Monday, July 4, 2011

Hepatitis C News;Liver Cancer,SVR/Genotypes,Fatty Liver,Worldwide HCV-US,Asia,Canada,Europe,Israel, Egypt and Latin America

New On The Blog;

The global health burden of hepatitis C virus infection

A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt

A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel

Trends and projections of hepatitis C virus epidemiology in Latin America

Applying a system approach to forecast the total hepatitis C virus-infected population size: model validation using US data 
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In The News
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Growth of hepatocellular carcinoma in the regenerating liver
Liver regeneration after partial hepatectomy facilitates the growth and malignant transformation of microscopic hepatocellular carcinoma, finds the most recent issue of Liver Transplantation.

Liver resection and liver transplantation are the treatment modalities with the greatest potential for curing hepatocellular carcinoma.

Tumor recurrence after resection for hepatocellular carcinoma is, however, a major problem, and an increased rate of recurrence after living donor transplantation versus cadaveric whole liver transplantation has been suggested.

Factors involved in liver regeneration may stimulate the growth of occult tumors.

Dr Pål-Dag Line and colleagues from Norway tested the hypothesis that a microscopic hepatocellular carcinoma tumor in the setting of partial hepatectomy would show enhanced growth and signs of increased invasiveness corresponding to the size of the liver resection.
Tumor volume increased with the size of the partial hepatectomy
Liver Transplantation

Hepatectomy was performed to various degrees in groups of Buffalo rats with the concomitant implantation of a fixed number of hepatoma cells in the remnant liver, and a control group underwent only resection.

After 21 days, the sizes and numbers of the tumors and the expression of alpha-fetoprotein, cyclin D1, calpain small subunit 1, CD34, vascular endothelial growth factor, and vascular endothelial growth factor receptor 2 were evaluated and compared between the groups.

The research team found that tumor volume and number increased significantly with the size of the partial hepatectomy.

The largest resections were also associated with increased hepatoma cell infiltration in the lungs and significant up-regulation of cyclin D1, alpha-fetoprotein, calpain small subunit 1, CD34, vascular endothelial growth factor receptor, and vascular endothelial growth factor receptor 2.

Dr Line's team commented, "The results suggest that liver regeneration after partial hepatectomy facilitates the growth and malignant transformation of microscopic hepatocellular carcinoma, and this could be significant for liver resection and partial liver transplantation strategies for hepatocellular carcinoma."
 Liver Transplant 2011: 17(7): 866–74
04 July 2011


Predictor of sustained virological response across genotypes in HCV
Rapid virological response is the most important predictor of sustained virological response across genotypes in patients with chronic hepatitis C virus infection, reports July's Journal of Hepatology.

The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors.

Attainment of a rapid virological response, defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response.

Dr Michael Fried from North Carolina, USA determined the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting sustained virological response.

A retrospective analysis of 1383 patients, encompassing genotypes 1–4, treated with peginterferon alfa-2a and ribavirin, was performed.

Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with rapid virological response were identified.
Rapid virological response was achieved by 71% with genotype 2
Journal of Hepatology

The team compared the relative significance of rapid virological response to other baseline factors for predicting sustained virological response.

Rapid virological response was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively.

The research team found that among patients who achieved rapid virological response, the rate of sustained virological response was high across all genotypes and ranged from 88% to 100%.

The team identified baseline factors predictive of rapid virological response, that included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age.

Notably, the presence of rapid virological response generated the highest odds ratio for predicting sustained virological response in multiple logistic regression analysis of these factors.

Dr Fried's team concludes, "Attainment of rapid virological response varies by genotype and is associated with several baseline factors."

"Patients who achieve rapid virological response have the highest rates of sustained virological response, regardless of genotype."

"These findings have important implications for predicting and managing response-guided combination antiviral therapies."
J Hepatol 2011: 55(1): 69-75
04 July 2011


HCV testing practices in a high-risk urban ambulatory care setting
The latest issue of the Journal of Viral Hepatitis investigates hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting.

Approximately 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S.

Most are not aware of their infection.

Dr Southern and colleagues from New York, USA examined HCV testing practices to determine which patient characteristics are associated with HCV testing and positivity, and estimated the prevalence of HCV infection in a high-risk urban population.

The study subjects were all patients included in the baseline phase of the Hepatitis C Assessment and Testing Project (HepCAT), a serial cross-sectional study of HCV screening strategies.

The researchers examined all patients with a clinic visit to Montefiore Medical Center in 2008.
The overall prevalence of HCV infection was estimated to be 8%
Journal of Viral Hepatitis

Demographic information, laboratory data and ICD-9 diagnostic codes were extracted from the electronic medical record.

The team defined risk factors for HCV based on birth date, ICD-9 codes and laboratory data.

The prevalence of HCV infection was estimated assuming that untested subjects would test positive at the same rate as tested subjects, based on risk-factors.

Of 9579 subjects examined, 40% had been tested for HCV, and 12% were positive.

The team noted that the overall prevalence of HCV infection was estimated to be 8%.

The research team found that risk factors associated with being tested and anti-HCV positivity included being born in the high-prevalence birth-cohort, substance abuse, HIV infection, alcohol abuse, diagnosis of cirrhosis, end-stage renal disease, and alanine transaminase elevation.

Dr Southern's team concluded, "In a high-risk urban population, a significant proportion of patients were tested for HCV and the prevalence of HCV infection was high."

"Physicians appear to use a risk-based screening strategy to identify HCV infection."

J Vir Hep 2011: 18(7): 474–81
04 July 2011

Reprocessing single-use devices: An international perspective
Do you dispose of the plastic baggie or save it for tomorrow’s ham Sandwich? Do you throw away the plastic fork or wash it and stick it in the drawer with your stainless steel cutlery? With respect to cost and safety, these are minor decisions. Matters become more complicated when the disposable item is a $5000 ultrasound catheter.
Reusing medical devices labelled as single-use by manufacturers is a common practice in hospitals all over the world. Advocates of reprocessing these devices say it is safe, if done properly, and is good for both the environment and hospital budgets. But concerns about patient safety and liability for adverse events make it a practice non grata in some hospitals.
In Canada, just over a quarter of hospitals report reusing single-use medical devices. The practice is of similar popularity in the United States. When it comes to regulating the practice, however, the countries differ substantially.
“Across Canada, there is no common regulation with regard to reprocessing single-use devices,” says Julie Polisena, clinical research manager for the Canadian Agency for Drugs and Technologies in Health. “Provinces can provide direction, and regulations can be imposed or it may be up to hospitals or regional health authorities.”
Polisena is the lead author of a survey that found that 28% of Canadian hospitals reprocess single-use medical devices (www.cadth.ca/en/products/health-technology-assessment/publication/800).

Of those that don’t, 81% have done so in the past. The most commonly reprocessed devices are breast pump kits, ventilator circuits and burrs. Most hospitals that reprocess these devices clean and sterilize them in-house, though only 60% have written policies on the practice. Also lacking was information on patient safety, such as the number of adverse events linked to reprocessed devices.
“They were reluctant to relay that information,” says Polisena. “Or they didn't capture that information.”
In the United States, the Food and Drug Administration (FDA) regulates which single-use medical devices can be reprocessed. The devices are divided into three categories: high-risk (balloon angioplasty catheters, implanted infusion pumps), which can only be reprocessed if there is sufficient evidence of safety and effectiveness and the reprocessing facility has been inspected; medium-risk (ultrasound catheters, laparoscopic equipment), which require the same evidence as high-risk devices but not the inspection; and low-risk (elastic bandages, tourniquet cuffs), which can be reprocessed without submission of efficacy or safety data.
The FDA currently permits the reprocessing of about 70 single-use devices. In addition to these regulations, the 2002 Medical Device User Fee and Modernization Act states that all single-use devices prepared for reuse in the United States must be labelled as reprocessed and indicate the reprocessor (40–50% of devices are reprocessed by third-party companies).
According to a 2010 report in the International Journal of Hygiene and Environmental Science, reprocessing of single-use items is also common in Spain (80% of hospitals), Germany (40% of hospitals) and Japan (80%–90% of hospitals), as well as in third-world countries (IJHEH 2010; 213:302-7). In developing nations, reprocessed items include needles, syringes and urinary catheters, which are shared without being adequatelycleaned, leading to infections of HIV and hepatitis B and C. In developed nations, however, only expensive, high-tech devices are reprocessed and the practice is safe if regulated and conducted carefully.
“In developed countries it seems reasonable to validate reprocessing,” the report states. “Clear guidelines and defaults for the reprocessing of medical devices including appropriate control mechanisms are the preconditions to using the medical devices safely and with economic advantage.”
Still, some countries have moved away from the practice. In Australia, for example, half of hospitals used to reprocess single-use devices, but that dropped sharply after the introduction of a law in 2005 that required all reprocessors, including hospitals that reprocess in-house, to meet the same regulatory standards as medical device manufacturers.
Other nations, the report states, have no national regulations. Canada is among them. Health Canada has collaborated with the Canadian Health Care Association to produce guidelines for reprocessing single-use items (www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/md-im/reprocess_retraitement_let-eng.pdf).

The recommendations include the creation of a reuse committee, written reprocessing procedures for each device reused, validation of sterility and functionality of devices and assurance of quality through monitoring, sampling, inspection and periodic review of external factors (such as changes in device design or materials).
The Canadian Patient Safety Institute, a nonprofit advocate for patient safety, has not issued guidelines or policies in the area of reuse of single-use medical devices.
Any regulations that do exist in this area set at the provincial level. “Nevertheless,” the International Journal of Hygiene and Environmental Science report states, “in some Canadian jurisdictions the practice occurs with little or no regulation.”
— Roger Collier, CMAJ
DOI:10.1503/cmaj.109-3906

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Liver Cancer
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Genetic variant linked to development of liver cancer in hepatitis C virus carriers




IMAGE: Results of genome-wide association study (GWAS) on HCV-related HCC (977 subjects). Horizontal axis represents chromosome position, vertical axis represents P-values. An SNP with statistically significant association (P=1.07x10-7) was confirmed on...




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A genome-wide study by researchers at the RIKEN Center for Genomic Medicine, Hiroshima University Hospital and Sapporo-Kosei General Hospital has identified a genetic variant associated with the development of liver cancer in chronic hepatitis C virus carriers. The findings are based on a study of 3,312 Japanese individuals and appear in the journal Nature Genetics.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide. The hepatitis C virus (HVC) is the main risk factor for HCC in many western countries and in Japan, where of the more than 30,000 deaths each year from HCC, 70% involve HVC.
To identify risk factors connecting HVC and HCC, the research group conducted a genome-wide study on a group of 3,312 Japanese individuals carrying the hepatitis C virus. Analyzing a total of 467,538 genetic markers (called single nucleotide polymorphisms or SNPs) in a group of 212 HCV carriers with HCC and 765 HCV carriers without HCC, the group uncovered one SNP associated with HCC risk, located on a gene called DEPDC5. The association was confirmed in an independent replication study on a population of 2335 HVC carriers, 710 with HCC and 1625 without HCC.




IMAGE: Comparison of DEPDC5 expression level in cancerous liver tissue. Left: Results from study of liver samples from 43 hepatitis-C carriers with liver cancer showed that DEPDC5 was more highly expressed...




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The significance of the findings was further highlighted when the researchers adjusted their results for gender, age and platelet count, revealing that among Japanese individuals with chronic HVC infection, the DEPDC5 SNP roughly doubles the odds of developing HCC.
While deepening our understanding of the mechanisms triggering HCC, the discovery of the DEPDC5 SNP locus also provides a valuable target for new therapy techniques, promising progress in the ongoing battle to overcome one of the world's most deadly cancers.


Journal of Neuroscience

Solving the puzzle of cognitive problems caused by HIV infection
A longstanding medical mystery -- why so many people with HIV experience memory loss and other cognitive problems despite potent antiretroviral therapy -- may have been solved by researchers at Albert Einstein College of Medicine of Yeshiva University. Their findings are published in the June 29 issue of the Journal of Neuroscience.
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Fatty Liver
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Monday 4th July 2011

Hundreds of thousands of children face the risk of life-threatening liver disease related to excess weight and obesity, according to an expert.

Nearly 500,000 young people in England are under threat from a liver disease timebomb as they battle weight problems arising from overeating, says Professor Martin Lombard, National Clinical Director for Liver Disease at the Department of Health.

Being overweight can result in fat accumulation in the liver causing inflammation and impairing the functions of the organ.

Known as non-alcoholic fatty liver disease, this can lead in some cases to potentially fatal cirrhosis of the liver.

Although commonly associated with excessive alcohol consumption, liver cirrhosis can also result from excess weight gain and obesity.

Figures show that half a million children aged between four and 14 may be at risk of having too much fat in the liver and associated problems in later life.

Around 60,000 youngsters whose lives are at risk are aged 10, while a quarter of four to five-year-olds are currently overweight or obese.

Unless the problem of poor diet and the culture of overeating is addressed, by 2050 around 63% of children will be obese, experts warn.

Professor Lombard said: "We know that with childhood obesity on the rise we can expect more children to be at risk of fatty liver disease in the near future."

Novel Nanotechnology-Based Vaccination against Hepatitis C
Published on July 4, 2011 at 4:12 AM
By Cameron Chai

The European joint project, HCVAX, aims to develop an innovative nanotechnology-based vaccination against hepatitis C. The transnational consortium has researchers from France, Switzerland and Germany.
The Vaccinology and Applied Microbiology department of the German Helmholtz Centre for Infection Research (HZI) has joined the consortium.
Currently, no efficacious vaccine against the hepatitis C virus (HCV) exists. HCV infections may lead to development of cancer and liver cirrhosis. The virus affects around 3% of the European population and over 170 million in the world. HCV virus infections occur due to re-use of syringes and surgical operations, including transplantation surgeries. The current treatments are ineffective in most patients and have detrimental side effects. They are also expensive.
"RNA replicons" bring the genetic information of the HCV virus into the body using novel synthetic biocompatible nanogels. These nanogels are made up of a biopolymer matrix. They can be taken up by immune cells and harmless components of HCV can be produced. The immune cell will then generate memory cells leading to successful vaccination against HCV.
Adjuvants or drug amplifiers, improve the immune response. HZI aims to identify effective adjuvants for adding to the nanogel composition.
The Federal Department of Economic Affairs and Medipol in Switzerland, the Institut Pasteur and Hôpital Cochin in France, and the EDI and HZI from Germany have partnered in the joint HCV vaccine project. The "EuroNanoMed Joint Transnational Initiative" and the German Ministry for Research and Education are funding the project.
Source: http://www.helmholtz-hzi.de/


Researchers Test Benefit Of Fish Oil In Bowel Cancer Spread
04 July 2011
Researchers from the University of Leeds will carry out a series of experiments to see whether fish oil can prevent or treat the spread of bowel cancer to the liver. The cancer scientists will test the effectiveness of pure...
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Transplant

25% Increase In One Year For People Waiting For A New Liver, UK

New figures from NHS Blood and Transplant (NHSBT) show that there has been a 24.8% increase in people registered on the national liver transplant list. The British Liver Trust has expressed its concern over the new statistics calling for more people to sign up to the organ donor list.

Figures show that on the 20th June this year there were 468 people registered on the liver transplant waiting list, compared to only 375 people on the same day in 2010. There was also a 12.4% increase in the number of liver transplants carried out in 2010.

Sarah Matthews, spokesperson for the British Liver Trust, says: "Even though there was an increase in the number of transplants performed in the last year, we are still failing to meet demand. We also have to remember that this demand is likely to be higher than the official list as not everyone who needs a liver transplant is listed due to clinicians being mindful of the shortage of organs."

Currently two people a week die waiting for a liver transplant and this figure is set to increase further unless we see the upward mortality trend of liver disease fall. 300 people each week die from liver disease and when compared to the other five big causes of death, liver disease is the only one showing an upward trend.

"These increasing rates of liver disease are not just driving demand for transplants; they're driving demand for all liver services and pushing up NHS costs. We don't believe that there is a one-hit wonder approach to reducing rates of liver disease because it is such a demographically diverse killer. However we strongly back the evidence for proven effective measures such as a minimum price for alcohol, earlier identification of viral hepatitis anda universal vaccination for hepatitis B," added Matthews.

In supporting National Transplant Week (4th - 10th July 2011) the British Liver Trust is promoting NHSBT's campaign theme, 'What Are You Waiting For? With three people dying every day whilst waiting for organs, NHSBT is calling on people to discuss the issues around organ donation and sign up to the NHS Organ Donor Register.

Note

1. NHS Blood and Transplant figures show that the number of people on the liver transplant register has increased by 25%. 468 people were registered on 20th June 2011, compared to 375 people listed at the same time in June 2010.

2. Government mortality statistics for the UK indicate that deaths from liver disease continue to rise, increasing by 12% in the last three years, totalling 46,244 lives lost. In 2009, liver disease killed 15,993 people - an 11% increase since 2005. If these rates continue, deaths from liver disease are predicted to double in 20 years.

3. This graph overleaf, produced by the British Liver Trust, illustrates the true extent of liver disease in the UK. Liver disease, when compared to the other five big causes of death, is the only one showing a steady increase year-on-year:

Source:
British Liver Trust

FDA

Sprouts recalled; FDA sees link to salmonella outbreak

WASHINGTON (AP) - An Idaho sprout producer has recalled its alfalfa and spicy sprouts because they may be linked to 21 cases of salmonella poisoning.
Evergreen Produce of Moyie Springs, Idaho, initially refused to recall its sprouts after the Food and Drug Administration said the sprouts may be linked to the illnesses in Idaho, Montana, Washington state, North Dakota and New Jersey.
But the company relented under agency pressure.
The FDA warned people on Monday not to eat the sprouts.
Salmonella is an organism that can cause serious and sometimes fatal infections in people with weakened immune systems.
Raw sprouts often cause foodborne illness because they're grown in moist, warm conditions that bacteria enjoy.
An unrelated European E. coli outbreak believed to be caused by sprouts has killed 49 people and sickened 4,000.

Pharmaceuticals
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Harvard Docs Disciplined For Conflicts Of Interest
Three years after they were fingered in a US Senate probe into the interplay between academics who receive grant money from both pharma and the National Institutes of Health, three prominent psychiatrists from Harvard Medical School and Massachusetts General Hospital have been sanctioned for violating conflict of interest rules and failing to report the extent of their payments.
In a mea culpa addressed to their colleagues, Joseph Biederman, Thomas Spencer and Timothy Wilens wrote that “we want to offer our sincere apologies to HMS and MGH communities…We always believed we were complying in good faith with the institutional polices and our mistakes were honest ones. We now recognize that we should have devoted more time and attention to the detailed requirements of these policies and to their underlying objectives.”



Firms must navigate legal and linguistic hurdles for approval
By Carolyn Y. Johnson
Globe Staff / July 4, 2011
They are the public face of products that can take many years and hundreds of millions of dollars to develop. Over time, they often become household names: Think Prozac or Viagra. But drug names start out as alien words: random collections of syllables that can sometimes seem almost as mind-boggling as the complicated chemistry and biology that went into the development of the new medication.
 
Earlier this year, one such feat of linguistic alchemy took place at Cambridge-based Vertex Pharmaceuticals Inc., where an experimental drug to treat hepatitis C, which had been known for years as either VX-950 or telaprevir, was finally dubbed Incivek.

Looking behind the curtain at how drug names are born provides a window into a side of the drug industry that most people interact with but few understand, a process that is both art and science, and requires a delicate balance of regulatory, legal, and linguistic concerns.
“A name in the health care space, it can actually transform our relationship with medicine, with our disease, with our health,’’ said R. John Fidelino, executive director for creative at the health care division of Interbrand, a branding consultancy based in New York and London that created the name Prozac.
Fidelino cites the example of Prozac, an easy-to-pronounce, uplifting name that turned depression into a disease that people could talk about. Instead of getting a prescription for an unpronounceable drug that sounded like a chemical compound, people had a new word that had none of the negative associations that came with the disease, he said.
Pamela Stephenson, vice president of marketing for Incivek, said that much of the work stems from the need to come up with a distinct name that somehow personifies the character of the drug. Vertex decided its drug was a kind of hero: a strong drug that knocks out hepatitis C virus.
“We like the fact there’s a ‘c’ in the name - we wanted to relate it to hepatitis C,’’ Stephenson said. “The ‘k,’ the hard-sounding ending is a strong-sounding name. . . . The brand identity is what image does this conjure up in your mind when you think about [the drug]. . . . The ‘hero’ nature was this was such a breakthrough in its ability to clear the virus.’’..Continue Reading.......

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