August 31, 2010

August 30, 2010

HIV-positive women who are breastfeeding should not be given vitamin A supplements because it increases the risk of transmitting the AIDS virus to their infants, researchers said Thursday. Mother-to-child transmission of HIV has been largely controlled in the United States and other developed countries through the use of antiretroviral drugs, but is a major problem in the developing world. In 2008, there were 430,000 new HIV infections in infants, most of them in sub-Saharan Africa, and breast feeding accounted for more than 95% of them. Vitamin A supplements are commonly given to pregnant women in such countries, but physicians generally do not take into account the women's HIV status.

In one study reported in the American Journal of Clinical Nutrition, epidemiologist Eduardo Villamor of the University of Michigan School of Public Health and his colleagues studied 1,078 HIV-positive women who were pregnant. Half received 5,000 international units of vitamin A and 30 milligrams of beta-carotene every day during gestation and lactation and half received a placebo. The combination of supplements increased the risk of passing the virus to the infants, and it appeared that each supplement had an effect individually, Villamor said.

In a second study in the same journal, Villamor and his colleagues found that the supplements increase the risk of subclinical mastitis in HIV-positive women. Subclinical mastitis is an inflammatory condition that causes blood plasma to leak into the mammary gland, carrying virus particles with it.

"The takeaway is that daily supplementation of HIV-infected pregnant or lactating women with vitamin A and beta-carotene at the doses tested is probably not safe and efforts need to be strengthened on preventing mother-to-child transmission through other interventions, such as antiretroviral agents," Villamor said in a statement.

-- Thomas H. Maugh II / Los Angeles Times

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Bethesda, MD (Aug. 26, 2010) — Compliance with practice guideline-recommended treatment for cirrhosis is associated with a reduction in first esophageal variceal hemorrhage (EVH; bleeding), according to a new study in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute. Cirrhosis is a condition in which the liver is permanently scarred or injured.

“Esophageal variceal hemorrhage is a serious complication of cirrhosis, and the mortality rate associated with it is high at 20 percent,” said Jayavani Moodley, MD, of the Cleveland Clinic Foundation and lead author of the study. “This high mortality rate makes primary prevention of bleeding the best approach to improving outcomes for these patients.”

In this study, doctors conducted an Institutional Review Board-approved retrospective chart review on 179 adult patients selected by computerized randomization, newly evaluated for cirrhosis at the Cleveland Clinic from 2003 to 2006. These patients were followed for 23 months; doctors assessed actual compliance rates of gastroenterologists with current practice guidelines, which recommend screening and intervention for high-risk esophageal varices. Subsequent bleeding rates were also determined.

The study authors reported that 94 percent of the patients had a screening endoscopy (EGD), with 80 percent having one within six months of the initial visit. Varices were present in half of the patients. In addition, 68 percent of all patients screened and 91 percent with large varices received a practice guideline-recommended treatment. Seven percent had an episode of EVH; 82 percent of patients without bleeding had their screening EGD within six months versus 50 percent of those with bleeding. The likelihood of bleeding at two years, as predicted by the North Italian Endoscopy Club model, was 13 percent versus 27 percent.

“Our study suggests that the significant reduction in observed bleeding rates may be related to adherence to practice guideline-recommended care. Patients who did not bleed were more likely to have received their screening EGD within the six-month window as compared to those who bled, demonstrating the effectiveness of early variceal screening,” added Dr. Moodley.

The risk of developing gastroesophageal varices in patients with cirrhosis is between 50 percent and 66 percent, and 30 percent to 40 percent of patients with varices suffer a variceal hemorrhage. If untreated, variceal hemorrhage portends a 70 percent risk of death within one year.

About Cirrhosis

Cirrhosis occurs when the liver is permanently scarred or injured by chronic conditions and diseases. The scar tissue that forms in cirrhosis harms the structure of the liver, blocking the flow of blood through the organ.

To learn more about cirrhosis, visit the patient center on the AGA Web site at www.gastro.org/patient-center.

About the AGA Institute

The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. http://www.gastro.org/.

About Clinical Gastroenterology and Hepatology

The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org/.
 
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2010-08-30, Source: Bionor Pharma  

Bionor Pharma (OSLO: BIONOR) today reported preliminary findings of its Phase 2 trial that served to re-immunize, or "re-vaccinate" twenty five study volunteers from its original Phase 2a study conducted in 2002/2003. Previously, at the XVIII International AIDS Conference in Vienna in July 2010, the Company reported that about half of the study volunteers retained memory to Vacc-4x seven years after their initial immunization. Bionor Pharma researchers now report that this memory can be safely reactivated following re-immunization/re-vaccination resulting in improved anti-viral responses.
 
Two thirds of study volunteers responded to Vacc-4x, and these responses were found to be cross-reactive with the virus itself. The study also showed that Vacc-4x is capable of triggering the specific T-cells of the immune system that function to seek out and kill infected cells (CD8+ killer T-cells) which is the objective of a successful T-cell vaccine. The complete study results are being prepared for publication in an international peer reviewed journal.

'It is promising that Vacc-4x has been able to induce such durable memory in patients and that this can be re-boosted many years later even after long periods of treatment interruption,' says Prof. Dag Kvale from Oslo University Hospital, Norway, who has led the study. 'This therapeutic vaccination technique demonstrates clearly a potential to achieve sustained immune responses which can be boosted while on antiretroviral therapy.'

Vacc-4x is composed of four modified peptides corresponding to conserved regions of the HIV core protein (p24) that are injected intradermally beneath the skin. This method of immunization is relatively simple and suited to a regime involving periodic boosting. A phase IIa study carried out in 2002/2003 showed that Vacc-4x could support prolonged periods free of antiretroviral therapy (average 31 months). Twenty five of the study volunteers who participated in the original phase IIa study have now been successfully given a voluntary 're-vaccination' with Vacc-4x and followed while on antiretroviral therapy.

About Bionor Pharma

Bionor Pharma is an innovative biotech company developing synthetic peptide vaccines that stimulate cell-mediated immunity using T-cell stimulation.

Bionor Pharma carefully designs synthetic peptides from low-mutating parts of the virus with improved immunogenicity, resulting in improved efficacy and safety profiles. HIV is the first disease targeted, with the most advanced vaccine candidate about to finish clinical phase IIb. However, Bionor Pharma's platform technology is broadly applicable, and the company has vaccine candidates also for chronic infections such as Hepatitis C (HCV), Human Papilloma Virus (HPV) and Influenza. Bionor Pharma ASA is listed on the Oslo Stock Exchange under the ticker symbol [BIONOR].

Contact information:

Trond Syvertsen
CEO
+47 23 01 09 60
+47 91 72 14 57
Email Contact

Rolf Henning Lem
CFO
+47 23 01 09 60
+47 97 74 88 45
Email Contact

Birger Sorensen
EVP Head of Vaccines
+47 404 07 565
+47 23 01 09 60
Email Contact

Washington DC, USA
David Sheon
Investor Relations
+1 202 547-2880
+1 202 422-6999
Email Contact
 
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Update to Hepatitis C Infection Control Investigation

JACKSONVILLE, Fla. — Mayo Clinic is working closely with the Florida Department of Health and in consultation with the Centers for Disease Control and Prevention to determine which patients should undergo follow-up testing after the Clinic last week discovered that a now, former employee put patients at risk for exposure to hepatitis C.

Mayo Clinic terminated the radiology technologist’s employment after he admitted stealing injectable fentanyl for personal use. His admission came after he was questioned about why his strain of hepatitis C infection was found to be similar to the strain of hepatitis C in three patients who underwent interventional radiology procedures over the last four years. For more details, see Mayo Clinic’s news blog at http://newsblog.mayoclinic.org/2010/08/24/employee-terminated-after-confessing-to-drug-diversion/.

“We find it heartbreaking that the actions of this single individual may have impacted some of our patients,” said William C. Rupp, M.D., CEO of Mayo Clinic in Florida. “We are devoted to meeting patient needs as we respond to this situation. We pride ourselves on offering safe, high-quality patient care. Patients have my firm commitment and the commitment of our entire team that Mayo Clinic will do everything possible to maintain the trust they have placed in us.”

The number of patients who might be affected is still being determined. Mayo Clinic will send letters to these patients and will make hepatitis C testing available at no charge to them. Specific details about testing options for patients who are at risk will be released later this week.

Patients who have questions or may be concerned that they may be at risk of infection can call the toll-free hotline at 877-956-1768 or 904-956-1768. Mayo Clinic nurses staffing the hotline can answer questions or concerns from patients about hepatitis C. Approximately 725 people have called the hotline since it was established last Wednesday.

Further information about hepatitis C is available on the Mayo Clinic website at http://www.mayoclinic.com/health/hepatitis-c/DS00097 or the Centers for Disease Control and Prevention website at http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf.

Mayo Clinic will provide additional information about this situation as it becomes available.

This entry was written by Newsletter Editor, posted on August 30, 2010 at 2:55 pm
 
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World J Gastroenterol 2010 August;16(32):4061-4065

Nash KL, Woodall T, Brown AS, Davies SE, Alexander GJ.

Department of Hepatology, Mailpoint 255, Southampton General Hospital, Tremona Road, Southampton, Hampshire SO16 6YD, United Kingdom. klnash11@yahoo.co.uk

AIM: To investigate and characterise patients with chronic hepatitis C virus (HCV) infection presenting with hepatocellular carcinoma (HCC) in the absence of cirrhosis. METHODS: Patients with chronic hepatitis C infection without cirrhosis presenting with HCC over a 2-year period were identified. The clinical case notes, blood test results and histological specimens were reviewed to identify whether additional risk factors for the development of HCC were present. RESULTS: Six patients (five male, one female) with chronic hepatitis C infection without cirrhosis presented to a single centre with HCC over a 2-year period. Five patients were treated by surgical resection and one patient underwent liver transplantation. Evaluation of generous histological specimens confirmed the presence of HCC and the absence of cirrhosis in all cases. The degree of fibrosis of the background liver was staged as mild (n = 1), moderate (n = 4) or bridging fibrosis (n = 1). Review of the clinical case notes revealed that all cases had an additional risk factor for the development of HCC (four had evidence of past hepatitis B virus infection; two had a history of excessive alcohol consumption; a further patient had prolonged exposure to immune suppression). CONCLUSION: HCC does occur in patients with non-cirrhotic HCV infection who have other risk factors for hepatocarcinogenesis.
 
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Articles in Press

Silvia Fargion, Luca Valenti, Anna Ludovica Fracanzani

Received 14 May 2010; accepted 22 July 2010. published online 27 August 2010.
Corrected Proof

Abstract

Following the model of hereditary hemochromatosis, the possible role of iron overload as a cofactor for disease progression in acquired liver diseases has been investigated with controversial results. In recent years, progress has been made in understanding the regulation of iron metabolism, thereby allowing the evaluation of the mechanisms linking liver diseases to excessive iron accumulation. Indeed, deregulation of the transcription of hepcidin, emerging as the master regulator of systemic iron metabolism, has been implicated in the pathogenesis of hepatic iron overload in chronic liver diseases. Whatever the cause, hepatocellular iron deposition promotes liver fibrogenesis, while an emerging possible aggravating factor is represented by the strong link between iron stores and insulin resistance, a recently recognized risk factor for the progression of liver diseases. Overall, these pathogenic mechanisms, together with the known proliferative and mutagenic effect of excess iron, converge in determining an increased susceptibility to hepatocellular carcinoma. Finally, an association between serum ferritin levels and mortality in patients with end-stage liver disease has recently been reported.

Prospective, randomized studies are required to evaluate whether iron depletion may reduce fibrosis progression, hepatocellular carcinoma development, and eventually mortality in patients with chronic liver diseases.

Keywords: Chronic hepatitis C, Hepatocarcinoma, Hepcidin, Nonalcoholic steatohepatitis

The Department of Internal Medicine, Università degli Studi, Fondazione IRCCS Ospedale Maggiore Policlinico “Ca’ Granda” IRCCS, Milan, Italy

Corresponding author. Tel.: +39 02 55033301; fax: +39 02 50320296.
PII: S1590-8658(10)00257-4
doi:10.1016/j.dld.2010.07.006
© 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Inc All rights reserved.

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Natural history and treatment of chronic delta hepatitis

J Viral Hepat. 2010 Aug 15.
Yurdaydın C, Idilman R, Bozkaya H, Bozdayi AM.
Gastroenterology Department, University of Ankara Medical School, Ankara, Turkey.

Abstract

Summary. Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead to disease in humans through co-infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV-HDV co-infection compared to HBV mono-infection. Chronic infection after acute hepatitis B + D co-infection is infrequent and similar to the rate in mono-infected patients. CDH develops in 70-90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10-15% of patients. However, as with any immune-mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.

PMID: 20723036 [PubMed - as supplied by publisher]

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J Viral Hepat. 2010 Aug 17. [Epub ahead of print]
Chotiyaputta W, Degertekin B, McKenna BJ, Samala N, Fontana RJ, Lok AS.
Division of Gastroenterology, Department of Internal Medicine Ann Arbor, MI, USA.

Abstract

Summary. Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT) but most studies performed biopsies on selected patients only. The aims of this study were to determine the rate of liver biopsy, characteristics of patients who underwent a biopsy and factors associated with significant liver disease in a cohort of such patients. Records of patients with chronic hepatitis B during a 10-year period were reviewed. Significant liver disease was defined as Knodell HAI >/= 7 and/or Ishak fibrosis >/= 3. Of 743 patients, 55.7% were Asian, 56.4% were men, and the mean age was 43.1 years. One hundred and ninety-three (26%) had undergone a biopsy. Biopsied patients were more likely to be men, HBeAg positive, and had lower platelet and higher alkaline phosphatase, bilirubin, ALT and hepatitis B virus (HBV) DNA. Significant liver disease was observed in 20% of patients who had normal ALT at presentation, 14% of those with normal ALT at the time of biopsy and in none of the patients with persistently normal ALT. Patients with normal ALT who were biopsied had higher HBV DNA and higher ALT than those not biopsied. Multivariate analysis showed that low albumin at the time of biopsy and HBV DNA >5 log(10) copies/mL were predictors of significant liver disease. Significant liver disease is rare in patients with chronic HBV and persistently normal ALT and liver histology of chronic HBV infected patients with normal ALT cannot be generalized to other patients with normal ALT that were not biopsied.

PMID: 20726947 [PubMed - as supplied by publisher]

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Clinical Infectious Diseases 2010;51:000–000
© 2010 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2010/5107-00XX$15.00
DOI: 10.1086/656235

MAJOR ARTICLE

Juan A. Pineda, 1 Antonio Caruz, 3 Antonio Rivero, 4 Karin Neukam, 1 Irene Salas, 3 Ángela Camacho, 4 José C. Palomares, 2 José A. Mira, 1 Antonio Martínez, 5 Carmen Roldán, 1 Julián de la Torre, 4 and Juan Macías 1

Units of 1 Infectious Diseases and 2 Microbiology, Hospital Universitario de Valme, Seville, 3 Immunogenetics Unit, Faculty of Sciences, Universidad de Jaen, Jaen, and 4 Unit of Infectious Diseases and 5 Molecular Genetics Laboratory, Unit of Clinical Analysis, Hospital Universitario Reina Sofía, Cordoba, Spain

Background. Variation in the IL28B gene is associated with sustained virologic response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)–monoinfected patients with genotype 1. Data on other genotypes and on patients coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We aimed to assess the predictive ability of variations in the single‐nucleotide polymorphism rs12979860 for SVR in HIV/HCV‐coinfected patients, regardless of HCV genotype.

Methods. The rs12979860 genotype was determined by polymerase chain reaction in 154 patients who had received therapy against HCV with pegylated interferon plus ribavirin.

Results. rs12979860 genotype was TT in 20 patients (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in patients with genotype CC and in those with genotype TC or TT, according to HCV genotype, were, respectively, 50% and 17% ( ) in patients with genotype 1, 80% and 25% ( ) in patients with genotype 4, and 93% and 77% ( ) in patients with genotype 3. The median (interquartile range) low‐density lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73–120 mg/dL) versus 75 mg/dL (55–91 mg/dL) ( ) in those with TC or TT. Independent predictors of SVR were HCV genotype 2–3 (odds ratio [OR], 13.98; 95% confidence interval [CI], 4.87–40.1; ), rs12979860 CC (OR, 5.05; 95% CI, 2.04–12.5; ), baseline plasma HCV RNA load of 600,000 IU/mL (OR, 1.99; 95% CI, 1.18–3.34; ), and female sex (OR, 4.28; 95% CI, 1.08–16.96; ).

Conclusions. IL28B gene variations independently predict SVR in HIV/HCV‐coinfected patients with HCV genotype 1 and non–genotype 1 HCV infection. The association between rs12979860 and plasma low‐density lipoprotein cholesterol suggests that the system low‐density lipoprotein ligand/receptor might be involved in the effect of this genotype.

Received 20 February 2010; accepted 9 June 2010; electronically published 30 August 2010.

Reprints or correspondence: Dr Juan A. Pineda, Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Avda de Bellavista, 41014 Sevilla, Spain (japineda@telefonica.net); or Dr Karin Neukam, Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Avda de Bellavista, 41014 Sevilla, Spain (keule165@gmail.com).
 
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From AIDS Clinical Care
Dan H. Barouch, MD, PhD
Posted: 08/30/2010; AIDS Clinical Care © 2010 Massachusetts Medical Society

Abstract and Introduction

Abstract

One monoclonal antibody neutralizes >90% of worldwide circulating HIV-1 isolates.

Introduction

One of the major roadblocks in the development of an HIV-1 vaccine has been the inability of vaccine immunogens to elicit broadly reactive HIV-1 Env–specific neutralizing antibodies. Some investigators have questioned whether the human immune system is even capable of generating such broadly reactive antibodies, given the extent of virus variability worldwide and the immune evasion tactics employed by the virus.

Researchers now describe the isolation and structural analysis of a new broadly reactive HIV-1 Env–specific monoclonal antibody (mAb) called VRC01, which was derived from an HIV-1–infected individual with broadly reactive serum neutralizing antibodies. Prior work from these investigators and others identified the CD4 binding site as a largely conserved site on HIV-1 Env that was the target of a different mAb (b12). VRC01 also targets the CD4 binding site, but it exhibits greater breadth, neutralizing >90% of HIV-1 isolates circulating worldwide. Moreover, it neutralizes these isolates with substantial potency. Interestingly, VRC01 partially mimics CD4 binding to HIV-1 Env, but the crystal structure shows that its orientation differs slightly from that of CD4, allowing it to target the vulnerable site of initial CD4 binding very precisely. Molecular sequence analysis also reveals that the variable loops of VRC01 have undergone extensive somatic hypermutation and affinity maturation — factors that likely contribute to the breadth and potency of this mAb.

Comment
 
Another study published last year described the isolation and characterization of two other new broadly reactive mAbs, PG9 and PG16, which were also derived from an HIV-1–infected individual with broadly reactive serum neutralizing antibodies (Science 2009; 326:285). These mAbs exhibit substantial breadth and potency, and they have been shown to bind to conserved portions of the variable V2 and V3 loops on the intact HIV-1 Env trimer — a previously undescribed epitope that could represent a potential new HIV-1 vaccine target.

Taken together, these studies demonstrate that exceptionally broadly reactive neutralizing antibodies with substantial potency can indeed be generated in HIV-1–infected humans, probably at higher frequencies than previously recognized. As basic research tools, these new mAbs will prove invaluable. Moreover, their identification and characterization may lead to insights into HIV-1 vaccine design by identifying new targets and defining mechanisms of action. A major challenge now is to use this knowledge to improve HIV-1 vaccine immunogens — a daunting task, given how difficult it has been in the past to translate increased understanding of mAbs into improved vaccine immunogens. Nevertheless, these recent advances offer increased hope that an HIV-1 vaccine may indeed be possible.

References

• Wu X et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010 Jul 8.

• Zhou T et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010 Jul 8.
 
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DEA Heads First-Ever Nationwide Prescription Drug Take-Back Day

News Release
FOR IMMEDIATE RELEASE
August 19, 2010
Contact: DEA Public Affairs
Number: 202-307-7977

DEA Heads First-Ever Nationwide Prescription Drug Take-Back Day

AUG 19 -- WASHINGTON, D.C. – The Drug Enforcement Administration and government, community, public health and law enforcement partners today announced a nationwide prescription drug “Take-Back” initiative that seeks to prevent increased pill abuse and theft. DEA will be collecting potentially dangerous expired, unused, and unwanted prescription drugs for destruction at sites nationwide o n Saturday, September 25 th from 10 a.m. to 2 p.m. local time. The service is free and anonymous, no questions asked.

This initiative addresses a vital public safety and public health issue. Many Americans are not aware that medicines that languish in home cabinets are highly susceptible to diversion, misuse, and abuse. Rates of prescription drug abuse in the U.S. are increasing at alarming rates, as are the number of accidental poisonings and overdoses due to these drugs. Studies show that a majority of abused prescription drugs are obtained from family and friends, including from the home medicine cabinet. In addition, many Americans do not know how to properly dispose of their unused medicine, often flushing them down the toilet or throwing them away – both potential safety and health hazards.

“Today we are launching a first-ever National Prescription Drug Take-Back campaign that will provide a safe way for Americans to dispose of their unwanted prescription drugs,” said Michele M. Leonhart, Acting Administrator of the Drug Enforcement Administration. “This effort symbolizes DEA’s commitment to halting the disturbing rise in addiction caused by their misuse and abuse. Working together with our state and local partners, the medical community, anti-drug coalitions, and a concerned public, we will eliminate a major source of abused prescription drugs, and reduce the hazard they pose to our families and communities in a safe, legal, and environmentally sound way.”

“With this National Prescription Drug Take-Back campaign, we are aggressively reaching out to individuals to encourage them to rid their households of unused prescription drugs that pose a safety hazard and can contribute to prescription drug abuse,” said Acting Deputy Attorney General Gary G. Grindler. “The Department of Justice is committed to doing everything we can to make our communities safer, and this initiative represents a new front in our efforts.”

“Prescription drug abuse is the Nation’s fastest-growing drug problem, and take-back events like this one are an indispensable tool for reducing the threat that the diversion and abuse of these drugs pose to public health,” said Director of National Drug Control Policy Gil Kerlikowske. “The Federal/state/and local collaboration represented in this initiative is key in our national efforts to reduce pharmaceutical drug diversion and abuse.”

Collection sites in every local community can be found by going to www.dea.gov . This site will be continuously updated with new take-back locations. Other participants in this initiative include the White House Office of National Drug Control Policy; the Partnership for a Drug-Free America; the International Association of Chiefs of Police; the National Association of Attorneys General; the National Association of Boards of Pharmacy; the Federation of State Medical Boards; and the National District Attorneys Association.

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SUMMARY: People with hepatitis C virus (HCV) who spontaneously clear the infection without treatment have a low risk of death, less than 10% over 5 years, according to a Danish study published in the July 2010 Journal of Hepatology. Individuals who develop chronic hepatitis C, however, have an elevated risk of overall and liver-related mortality, including deaths due to primary liver cancer.

By Liz Highleyman

Most experts estimate that approximately one-quarter to one-third of people initially infected with HCV will naturally clear the virus without treatment thanks to an effective immune response. Among those with persistent infection, however, HCV can over years or decades cause serious liver disease including cirrhosis and hepatocellular carcinoma, a form of primary liver cancer.

Research has shown that people with chronic hepatitis C have a higher risk of liver-related death, but outcomes among people who were once infected but naturally cleared the virus have not been extensively studied.

In the present analysis, Lars Haukali Omland and fellow investigators with the DANVIR Cohort Study examined the association between chronic HCV replication and mortality among Danish patients who tested positive for HCV antibodies.

This nationwide cohort study looked at more than 6000 patients with at least 1 HCV RNA (genetic material) viral load measurement available after testing positive for HCV antibodies between 1996 and 2005. To capture long-term outcomes, eligible participants needed to be alive for at least 1 year after HCV RNA assessment.

The researchers estimated mortality rate ratios (MRRs) for overall mortality and sub-distribution hazard ratios (SDHRs) for cause-specific mortality, after controlling for patient sex, age, co-existing conditions, heavy alcohol use, injection drug use, and income.

Results
  • Of the 6292 patients in the study, 37% spontaneously cleared HCV, while 63% developed chronic infection.
  • Overall 5-year survival rates were 92% for participants who cleared the virus, compared with 86% for those with chronic infection.
  • Chronic HCV infection was associated with higher overall mortality compared with viral clearance (MRR 1.55).
  • Chronic infection was also associated with a more than a 2-fold greater risk of liver-related death (SDHR 2.42).
  • In particular, chronic HCV infection greatly increased -- by more than 16-fold -- the risk of death due to primary liver cancer (SDHR 16.47). 
Based on these findings, the study authors concluded, "Patients with chronic HCV infection are at higher risk of death than patients who cleared the infection."

"The substantial association found between chronic HCV infection and death from primary liver cancer supports early initiation of antiviral treatment in chronically HCV-infected patients," they recommended.

Investigator affiliations: Department of Infectious Diseases, Rigshospitalet, Copenhagen; Department of Clinical Biochemistry, Aalborg Hospital; Department of Clinical Epidemiology, Aarhus University Hospital; Department of Clinical Immunology, Odense University Hospital; Department of Clinical Immunology and Blood Bank, Rigshospitalet, Copenhagen; Department of Clinical Immunology, Viborg Region Hospital; Department of Clinical Immunology, Hospital of Southern Jutland, Region of Southern Denmark; Department of Clinical Microbiology, Vejle Hospital; Department of Infectious Diseases, Odense University Hospital, Denmark; Department of Epidemiology, Boston University School of Public Health, Boston, MA.

8/31/10

Reference
LH Omland, H Krarup, P Jepsen, and others (DANVIR Cohort Study). Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study. Journal of Hepatology 53(1): 36-42 (Abstract). July 2010.

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SUMMARY: Children with hepatitis C virus (HCV) infection who were treated with pegylated interferon plus ribavirin showed a high rate of sustained virological response, greater than that seen in most adult studies, according to a report in the June 2010 Journal of Hepatology. Nearly 60% of children with hard-to-treat HCV genotypes including 1 and 4 -- and more than 90% of those with easier-to-treat genotypes 2 or 3 -- achieved a cure.

By Liz Highleyman

Studies of combination interferon-based therapy for chronic hepatitis C usually focus on adults, who typically demonstrate sustained virological response (SVR) rates of just under 50% for HCV genotype 1 and 70%-80% for genotypes 2 or 3 using a standard regimen of pegylated interferon plus ribavirin for 48 or 24 weeks, respectively. Treatment of children with hepatitis C has not been as extensively studied.

In the present study, Etienne Sokal from Catholic University Louvain in Belgium and an international team of colleagues evaluated the safety and efficacy of pegylated interferon alfa-2a (Pegasys) plus ribavirin in previously untreated HCV antibody positive children with detectable HCV RNA viral load.

This prospective analysis included 18 children with HCV genotypes 2 or 3, who were treated for 24 weeks, and 47 children with harder-to-treat genotypes 1, 4, 5, or 6, who were treated for 48 weeks.

Results
  • 83% of the genotype 2/3 children and 57% of the genotype 1/4/5/6 children achieved early virological response at week 12.
  • End-of-treatment response rates were 94% (at week 24) and 57% (at week 48), respectively.
  • Relapse rates were low, with 89% of easier-to-treat participants and 57% of hard-to-treat children achieving sustained response at 24 weeks after completion of therapy.
  • 10 participants overall (15%) stopped treatment prematurely -- 2 due to serious adverse events and 8 due to lack of virological response at week 24.
  • 15 children overall (23%) had their pegylated interferon or ribavirin doses adjusted -- 11 (17%) due to neutropenia and 3 (5%) due to anemia.
  • The most common treatment-related adverse events included:
          --Fever and flu-like symptoms (54%);
          --Abdominal pain (38%);
          --Irritability, depression, or mood changes (34%);
          --Dermatitis (29%);
          --Vomiting (23%);
          --Loss of appetite (22%).
  • Interferon-based treatment had no observed effect on the children's growth in height.
These results, the researchers concluded, show that children have an improved rate of sustained virological response compared with reference studies of adult chronic C patients treated with similar regimens.

Investigator affiliations: Université Catholique de Louvain, Cliniques universitaires St Luc, Bruxelles, Belgium; Paediatric Gastroenterology, Hospital de clinicas de Porto Alegre, Porto Alegre, Brazil; Unidade de Hepatologica Pediatrica, Hospital das clinicas da faculdade de medicina da universidade de Sao Paulo, Sao Paulo, Brazil; Department of Pediatrics, Stradinš University, Riga, Latvia; Department of Paediatrics, CLINTEC, Karolinska University Hospital, Huddinge, Stockholm, Sweden; Liver Unit, Birmingham Children's Hospital, Birmingham, UK.

8/31/10

Reference
EM Sokal, A Bourgois, X Stéphenne, and others. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in children and adolescents. Journal of Hepatology 52(6): 827-831 (Abstract). June 2010.

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