Hepatitis C News Ticker-Following response-guided therapy guidelines with boceprevir and telaprevir
- File Under boceprevir-victrelis, HCV Awareness, HCV News, spleen, telaprevir-incivek
"Reading the Paper" Lynne CrumpackerHepatitis Journal Options – Volume 5, Issue 1
This special edition includes all the pivotal phase III studies of the HCV protease inhibitors, with a range of commentaries exploring key aspects of the use of these agents, plus Capsule Summaries of each study and downloadable slidesets.
Topics include:
Now Available! CCO Hepatology inPractice™- Following response-guided therapy guidelines with boceprevir and telaprevir
- Understanding futility rules and their importance
- Outcomes and management of anemia
- Strategies for managing telaprevir rash and anorectal symptoms
- Using boceprevir and telaprevir in patients with advanced fibrosis or cirrhosis
- Effect of telaprevir on cyclosporine and tacrolimus pharmacokinetics
- Antiviral activity with telaprevir in patients with genotype 2 or 3 HCV
- Evaluation of HBV screening cost effectiveness
Treatment of chronic hepatitis C virus infection. A study of best predictors for response.
PDF in Spanish -Translate here
SourceMaría José Pena López, Servicio de Microbiología, Hospital Universitario de Gran Canaria Dr. Negrín, C/Barranco de la Ballena s/n, 35020 Las Palmas de Gran Canaria, Spain. mpenlopd@gobiernodecanarias.org.
Abstract
Objective:
The aim of this study was evaluate the rate of sustained viral response (SVR) and the influence of different factors on the SVR in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon alfa 2a and ribavirin. Methods: We retrospectively analysed 272 naïve patients with chronic hepatitis C who had been treated for 24 weeks or 48 weeks and had been followed for an additional 6 months thereafter.
Results:
Out of 272 patients, 243 completed the entire treatment. The overall SVR rate in intent-to-treat analysis was 66.5% and in treated patients was 74.5%. In an univariate analysis, the SVR was associated with age <40 years (84.4%),pre-treatment viral load <500.000 IU/ml (86.9%), non-1 genotype HCV (86.4%), non cirrhosis or pre-cirrhosis (76.5%), rapid virologic response (RVR) (91.4%) and early virologic response (EVR) (83.8%).
In the multivariate logistic regression analysis, the presence of an infection caused by a non-1 genotype and to achieve ERV were independent predictors of SVR. The RVR and histological stage of liver disease were not included in the multivariate analysis because these data were not available in most of the patients. The PPV and NVP of RVR were 91.5% and 48.7% respectively, of EVR were 83.8% and 95.8% respectively and of complete EVR were 91.3% and 78.7%, respectively. Conclusions: The SVR was higher than in other studies. The genotype and EVR were independent factors to predict the effect of antiviral therapy. The EVR had a high NPV and the complete EVR a high PPV.
Research article
Arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: A hospital-based study and review of literature in Taiwan
Neng-Chyan Huang, Shue-Ren Wann, Hong-Tai Chang, Shoa-Lin Lin, Jyh-Seng Wang and How-Ran Guo View PDF BMC Gastroenterology 2011, 11:142 doi:10.1186/1471-230X-11-142 Published: 26 December 2011
Abstract (provisional)
Background
View PDF.
Hepatic angiosarcoma (HAS) is a rare type of liver cancer that is often fatal, and arsenic and vinyl chloride monomer (VCM) are two major causal agents. Whereas Taiwan is an endemic area of liver cancer, epidemiologic data on HAS are limited. We reviewed the cases observed at a teaching hospital to evaluate the roles of VCM, arsenic, and viral hepatitis in the occurrence of HAS.
Methods
We reviewed the medical records of patients with pathological proof of HAS from January 2000 to December 2010 at a teaching hospital which is adjacent to the major VCM processing area in Taiwan and nearby an endemic area of arsenic exposure from drinking water. We also conducted a literature review and included all patients of HAS reported in Taiwan.
Results
Six male and three female cases aged from 50 to 82 years (64.1 +/- 9.1 years) were identified at the hospital. The differences in clinical features between men and women were not statistically significant. None of them had exposure to VCM or arsenic in drinking water. Two had evidence of hepatitis C infection, but none had evidence of hepatitis B infection. Five male and four female cases aged 30 to 82 years (58.6 +/- 15.5 years) were identified in the literature, including two with arsenic exposure and one with chronic hepatitis B infection.
Conclusions
HAS is rare in Taiwan, and we found no evidence supporting a major role of VCM, arsenic in drinking water, or viral hepatitis in its occurrence.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
FDA
On December 23, 2011, the Food and Drug Administration approved revisions to the product labeling for Tyzeka (telbivudine) to include a contraindication regarding the use of Tyzeka with Pegasys (pegylated interferon alfa-2a) due to increase risk and severity of peripheral neuropathy. The Medication Guide was also revised accordingly. The following sections were revised:
Contraindications
Combination of Tyzeka with pegylated interferon alfa-2a is contraindicated because of increased risk of peripheral neuropathy
Warnings and Precautions
Peripheral Neuropathy
Peripheral neuropathy has been reported with Tyzeka alone or in combination with pegylated interferon alfa-2a and other interferons. In one clinical trial, an increased risk and severity of peripheral neuropathy was observed with the combination use of Tyzeka 600mg daily and pegylated interferon alfa-2a 180 micrograms once weekly compared to Tyzeka or pegylated interferon alfa-2a alone [see Contraindications (4) and Drug Interactions (7)]. Such risk cannot be excluded for other dose regimens of pegylated interferon alfa-2a, or other alfa interferons (pegylated or standard). The safety and efficacy of Tyzeka in combination with pegylated interferons or other interferons for the treatment of chronic hepatitis B has not been demonstrated. Patients should be advised to report any numbness, tingling, and/or burning sensations in the arms and/or legs, with or without gait disturbance. Tyzeka therapy should be interrupted if peripheral neuropathy is suspected, and discontinued if peripheral neuropathy is confirmed
Drug Interactions:
A clinical trial investigating the combination of Tyzeka, 600 mg daily, with pegylated interferon alfa-2a, 180 micrograms once weekly by subcutaneous administration, indicates that this combination is associated with an increased risk of peripheral neuropathy occurrence and severity, in comparison to Tyzeka or pegylated interferon alfa-2a alone
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Big Pharma
Causes are hard. Explaining pharma’s problems is harder
We all know the pharmaceutical industry is in trouble — what, with the precipitous patent cliff, soaring price of drug development and the death of the megablockbuster. And much ink has been spilled about the potential solutions to pharma’s problems, from mergers to academic partnerships to new research units. But what if the entire R&D enterprise is fundamentally flawed?
That’s the hypothesis of a new article in Wired magazine by science writer Jonah Lehrer postulating that the reductionist dogma of modern biomedicine has prompted scientists to desperately seek causal narratives where there are only statistical correlations to be found. In turn, Lehrer’s theory goes, such causal stories that scientists tell themselves have led drug developers on expensive and ultimately futile pharmaceutical goose chases.
Research
Discovered the existence of neutrophils in the spleen
This release is available in Spanish.
Barcelona, 23rd of December 2011.- For the first time, it has been discovered that neutrophils exist in the spleen without there being an infection. This important finding made by the research group on the Biology of B Cells of IMIM (Hospital del Mar Research Institute) in collaboration with researchers from Mount Sinai in New York, has also made it possible to determine that these neutrophils have an immunoregulating role.
Neutrophils are the so-called cleaning cells, since they are the first cells to migrate to a place with an infection and inflammation to destroy the pathogens. Until now, scientific literature had considered neutrophils essentially as lowly qualified soldiers that simply limited the expansion of an infection, as a first action to pave the way for other cells of the immune system in charge of eradicating the infection permanently.
"This study has revealed that neutrophils are found in the spleen without there being an infection, contributing totally new knowledge in the field of biology" explains Andrea Cerutti, the coordinator of the research group on the Biology of B Cells of IMIM, a professor at ICREA and the last signatory of the article.
Researchers noticed that the existence of neutrophils in the spleen started when the fetus is developing, even when there is no infectious process involved; this was not known in scientific literature. The study was expanded to people of different ages and other mammals. Detecting the presence of neutrophils in the spleen suggested that these played a different role in the spleen to the one usually given to them.
The neutrophils in the spleen are located around B lymphocytes to help their activation and offer a first rapid response when there are pathogens. "through several different experimental approaches we have proven that neutrophils in the spleen acquire the ability to interact with B cells or B lymphocytes, inducing the production of antibodies, a role that lymphocytes circulating in blood are not able to do" states Irene Puga, researcher of the IMIM and a signatory of this article.
This finding improves the understanding of the mechanisms with which our immune system protects us against an infection, an essential requirement to better control all pathologies linked to it. Also, when faced with certain diseases, such as neutropenia (or a numeric deficiency of neutrophils), it will become necessary to study not only the deficiency of neturophils, but also how this affects the production of antibodies.
This work opens the door to therapies which are geared at, and more affective against, different pathogens, for example, to develop vaccines to increase the capacity of neutrophils in the spleen so as to have an incidence on the production of antibodies by type B lymphocytes.
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This study has been made possible thanks to the simples gathered mainly in different Catalan hospitals such as Hospital del Mar, Hospital Clínic, Hospital de la Vall d'Hebron and Hospital Sant Joan de Déu, together with other centres in the USA and Europe.
Reference article
"B–helper neutrophils stimulate immunoglobulin diversification and production in the marginal zone of the spleen" Irene Puga, Montserrat Cols, Carolina Barra, Bing He, Linda Cassis, Maurizio Gentile, Laura Comerma, Alejo Chorny, Meimei Shan, Weifeng Xu, Giuliana Magri, Daniel M.Knowles, Wayne Tam, April Chiu, James B Bussel, Sergi Serrano, José Antonio Lorente,Beatriz Bellosillo, Josep Lloreta, Nuria Juanpere, Francesc Alameda, Teresa Baró, Cristina Díaz de Heredia, Núria Torán, Albert Català, Montserrat Torrebadell, Claudia Fortuny,Victoria Cusi, Carmen Carreras, George A. Diaz, J. Magarian Blander, Claire-Michèle Farber, Guido Silvestri, Charlotte Cunningham-Rundles, Michaela Calvillo, Carlo Dufour, Lucia Dora Notarangelo, Vassilios Lougaris, Alessandro Plebani, Jean-Laurent Casanova, Stephanie C. Ganal, Andreas Diefenbach, Juan Ignacio Aróstegui, Manel Juan, Jordi Yagüe, Nizar Mahlaoui, Jean Donadieu, Kang Chen & Andrea Cerutti. Nature Immunology 2011
For further information
Rosa Manaut, head of communications at IMIM, Tel: +34 618 509 885 or Marta Calsina, Communication service at IMIM, Tel: +34 933 16 06 80.
Active Compounds in 'Bath Salts' and Ecstasy Similar
December 20, 2011 — Mephedrone and methylone, which are the active compounds found in so-called "bath salts," have mechanisms of action similar to those found in 3,4-methylenedioxymethamphetamine (MDMA), popularly known as ecstasy — a finding that may explain the product's potential for addiction, new research suggests.
Investigators found that these compounds bind to monoamine transporters on the surface of some neurons, leading to an increase in both serotonin and, to a lesser degree, dopamine.
"Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation," write lead author Michael H. Baumann, PhD, from the Translational Pharmacology Section and Intramural Research Program at the National Institute on Drug Abuse (NIDA) in Baltimore, Maryland, and colleagues.
In a message posted on NIDA's Web site, Nora Volkow, MD, director of NIDA, notes that because "bath salts" are a product that is "relatively new to the drug abuse scene," knowledge about their precise chemical composition and effects is limited.
"The information we do have is worrisome and warrants a proactive stance to understand and minimize any potential dangers to the health of the public," writes Dr. Volkow.
"Mephedrone is of particular concern because, according to the United Kingdom experience, it presents a high risk for overdose. These chemicals act in the brain like stimulant drugs (indeed they are sometimes touted as cocaine substitutes); thus they present a high abuse and addiction liability," she adds.
The study was published online December 14 in Neuropsychopharmacology.
Caution Urged
"The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide," write the investigators.
However, there is little information available on their mechanism of action.
For this study, the researchers examined rats to compare neurological effects after the administration of mephedrone or methylone with the effects after receiving 3,4-metlhylenedioxymethamphetamine (MDMA, or ecstasy) or methamphetamine.
In vitro release assays from the rat brains showed that both mephedrone and methylone "are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity," report the investigators.
In vivo microdialysis of the rats' nucleus accumbens showed that mephedrone and methylone produced dose-related increases in extracellular dopamine, and even greater increases in serotonin.
The peak magnitude of dopamine increase was 1.8-fold above baseline after doses of 0.3 mg/kg of mephedrone were given and 2.9-fold after doses of 1.0 mg/kg were given. The peak magnitude of serotonin increase was 4.2-fold and 11.1 fold, respectively.
For methylone, the peak magnitude of dopamine increase was 1.7-fold above baseline after doses of 1.0 mg/kg were given. For serotonin, it was 6.3-fold above baseline.
Nevertheless, both mephedrone and methylone were considered weaker motor stimulants than methamphetamine.
Repeated high-dose administration of mephedrone or methylone led to hyperthermia but no "long-term change in cortical or striatal amines." On the other hand, extended doses of MDMA let to "robust" hyperthermia and persistent depletion of cortical and striatal serotonin.
"Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study," write the researchers.
"In the meantime, I would like to urge parents, teachers, and the public at large to be aware of the potential dangers associated with the use of these drugs and to exercise a judicious level of vigilance that will help us deal with this problem most effectively," writes Dr. Volkow.
The study was supported by grants from NIDA and from the Retina Research Foundation/UW Eye Research Institute Edwin and Dorothy Gamewell Professorship. Dr. Baumann has disclosed no relevant financial relationships.
Neuropsychopharmacology. Published online December 14, 2011.
is a freelance writer for Medscape.
Deborah Brauser has disclosed no relevant financial relationships.
HCV Awareness
According to available data 6.7% of Georgia's adult population close to (200 000 people) are infected with Hepatitis C virus. The prevalence level is two-times higher than World's average. Absence of statistical data and effective state policy in relation to Hepatitis C deepens the epidemic. Hepatitis C can cause liver decease including liver cirrhosis and cancer.
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