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Week Ending: July 1st , 2006
Alan Franciscus
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June 17th, 2006
Fatty Liver Drug Does Well in S.A. Study
SourceURL:http://www.mysanantonio.com
Cindy Tumiel
Express-News Staff Writer
America's growing girth is giving rise to a new health problem – a form of hepatitis brought on by abnormally fatty livers.
Once uncommon, doctors now say the number of cases is on the rise -- particularly among those who are obese and at high risk for diabetes. It is even being diagnosed in children.
There aren't any approved drug treatments yet, but the push is on to find some. One pilot study involved San Antonio patients who took a diabetes drug called pioglitazone and showed encouraging results.
That drug and others now are being studied further in nationwide clinical trials.
"You eat too much food, take in too many calories and the fat gets deposited in your liver," said Dr. Ralph DeFronzo, professor of medicine at the University of Texas Health Science Center. "You can get hepatitis and cirrhosis. It is becoming a huge problem. It's becoming the commonest cause of liver disease."
Estimates are 30 percent of Americans have excessive fat in their livers. In most people, the fat doesn't cause any observable health problems, but 5 percent to 6 percent of them will go on to develop liver inflammation, said Dr. Arthur McCullough, chairman of gastroenterology and hepatology at the Cleveland Clinic in Ohio.
That condition is called non-alcoholic steatohepatitis, or NASH. The patients drink little or no alcohol, but liver enzymes are elevated in standard blood tests, and biopsies show the same sort of inflammation and scarring that is seen in alcoholics. If it progresses, patients can suffer liver failure.
Hispanics may be more susceptible. A 2002 study in Dallas County suggested that 45 percent of Hispanics there had elevated fat in their livers. The study, directed by Dr. Jeffrey Browning of the University of Texas Southwestern Medical Center, found that 34 percent of Anglos and 20 percent of blacks had elevated liver fat.
Doctors agree that the best thing for people to do is to lose weight and exercise. But because most people aren't successful at dieting, the search is on for medications that can help the liver get rid of accumulated fat.
Pioglitazone, sold under the brand name Actos, is a diabetes medication that makes the body more sensitive to insulin and helps mobilize fat out of the liver, said Dr. Kenneth Cuzi, an assistant professor at the health science center who directed the local study.
San Antonio researchers tested the drug in 54 people with NASH who were resistant to insulin, a condition that puts them at higher risk for developing diabetes. Half of them took pioglitazone and half took a placebo. All of them had liver biopsies before and after the study.
Patients who took the drug showed significant decreases in liver fat and significant improvement in blood sugar metabolism, Cuzi said. Liver scarring also was reduced, but by lesser amounts.
"We think that is because they only took the drug for six months and that is not long enough to reduce scarring," he said.
Follow-up studies of pioglitazone and other medications are under way by the recently formed NASH Clinical Research Network, a nationwide collaboration of liver experts. McCullough said one study in 240 adults is testing pioglitazone and vitamin E. The researchers also are testing another diabetes drug, metformin, in children with NASH.
Elsewhere, McCullough said, researchers are testing fish oil and pentoxifylline, a circulatory system medication.
ctumiel@express-news.net
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Appeal in Firing over Death Is Delayed
SourceURL:http://www.kansas.com
BY MARK E. MCCORMICK
The Wichita Eagle
A hearing has been postponed to Sept. 5 for a state Department of Corrections officer who appealed his firing in the wake of the death of an inmate at the Wichita Work Release Center.
An autopsy report listed cirrhosis of the liver as one of the causes of death for Alexis McCullough.
The hearing before the Kansas Civil Service Board for William A. DelGaudio Sr., one of the work release center's shift supervisors, had been scheduled for Monday but was pushed back at DelGaudio's request.
The board considers appeals from civil service employees dissatisfied with personnel actions. The board can affirm the action taken against an employee, reduce it or even increase it.
DelGaudio was on duty when McCullough, who'd complained for several hours of shoulder pain and shortness of breath, fell silent.
Inmates at the work release center told The Eagle that the 6-4, 300-pound McCullough, 41, was sweating profusely and that some corrections officers, including DelGaudio, ignored pleas for medical attention.
DelGaudio was fired, another shift supervisor was demoted and suspended, and a nurse who saw McCullough shortly before he died was barred from Kansas corrections facilities.
A coroner's autopsy report, filed June 8th, said McCullough suffered from multiple, serious conditions.
"In my opinion, Alexis McCullough died as a result of cirrhosis of the liver. Other: Chronic hepatitis C; atherosclerotic cardiovascular disease," Sedgwick County Coroner Mary Dudley wrote in the report. "The manner of death is natural."
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June 19th, 2006
Anger as Hepatitis Inquiry Ruled out Campaigners Furious after Health Minister Refuses Appeal
SourceURL:http://www.redorbit.com
By MARTYN McLAUGHLIN
THE Scottish Executive yesterday sparked anger by ruling out a public inquiry into how patients contracted hepatitis C through infected blood products in the 1970s and 1980s.
Andy Kerr, Health Minister, said an inquiry would not add significantly to an understanding of how the blood supplies came to be contaminated.
"A full judicial inquiry would be a major and time-consuming exercise which would depend on the recollections of witnesses about events which took place 20 or more years ago, " he said. "This would make it difficult to construct a clear and detailed picture of what took place."
Campaigners who have fought for years for a public inquiry reacted furiously, accusing the executive and Westminster of engaging in a cover-up affecting up to 35,000 Scots.
Mr Kerr's announcement comes two months after MSPs on Holyrood's health committee called for an inquiry into how thousands of people contaminated hepatitis C.
Patients using blood products became infected with the virus before a test to identify it was developed in 1991.
In a letter to the committee, Mr Kerr pointed to the decision to set up a payment scheme for victims UK-wide. He said a "look-back" exercise had been decided on by UK ministers before devolution, and testing and counselling were still available for those who feared they were at risk from pre-1991 transfusions. He said: "I do not believe a public inquiry would either uncover any new evidence or information that is relevant to the causes of the infection of NHS patients through blood and blood products, or lead to significant lessons for the future.
"I cannot see that there is any possible justification for the efforts and costs that would be involved, or that this would bring any benefit to the patients involved."
Roseanna Cunningham, SNP MSP and convener of the health committee, said: "People are still coming forward and it's unacceptable that people are still out there who do not realise that they have been infected. I'm disappointed. I don't think it does Scotland any good to have real concerns such as these ignored by the executive."
Frank Maguire, a solicitor advocate with Thompson Solicitors in Glasgow, is handling hundreds of cases of people throughout Scotland infected with hepatitis C, and their relatives. He said yesterday: "The health committee has clearly called for an inquiry to be held but the minister is riding roughshod over it all.
"It's disrespectful to raise more questions than answers, and fail to address the concerns that have been raised.
Carolyn Leckie, SSP health spokeswoman, said: "There has never been an independent judgment of the information available or not available and that's a crucial question. Again we're being patronised and asked to trust the judgment of civil servants, the medical establishment and government and they don't think there's anything more to be said."
The Hepatitis C Trust estimated 18,000 Glaswegians could have the disease, and it is estimated it will cost the NHS GBP1.6bn to manage it by 2035.
Philip Dolan, chairman of the Scottish Haemophilia Group Forum, said: "I'm very angry and yet again this fails a vulnerable group of people. [The minister] has ignored the recommendations of a number of people and there's sufficient evidence from a range of different sources about people who have never been told."
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First Ruling Near in Suit over Drug-Caused Hepatitis C Debacle
SourceURL:http://search.japantimes.co
By YOHEI SEKI and JUN NAGATA
OSAKA (Kyodo) Life changed drastically for Osaka resident Etsuko Morigami in 1987 when she was diagnosed with cirrhosis of the liver, some 13 years after being infected with hepatitis C through a tainted blood-clotting agent given to her while she was giving birth.
Morigami was treated with a blood-clotting product to stop her bleeding when she had her first son, Minoru, now 32.
After contracting cirrhosis, she developed diabetes and kidney damage. Insulin injections three times a day were a must.
"I often went out with my family and I was really in good shape," Morigami, 56, said of the time before the symptoms became severe, looking at the more than 10 kinds of drugs on a table beside her.
Considering her condition, treatment of hepatitis C with interferon, which eliminates the virus but whose side effects are severe, was halted. She developed liver cancer, and a long tube was inserted into her side to kill cancer cells with ethanol.
But she had relapses, with the intervals becoming shorter and shorter. Eventually she had no other option than a partial liver transplant, and Minoru was the donor.
"As you were infected when I was born, I will repay my debt to you," he told her.
Morigami underwent the transplant last June. To prevent rejection, she took an immuno-suppression drug, and to avoid infectious diseases she could not leave home, except to go to the hospital.
But her new liver gradually deteriorated, and the interferon treatments were resumed in February, now that there are more drugs available to control its side effects. Although she has also been diagnosed with lung cancer, it is inoperable.
"There is a time bomb inside you. If it explodes, you will blow up," a group of lawyers said in a statement aimed at trying to explain the plight of patients, many of them unwittingly infected with hepatitis C.
Although initial symptoms may not be critical, the hepatitis will eventually lead to cirrhosis and liver cancer.
"Swift measures should be taken before it is too late," said Morigami, one of the plaintiffs in a damages lawsuit against the government and Mitsubishi Pharma Corp.
Mitsubishi Pharma is the successor of Green Cross Corp., the firm that produced the blood product that caused her hepatitis C infection. The blood product was marketed under the brand name Fibrinogen-BBank.
The Osaka District Court will rule on the suit Wednesday in the first legal judgment involving tainted blood products leading to hepatitis C infections.
Besides the physical effects of hepatitis C, patients face discrimination often born out of ignorance and fear.
At a gathering in Tokyo's political center of Nagata-cho in late May, plaintiffs complained of discrimination and prejudice against them by employers and other sectors of society.
"I may not be employed if I tell (my employer) I am suffering from hepatitis C," a man in his 20s, one of the plaintiffs in a lawsuit filed with the Tokyo District Court, said.
A woman said, "I am hiding my disease because I fear that my children's friends' parents may tell them not to play with my kids."
Hepatitis C is caused mostly by direct infection of the blood and is not transmitted by ordinary social contact, but at the gathering many patients complained of the agony of not being able to tell people they have the disease.
Some reported having been refused dental treatment, and one woman was fired from her job in a company cafeteria. Management told her the disease was infectious.
Since the end of World War II, Japan has suffered several drug-induced disasters, including the childbirth deformities caused by thalidomide in the 1950s and '60s, SMON (a disease similar to polio), another disease caused by defective chloroquine in the 1950s, and the HIV/AIDS outbreak caused by contaminated blood products -- also marketed by Green Cross -- in the 1980s.
"The suffering can be said to be on a historically large scale, but the real situation is not well-known in society," said Kiyohiko Katahira, a professor of health and welfare at Toyo University.
Regarded as the largest of these drug-induced diseases is SMON, caused by the antiflatulence drug chinoform in the 1950s and 1960s, which affected some 10,000 people.
According to Mitsubishi Pharma, the number of patients since 1980 infected with hepatitis C as a result of taking the tainted blood product based on the naturally occurring protein fibrinogen is estimated at 10,000.
But as the product had been sold since its approval by the government in 1964, Katahira said, "The number of victims will be about 30,000 if the average annual number of victims before 1979 is assumed to be the same," making it much larger than the SMON disaster.
There is more than one similarity between this case and the HIV/AIDS fiasco, in which a doctor and a high-ranking official at the old Health and Welfare Ministry were prosecuted for allowing tainted products to stay on the market after being officially warned of their dangers. Victims in both cases have been plagued by discrimination and prejudice, and are waging lawsuits without revealing their real names.
In the case of hepatitis C, only 10 of the 96 plaintiffs across the country have made their real names public.
There are also many other victims who cannot become plaintiffs even if they wanted to, because their medical records have been lost and their link to tainted blood products cannot be proved.
Fibrinogen is a globulin in the blood that aids coagulation, and products containing it were widely used by obstetricians, gynecologists and surgeons. But the U.S. government canceled its approval for such blood products in 1977 because there was a danger that the products, made from donated blood, could be infected.
Despite that, 50,000 to 70,000 packages of the Green Cross product were sold annually between 1980 and 1986. When an epidemic of liver inflammation-infection cases erupted in Aomori Prefecture in 1987 and similar reports continued, Green Cross began to recall the product.
Although the government began to study ways to strengthen the medical examination and treatment system, Norio Hayashi, a professor at the graduate school of Osaka University, said the system is not satisfactory. "Hepatitis C patients are estimated to number 1.5 million in Japan, but there are only some 3,000 liver-specialist doctors," he said.
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Patients Treated with Baraclude Experience Virologic Suppression to Undetectable Levels
SourceURL:http://www.therapeuticsdaily.com/
2006 JUN 19 - (NewsRx.com) -- Bristol-Myers Squibb Company (BMY) presented 96-week clinical trial data at Digestive Disease Week from two phase III studies demonstrating that Baraclude (entecavir) led to a significant difference in viral load suppression to undetectable levels compared to lamivudine in two chronic hepatitis B patient types.
After up to 96-weeks of treatment, 94% of nucleoside-naive HBeAg-negative chronic hepatitis B patients treated with Baraclude experienced an undetectable viral load, defined as HBV DNA less than 300 copies per milliliter of blood (mL), compared to 77% of patients treated with lamivudine. This difference was statistically significant based on a cumulative analysis of all patients (p<0.0001). In addition, no evidence of Baraclude resistance was identified in these patients.
Additional 96-week study data presented evaluated the use of Baraclude compared to continued lamivudine in lamivudine-refractory, HBeAg-positive chronic hepatitis B patients. After up to 96-weeks of treatment, 30% of patients who were switched to Baraclude treatment achieved an undetectable viral load, compared to less than 1% of patients who continued lamivudine treatment (p< 0.0001, based on cumulative analysis of all treated patients). Viral rebound due to Baraclude resistance occurred in 9% of patients through Week 96 and required the prior presence of LVD-resistance substitutions.
"It is increasingly recognized that hepatitis B viral load is an important evaluation tool for physicians when assessing, monitoring, and managing patients," said Morris Sherman, MD, a Baraclude study investigator and associate professor of medicine at the University of Toronto.
Study ETV-027 was a large-scale, multinational, phase III clinical trial of 638 HBeAg-negative chronic hepatitis B patients who had not previously received nucleoside treatment. In the study, patients received either Baraclude 0.5 mg once daily (n=325) or lamivudine 100 mg once daily (n=313) for a minimum of 52 weeks.
At Week 52, patients were categorized into one of three groups based on evaluations at Week 48: non-responders (HBV DNA by branched DNA (bDNA) greater than or equal to 0.7 MEq/mL) who discontinued treatment; responders (HBV DNA by bDNA <0.7 MEq/mL and alanine aminotransferase (ALT) <1.25 times the upper limit of normal) who discontinued treatment and were followed for 24 weeks off-treatment; and virologic responders (HBV DNA by bDNA <0.7 MEq/mL and ALT greater than or equal to 1.25 x ULN) who went on to receive blinded treatment up to Week 96.
In a cumulative analysis of all patients treated through 96 weeks, 94% of patients in the Baraclude treatment group (n=325) experienced virologic suppression to undetectable levels, compared to 77% of patients given lamivudine (n=313) (p<0.0001). Additionally, the proportion of patients achieving or maintaining ALT level normalization was 89% for patients treated with Baraclude, compared to 84% of patients treated with lamivudine (p=0.05).
No evidence of Baraclude resistance was identified in patients treated for up to 96 weeks who had no prior lamivudine-resistance substitutions at baseline.
Safety was comparable between the treatment groups, with similar incidence of serious adverse events (6% with Baraclude, 8% with lamivudine) and any adverse event (76% with Baraclude, 80% with lamivudine). Discontinuations due to adverse events were observed in 2% of patients treated with Baraclude and 3% of patients treated with lamivudine. The incidence of ALT flares in patients treated with Baraclude on- or off-treatment were <1% and 8%, respectively, and in patients treated with lamivudine were 2% and 11%, respectively.
These 96-week results of Study ETV-027 are an update to the 48-week study results recently published in the March 9, 2006 issue of the New England Journal of Medicine.
As part of Study ETV-026, a multinational phase III clinical trial, 286 lamivudine-refractory, HBeAg-positive chronic hepatitis B patients were randomized to receive Baraclude 1.0 mg once daily (n=141) or continued lamivudine 100 mg once daily (n=145) for a minimum of 52 weeks.
At Week 52, patients were categorized into one of three groups based on evaluations at Week 48: non-responders (HBV DNA by branched DNA larger than or equal to 0.7 MEq/mL) who discontinued treatment; responders (HBV DNA by bDNA <0.7 MEq/mL and HBeAg loss) who discontinued treatment and were followed for 24 weeks off-treatment; and virologic responders (HBV DNA by bDNA <0.7 MEq/mL and but HBeAg-positive) who went on to receive blinded treatment up to Week 96.
In a cumulative analysis of all patients treated through 96 weeks, 30% of patients treated with Baraclude (n=141) compared to less than 1% of patients who continued treatment with lamivudine (n=145) achieved an undetectable viral load. The difference was statistically significant (p<0.0001). Additionally, 17% of Baraclude patients compared to 6% of lamivudine patients experienced HBeAg seroconversion (p=0.0011). The proportion of patients achieving ALT normalization was significantly greater for patients treated with Baraclude (85%), compared to patients treated with lamivudine (29%) (p=0.0001).
Viral rebound due to Baraclude resistance mutations occurred in 9% of lamivudine-refractory patients during the second year of treatment.
Safety was comparable between the treatment groups, with similar incidence of serious adverse events (11% with Baraclude, 7% with lamivudine) and any adverse event (83% with Baraclude, 80% with lamivudine). Discontinuations due to adverse events were observed in 1% of patients treated with Baraclude versus 7% of patients treated with lamivudine. The incidence of ALT flares in patients treated with Baraclude on- or off-treatment were 1% and 12%, respectively, and in patients treated with lamivudine were 11% and 0%, respectively.
Discovered at Bristol-Myers Squibb, Baraclude is a nucleoside analogue approved for marketing in the United States by the U.S. Food and Drug Administration (FDA) on March 29, 2005. Baraclude is indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication with either evidence of serum aminotransferases (ALT or AST) or histologically active disease.
In addition to the U.S., Baraclude has been approved in more than 20 countries and regions around the world including Argentina, Brazil, China, Indonesia, Vietnam, Mexico, the Philippines and Singapore. Bristol-Myers Squibb has submitted marketing applications for entecavir in other regions and countries around the world, including the European Union.
This article was prepared by Hepatitis Weekly editors from staff and other reports.
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Coley's Actilon for Chronic Hepatitis C Virus Therapy Granted Fast Track Designation
SourceURL:http://www.therapeuticsdaily.com/
Hepatitis Weekly - Jun. 19, 2006
2006 JUN 19 - (NewsRx.com) -- Coley Pharmaceutical Group, Inc. (COLY) announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ACTILON (CPG 10101) for use in treatment-refractory patients chronically infected with the hepatitis C virus (HCV).
"A Fast Track designation for our ACTILON development program allows Coley to work closely and expeditiously with the FDA to potentially benefit patients who currently have no other treatment alternatives," said Ferdinand E. Massari, MD, senior vice president, drug development and chief medical officer of Coley Pharmaceutical Group.
ACTILON is an investigational Toll-like receptor 9 (TLR9) agonist designed to induce both rapid and sustained immune responses that can have durable anti-viral effects.
Positive data from the company's 12-week Phase Ib clinical study of ACTILON in combination with pegylated interferon and ribavirin among treatment-refractory patients, who had initially responded but then relapsed after treatment with pegylated interferon and ribavirin, were presented in April 2006 at the European Association for the Study of the Liver (EASL) meeting in Vienna, Austria.
A 48-week Phase II clinical study evaluating safety and activity of ACTILON in combination with pegylated interferon and ribavirin is currently enrolling treatment-refractory HCV patients who never responded after a minimum of 12 weeks of pegylated interferon and ribavirin treatment.
This article was prepared by Hepatitis Weekly editors from staff and other reports.
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Vertex Initiates First of Two Phase 2 Studies of Oral Protease Inhibitor in HCV Patients
SourceURL:http://www.therapeuticsdaily.com/
Hepatitis Weekly - Jun. 19, 2006
2006 JUN 19 - (NewsRx.com) -- Vertex Pharmaceuticals Incorporated (VRTX) reported that it has initiated PROVE 1, a major phase 2 study of VX-950, an investigational oral hepatitis C virus (HCV) protease inhibitor.
In addition, the company announced it expects to initiate PROVE 2, a second major phase 2 study in June. The studies will be conducted in the United States and Europe as part of a global phase 2 development program for VX-950. Together, the two studies are expected to evaluate sustained viral response (SVR) rates in 580 treatment-naive patients infected with genotype 1 HCV.
Vertex's global phase 2 development program in treatment-naive patients has three objectives: to evaluate the optimal SVR rate that can be achieved with VX-950 therapy in combination with the current standard of care, to evaluate the optimal treatment duration for VX-950, and to evaluate the role of ribavirin in VX-950-based therapy.
In addition to these two major studies, Vertex expects to begin additional clinical studies of VX-950 in the second half of the year, including a phase 2b study in patients who failed prior standard of care treatment. Vertex anticipates this phase 2b study to enroll approximately 400 patients. By the end of the first quarter of 2007, Vertex expects to have enrolled approximately 1,000 patients in clinical trials of VX-950.
The two studies announced are the initial studies in a program of the "Investigation of HCV Protease Inhibition for Viral Eradication" (PROVE). The PROVE 1 and PROVE 2 studies have been designed as major, complementary studies to be conducted in the United States and Europe that will evaluate the ability of VX-950 to achieve SVR with short duration combination therapy. Following consultations with regulatory authorities in the U.S. and Europe, trial designs have been completed.
Vertex expects the PROVE 1 and PROVE 2 studies to enroll 580 patients at more than 55 centers worldwide. Vertex expects that these studies, taken together, will provide a substantial evaluation of the potential of VX-950-based therapy to achieve SVR.
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The company's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
This article was prepared by Hepatitis Weekly editors from staff and other reports.
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June 20th, 2006
Study Analysis Shows that Eltrombopag Significantly Improves Platelet Count and Response Rates in Idiopathic Thrombocytopenic Purpura (ITP)
SourceURL:http://www.medicalnewstoday.com
GlaxoSmithKline plc (NYSE: GSK; London) today announced results from a global Phase II study of its investigational small molecule oral platelet growth factor, eltrombopag. Data from this study demonstrated that treatment with eltrombopag resulted in a significant increase in platelet count compared to placebo across a variety of typically poorly responding ITP patients including those with prior splenectomy or those having a very low baseline platelet count (<15,000/micro liter).
(1) At doses of 50mg and 75mg, 70% and 81% of patients respectively, achieved the primary clinical endpoint of having a platelet count greater than 50,000/ micro liter after up to 6 weeks of dosing compared to 11% of patients on placebo.(1) Full results from this randomized, double-blind, placebo- controlled trial are being presented today at the 11th Annual Congress of the European Hematology Association (EHA) in Amsterdam. Based on these and previous clinical trial results, eltrombopag has the potential to be the first oral platelet growth factor for patients with thrombocytopenia, a disorder characterized by low platelet counts leaving patients at risk of episodes of spontaneous bruising, mucosal bleeding, and in severe cases intracranial hemorrhage.
"Results demonstrating the beneficial effect of an oral therapy such as eltrombopag, which may potentially work by stimulating the production of platelets, is very exciting and a major scientific advance," says Adrian Newland, Professor of Hematology at Queen Mary, University of London and a principal investigator for this trial. "This is highly encouraging news for patients who are in real need of new therapies to combat ITP because current treatment options such as steroids or removal of the spleen all have significant limitations, particularly in terms of side effects."
Eltrombopag is an investigational non-peptide small molecule that is administered orally and interacts with the thrombopoietin receptor. This receptor is located on the surface of specific cells in the bone marrow and its stimulation leads to the production of platelets.
The global Phase II trial enrolled 118 adult patients with chronic ITP. Patients were permitted to continue receiving stable doses of maintenance immunosuppressive therapy while participating in the study. Baseline platelet counts were <30,000/micro liter and the primary efficacy endpoint was the proportion of patients with platelets greater than or equal to 50,000/micro liter after up to 6 weeks of dosing. A dose dependent increase in the proportion of responders was observed: placebo (11%), 30mg (28%), 50mg (70%) and 75mg (81%).(1) Difficult to treat subgroups including patients with previous splenectomy, patients who did not respond to previous treatments and patients with very low platelet counts (<15,000/micro liter) showed response to treatment with eltrombopag.
(1) Overall, the safety profile was similar across the treatment groups, with the following percentage of patients experiencing at least one adverse event (AE) during treatment: placebo (59%), 30mg (47%), 50mg (47%) and 75mg (61%). The most common AE in the eltrombopag 75mg arm was headache reported by 21% of patients; 21% of patients exposed to placebo also reported headache. A total of 3 (10%), 2 (7%) and 1 (4%) patients in the placebo, 50 mg and 75 mg groups respectively experienced an AE leading to withdrawal during treatment. No patients in the 30mg eltrombopag arms withdrew from the trial due to adverse events. No dose dependent safety concerns were identified.(1)
"ITP is a frightening disease which does not follow a predictable course. Severity and symptoms vary enormously from one patient to another," says Shirley Watson, Founder of the ITP Support Association. "It is exciting news that a new drug is in development for ITP sufferers whose condition requires treatment. As eltrombopag stimulates platelet production rather than preventing platelet destruction, it offers a different approach for those with chronic refractory ITP."
Also during the EHA, Joseph A Erhardt of GlaxoSmithKline gave an oral presentation of data (abstract 1024) showing that in vitro stimulation of platelet production by eltrombopag induces the same level of platelet function as those produced in vivo.(2)
"As we move into Phase III studies, the development of eltrombopag treatment represents a significant milestone for GSK Oncology in supportive care and underscores our continued commitment to delivering novel treatments to potentially meet a significant unmet medical need," says Paolo Paoletti, MD, Senior Vice President, Oncology Medicine Development Center, GSK.
About Eltrombopag
Eltrombopag is an investigational small-molecule thrombopoietin receptor agonist that has been shown in pre-clinical research and clinical trials to stimulate the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets, and thus may be considered a platelet growth factor. Because it is a small molecule, eltrombopag is administered orally as a tablet and may have less potential than large protein molecules for causing an immune system reaction.
Eltrombopag was discovered as a result of a research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by GlaxoSmithKline.
About Thrombocytopenia and ITP
A reduction in platelet count is the defining characteristic of any type of thrombocytopenia and diagnosis can be confirmed following a routine blood test. Thrombocytopenia occurs in 5% to 10% of all patients hospitalized for any cause.(3)
ITP is an autoimmune disorder that is marked by platelet destruction and/or inadequate platelet production. Primary ITP is estimated to affect 50 to 100 new persons per million per year in the United States and Europe. (4) Some patients with ITP are asymptomatic or have mild bruising while others develop mucosal bleeding that can become severe.(5) ITP is associated with a 5% fatality rate largely due to intracranial hemorrhage.(6)
Thrombocytopenia also can occur as a consequence of chemotherapy treatment, interferon treatment, or chronic liver disease. Thrombocytopenia can impede a variety of medical treatments. It can prevent cancer patients from receiving their full dose of chemotherapy, prevent patients with hepatitis C infection from receiving interferon therapy or lead to dose reductions or discontinuation, and it can prevent or complicate procedures (surgical, dental etc.) in patients with chronic liver disease and ITP.
About GlaxoSmithKline
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit http://www.gsk.com.
Information about trial enrolment can be obtained by visiting http://www.itpstudy.com or http://www.clinicaltrials.gov.
Cautionary statement regarding forward-looking statements Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the 'Operating and Financial Review and Prospects' in the company's Annual Report 2005.
References:
(1) Newland, A., Cheng, G., et al. Eltrombopag increases platelets during 6-week treatment of ITP - results of a randomized, double-blind, placebo-controlled phase II study. Presented 18 June, 11:00-11:15 CET.
(2) Erhardt, J, Abboud, M. et al. The low molecular weight TpoR agonist, eltrombopag, does not prime platelet activation in vitro. Presented 18 June, 11:30-11:45 CET.
(3) Mocharnuk R. Growth factors in granulocytopenia and thrombocytopenia. Presented at: 44th Annual Meeting of the American Society of Hematology; December 6-10, 2002; Philadelphia, Pa.
(4) Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic purpura. Annu Rev Med. 2005;56:425-442.
(5) Stasi, R., Provan, D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004;79:504-522.
(6) George, JN., Woolf, SH., Raskob, GE., et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996,88:3-40.
GlaxoSmithKline plc
http://www.gsk.com
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Arctic Nations Team up to Fight Hepatitis B
SourceURL:http://www.cbc.ca/
Circumpolar countries have joined forces to deal with high northern rates of Hepatitis B, a virus that can lead to liver cancer and cirrhosis.
The rate of the virus in Canada's north is between two and eight per cent while in southern Canada and the U.S. it's less than half of one per cent, a conference on circumpolar health held in Siberia this month was told.
Hepatitis B can be passed on during birth, sexual activity or through open cuts.
Dr. Brian McMahon, who works at the Alaskan Native Medical Centre in Anchorage, said the circumpolar group wants to learn more about which variations of Hepatitis B cause cancer or cirrhosis in order to enable earlier intervention.
"More than 68 per cent, 70 per cent of people can get Hepatitis B and go through life and live a normal life without ever getting sick with it, but 30 per cent will," he noted.
There are anti-viral drugs available, but they only suppress the virus and do not kill it, he said.
"It's a very big concern because the rates are so high and even if we vaccinate we still have people who are chronically infected and who have risk of getting cancer," said McMahon.
Nunavut's chief medical health officer, Dr. Isaac Sobol, who is also part of the circumpolar group, saw advantages to joining forces with other northern countries.
"We could look into some research that's been done in other places about treatment regimes and what's best for people to keep anyone who's infected from becoming actively sick from it," he said.
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120 Million Hepatitis B Virus Carriers in China Face Discrimination
Versi SourceURL:http://www.theepochtimes.com
By Wen Hua
Epoch Times Staff
As reported by Beijing Daily on June 13, Beijing has become a moderate hepatitis B virus (HBV) epidemic region in the country. Based on China's statistic in 1992, there were at least 30 million HBV patients and 120 million HBV carriers in China. The epidemic situation is serious but prevention and education are insufficient, causing millions of HBV carriers to severely suffer not only in body, but also in spirit as they face discrimination by the uninformed,
Serious HBV Epidemic
Based on a recent survey revealed by Beijing Health Bureau, 5.76 percent of Beijing citizens carry the hepatitis B virus, and the infection rate is 45 percent. The incidence rate in recent years is approximately 20 out of 100,000.
According to medical experts, the incidence of the hepatitis B disease in China is the highest in the world. For instance, the incidence rate of hepatitis B is more than 17 percent in Guangdong Province.
Liu Gengtao, a member of the Chinese Academy of Engineering and a liver biochemistry pharmacologist, said that the survey in 1992 showed that there were 30 million HBV patients and 120 to 150 million HBV carriers, more than 10 percent of the population, and accounted for one third of the total HBV carriers in the world. Nearly half a million people die of this disease each year, and the annual cost for medical treatment of the disease in China was over 100 billion yuan (US$12.5 billion).
As reported by Xinmen Weekly, Zhuang Hui, a member of the China Academy of Engineering and an professor at Department of Etiology in Medical Institute of Beijing University pointed out that due to the lack of a standardized diagnosis of the hepatitis B and a comprehensive assessment of the social effect in China, the quality of epidemic report was underestimated and the degree of seriousness was attenuated. .
Omnipresent Discrimination Against HBV Carriers
With ineffective publicity and education regarding the HBV disease, the public does not understand HBV, which cannot be transmitted through common contacts.
According to an investigation on ten non-food and daycares professions in Shanghai and Beijing cities, seven of them simply refused to accept hepatitis B virus carriers, two said there is a small chance of being considered, and only one said it would recruit HBV carriers.
Among ten randomly selective people on a spot investigation in Beijing and Shanghai, everyone believes that saliva is the main vehicle of HBV infection. Seven people think that daily contact with virus carriers can also cause infection. Three people think body fluids such as sweat glands can infect other people. However, they are all mistaken. Where did all these wrong impressions come from?
An analysis from a forum named "Heart to Heart" on a well-known HBV carriers website in China indicated that in order to make profit, numerous fake anti-hepatitis B advertisements twisted and exaggerated the hazardous nature of HBV carriers; some medical clinics even abuse their right in diagnosing and treating the HBV carriers. With the disguised support and tacit permission from the government apparatus, rather relatively backward education of popular science, and retarded regulations stipulated by the Chinese authorities, the substantial discrimination against HBV carriers has become prevalent in society.
Eighty thousand registered members in the "Heart to Heart" forum indicated that they live in an isolated and discriminated environment every moment of every day, and many of them are forced to lose their opportunity to work, study, family and social activities. Their lives are miserable beyond description. In recent years, many of them have moved towards human rights protection using their rights entrusted by law.
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Hep C Patients' Insurance Scheme
http://www.irishhealth.com
Health Minister Mary Harney has announced the publication of a Bill by the Government to establish a statutory scheme to address insurance difficulties experienced by persons infected with Hepatitis C and HIV through the administration within the State of blood and blood products.
The Tanaiste said this is an important measure to provide further support to people, mainly women, diagnosed with Hepatitis C and HIV as a result of contaminated blood products being administered to them.
"Since 1997, it has been clear that infected people's inability to buy life assurance or mortgage protection policies added further problems to the damage they had already suffered. With this Bill there will be three forms of recompense: compensation, a special health card and life assurance support," the Tanaiste said.
The Bill also allows for the development of a scheme for travel insurance.
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June 21st, 2006
Tacrolimus a Primary Immunosuppressant post Liver Transplant
SourceURL:http://www.gastrohep.com
Treating recipients with tacrolimus instead of cyclosporin avoids rejection in more patients, but some may develop diabetes after the transplant, finds this month's issue of the American Journal of Transplantation.
Dr McAlistera and colleagues from Denmark evaluated the beneficial and harmful effects of immunosuppression with cyclosporin vs tacrolimus for liver transplanted patients.
The research team undertook a systematic review of randomized clinical trials.
MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched.
The team used fixed and random effects models, relative risk, and values less than 1 favoring tacrolimus with 95% confidence intervals were calculated.
Of 717 potentially relevant references, 16 randomized clinical trials were eligible for inclusion.
Mortality and graft loss at 1 year were reduced with tacrolimus -- American Journal of Transplantation
Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients.
The researcher observed that tacrolimus reduced the number of recipients with acute rejection and steroid-resistant rejection in the first year.
Lymphoproliferative disorder or dialysis rates were not different but more de novo diabetes occurred with tacrolimus.
The team noted that more patients stopped cyclosporin than tacrolimus.
Dr McAlistera's team concluded, "Treating 100 recipients with tacrolimus instead of cyclosporin would avoid rejection and steroid-resistant rejection in 9 and 7 patients respectively."
"Graft loss and death would be reduced in 5 and 2 patients respectively, but 4 additional patients would develop diabetes after liver transplantation."
Am J Transplant 2006: 6(7): 1578
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Japanese State and Firm Blamed for Hepatitis C Infection
http://www.todayonline.com/
A Japanese court has ruled that drugmakers and the state were responsible for transmitting hepatitis C through a tainted medical product, and awarded damages to nine people with the disease.
It was the first ruling in a number of court cases filed by hepatitis C carriers across Japan.
The Osaka District Court Wednesday ordered the government and Mitsubishi Pharma Corp. to pay a total of 256.3 million yen (2.24 million dollars) to nine plaintiffs, although it turned down claims by four others.
The plaintiffs said they contracted the potentially fatal disease, which attacks the liver, when they were given contaminated fibrinogen, which forms clots to stop bleeding.
All but one of the plaintiffs were women treated with the product when they gave birth. Ten of the 13 plaintiffs have since shown symptoms of the disease.
Presiding judge Toshitsugu Nakamoto ruled that the drugmaker, then called Green Cross Corp., was responsible for the nine who were infected after August 1985, the date that the risks became known. He rejected damages for the four who contracted the virus before the date.
He also said the state was responsible for failing to stop use of the product.
But plaintiffs did not welcome the ruling with open arms.
"The ruling recognizes the responsibility of the state but it also draws the line late" on when risks were known, said Satoko Kuwata, one of the few plaintiffs who revealed her identity.
"The ruling was not anything we can accept without reservation," she said.
Yoshiaki Yamanishi, one of the lawyers representing the plaintiffs, said: "With the ruling handed out, which clearly recognizes the state's responsibility, we want to directly negotiate with the health minister."
The hepatitis C carriers in the case represent only the tip of the iceberg. More than 280,000 people are estimated to have been administered with fibrinogen -- produced and sold by the company with the state's certificate -- after 1980. At least 10,000 of those are said to have contracted the disease.
The first case was filed against the drugmaker and the government in 2002. Since then more than 90 people have joined as plaintiffs in four other major cities including Tokyo.
The tainted blood product was widely used at Japanese hospitals until 1988 even though the US government had informed the public of the danger and retracted its certificate in 1977.
Green Cross Corp. was hit by a series of scandals due to its HIV- and hepatitis C-tainted products and was rescued through a merger.
The Japanese Supreme Court last week awarded damages to five people who said they had contracted hepatitis B because needles were reused in a government immunization program. -- AFP
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Prisoners Have High Rates of Hepatitis C
SourceURL:http://news.ninemsn.com.au
Australian prisoners have hepatitis C rates 25 times higher than the rest of the population, and are more likely to have drug addictions and mental illness, a new report shows.
As part of its two-yearly snapshot of the nation, the Australian Institute of Health and Welfare (AIHW) has outlined the major health issues facing those in the country's jails.
Australia's Health 2006 says more than 25,000 people - that's one in every 600 adults - were in prison in mid-2005, an increase of 45 per cent since 1995. Almost 10,000 were from NSW.
Twenty-two per cent were indigenous - a marked over-representation - and 93 per cent were male.
The prisoners faced major health issues, including high rates of communicable diseases, mental illness, and risky behaviour like injecting drugs, the report says.
Rates of the blood-borne disease hepatitis C were 25 per cent higher among prisoners compared with the general population.
And almost 60 per cent of prison entrants had a history of drug injection, mostly heroin and amphetamines.
Depression was the most common mood disorder, and post-traumatic stress disorder was the most common anxiety disorder suffered by inmates, the report said.
Female prisoners aged under 25 and men over 40 were most likely to suffer from a psychiatric disorder.
"Since most prisoners will return to the community, it is important that their health needs are addressed while they are in prison, and that their health does not deteriorate during incarceration," the report warns.
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Alcohol Users with Hepatitis Often Untreated
SourceURL:http://news.yahoo.com
NEW YORK (Reuters Health) - Individuals who are infected with hepatitis C virus (HCV) and who drink alcohol are often considered ineligible for anti-HCV drug treatment, researchers report. However, alcohol drinkers have responses that are comparable to non-drinkers, they've found.
"Our observations are clinically important because they indicate that alcohol use should not be considered an exclusion criterion when evaluating patients for anti-HCV treatment, especially in view of the fact that nearly one third of patients with HCV infection have a history of recent alcohol use," note investigators in the journal Gastroenterology.
Dr. Bhupinder S. Anand, of the Michael E. DeBakey VA Medical Center, Houston, and colleagues examined the impact of alcohol use on HCV treatment outcomes. Their study involved 4,061 subjects, 726 of whom received treatment for HCV.
The investigators found that subjects who reported using alcohol were more likely to discontinue anti-HCV treatment. Drinkers also had lower response rates to anti-HCV treatment.
However, alcohol drinkers who stuck with their anti-HCV medication had response rates comparable to that of nondrinkers.
"Patients with a history of alcohol use," Anand and colleagues conclude, "should not be excluded from HCV therapy." Instead, they should be given additional support to ensure they complete treatment.
"The current attitude among physicians against offering treatment to patients who use alcohol should be reassessed," the team concludes.
SOURCE: Gastroenterology May 2006.
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Caring Ambassadors Program Offering Free Hepatitis C Counseling and Screening at Portland Waterfront Blues Festival
SourceURL:http://biz.yahoo.com
OREGON CITY, OR--(MARKET WIRE)--Jun 21, 2006 -- Free, confidential hepatitis C counseling and screening will be provided by the Hepatitis C Caring Ambassadors Program (HCCAP) at the upcoming Portland Waterfront Blues Festival. HCCAP staff and volunteers will be available in the Good Neighbor Pharmacy Health Pavilion throughout the festival hours of operation. The festival takes place from June 30th through July 4th at Tom McCall Waterfront Park.
Hepatitis C is the most common chronic, blood-borne infection in the U.S. Nearly 5-times more Americans have been infected with the hepatitis C virus (HCV) than have been infected with HIV. Approximately 174,000 people in Oregon and Washington are among the estimated 5 million Americans who have already been infected with HCV. Hepatitis C is the leading cause of chronic liver disease, now among the top 10 killers of Americans over the age of 25. Hepatitis C has been dubbed "the silent epidemic" because the majority of people with HCV are unaware of their status. The best estimates available indicate that at least 3.5 million Americans with HCV have not yet been diagnosed. The Hepatitis C Caring Ambassadors Program believes each and every person with this potentially life-threatening virus has the right to be diagnosed.
"The incidence of liver cancer and the need for liver transplantation are rising at alarming rates in this country, primarily as a consequence of undiagnosed, untreated chronic hepatitis C. Our presence at the Waterfront Blues Festival is part of our organization's mission to change that legacy. It is critically important for those that may have been exposed to the hepatitis C virus to be tested so that those who are infected have the opportunity to potentially alter the course of their disease," said HCCAP Manager, Lorren Sandt.
"The hepatitis C screening process we'll be using is quick, easy, and highly accurate. Knowing your hepatitis C status can bring great peace of mind, and may end up saving your life. It's certainly 10 minutes well spent!" said Dr. Tina St. John, Medical Director of the Caring Ambassadors Program.
The Hepatitis C Caring Ambassadors Program screening facilities will be located in the Good Neighbor Pharmacy Health Pavilion. Other health care information and services will also be available in the Health Pavilion including free blood sugar testing, bone density testing, and cardiovascular risk assessment.
Be good to yourself and your loved ones -- know your hepatitis C status!
For additional information about the hepatitis C screening available at the Waterfront Blues Festival, contact Lorren Sandt at 1.503.632.9032 or lorren@hepcchallenge.org.
Source: Hepatitis C Caring Ambassadors Program
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Hepatitis C Virus-Associated Diabetes May Involve Insulin Resistance
SourceURL:http://www.therapeuticsdaily.com
Recent research from Spain has chronicled proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis C patients.
"The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection," wrote A. Lecube and colleagues, Universitat Autònoma de Barcelona.
They explained, "Insulin resistance, proinflammatory cytokines, and P-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV-).
"Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin."
"Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay," the researchers continued.
"Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-beta) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes -HOMA-IR was higher in anti-HCV+ than in anti-HCV-patients (4.35±2.27 vs. 2.58±1.74; p=.01).
"All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV-patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-beta as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC-patients," the scientists wrote.
They concluded, "Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection."
Lecube and colleagues published their study in Diabetes Care (Proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis C patients - A case-control study. Diabetes Care, 2006;29(5):1096-1101).
For additional information, contact R. Simo, Universitat Autònoma de Barcelona, Diabetes Research Unit, Division of Endocrinology, Pg Vall Hebron 119-129, Barcelona 08035, Spain.
Publisher contact information for the journal Diabetes Care is: American Diabetes Association, 1701 N Beauregard St., Alexandria, VA 22311-1717, USA.
This article was prepared by World Disease Weekly editors from staff and other reports
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June 22nd, 2006
Graphic Hepatitis C Ads Raise Ethical Qualms
SourceURL:http://www.philly.com
By John Sullivan
Inquirer Staff Writer
As the head of liver transplantation at Thomas Jefferson University Hospital, Victor J. Navarro has seen many ailing patients with hepatitis C. But they don't look like the man in a half-page, color newspaper ad with a battered and bruised face, his eyes glassy.
"If Hep C was attacking your face instead of your liver, you'd do something about it," the ad reads. "Ready to fight back?"
While Navarro and other experts applaud the ads for raising interest in the viral disease, they think the campaign by drugmaker Hoffmann-La Roche Inc. could cause unnecessary alarm, in part because the vast majority of hepatitis C patients will not die of it.
"It's a marketing tool to make people fearful of hep C," Navarro said.
Roche's drugs, which are improvements over past medications, also work on only half of all patients, and cause considerable side effects. The campaign could leave those who cannot benefit believing they will wind up like the man in the ad.
The ad also is part of a larger marketing effort by Roche to quietly sponsor hep C seminars for the public and support patient groups and many liver physicians. Ethicists say the financing raises questions about whether the advice at such seminars can be objective.
Roche spokesman Mike Nelson said the company was simply trying to get out the word about the disease so more people can be helped. Nelson says nearly 600,000 hepatitis C patients have been diagnosed but haven't been treated, and may not know about the company's current market-leading options: Pegasys (interferon and an antiviral substance) and Copegus (an antiviral).
Nelson also said the ad was meant to be strong "to break through the clutter."
Roche said nearly 56 million people had seen the ad as of April, and more would see the ad in the coming weeks, part of a national blitz Roche launched last year in 250 newspapers, including The Inquirer and Philadelphia Daily News, and seven major magazines, such as Time. The ads also are plastered on 4,000 billboards and in 40,000 posters.
Roche officials would not disclose the cost of the campaign, which will run through July, but such large newspaper ads cost as much as $50,000 a day.
Leonard B. Seeff, who oversees hepatitis research at the National Institutes of Health, originally thought the ad came from an advocacy group.
"I think the ad is awful. Patients with hepatitis C do not look like that," said Seeff, who has been working on a study partly funded by Roche. "On the other hand, if you're trying to get the message across, one way is to make it look bad."
Seeff, who said his opinion did not reflect that of the NIH, said that he also was concerned because only a few people will die from hepatitis C.
"They mostly die from all kinds of things other than chronic liver disease," he said. "They should not think it's a death sentence."
Some doctors and advocates see a strong profit motive behind the campaign. "Ultimately it sells more of their drug," said Sidney M. Wolfe, director of Public Citizen's Health Research Group.
Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, said it was not good policy for the United States to rely on companies to sponsor public-health campaigns. Such efforts tend to go to diseases for which companies have developed drugs, while other needy areas are ignored, he said.
Hepatitis C is a viral liver ailment that is the most common chronic blood-borne disease in the country.
The National Institutes of Health estimates that about four million people have hepatitis C in the United States. That number is expected to double in the coming decade as more people learn they are infected.
Many people got the disease from having received tainted blood or organs before adequate tests were developed in 1992. Most new cases are caused by intravenous drug use. A few contract the disease through high-risk sexual behavior, according to the Centers for Disease Control and Prevention.
Most people don't know they've been infected because the disease often doesn't cause symptoms for decades. The only way to confirm a diagnosis is to take a sample of the liver and examine it for scarring.
Only a fraction of those infected - from 1 percent to 5 percent - die of the disease. Yet it remains the No. 1 cause of liver transplants.
About 70 percent to 80 percent of those with the liver disease suffer from a stubborn genetic variant called genotype 1 that resists treatment.
The cocktail of antiviral drugs works in only 30 percent to 40 percent of those cases, and even less often in African Americans, according to the World Health Organization.
For the remaining 20 percent to 30 percent who have genotype 2 or 3, treatment works about 80 percent of the time. Averaging the two groups means that treatment only works in half the cases. Roche claims higher success rates.
While most insurance covers the therapy, uninsured patients must weigh that success rate against the cost, which can run up to $64,000 per year for some genotypes. The drugs are given several times a week, from 24 weeks to 48 weeks.
Still, hepatitis drug sales and advertising have been brisk. Over the last five years, drug company spending to advertise interferon, including Roche's drugs, has jumped from $14 million to $75 million. For Roche's Pegasys, ad spending rose from $30,000 in 2004 to more than $965,000 last year, according to Yardley, Pa.-based Verispan, which tracks pharmaceutical marketing.
The push has paid off. The company sold $1.4 billion worth of hepatitis C drugs, making it a top seller for the firm, according to its 2005 annual report.
Some hepatitis C activists, including those supported by the company, say the ads may seek to take advantage of a small window of opportunity. Roche now controls more than 60 percent of the hepatitis-therapy market, but that could change as other companies win approval for new antiviral treatments due out in coming years.
"We have been advising most people that they should probably wait for the next class of drugs," said Michael Ninburg, president of the National hepatitis C Advocacy Council, who heads the hepatitis Education Project in Seattle, which gets funding from Roche.
Also recommending that are HepTREC, a hepatitis education and support group started by Amy Jessop and a doctor and nurse at Temple University. Roche gave the group more than $250,000 in its first two years.
"I wish that there was public funding that we could turn to," said Jessop, who taught public health at Temple. "But the reality is there is no funding."
Earlier this year, about 15 people sat in a dimly lit auditorium at Graduate Hospital in Center City to hear a lecture on hepatitis C. Jessop told the group that Roche was a sponsor. She never promoted Roche products.
In the crowd sat Marc B. Saxe, a 46-year-old drug counselor from Philadelphia, who was diagnosed with hep C in 1998.
Saxe says he was "freaked out" by the diagnosis and went untreated until last year, about the time the Roche ad first appeared. It has worked, he said.
"I thought it was disgusting," he said of the ad. "But if it gets people to think about it, great."
"I just want to get fixed."
Hepatitis C At a Glance
- About 3.9 million Americans are chronically infected with hepatitis C.
- Prevalence rates are up to 8 percent to 10 percent of African Americans.
- Dialysis patients, hemophiliacs, drug addicts and people transfused with blood before 1990 are particularly affected by the disease.
- Injectable drug use remains the main route of transmission.
- Sexual transmission is thought to be relatively infrequent.
- Of every 100 people infected with hepatitis C:
- About 55 to 85 people may develop long-term infection.
- 70 people might develop chronic liver disease.
- 5 to 20 people may develop cirrhosis over a period of 20 to 30 years.
- 1 to 5 people might die from the consequences of liver cancer or cirrhosis.
SOURCES: World Health Organization and the Centers for Disease Control and Prevention
Contact staff writer John Sullivan at 215-854-5568 or johnsullivan@phillynews.com.
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Poor Parents Sell Daughter
SourceURL:http://www.news24.com
Nasir Jaffry
Islamabad - The impoverished parents of 16-year-old Robina Bibi, in Pakistan's North-Western Frontier Province (NWFP), had never thought of selling their daughter, but poverty forced them to look for buyers.
For Sakeena Bibi, 40, and her husband Izat Gul, 43, it was the only option they could think of to raise money to treat their five children, who had hepatitis C.
They struck a deal with a family they claimed as their relatives for about $2Â 157 to pay off their debt of $829 and spend the remaining amount on treatment of the ailing kids.
However, the deal fell apart after Robina too was diagnosed with hepatitis C.
Bibi said: "I have 10 children and six of them including three girls, between nine and 16 years of age, are now hepatitis C patients."
Hepatitis treatment 'very expensive'
Bibi, who lived in remote town of Dir, said her children had had the deadly disease for the past year.
She said: "We can't take them to even state-run hospitals in Peshawar (NWFP's capital), or any other cities where patients are provided free consultancy, but have to pay for the tests from their own pocket."
Senior NWFP minister Siraj-ul-Haq said that hepatitis treatment was very expensive and it costs $995 per patient.
Haq, whose six-party Islamic alliance, Muttahida Majlis-e-Amal ruled NWFP, said the provincial government had set up an endowment fund and earmarked about $300Â 000 for treatment of poor patients.
However, he admitted that the fund was inadequate to cater to thousands of patients, who can't afford to pay for treatment of diseases like hepatitis C.
Free vaccine provided
The World Health Organisation (WHO), which was co-operating with the Pakistani government in controlling the disease, estimated that patients of hepatitis B and C ran in the millions.
Dr Khalif Bile of the WHO said: "We fear there are about seven million patients of hepatitis B and C all over Pakistan."
He said a free vaccine was provided to Pakistan for every new-born baby in the country to control hepatitis B.
Bile lauded Pakistani government's national programme to control hepatitis infections, saying the WHO was helping the government create awareness through a programme about safe blood transfusion and proper disposal of syringes used to vaccinate patients.
But for Sakeena and her husband, there was nothing more important than saving the lives of their children from hepatitis C, which was usually caused by consuming contaminated water.
Gul, who was a labourer and earned less than $10 a week, said he felt helpless. "How can I pay for the treatment of my six kids, which is very expensive?"
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Prison Health Costs Burst Yearly Budget: Lawmakers Grouse about the Funding
SourceURL:http://www.concordmonitor.com
By ERIC MOSKOWITZ
Monitor staff
Health-care costs for the Department of Corrections ran $1.63 million over budget this year. Prison officials attributed that to a high number of inmate emergencies and extraordinary medical expenses, such as cancer care, that require treatment outside the prison.
Some lawmakers said they're weary of responding to the corrections department, which consistently exceeds its annual medical budget and turns to the Legislature for end-of-the-year appropriations. Lawmakers on the joint fiscal committee usually grant those requests, accepting prison health-care as an unpredictable but mandatory expense. But some said it's time for more scrutiny.
Senate Majority Leader Bob Clegg thinks more could be done to control inmate medical expenses and prevent the need for additional appropriations. "I think it's a huge issue," said Clegg, a Hudson Republican.
Clegg, a member of the fiscal committee, questioned whether all specialty treatments were necessary. He wants to know if the prison system could make more frequent use of a law allowing for inmates with extraordinary medical bills to be released from prison, provided they're not considered a threat to society.
"We've had the medical community from the prison system come in and tell us that they think it's their duty to make sure that if some guy's got less-than-perfect teeth while he's in there at state expense, they give him all-new dentures. There's been elective surgery performed because they want to make sure that when they get out of prison, they have every advantage possible," Clegg said. "A lot of people say, 'Wait a minute. I don't get that, and I haven't done anything bad to anyone.'"
Over the past five years, medical and dental expenses for the prison system have exceeded the amount budgeted by more than $26 million, or nearly 25 percent. In each of those years, corrections officials requested additional money from the Legislature; lawmakers on the fiscal committee granted the requests four times and told the prison to make up the difference internally in the other year (2003), according to records provided by the Department of Corrections and the Legislative Budget Assistant.
The fiscal committee approved the latest appropriation - $1.2 million transferred from the general fund, along with permission for the department to transfer another $427,000 internally to pay the rest of its medical bills - earlier this month, and the governor and Executive Council authorized the move yesterday.
That will allow the department to meet its medical expenses in the budget year that ends next Friday. The prison system began the year with $6.24 million for health care -part of a roughly $90 million overall budget for the corrections department - but finished with about $7.87 million in medical expenses. (The medical budget includes dental costs but not psychiatric care, which is covered by a separate appropriation.)
Prison officials said this year's deficit was caused by a high number of unpredictable and expensive conditions, including cardiac emergencies, cancer, cirrhosis and kidney failure. Thirty seven inmates had individual medical bills of $10,000 or more, including four whose expenses topped $100,000 apiece. That means less than 1.5 percent of the state's 2,600-plus inmates accounted for more than 20 percent of medical expenses.
Prison doctors and nurses provide in-house primary care for inmates, and the department also offers some specialties on location, such as eye care and podiatry. Other specialties and emergencies are treated outside the prison. Those procedures are ordered only when prison medical staff consider them necessary, and elective surgery for inmates is prohibited, said Jeff Lyons, a corrections spokesman.
Rep. Fred King, chairman of the fiscal committee, said he considers the prison medical requests to be inevitable but necessary. "The citizens of the state want people locked up if they do bad things, and they want them kept locked up,"said King, a Colebrook Republican.
The tough-on-crime movement of the 1980s brought longer prison sentences. King, a former state senator, has tried multiple times to introduce legislation that would reduce prison sentences for good behavior. Lawmakers have shown little support for the idea, he said. "I don't envision that would ever happen," he said.
Short of letting more inmates go, lawmakers need to understand that rising health-care expenses are the "nature of the game," King said.
Corrections Commissioner William Wrenn, who took office in December, said he has learned quickly that it can be difficult to predict and manage medical costs. Inmates are ineligible for federal health assistance provided through Medicare or Medicaid, so the state shoulders all of the financial burden, he said.
"It's a daunting task at times, because these inmates require medical care while they're in our custody and control," Wrenn said yesterday. "I don't have a crystal ball to see who's going to require certain procedures."
Wrenn said he is collaborating with Health and Human Services Commissioner John Stephen to examine ways to reduce costs. Among other possibilities, corrections officials are looking into buying a dialysis machine to treat kidney failure in-house. This year, the state spent $730,000 on dialysis for four inmates. The most severe case of kidney failure - an inmate who was sent to Oregon for treatment -cost New Hampshire more than $285,000. By comparison, the state's entire dialysis bill last year was $169,000, according to prison statistics.
When Wrenn appealed to the fiscal committee earlier this month, lawmakers granted the money unanimously but grumbled about it. Clegg and others asked to see details for the most expensive inmate treatments and questioned whether any might be candidates for release under the medical-parole law that passed two years ago. They also wanted to know why the department sent that inmate to Oregon and how that cost would have compared with in-state care, because a two-year-old law prevents New Hampshire hospitals from charging the state more than 110 percent of Medicare rates to treat inmates.
Wrenn and Bob Mullen, director of the prison's administration division, were unable to provide immediate answers at the meeting. Last week, the department sent the fiscal committee details on the most expensive inmates and an explanation of the medical-parole law. The response was helpful but fell short, Clegg said.
"The fiscal committee has always asked the same questions we're asking now, and it's very difficult to get the answers," Clegg said.
Prison officials told the Monitor this week that they could not provide a breakdown of the department's $7.87 million in medical expenses, aside from the explanation of the $1.7 million in extraordinary cases supplied to lawmakers.
All inmates receive a physical when they enter prison. Inmates over 65 get another checkup every year, while younger inmates get them every two or three years, depending on age, said Bob MacLeod, administrative director of medical services for the prison system. The department tries to keep costs in check in a variety of ways, from using generic prescription drugs to arranging emergency-care contracts with certain hospitals to obtain better rates than the maximum set by state law, he said.
That law, which caps the hospital rates at 110 percent of the cost that would be allowed by Medicare, covers emergency and inpatient care; it has saved the department more than $100,000 a year, prison officials said. But treatments such as dialysis are not capped, which is why the state sends some inmates to Oregon for treatment, MacLeod said. That state has an in-house dialysis machine and can provide the service at a lower rate than a New Hampshire hospital, even with transportation and other expenses, he said. The bill for the inmate sent to Oregon this year exceeded $285,000 because of serious infection and other complications.
That inmate, a 26-year-old who was serving time for attempted homicide, was paroled for non-medical reasons in March, and New Hampshire sent another inmate to Oregon for treatment, MacLeod said.
The medical-parole law allows the department to release inmates with high health-care bills, but the state uses it sparingly. The department continually looks for likely candidates and releases about one or two a year, MacLeod said.
Prison medical expenses have risen 33 percent in three years. That's partly a result of rapid increases in the cost of health care and partly a result of a swelling inmate population; the average number of state inmates grows about 2 to 4 percent a year in New Hampshire.
Inmates are also aging, meaning an increase in age-related health problems such as diabetes, high blood pressure and stroke, MacLeod said. As of July 1, 1996, 9.2 percent of state inmates were 51 years old or older. As of last June 30 - the most recent date for which prison age statistics were available - 15.8 percent of inmates were 49 or older.
Conditions that aren't tied to age are also on the rise, MacLeod said. About one in four prison inmates in New Hampshire has tested positive for hepatitis C, a liver disease often caused by substance abuse; that's roughly double the rate of three years ago, he said.
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June 23rd, 2006
Researchers Map Infectious Hepatitis B Virus
SourceURL:http://www.sciencedaily.com/
Scientists at The Scripps Research Institute have analyzed the structure of hepatitis B virus and found that it has unique features that distinguish it from other enveloped viruses such as influenza and herpes virus.
Using electron cryomicroscopy and computer image analysis, the scientists visualized two intermediate forms of the virus that exist within infected cells. In addition, they were able to determine a three-dimensional map by analysis of infectious hepatitis B virus isolated from patient blood samples. These results could help future researchers understand more clearly how hepatitis B virus replicates in the cell and point the way toward new therapeutic approaches that could disrupt the hepatitis B virus infection pathway.
The study, a collaborative effort between the laboratories of Scripps Research scientists Professor Mark Yeager, M.D., Ph.D., and Professor Francis V. Chisari, M.D., was published in the June 23, 2006 (Volume 22, Issue 6) edition of the journal Molecular Cell.
More than 350 million people worldwide are infected with hepatitis B virus, which kills more than a million each year due to acute and chronic hepatitis, and hepatocellular carcinoma. The virus, which attacks the liver, is spread through infected blood transfusions, needle sharing by intravenous drug abusers and sexual contact.
Virions are inert virus particles that carry the virus genome from cell to cell. In the hepatitis B virus, this genetic material is protected by a shell of protein molecules called a capsid. Hepatitis B virions, also known as Dane particles, are approximately 40 nanometers in size, and the capsid is surrounded by a membrane envelope. While the structure of the hepatitis B capsid has been studied intensively in vitro, until this study little was known about the structure and assembly of native capsids present in infected cells in vivo, and even less was known about the structure of mature virions.
"We used cryomicroscopy and image analysis to examine the native structure of HBV [hepatitis B virus ] capsids from transgenic mice and virions isolated from patient blood samples," Yeager said. "By rapidly freezing the samples we were able to use cryo-electron microscopy to image the particles while they were maintained at the temperature of liquid nitrogen-around-300º F-which preserves them in a state close to what exists in vivo. Image processing allowed us to derive 3-D maps that revealed for the first time how the outer lipid envelope interacts with the capsid shell. "
The 3-D maps showed that in terms of molecular size, hepatitis B virus is enormous-nearly 10 times larger than a hemoglobin molecule. Like the human genome, the genome of the hepatitis B virus is formed by double-stranded DNA and enclosed by the capsid, which has icosahedral symmetry, resembling the geometric structure of a geodesic dome. The capsid itself is contained within an outer envelope formed by a lipid bilayer, similar to the membranes that enclose all human cells. The membrane of hepatitis B virus is studded with glycoprotein spikes, which bind to receptors on liver cells that mediate infection.
In hepatitis B-infected liver cells, transcription of the viral DNA produces a type of RNA that is packaged into capsids. Within the capsid, reverse transcription produces a single-strand DNA copy that serves as the template for second strand DNA synthesis. The resulting particles bud through membranes of the endoplasmic reticulum-the part of the cell involved with protein folding, assembly, and transport-to acquire the outer membrane envelope of the virus, a step that confers infectivity.
"In the transgenic mice, we found two types of capsids with different densities," Yeager said. "While both types of capsids were assembled as similar icosahedral structures, we found that the lower density capsids did not contain any viral DNA or viral RNA, while the higher density capsids contained viral DNA intermediates. It seems likely that these lower density capsids were released from the cell nucleus. These results may offer new clues how the virus replicates in vivo."
Other researchers of the study, titled "Native Hepatitis B Virions and Capsids Visualized by Electron Cryomicroscopy," were Kelly A. Dryden, Stefan F. Wieland, Christina Whitten-Bauer, and John L. Gerin.
The study was supported by the National Institutes of Health.
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Health Ministry Sweating after 'Double Blow' in Hepatitis Rulings
SourceURL:http://www.asahi.com/
THE ASAHI SHIMBUN
Two court rulings holding the state responsible for hepatitis infections have put health ministry officials on edge.
They warn that government coffers will run dry if they have to provide relief measures to the millions of patients infected with the hepatitis C and hepatitis B viruses.
On Wednesday, the Osaka District Court ordered the government and two companies to pay a total of 256.3 million yen in compensation to nine people infected with hepatitis C virus through the blood coagulant fibrinogen.
Last week, the Supreme Court found the government responsible for hepatitis B infections contracted through state-sponsored inoculation programs.
A senior ministry official termed the court rulings a "double blow."
"We don't know where to begin in setting up measures for hepatitis," the official said.
Ministry officials fear the recent decisions will spur a raft of new claims by people infected with the hepatitis viruses.
The ministry's concerns have not prevented hepatitis patients from reacting to the court rulings.
On Thursday, the plaintiffs in the hepatitis C case submitted a letter to the Ministry of Health, Labor and Welfare requesting relief programs for the estimated 3.5 million people infected with either hepatitis B or C--many of them through inappropriate medical procedures.
"Through insufficient treatment programs, the patients have suffered at many levels, such as fighting illnesses, shouldering medical costs and social discrimination against the infected," the letter read.
A string of other hepatitis C-related lawsuits against the government are now pending at four district courts. And the government has said it will appeal the Osaka District Court's ruling.
While some local governments have developed their own relief programs for hepatitis sufferers, central government medical support currently stretches only to patients with acute symptoms.
However, the state is under pressure to make a change considering the June 16 Supreme Court decision.
As well as awarding damages to the five plaintiffs, the top court called on the central government to devise a relief program for those infected through inoculations.
If compensation is granted to all who fall in that category, the total costs could easily be in the trillions of yen.
And that's not counting the funds needed to establish hepatitis testing and treatment regimes which, according to one estimate, could amount to 100 billion yen annually.
"If we deal squarely with relief, the nation's coffers will be bankrupted," a ministry official said.
Panic has not quite set in, with many in the ministry noting there is no telling which way the other court rulings will swing. Yet, some believe the ministry must act in light of intense public scrutiny.
The ministry has taken significant steps in its handling of the hepatitis C virus in recent years.
In 2002, the ministry established a program to combat hepatitis C, providing 5 billion to 6 billion yen annually for research on ways to treat the virus. The drive also included setting up hepatitis C testing in municipal health checks for people aged 40 or over.
From April this year, public health centers have also been offering the tests regardless of age.
Between 2.2 million and 3.4 million people nationwide are estimated to be infected with either the hepatitis B or C virus. (IHT/Asahi: June 23,2006)
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Healey Says Addicts Shouldn’t be Able to Buy Needles
http://www.telegram.com/
By John J. Monahan TELEGRAM & GAZETTE STAFF
jmonahan@telegram.com
House and Senate send veto-proof bill for Romney to sign
BOSTON— A war of words intensified over a bill to legalize hypodermic needles for illicit drug use, as Lt. Gov. Kerry Healey warned of dangers to the public from discarded needles and supporters claimed the measure would save lives and prevent the spread of HIV and hepatitis.
Passed earlier in both the House and Senate with veto-proof majorities, the bill that would allow drug addicts to buy clean needles at pharmacies without a prescription was sent to Gov. Mitt Romney yesterday after final enactment votes in both chambers.
Ms. Healey, who said the governor will veto the measure, enlisted a father from Chelmsford at a press conference in front of the Statehouse to explain that his son walked past two used needles on the ground at the Boston Common during a school field trip to see the Freedom Trail last week, and complained that discarded needles pose a serious danger to the public.
While Ms. Healey told reporters members of the public will find themselves “standing next to drug addicts in line” at pharmacies and that discarded needles would pose infection threats to unsuspecting children and adults walking in parks and on beaches, about 200 demonstrators lining the opposite side of Beacon Street chanted, “Clean needles save lives.”
Ms. Healey, a candidate for governor, acknowledged that all but three other states already allow needle purchases by drug addicts to reduce the spread of diseases, but she said the issue is different in Massachusetts. “I don’t think those 47 other states have the problem with heroin abuse we do here,” she said, describing heroin use as an “epidemic” in the Bay State.
At a press conference held immediately after Ms. Healey’s, supporters of the legislation said it will save many lives and prevent incurable infections by eliminating the sharing of needles by intravenous drug users. One AIDS prevention advocate accused the lieutenant governor of “fear mongering.”
Middlesex District Attorney Martha Coakley, a Democratic candidate for attorney general, said 39 percent of the people with AIDS in Massachusetts were infected by sharing drug needles. “It only makes sense for Massachusetts to join 47 other states who understand this is an important public health issue,” she said, adding that taxpayers spend an average of $200,000 for each person treated for AIDS.
“There is little or no effect on the public safety issue. The states where the needles are available have not found any increase in drug use or crime as a result of it,” Ms. Coakley said. Moreover, she said, making needles illegal to posses as the law currently does, “has done little to help public safety.”
Charges against drug users for illegal possession of needles are almost always dismissed in court, she said. “In this case, the benefits of this particular bill far outweigh any perceived public safety risks,” Ms. Coakley said.
Also supporting the legislation was John Auerbach, the director of the city of Boston’s Aids Prevention program, who said Mayor Thomas M. Menino supports the bill because it has proven an effective way to prevent transmission of AIDS and hepatitis. “There is absolutely no evidence at all in states that have similar bills of increases in the discarding of needles in public places,” Mr. Auerbach said. Police officials in Boston also support the bill, he said.
Other proponents accused the lieutenant governor of using the issue to get votes at the expense of people who risk contracting a fatal disease.
“The reality is they are playing to people’s prejudice. We know this is all about public health. It’s about saving lives, and the lieutenant governor and the governor, who are suggesting they will veto it, are really playing politics,” said a sponsor of the legislation, state Sen. Robert A. O’Leary, D-Barnstable. “When it is done in a way for their political purpose and it is going to cost people’s lives, it is unconscionable.”
Lawrence Day, of AIDS Action of Massachusetts, said he was “absolutely appalled and frightened … that one of the candidates for the highest elective office in the commonwealth stood before the media and stood before the public and fear mongered her way into making you believe this bill was a bad thing.
“This bill is about saving lives. She totally dismissed this,” Mr. Day said, adding that Ms. Healey lacked compassion.
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Cycles of Cell Death, Proliferation Key to Liver Cancer
http://www.sciencedaily.com
Research at the University of California, San Diego (UCSD) School of Medicine shows that liver cancer is likely caused by cycles of liver cell death and renewal.
The research, appearing online the week of June 19 in advance of publication in the journal Proceedings of the National Academy of Sciences, underscores the importance of JNK1-mediated cell death and compensatory proliferation. The findings by Michael Karin, Ph.D., professor pharmacology in UCSD’s Laboratory of Gene Regulation and Signal Transduction, and colleagues strongly suggest that the control of tissue renewal through the IKK and JNK pathways plays a key role in liver cancer in mouse models.
One link between inflammation and cancer is known to involve the NF-kB pathway, which regulates gene expression. In research published in the journal Cell in 2005, Karin and his colleagues at UCSD implicated the pathway's activator, IKK , in chemically induced liver cancer. However, the surprising outcome of those studies was the finding that while NF-ƒÛB activation in hepatocytes (liver cells) prevents liver cancer, its activation in inflammatory cells, such as tissue macrophages, promotes tumor development.
In their latest work, the research team studied what precedes inflammation -- the injury of hepatocytes caused by toxic chemicals, which sets in motion the inflammation process.
Their research showed that the absence of IKKƒÒ in hepatocytes led to increased c-Jun N-terminal kinase (JNK) activation after exposure to a chemical carcinogen used to elicit liver cancer in mice. Importantly, deletion of the gene that codes for the major isoform of JNK in liver cells, JNK1, prevented the development of liver cancer and reversed the tumor-enhancing effect caused by ablation of IKKƒÒ.
"We found that long-term JNK activation leads to cell death; if activated briefly, it stimulates proliferation of pre-malignant and cancerous tumor cells," said Karin. Blocking JNK prevents liver injury but also inhibits liver regeneration, so the timing and context of activation are very important, he added.
"In this research, we set out to identify what causes inflammation in response to liver injury, as well as what stimulates the proliferation of surviving hepatocytes," said Karin. "Since we previously knew that JNK activity is required for normal liver cell proliferation, we wondered if the same activity is required for production of liver cancer in carcinogen-exposed mice. The results were clear JNK1 is critical for tumor development."
The scientists genetically removed JNK1 to test if its increased activation, caused by the absence of IKKƒÒ, was responsible for accelerated tumor development. When JNK1 was removed, the number and size of cancerous liver tumors decreased, and the tumors grew more slowly. Increased JNK1 activation was found in diseased liver and tumors when compared to normal tissue.
Hepatocellular carcinoma (HCC), the most common form of liver cancer, is the third leading cause of cancer deaths worldwide. Its major risk factors are persistent infection with hepatitis B and C viruses, and exposure to toxic chemicals, including alcohol -- all of which cause chronic liver injury and inflammation. Although not common in the United States., the incidence of HCC is on an upward trajectory, with little hope for treatment or cure through chemotherapy, radiation or other traditional cancer treatments.
"We now understand development of liver cancer in mice. Since inflammation drives both damage and regeneration in liver tissue, it is the repeating cycle of damage, inflammation and regeneration that leads to liver cancer," said Karin. "However, this knowledge is not satisfactory until we find out if it applies to humans."
Contributors to the paper include Toshiharu Sakurai, UCSD Laboratory of Gene Regulation and Signal Transduction and Kyoto University, Japan; Shin Maeda, UCSD and the Asahi Life Foundation, Tokyo; and Lufen Chang, UCSD and the Beckman Research Institute at City of Hope National Medical Center, Duarte, CA.
The research was supported by the National Institutes of Health and the Superfund Basic Research Program. Karin is an American Cancer Society Research Professor.
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