Response to standard of care antiviral treatment in patients with HCV liver cirrhosis - a systematic review.
Bota S, Sporea I, Popescu A, Sirli R, Neghina AM, Danila M, Strain M.
Abstract Only For Full Text Download Full Article (PDF file)
SourceDepartment of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Timisoara, Romania; Email: isporea@umft.ro.
Abstract
BACKGROUND:
Patients with HCV liver cirrhosis are a category difficult to treat. The AIM of this study was to establish the sustained virological response (SVR) rates in HCV patients with liver cirrhosis treated with standard of care therapy (Pegylated Interferon and Ribavirin for 48 weeks in genotypes 1 and 4 and 24 weeks in genotypes 2 and 3).
METHODS:
Searching the PubMed, Medline, Lilacs, Scopus, Ovid and Medscape databases we identified all the articles published until February 2011 that included only HCV cirrhotic patients. These studies evaluated the SVR after standard of care treatment: Pegylated Interferon alpha 2a (doses ranging between 135-180 µg/week) or Pegylated Interferon alpha 2b (1 or 1.5 µg/kg/week) and Ribavirin (doses ranging between 800-1200 mg/day). We used the following key words: HCV, liver cirrhosis, sustained virological response (SVR).
RESULTS:
The overall SVR rate was 33.3% (95%CI-confidence interval=30.6-36.2%). SVR was significantly higher in patients with genotypes 2 and 3 (422 patients) as compared to those with genotypes 1 and 4 (692 patients): 55.4% (95%CI=50.7-60.1) versus 21.7% (95%CI=18.7-25), p less then 0.0001.
CONCLUSION:
The overall SVR rate in cirrhotic patients treated with standard of care therapy is 33.3%, but lower in cases affected by genotypes 1 and 4 (21.6%) which makes them a priority regarding the development of more potent drugs for effective treatment.
Full Text
Study finds curcumin able to inhibit traumatic death of liver cells
2011/10/08 17:35:21Taipei, Oct. 8 (CNA)
Taiwanese researchers have discovered that curcumin, a compound that gives turmeric its yellow color, is effective in inhibiting liver cells from turning fibrous before they lead to cirrhosis and liver cancer.
National Taiwan University assistant professor Chiu Chih-hsien and his research team found that feeding laboratory mice with high concentrations of curcumin extract brought about "apoptosis" in their inflamed liver cells. Apoptosis is a process describing programmed cell death. Normally, liver cells are replaced by new ones after their life circle ends through the naturally controlled process.
But when the cells develop inflammation under the influence of alcohol, drugs and chemical substances, they undergo traumatic deaths, called "necrosis." In the process of necrosis, liver cells gradually turn fibrous and stiffen, and then become cirrhotic and carcinogenic, Chiu said. "(The natural substance) can bring injured liver cells under the process of apoptosis, preventing their taumatic death," according to the team's study, the first anywhere in the world to focus on the effect of curcumin in inhibiting fibrosis on the liver. They discovered that "curcumin can control the way liver cells die," the professor said.
The research was conducted through the cooperation of National Taiwan University Department of Animnal Science and Technology and Kaohsiung Veterans General Hospital. The results will be published in the Journal of Nutritional Biochemistry by the end of this year, Chiu revealed. Curcumin is one of the most common ingredients in curry, and is frequently used as a herbal medicine in India and China to fight inflammation.
In recent years, it has also been touted by some as effective in combating cancer and even Alzheimer's disease. Chiu said the study could help scientists learn more about how the liver turns fibrous and would also pave the way for people to develop drugs to treat liver fibrosis. Asked if eating foods containing curry or taking curcumin food supplements would have the same effect they had in the laboratory, Chiu said it would not help because the amounts were too low
Translocation of gut-derived bacterial products such as endotoxin is a major problem in liver cirrhosis.
Methods:
To assess the hepatic clearance of bacterial products in individuals with cirrhosis, we tested concentrations of Gram-negative bacterial lipopolysaccharide (LPS), LPS-binding protein (LBP), and the precursor of nitric oxide (NO), L-arginine, in a cohort of 8 stable patients with liver cirrhosis before and after elective transjugular portosystemic shunt (TIPS) implantation, including central venous, hepatic venous, and portal venous measurements.
Results:
Using an adapted LPS assay, we detected high portal venous LPS concentrations (mean 1743+/-819 pg/mL). High concentrations of LPS were detectable in the central venous blood (931+/-551 pg/mL), as expected in persons with cirrhosis, The transhepatic LPS gradient was found to be 438+/-287 pg/mL, and 25+/-12% of portal LPS was cleared by the cirrhotic liver.After TIPS, central venous LPS concentrations increased in the hepatic and central veins, indicating shunting of LPS with the portal blood through the stent. This paralleled a systemic increase of L-arginine, whereas the NO synthase asymmetric dimethylarginine (ADMA) remained unchanged, suggesting that bacterial translocation may contribute to the pathogenesis of circulatory dysfunction post-TIPS.
Conclusions:
This study provides quantitative estimates of the role of the liver in the pathophysiology of bacterial translocation.The data indicate that the cirrhotic liver retains the capacity for clearance of bacterial endotoxin from the portal venous blood and that TIPS implantation attenuates this clearance. Thus, increased endotoxin concentrations in the systemic circulation provide a possible link to the increased encephalopathy in TIPS patients.
Author: Daniel Benten Julian Schulze zur Wiesch Karsten SydowAnd reas KoopsPeter Buggisch Rainer BogerCharlotte GaydosHelen WonVeronica Franco Ansgar LohseStuart RayAshwin Balagopal
Credits/Source: BMC Gastroenterology 2011, 11:107
Coffee Helps Reduce Side Effects in HIV/HCV Coinfected People during Interferon-based Therapy
Oct 7
HIV/HCV coinfected people who drink at least 3 cups of coffee daily were less likely to experienced adverse events related to interferon-based therapy for hepatitis C, according to a French study presented at the 10th AIDS Impact Conference last month in Santa Fe. However, whether coffee somehow directly relieves side effects remains unknown.
Several studies have shown that coffee appears to have a beneficial effect on liver inflammation and fibrosis among people with hepatitis C, and it has also been linked to higher rates of sustained response to interferon-based treatment.......
Hepatitis C Report: Four Food Groups to Lift Depression
October 6, 2011
Applicable to many with chronic Hepatitis C, eating foods rich in these four elements has been shown to help depression sufferers lift their spirits.
by Nicole Cutler, L.Ac.
More than most other populations, people with chronic Hepatitis C are particularly prone to depression. Getting relief from clinical depression typically requires a physician's guidance; but eating the right foods is a relatively simple way to help those affected get started on feeling better. Food can be either beneficial or detrimental to one's health. As such, diet can be a powerful tool for lifting depression. Even more specifically, the four food groups described below are known to help boost emotional well-being....
Lifetime probabilities of needing an organ transplant vs donating an organ
A study in the most recent issue of the American Journal of Transplantation investigates lifetime probabilities of needing an organ transplant vs donating an organ after death.
The lifetime probabilities of becoming a deceased organ donor and requiring or receiving an organ transplant are unknown.
An actuarial analysis was performed in a representative Canadian sample.
Dr Sam Shemie and colleagues from Canada used Canadian organ donation data from 1999 to 2007, provincial waiting list and population census data, actuarial rates were produced that provide the probabilities, by age band and gender, of becoming a deceased organ donor, needing an organ transplant, and receiving all organs needed.
Regardless of age, the lifetime probability of needing a transplant for males is approximately twice that of females.
Depending on age, Canadians are 5 to 6 times more likely to need an organ transplant than to become a deceased organ donor.
The lifetime probabilities of not receiving a required organ transplant, expressed as a percentage of individuals on the waiting list, ranges from approximately 30% at birth, 20 years and 40 years to approximately 40% at 60 years.
Across provinces and genders, Canadians at all ages are much more likely to need an organ transplant than to become an organ donor.
Approximately one-third of those in need of a transplant will never receive one. How this information may influence organ donation decisions is currently under study.
Am J Transplant 2011: 11(10): 2085–2092
07 October 2011
Cleveland Clinic study discovers new targets for treating inflammatory, autoimmune diseases
Researchers find pathway to potentially block disease-inducing inflammation
Friday, October 7, 2011, Cleveland: Researchers have discovered a cellular pathway that promotes inflammation in diseases like asthma, rheumatoid arthritis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Understanding the details of this pathway may provide opportunities for tailored treatments of inflammatory and autoimmune diseases.
Discovery of this pathway was the work of an active collaboration between Xiaoxia Li, Ph.D., and Thomas Hamilton, Ph.D., Department Chair, both of the Department of Immunology at Lerner Research Institute of Cleveland Clinic.
Their publications in Nature Immunology, selected for a News and Views article in the same issue, portray how a protein molecule known as interleukin-17 (IL-17) spurs inflammation by recruiting specific white blood cells to sites of infection and injury, producing a strong, pathogenic response.
Being able to block this pathway may treat IL-17-induced inflammatory diseases. Molecular factors discovered by Li and Hamilton make this concept a potential strategy.
"We are excited by the possibilities that this new research opens up for developing improved therapeutics for these difficult diseases," Hamilton said.
"Being able to collaborate like this really expedites the science," Li added, "ultimately leading, we hope, to profound improvement for those suffering from these autoimmune and inflammatory conditions."
###
About Cleveland Clinic
Celebrating its 90th anniversary, Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. It was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S.News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. About 2,800 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. Cleveland Clinic Health System includes a main campus near downtown Cleveland, eight community hospitals and 16 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and opening in 2013, Cleveland Clinic Abu Dhabi. In 2010, there were 4 million visits throughout the Cleveland Clinic health system and 155,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at http://www.clevelandclinic.org/.
Follow us at www.twitter.com/ClevelandClinic.
Stem Cells
Stem Cell Breakthrough Means Human Cloning Possible
By Clint Demeritt October 8, 2011 10:25 AM EDT
Stem cells are young cells that have yet to be developed into a specific cell type and are used by the body to renew tissue and repair damage. In adult stem cells, there are only so many types the cell can develop into. Embryonic stem cells are those present in a developing person when they are still in its mother's womb. Embryonic stem cells have the ability to become any cell in the body, which have a much better applications for medical use........
METHODS:
Searching the PubMed, Medline, Lilacs, Scopus, Ovid and Medscape databases we identified all the articles published until February 2011 that included only HCV cirrhotic patients. These studies evaluated the SVR after standard of care treatment: Pegylated Interferon alpha 2a (doses ranging between 135-180 µg/week) or Pegylated Interferon alpha 2b (1 or 1.5 µg/kg/week) and Ribavirin (doses ranging between 800-1200 mg/day). We used the following key words: HCV, liver cirrhosis, sustained virological response (SVR).
RESULTS:
The overall SVR rate was 33.3% (95%CI-confidence interval=30.6-36.2%). SVR was significantly higher in patients with genotypes 2 and 3 (422 patients) as compared to those with genotypes 1 and 4 (692 patients): 55.4% (95%CI=50.7-60.1) versus 21.7% (95%CI=18.7-25), p less then 0.0001.
CONCLUSION:
The overall SVR rate in cirrhotic patients treated with standard of care therapy is 33.3%, but lower in cases affected by genotypes 1 and 4 (21.6%) which makes them a priority regarding the development of more potent drugs for effective treatment.
Full Text
Study finds curcumin able to inhibit traumatic death of liver cells
2011/10/08 17:35:21Taipei, Oct. 8 (CNA)
Taiwanese researchers have discovered that curcumin, a compound that gives turmeric its yellow color, is effective in inhibiting liver cells from turning fibrous before they lead to cirrhosis and liver cancer.
National Taiwan University assistant professor Chiu Chih-hsien and his research team found that feeding laboratory mice with high concentrations of curcumin extract brought about "apoptosis" in their inflamed liver cells. Apoptosis is a process describing programmed cell death. Normally, liver cells are replaced by new ones after their life circle ends through the naturally controlled process.
But when the cells develop inflammation under the influence of alcohol, drugs and chemical substances, they undergo traumatic deaths, called "necrosis." In the process of necrosis, liver cells gradually turn fibrous and stiffen, and then become cirrhotic and carcinogenic, Chiu said. "(The natural substance) can bring injured liver cells under the process of apoptosis, preventing their taumatic death," according to the team's study, the first anywhere in the world to focus on the effect of curcumin in inhibiting fibrosis on the liver. They discovered that "curcumin can control the way liver cells die," the professor said.
The research was conducted through the cooperation of National Taiwan University Department of Animnal Science and Technology and Kaohsiung Veterans General Hospital. The results will be published in the Journal of Nutritional Biochemistry by the end of this year, Chiu revealed. Curcumin is one of the most common ingredients in curry, and is frequently used as a herbal medicine in India and China to fight inflammation.
In recent years, it has also been touted by some as effective in combating cancer and even Alzheimer's disease. Chiu said the study could help scientists learn more about how the liver turns fibrous and would also pave the way for people to develop drugs to treat liver fibrosis. Asked if eating foods containing curry or taking curcumin food supplements would have the same effect they had in the laboratory, Chiu said it would not help because the amounts were too low
Translocation of gut-derived bacterial products such as endotoxin is a major problem in liver cirrhosis.
Methods:
To assess the hepatic clearance of bacterial products in individuals with cirrhosis, we tested concentrations of Gram-negative bacterial lipopolysaccharide (LPS), LPS-binding protein (LBP), and the precursor of nitric oxide (NO), L-arginine, in a cohort of 8 stable patients with liver cirrhosis before and after elective transjugular portosystemic shunt (TIPS) implantation, including central venous, hepatic venous, and portal venous measurements.
Results:
Using an adapted LPS assay, we detected high portal venous LPS concentrations (mean 1743+/-819 pg/mL). High concentrations of LPS were detectable in the central venous blood (931+/-551 pg/mL), as expected in persons with cirrhosis, The transhepatic LPS gradient was found to be 438+/-287 pg/mL, and 25+/-12% of portal LPS was cleared by the cirrhotic liver.After TIPS, central venous LPS concentrations increased in the hepatic and central veins, indicating shunting of LPS with the portal blood through the stent. This paralleled a systemic increase of L-arginine, whereas the NO synthase asymmetric dimethylarginine (ADMA) remained unchanged, suggesting that bacterial translocation may contribute to the pathogenesis of circulatory dysfunction post-TIPS.
Conclusions:
This study provides quantitative estimates of the role of the liver in the pathophysiology of bacterial translocation.The data indicate that the cirrhotic liver retains the capacity for clearance of bacterial endotoxin from the portal venous blood and that TIPS implantation attenuates this clearance. Thus, increased endotoxin concentrations in the systemic circulation provide a possible link to the increased encephalopathy in TIPS patients.
Author: Daniel Benten Julian Schulze zur Wiesch Karsten SydowAnd reas KoopsPeter Buggisch Rainer BogerCharlotte GaydosHelen WonVeronica Franco Ansgar LohseStuart RayAshwin Balagopal
Credits/Source: BMC Gastroenterology 2011, 11:107
Coffee Helps Reduce Side Effects in HIV/HCV Coinfected People during Interferon-based Therapy
Oct 7
HIV/HCV coinfected people who drink at least 3 cups of coffee daily were less likely to experienced adverse events related to interferon-based therapy for hepatitis C, according to a French study presented at the 10th AIDS Impact Conference last month in Santa Fe. However, whether coffee somehow directly relieves side effects remains unknown.
Several studies have shown that coffee appears to have a beneficial effect on liver inflammation and fibrosis among people with hepatitis C, and it has also been linked to higher rates of sustained response to interferon-based treatment.......
Hepatitis C Report: Four Food Groups to Lift Depression
October 6, 2011
Applicable to many with chronic Hepatitis C, eating foods rich in these four elements has been shown to help depression sufferers lift their spirits.
by Nicole Cutler, L.Ac.
More than most other populations, people with chronic Hepatitis C are particularly prone to depression. Getting relief from clinical depression typically requires a physician's guidance; but eating the right foods is a relatively simple way to help those affected get started on feeling better. Food can be either beneficial or detrimental to one's health. As such, diet can be a powerful tool for lifting depression. Even more specifically, the four food groups described below are known to help boost emotional well-being....
Lifetime probabilities of needing an organ transplant vs donating an organ
A study in the most recent issue of the American Journal of Transplantation investigates lifetime probabilities of needing an organ transplant vs donating an organ after death.
The lifetime probabilities of becoming a deceased organ donor and requiring or receiving an organ transplant are unknown.
An actuarial analysis was performed in a representative Canadian sample.
Dr Sam Shemie and colleagues from Canada used Canadian organ donation data from 1999 to 2007, provincial waiting list and population census data, actuarial rates were produced that provide the probabilities, by age band and gender, of becoming a deceased organ donor, needing an organ transplant, and receiving all organs needed.
Regardless of age, the lifetime probability of needing a transplant for males is approximately twice that of females.
Depending on age, Canadians are 5 to 6 times more likely to need an organ transplant than to become a deceased organ donor.
The lifetime probabilities of not receiving a required organ transplant, expressed as a percentage of individuals on the waiting list, ranges from approximately 30% at birth, 20 years and 40 years to approximately 40% at 60 years.
Across provinces and genders, Canadians at all ages are much more likely to need an organ transplant than to become an organ donor.
Approximately one-third of those in need of a transplant will never receive one. How this information may influence organ donation decisions is currently under study.
Am J Transplant 2011: 11(10): 2085–2092
07 October 2011
Cleveland Clinic study discovers new targets for treating inflammatory, autoimmune diseases
Researchers find pathway to potentially block disease-inducing inflammation
Friday, October 7, 2011, Cleveland: Researchers have discovered a cellular pathway that promotes inflammation in diseases like asthma, rheumatoid arthritis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Understanding the details of this pathway may provide opportunities for tailored treatments of inflammatory and autoimmune diseases.
Discovery of this pathway was the work of an active collaboration between Xiaoxia Li, Ph.D., and Thomas Hamilton, Ph.D., Department Chair, both of the Department of Immunology at Lerner Research Institute of Cleveland Clinic.
Their publications in Nature Immunology, selected for a News and Views article in the same issue, portray how a protein molecule known as interleukin-17 (IL-17) spurs inflammation by recruiting specific white blood cells to sites of infection and injury, producing a strong, pathogenic response.
Being able to block this pathway may treat IL-17-induced inflammatory diseases. Molecular factors discovered by Li and Hamilton make this concept a potential strategy.
"We are excited by the possibilities that this new research opens up for developing improved therapeutics for these difficult diseases," Hamilton said.
"Being able to collaborate like this really expedites the science," Li added, "ultimately leading, we hope, to profound improvement for those suffering from these autoimmune and inflammatory conditions."
###
About Cleveland Clinic
Celebrating its 90th anniversary, Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. It was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S.News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. About 2,800 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. Cleveland Clinic Health System includes a main campus near downtown Cleveland, eight community hospitals and 16 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and opening in 2013, Cleveland Clinic Abu Dhabi. In 2010, there were 4 million visits throughout the Cleveland Clinic health system and 155,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at http://www.clevelandclinic.org/.
Follow us at www.twitter.com/ClevelandClinic.
Stem Cells
Stem Cell Breakthrough Means Human Cloning Possible
By Clint Demeritt October 8, 2011 10:25 AM EDT
Stem cells are young cells that have yet to be developed into a specific cell type and are used by the body to renew tissue and repair damage. In adult stem cells, there are only so many types the cell can develop into. Embryonic stem cells are those present in a developing person when they are still in its mother's womb. Embryonic stem cells have the ability to become any cell in the body, which have a much better applications for medical use........
Stem cell research has a number of applications in the medical field. Stem cells can help with heart diseases, diabetes and cancer. It can also help cure aliments like Parkinson's Disease and Alzheimer's. The cloning techniques can also be used to grow organs for patients with a failing liver or kidney. The cloned organs will be much less likely to be rejected than those donated from other individuals, since the new organs will be genetically identical to the one being replaced.
Pharmaceuticals
Developers should fess up about drug trial failures, researchers say
October 7, 2011 — 11:38am ET
By Ryan McBride
Naturally, drug researchers like to tout their victories and downplay their failures. But there are ramifications of not reporting results of experiments that go poorly, and two academics recently took on the issue in an a Science Translational Medicine article that says "translational medicine cannot approach its full potential if negative drug developments are unpublished," as Pharmalot's Ed Silverman cited in his interview with one of the authors. Michael Rogawski, chair of the department of neurology at UC Davis School of Medicine, talks to Silverman about his efforts to get developers to publish data they might rather keep under wraps. Interview
There’s no tiring of controversy in the XMRV–chronic fatigue syndrome link
It’s been a hectic couple of weeks for Judy Mikovits. First, her controversial research on the viral cause of chronic fatigue syndrome was condemned by the journal that published it. Then, her alternative hypothesis — that a new gammaretrovirus closely related to the originally proposed culprit, xenotropic murine leukemia virus-related virus (XMRV), is responsible for chronic fatigue — was received with misgivings by the scientific community at a major international conference. Add to the mix allegations of fabricated results and a blow-out with her boss, and Mikovits ended up being fired from her job at the Whittemore Peterson Institute (WPI) for Neuro-Immune Disease in Reno, Nevada.
The research that spawned the drama was originally published in Science in October 2009, and purported to show a link between the infectious retrovirus XMRV and chronic fatigue syndrome in two-thirds of CFS patients examined. The study, conducted by Mikovits and her collaborators, was the first sign of an infectious cause for the disease. However, follow-up studies since 2009 showed that other labs could not reproduce these results and scientists began to suspect that Mikovits’ original patient samples had been contaminated.
On 22 September, a large study published by Science showed that, of nine national laboratories, none could find XMRV in their patients’ blood — including Mikovits’ own lab. Notably, Science issued a partial retraction of the original 2009 paper on the same day, stating that one of Mikovits’ collaborators had found XMRV contamination in the patient blood samples. The saga was documented in a long feature by Science, ending with Mikovits pledging to continue studying the CFS and its viral links.
U.S. Attorneys in California Set Crackdown on Marijuana
By JENNIFER MEDINA
Prosecutors said they would concentrate on large, for-profit operations that use the medical law as a cover for large-scale drug operations, with marijuana being sent across state lines...
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