Massachusetts researchers have found that a compound in grapefruit blocks the Hepatitis C virus from infecting additional cells. Since the Hepatitis C virus depends on cholesterol metabolism to proliferate, future trials may prove that lipid-lowering drugs or supplements, such as that found in grapefruit, may inhibit the virus.
A compound naturally occurring in grapefruit and other citrus fruits may help get rid of hepatitis C virus, according to a study published in an upcoming issue of the journal Hematology.
The study led by researchers at the Massachusetts General Hospital Center for Engineering in Medicine showed naringerin, a flavonoid found in grapefruit, blocks the secretion of hepatitis C virus from infected cells.
Hepatitis C virus needs to latch onto a very low-density lipoprotein (vLDL, a so-called bad cholesterol) to pass on the infection to other cells in the liver.
The effect was observed in cultured cell lines.
"These results suggest that lipid-lowering drugs, as well as supplements, such as naringenin, may be combined with traditional antiviral therapies to reduce or even eliminate HCV from infected patients," said Yaakov Nahmias, PhD, of the MGH-CEM, the paper's lead author.
"Identifying the route by which HCV is released from cells introduces a new therapeutic target," said Martin Yarmush, MD, PhD, director of the MGH-CEM and the paper's senior author.
"That pathway's dependence on cholesterol metabolism could allow us to interfere with viral propagation to other cells and tissues, using tools already developed for atherosclerosis treatment."
Early studies showed hepatitis C virus needs vLDL to maintain its infection and naringenin can reduce secretion of vLDL from liver cells. The current study was meant to examine whether the compound might also lower HCV secretion from infected cells.
Hepatitis C virus is the leading cause of chronic viral liver disease in the United States that infects about 3 percent of the world population.
Eighty percent of persons with hepatitis C have no signs or symptoms but common symptoms include jaundice, fatigue, dark urine, abdominal pain, loss of appetite and nausea. Often it transmits from one person to another through contact of blood.
The current antiviral medications can treat 50 percent of cases, but 70 percent are expected to develop chronic infection, leading to cirrhosis or liver cancer in the end.
The researcher said naringerin or other lipid-lowering drugs could be used with other antiviral medications to treat hepatitis C infection if the effect is confirmed in human trials.
January 28, 2008
Hep C May Affect More than the Liver
A new study from Bulgaria proves that Hepatitis C infection is not only a liver disease, but affects many different parts of the body. Their research demonstrates that over three quarters of people with Hepatitis C have extra-hepatic manifestations and it helps physicians identify who is at the greatest risk.
Hepatitis C Virus Affects Many Organs And Tissues, Not Just Liver
www.sciencedaily.com
ScienceDaily (Jan. 18, 2008) — In 1994, the team of Tchernev and Petrova from Alexandrovska Hospital in Sofia examined a female patient with liver cirrhosis caused by chronic Hepatitis C virus (HCV). They were intrigued by the patient's many extra-hepatic manifestations -- vascular lesions on the lower limbs, acute pain in the joints, intense tingling of the fingers, and extreme labor-impairing fatigue. They were also intrigued by the presence of cryoglobulins in the patient's blood. Two years later, the patient developed enlarged lymph nodes on the neck. When one of the nodes was histologically tested, the patient was found to have lymphoma.
This case spurred the interest of the investigators in the extra-hepatic manifestations and complications of HCV infection, and for over a decade they studied the links between HCV infection, cryoglobulinemia, and lymphoma.
Hepatitis C virus is a major health problem worldwide, and more than 3 percent of the world's population is infected with HCV. Despite popular belief, HCV is not only a liver disease, but affects many organs, tissues, and systems.
In a new study of 136 Bulgarian patients with HCV, the team of Tchernev and Petrova found 76.5% of the patients had extra-hepatic manifestations. Common manifestations were fatigue (59.6%), renal impairment (25%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), and purpura predominantly of the lower limbs (17.6%). Over 37% of the patients had cryoglobulins, and 8.8% had B-cell lymphoma.
The study found positive links between the presence of extra-hepatic manifestations and age, female gender, duration of the infection, infection by transfusion of blood and blood products, and extensive liver fibrosis. Therefore, elderly women with chronic HCV and advanced liver fibrosis, who were infected by transfusion during childbirth, are at the highest risk of developing extra-hepatic manifestations of HCV infection.
The study also showed most extra-hepatic manifestations of HCV infection are associated with the presence of cryoglobulins. In particular, the risks of developing B-cell non-Hodgkin lymphoma are much higher in cryoglobulin-positive than in cryoglobulin-negative patients. In the study, 17.6% of cryoglobulin-positive patients had lymphoma, whereas only 3.5% of cryoglobulin-negative patients did.
Given the prevalence of HCV around the world, it is important for physicians to recognize the extra-hepatic signs and symptoms of HCV infection. Patients who exhibit such manifestations should be tested for HCV infection. This can lead to prompt diagnosis and effective treatment of the infection before the development of cryoglobulinemia, when treatment gives poor results or is ineffective.
Journal reference: Stefanova-Petrova DV, Tzvetanska AH, Naumova EJ, Mihailova AP, Hadjiev EA, Dikova RP, Vukov MI, Tchernev KG. Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients. World J Gastroenterol 2007; 13(48): 6518-6528 http://www.wjgnet.com/1007-9327/13/6518.asp
Adapted from materials provided by World Journal of Gastroenterology, via EurekAlert!, a service of AAAS.
Posted by Editors at 11:41 AM --- Printer-friendly version
Roche Stands By Their HCV Drugs Citing "IDEAL" Study Design Issues
Indicating patient preference for PegIntron™, Schering-Plough recently publicized their Hepatitis C trial, "IDEAL." However, competitor Roche indicates several IDEAL trial design issues that make for a poor comparison to their PEGASYS® with COPEGUS®.
Media Release
Contacts:
Brad Jenkins, Roche
+41 61 68 86404
Michelle Marchione
Axon Communications
+1 416 848 1419
Roche responds to announcement of “IDEAL” hepatitis C study
BASEL – January 14, 2008 – Following an announcement from Schering-Plough, Roche today affirmed the value of PEGASYS® (peginterferon alfa-2a) in combination with COPEGUS® (Roche’s brand of ribavirin) as the market-leading treatment for patients with hepatitis C. Despite clear biases in the design of the “IDEAL” study that potentially favoured patients taking PegIntron™ (peginterferon alfa-2b) regimens – particularly the ribavirin dose reduction protocol – the study results have shown that patients treated with a PEGASYS regimen had a similar chance of being successfully treated for hepatitis C.
“I do not expect that the results of the IDEAL study will meaningfully impact clinical practice, except to inform physicians on the appropriate dosing of PegIntron and to reinforce the already widely-accepted view that optimising ribavirin dosing throughout treatment is critical to achieving success and preventing treatment relapse in hepatitis C,” said Douglas Dieterich, M.D., Professor of Medicine in the Division of Hepatology at Mt. Sinai School of Medicine in New York, New York.
In 2001, the U.S. Food and Drug Administration (FDA) required Schering-Plough to conduct a post-approval commitment trial to determine if a lower dose of PegIntron (1.0 mcg/kg) was as effective as the approved dose of 1.5 mcg/kg, both in combination with identical ribavirin regimens.1 A third arm was added to the study in which patients received PEGASYS 180 mcg with a different ribavirin dosing schedule. This mismatch of ribavirin dosing introduces several potential biases into the study because experts agree that an optimised dose of ribavirin, with either pegylated interferon, is critical to achieving success in hepatitis C treatment. In particular, maintaining a full dose of ribavirin has shown an important ability to reduce relapse following the end of treatment.
“PEGASYS quickly became the market leader after its launch, based on robust clinical data and patient and physician preference. We are convinced that physicians and patients will continue to choose the PEGASYS plus COPEGUS combination therapy based on positive experience and sound clinical evidence,” said Rob Mitchell, Head of Viral Diseases Strategic Marketing at Roche. “Our current focus at Roche is on advancing the treatment of hepatitis C by optimising doses and duration of PEGASYS and ribavirin in patients with unmet medical need, while developing new compounds that have the potential to offer a successful outcome to even more patients.”
Roche believes that it is critical for patients and physicians to receive complete information to fully understand the results of “IDEAL” so that treatment decisions can be based on scientific data.
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Please see below for additional information about the “IDEAL” trial, Roche and PEGASYS including important safety information.
“IDEAL” Trial Design Issues
· Starting doses of ribavirin were different in the PegIntron and PEGASYS arms of the study
· The design calls for a more drastic ribavirin dose reduction for side effect management in most patients in the PEGASYS arm compared to patients in the PegIntron arms; in some cases, ribavirin dose reductions for patients in the PEGASYS arm were three times greater than for patients in the PegIntron arms. This is important because a substantial number of patients being treated for hepatitis C require their ribavirin dose to be reduced to manage side effects, and this could have an impact on the efficacy of the regimen
· The PEGASYS arm was not blinded, meaning that patients and physicians knew which treatment was being administered. Many comparative studies are blinded to ensure that bias does not compromise the results
· Erythropoetin (EPO) is a medication that is often given to treat ribavirin-related anemia and help patients maintain a higher ribavirin dose. However, physicians could only prescribe EPO after the first dose ribavirin reduction in the “IDEAL” trial. Since patients in the PegIntron arms generally had smaller ribavirin dose reductions, this introduces another potential bias and means those PegIntron patients were potentially able to maintain a higher dose of ribavirin compared to PEGASYS patients
Efficacy of PEGASYS plus COPEGUS Combination Therapy
PEGASYS was launched by Roche in 2002 and quickly became the leading treatment for patients with hepatitis C. PEGASYS plus COPEGUS is the only pegylated interferon combination regimen to have demonstrated significantly superior benefits over conventional interferon combination therapy across all HCV genotypes, irrespective of viral load.2-4 The combination of PEGASYS and COPEGUS consistently shows high cure rates – up to 66% overall sustained virological response – across a number of large, randomised clinical studies including in patients with difficult-to-cure disease such as genotype 1 HCV, cirrhosis, and HIV-HCV co-infection.2-7
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.
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All trademarks used or mentioned in this release are protected by law.
References:
1. FDA letter to Schering-Plough, August 7, 2001. Accessed Nov. 26, 2007 at: http://www.fda.gov/cder/foi/appletter/2001/pegsche080701L.htm
2. Swan, T. Expediency, Cost-Cutting, Expediency Trump Science in Clinical Development Plan for Peg-Intron: The head-to-head that wasn’t. TAGLine 2003: 10(10)1-4. Also available at: http://www.aidsinfonyc.org/tag/taglines/0312.pdf
3. Raymond, D. The Real IDEAL: Peg-Intron vs. Pegasys. Hepatitis C Harm Reduction Project Web site. Accessed Dec. 17, 2007 at: http://hepcproject.typepad.com/hep_c_project/2004/05/the_real_ideal_.html
4. Hadziyannis SJ, Sette H, Jr., Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140(5):346-55.
5. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004;351(5):438-50.
6. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347(13):975-82.
7. Marcellin P, Brillanti S, Cheinquer H. Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) is an efficacious and safe treatment for chronic hepatitis C (CHC) in patients with compensated cirrhosis. . In: 38th Annual Meeting of the European Association for the Study of the Liver (EASL) July 3-6; 2003; Geneva, Switzerland; 2003.
Posted by Editors at 11:40 AM --- Printer-friendly version
Non-Hodgkin's Lymphoma Less Likely with Hepatitis C Treatment
After following participants for one year, a large Japanese study concludes that treating Hepatitis C aggressively reduces the occurrence of non-Hodgkin's lymphoma.
Treatment of Hepatitis C Reduces Incidence of Non-Hodgkin’s Lymphoma
http://professional.cancerconsultants.com
Researchers from Japan have reported that viral elimination in hepatitis C virus (HCV) infected patients reduces the incidence of non-Hodgkin’s lymphoma (NHL). The details of this study appeared in the December, 2007 issue of the American Journal of Medicine.
Hepatitis C affects approximately 170 million individuals worldwide. Following acute infection, the virus persists in many patients and a minority of patients develop chronic disease. Chronic hepatitis can progress slowly over many decades to chronic active hepatitis and cirrhosis, ultimately leading to end-stage liver disease or hepatocellular carcinoma. Studies from other countries, but not from the United States, have also shown an increased incidence of NHL in patients with HCV infection. Some researches suspect that this correlation can only be observed in populations where HCV is highly prevalent.
The current study was carried in 501 patients with HCV infection who had never received interferon and 2,708 patients who had received interferon. These authors reported that by one year, 0.6% of untreated patients had developed NHL which by 5 years had increased to 2.3% and by 10 years to 2.6%. In contrast, there were no cases at 5, 10 and 15 years for the 1,048 patients with HCV infection who had sustained virologic response. The remaining patients who were treated and had persistent viral infection had an incidence of NHL of 0.4% at the fifth year, 1.5% at the tenth year and 2.6% at the fifteenth year.
Comments: These data support the concept that treating HCV infection aggressively can reduce the incidence of NHL.
Posted by Editors at 11:39 AM --- Printer-friendly version
HCV Alert: Another Doctor Reuses Syringes
Unfortunately, another Long Island doctor put patients in jeopardy of acquiring Hepatitis C when it was discovered that he reused syringes between patients. Unlike the Finkelstein case, New York authorities are moving quickly to inform the public and notify patients.
Another Long Island Doctor Commits Malpractice By Reusing Syringes
www.newsinferno.com
Date Published: Wednesday, January 16th, 2008
It’s been revealed that another Long Island doctor has reused syringes when administering injections to patients. Dr. E. Jacob Simhaee, a Manhasset-based obstetrician-gynecologist reused syringes when administering flu shots to at least 36 patients last fall. Simhaee is not the first Long Island doctor to commit such medical malpractice. Late last year, it was learned that Dix Hills doctor Harvey Finkelstein had infected several of his patients with blood borne diseases after reusing syringes.
According to the New York State Department of Health, Simhaee is contacting these patients in writing. The state Department of Health composed the letter for the physician. Simhaee was asked to sign the letter and is also contacting patients by telephone. The state initiated its investigation of Simhaee’s practice in December following a complaint filed with the Nassau County Department of Health.
The state’s release of information yesterday contrasts sharply with its handling of the Dr. Harvey Finkelstein case. It waited three years before telling the public last fall and notifying nearly 11,000 patients that Finkelstein had reused syringes—exposing thousands of patients to blood-borne pathogen infections—resulting in transmission of hepatitis C. As of Tuesday, 13 of Finkelstein patients have tested positive for hepatitis B and nine for hepatitis C. The state said it is impossible to determine whether Finkelstein’s office was the source of these infections. Finkelstein has more malpractice settlements than any other pain-management specialist on Long Island and, was sued, on average, once or twice yearly. Fifteen suits concerned epidural injections; at least 10 led to settlements. On his resume—posted on his now offline Web site—Finkelstein was described as a 1985 fellow in pediatric and cardiac anesthesia and a 1986 fellow in pain management via Stony Brook Hospital. A hospital spokeswoman said they were not accredited to offer fellowships in pain management until 1994, in pediatric anesthesia until recently, and are not accredited in cardiac anesthesia.
Mary Curtis, Nassau’s deputy executive of health and human services said, regarding the Simhaee investigation, “It’s amazing that in this amount of time, they conducted an investigation and made a notification,” adding, “The state and Nassau County did a great job. We’ve really learned from the past.” State senator Kemp Hannon (R-Garden City) feels the discovery of a second such case might warrant legislative action. “We’re going to have to look into the prohibition of multiple-use vials or limiting the use of syringes to single-use syringes,” he said.
As with Finkelstein, the department determined Simhaee used a single syringe, which held up to six doses, on multiple patients; infection-control procedures require a new syringe be used for each patient. The state said no diseases have been transmitted and Simhaee has cooperated fully. Simhaee’s patients who received the flu shot between September and December are being urged to be tested for hepatitis C, hepatitis B, and HIV and to be revaccinated against the flu.
According to Simhaee’s attorney, Craig Schaum of Garden City “This is a very highly respected doctor who has been cooperating in every way with state and county officials and will continue to do so.” Simhaee graduated in 1982 from the Albert Einstein School of Medicine at Yeshiva University in the Bronx, according to the state health department Web site; completed his graduate medical education at Maimonides Medical Center in the Bronx in obstetrics and gynecology; and is board certified in obstetrics and gynecology.
Posted by Editors at 11:35 AM --- Printer-friendly version
January 17, 2008
Fibrin Glue May Have Transmitted HCV
Used in Japan in the 1980s, a surgical adhesive made from fibrin is another suspect for the transmission of Hepatitis C. Primarily utilized for treating burns, nosebleeds and to aid in plastic surgery, fibrin glue may have been tainted with HCV-infected fibrinogen before proper testing was conducted.
Fibrin glue used for burns, facelifts
The Yomiuri Shimbun
www.yomiuri.co.jp
Fibrin glue, a surgical adhesive linked to the transmission of the hepatitis C virus, was used in a wide variety of areas, such as dealing with burns, stopping nosebleeds or in plastic surgery, according to doctors and other sources.
The tainted glue is estimated to have been used on about 79,000 patients, and those infected with the virus via the glue are eligible for relief under a law enacted Friday offering blanket relief to HCV suffers who contracted the disease through tainted blood products.
However, many patients do not realize the wide extent of the glue's use, causing delays in the investigation into how many patients have been infected with the virus via the glue. "The Health, Labor and Welfare Ministry should alert the public by announcing the names of hospitals that used the glue and for what kind of treatment the glue was often used," said Shiro Iino, former health ministry official in charge of research into issues concerning hepatitis.
The contaminated glue was made from a combination of substances including HCV-tainted fibrinogen manufactured by the defunct Green Cross Corp. mainly between 1981 and 1987. The glue was mostly used for stopping bleeding or as an adhesive during surgery. While it was not formally approved under the Pharmaceutical Affairs Law, Green Cross promoted the glue by issuing a booklet that gave details of how the glue could be used, resulting in many hospitals using it.
A private hospital in western Japan started using the glue from around 1982 as a surgical adhesive when it conducted major skin grafts on patients who had suffered severe burns. "As the glue had hemostatic and adhesive properties, we could conduct surgery quickly. I think we used the glue in treating between 10 to 20 patients a year," a doctor at the hospital said.
The hospital stopped using the glue in the late 1980s, when the risk of hepatitis infection came to light. They have not confirmed any cases of HCV infection via the glue.
"We no longer have the medical records of the patients as the storage term has already expired. But I think it's possible some patients will have contracted HCV via the glue as it was applied directly to the surface of the burned skin," the doctor said. "What has happened to those patients subsequently is a concern."
Meanwhile, a doctor in the ear, nose and throat department of another hospital in western Japan used the glue in the mid-1980s to treat patients suffering from nosebleeds. When it was difficult to identify from which part of the nose a patient was bleeding, the doctor filled the nose with the glue to stop the bleeding. The treatment was conducted on about 20 patients.
Several years ago, the doctor informed patients about the possibility of infection, and recommended them to undergo medical tests. But results obtained did not show any infection.
"As the glue was removed from the nose after treatment, that might have lowered the infection risk," the doctor said.
In the 1980s, the glue was also used in plastic surgery. According to an academic journal, an aesthetic plastic surgeon in Tokyo used the glue as a hemostatic agent or as a surgical adhesive in facelift operations.
According to a report submitted in 2001 to the Health, Labor and Welfare Ministry by the then Welfide Corp., which took over Green Cross, the glue was used in about 270 medical procedures, including some related to the treatment of pneumothorax and stomach ulcers.
(Jan. 15, 2008)
Posted by Editors at 03:15 PM --- Printer-friendly version
Proteomic Profiling Improves Liver Cancer Identification
Boston researchers have demonstrated that proteomics demonstrates a higher specificity and sensitivity for detecting liver cancer than traditional methods. This breakthrough may detect liver cancer tumors earlier, when they are easier to treat.
Proteomic profiling shown more accurate than traditional biomarkers in identifying liver cancer
Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
www.eurekalert.org
BOSTON – As the incidence of liver cancer continues to grow-- fueled in large part, by rising rates of hepatitis C infections – so too does the need for tests to help diagnose the disease at an earlier stage. A study appearing in the January 15 issue of Clinical Cancer Research demonstrates that a novel mass-spectrometry based form of proteomic profiling is more accurate than traditional biomarkers in distinguishing liver cancer patients from patients with hepatitis C liver cirrhosis, particularly with regard to identifying patients with small, curable tumors. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the study could help lead to earlier diagnostic methods – and subsequent treatments -- for liver cancer.
“Proteomics represents a potentially powerful tool for the serologic recognition of protein profiles associated with cancer,” explains co-senior author Towia Libermann, PhD, Director of the Genomics Center at BIDMC and Associate Professor of Medicine at Harvard Medical School.
“Although this particular proteomics technology, SELDI-TOF MS [surface enhanced laser desorption/ionization time of flight mass spectrometry] had alrea