposure, Oh My...Weight loss is a good thing and indeed a goal for contestants on Biggest Loser. On other shows, such as Survivor, weight loss comes as a result of semi-starvation diets, eating bizarre foods like insect larvae, grueling physical exertion and exposure to the elements. Most seasons of Survivor are in hot climates probably so contestants have to prance around semi-nude (good for ratings) but this can lead to sunburn, heat exhaustion and dehydration. On I'm a Celebrity...Get me out of Here! actor Stephen Baldwin got 125 bug bites in the 8 days he was there. An allergic reaction caused him to lose 22 pounds. On the same show, Heidi Montag left complaining of abdominal pain due to gastritis. Contestants who have preexisting conditions can be made worse by their participation in the show. American Idol contestant Casey Abrahms, had to be hospitalized and given a blood transfusion when his ulcerative colitis flared up............

Parasite Is New Concern for U.S. Blood Supply
Marie McCullough(The Philadelphia Inquirer, September 7, 2011)
"Blood-bank experts have identified 68 nasty microbes -- the causes of diseases ranging from dengue fever to chronic wasting disease -- that potentially or definitely could be transmitted through a blood transfusion. One of these organisms, a parasite called Babesia, has become such a concern that the U.S. Centers for Disease Control and Prevention, the Food and Drug Administration, and the American Red Cross want to add 'babesiosis' to HIV and the six other transmissible diseases for which blood donors are now tested…Most Babesia infections cause mild flulike symptoms -- or no symptoms at all -- and resolve without treatment. However, in the very young, the old, and the sick, babesiosis can lead to severe kidney, liver, heart, or respiratory complications, and even death."

FDA

More ground turkey recalled because of salmonella

CHICAGO (AP) -- Cargill Inc. announced a second recall of ground turkey products Sunday after a test showed salmonella in a sample from the same Arkansas plant tied to a recall issued last month.
The second recall is much smaller than the one the company issued Aug. 3 for 36 million pounds of ground turkey. That recall followed a salmonella outbreak that federal health officials said had sickened 107 people in 31 states, killing one person.
No illnesses have been tied to the second recall, which was initiated after a sample from the company's plant in Springdale, Ark., tested positive for salmonella, the U.S. Department of Agriculture said.
Cargill halted production of ground turkey products at the plant Aug. 2 in anticipation of the recall announced the next day, spokesman Mike Martin said. Equipment was taken apart and steam-cleaned. Limited production resumed Aug. 10 after the USDA approved additional anti-bacterial safety measures, Martin said.
The sample that tested positive for salmonella was taken Aug. 24, the USDA said. It was the same strain of salmonella tied to the earlier illnesses, the agency said.
Martin said Cargill added two additional anti-bacterial washes to its processing process in Springdale after the first recall and instituted what he called "the most advanced sampling and monitoring system in the poultry industry."
The problem, he said is that salmonella is "ubiquitous" and can come from soil, water, poultry feed and any number of sources. The challenge for Cargill and other food processors is to try to identify and eliminate the sources, reduce the amount during processing and then test for it.
"Food safety is a top priority and taken extremely seriously at Cargill because we know that millions of people throughout the U.S. are eating food that we produce every day and we want to do everything we can to make sure that people are getting the safest food possible," Martin said.
Ground turkey production at the Springdale plant has been suspended again while the Minnesota-based company looks at what other safety procedures might be needed, he said. Production of other products, such as whole turkeys, continues, he said.
USDA officials did not immediately respond Sunday to messages requesting comment.
The second recall covers about 185,000 pounds of ground turkey products, including trays of ground meat, patties and chubs, the USDA said. The products were distributed nationwide under the Kroger, Fresh HEB and Cargill's Honeysuckle White brands.
All ground turkey made at the Springdale plant has "P-963" or "963" on the package, in a USDA seal or perhaps on the cellophane, Martin said. Consumers who bought products bearing that identification number can call 1-888-812-1646 for instructions on what to do, he said.
The recall covers products made Aug. 23 and 24. Cargill also is recalling ground turkey made on Aug. 30 and 31 pending a positive match with a sample, the USDA said.
The Centers for Disease Control and Prevention estimates 50 million Americans get sick each year from food poisoning, including about 3,000 who die. Salmonella causes most of these illnesses.
Government officials say even contaminated ground turkey is safe to eat if cooked to 165 degrees. But it's also important that raw meat be handled properly before it's cooked and that people wash their hands with soap for at least 20 seconds before and after handling it. Turkey and other meats should also be properly refrigerated or frozen and leftovers heated.
The most common symptoms of salmonella are diarrhea, abdominal cramps and fever within eight hours to 72 hours of eating a contaminated product. It can be life-threatening to some with weakened immune systems.
---
Online:
USDA recall announcement: http://www.fsis.usda.gov/News-&-Events/Recall-071-2011-Release/index.asp
Cargill recall announcemen t: http://www.cargill.com/news/releases/2011/NA3049298.jsp