Back to News Review
Week Ending: July 17, 2010
Alan Franciscus
Editor-in-Chief
To download pdf version click
here
This Issue:
July 10, 2010
EDITORIAL: Hepatitis B Redress
http://www.asahi.com
Many people contracted hepatitis B through group vaccinations they received as children. The government, which conducted vaccination, has a responsibility to redress victims. But vaccination is not the only route of infection.
If compensation is limited to patients who have firm proof that they underwent vaccination, some people who should be eligible would not be covered.
On the other hand, if a standard that is too broad is applied, the government would have no choice than to pay compensation to people who developed the disease through other means for which it is not responsible.
What standard should be applied to recognize eligible patients? The government has presented its "basic thinking" about this difficult question in negotiations for a settlement in a group lawsuit filed by patients seeking compensation.
The government had insisted that patients would not be eligible unless vaccination can be confirmed by mother-and-child health handbooks. But now, officials say those without the handbooks would also be eligible provided that they can prove they underwent vaccination.
Of the approximately 450 plaintiffs, about 60 percent say they no longer have their mother-and-child health handbooks. Given this fact, the decision is reasonable.
The problem is what kind of proof should be sought. The government only said it would discuss the matter with the plaintiffs.
We hope the both parties would come up with a standard to recognize patients as broadly as possible. The Sapporo District Court, which recommended a settlement, had called for "a decision to broaden the scope of redress."
In its "basic thinking," the government also demanded that patients, including those who have their handbooks, provide proof that they did not get the disease by mother-to-child transmission. In case their mothers are dead, it called on patients to show that their older siblings are not infected.
In a lawsuit filed by five patients, the Supreme Court ruled in 2006 that the government is responsible, saying that the cause of infection was group vaccinations. The decision came after the court confirmed test results showing that mother-to-child transmission was not the cause.
The plaintiffs in the Sapporo case are demanding that patients and infected individuals be recognized as eligible for compensation as long as they did not get the disease from their mothers and were younger than 6 from 1948 to 1988 when vaccination was mandatory.
That is all the more reason the plaintiffs are strongly opposed to the government's "basic thinking."
We can very well understand how they feel. Still, the number of hepatitis B patients is estimated at about 70,000, and that of infected persons at between 1.1 million and 1.4 million.
As long as compensation is to be paid from public funds, there is a need to decide the scope of redress by excluding, as much as possible, mother-to-child transmission and causes for which the government is not responsible. Otherwise, it would be difficult to win public understanding toward broad redress.
Hepatitis B infection by group vaccination was caused by reuse of needles and syringes. The danger was known at the time, but practically nothing was done to stop the practice until 1988.
Anyone who was a child during this time could have become infected. This is not someone else's problem. We urge the advancement of broad and reasonable redress.
To solve this difficult problem, it is essential that the government "win public understanding," as health minister Akira Nagatsuma put it. In that sense, it was a right decision for the government to disclose what it presented at the settlement talks after negotiations were over. We expect the government to stick to this method to the end.
July 11, 2010
Extended Treatment of HCV Type 1 Beneficial in Slow Responders
http://thedoctorschannel.com/video/3437.html
NEW YORK (Reuters Health) – Patients infected with hepatitis C virus (HCV) type 1 who have a slow response to pegylated interferon-alfa and ribavirin can benefit from continuing treatment for up to 72 weeks, a German team reports in an advance release from Clinical Gastroenterology and Hepatology.
Dr. Eva Herrmann and colleagues at J.W. Goethe University in Frankfurt note that there’s conflicting evidence about the value of extending treatment beyond the standard 48 weeks for patients with HCV genotype 1, who often have a slow response to therapy. “Therefore,” they explain, “we performed a systematic review and meta-analysis of randomized controlled clinical trials which compared extended duration of treatment with pegylated interferon-alfa and ribavirin with standard treatment in treatment-naive HCV genotype 1 slow responders.”
The team identified seven appropriate studies that met inclusion criteria; one of the studies was excluded because it did not report the number of slow responders based on HCV RNA status at 12 weeks, leaving a total of 669 patients in the analysis.
“The overall SVR (sustained virologic response) rates of these slow responders were 19.4% and 35.6% after standard treatment versus extended treatment, respectively (p=0.0072),” the team reports. Further analysis showed that extended therapy produced a 14.7% higher likelihood of achieving a sustained virologic response compared with standard treatment.
“The frequency of viral relapse appears to be associated with the time of being HCV RNA negative during treatment and the reduced frequency of relapse is a likely explanation of improved SVR rates after extended treatment,” the investigators surmise.
Noting that numerous side effects can occur with interferon-ribavirin treatment, Dr. Herrmann and colleagues looked at safety and tolerance during extended therapy. While there was not a significant increase in serious side effects with extended treatment (8%) versus standard treatment (7%), more patients did voluntarily discontinue treatment (7.0% vs. 2.3%).
The researchers note that new treatments targeting HCV specifically are being developed and some patients might be safely watched until these new antivirals become available. However, treatment is urgent in patients with advanced liver fibrosis, so “optimization of combination therapy with pegylated interferon-alfa and ribavirin is still of high relevance.”
Reference:
Meta-Analysis Shows Extended Therapy Improves Response of Patients with Chronic Hepatitis C Virus Genotype 1 Infection. Article in Press Clin Gastroenterol Hepatol 2010.
Twilight Effect? Teens Biting Each Other
http://abclocal.go.com
A bizarre trend is growing among teens that may be inspired by the popularity of all the vampire movies, TV shows and books.
The forbidden love story of Bella and Edward of Twilight is sending many teens into a biting frenzy. Teen biting, sometimes to draw blood, is a secretive but growing trend steadily picking up steam. Doctors caution that breaking the skin can lead to serious illness.
Sexologist, Dr. Logan Levkoff said, "For the same reason we never thought becoming blood brothers or blood sisters was a big deal, it was just another one of these rites of passages years ago, we learned more everyday and recognized there are some things we just shouldn't do."
Doctors say teens need to be concerned about the biting trend. They could be infected with hepatitis, syphilis and HIV. Doctors say up to 15 percent of bites can become infected.
Disease Detection in the Palm of Your Hand
http://www.upi.com
ALBUQUERQUE, July 9 (UPI) -- University of New Mexico researchers brought sci-fi technology to the doctor's office by creating a device that can diagnose a number of ills in seconds.
Best of all, researchers said, the hand-held "biosensor" eliminates the need for expensive and time-consuming tests, The Albuquerque Journal reported Friday. And it runs on AA batteries.
Researchers determined biosensor can identify hepatitis B and C, HIV, hantavirus, flu, and other viral and bacterial pathogens, said David Larson, vice president for research at UNM Health Sciences Center and the project's lead researcher.
The biosensor can test blood, saliva, urine or any other water-based compound, Larson said, returning results in a few minutes to as soon as five seconds.
The device's ability to detect blood-borne illness would be a godsend during disasters, such as the Jan. 12 earthquake in Haiti where health officials needed to quickly identify safe blood donors, Larson said.
"In a situation like Haiti, you can't easily test someone's blood for infection, and you can't ship blood units in and out of the area," Larson said.
R&D Magazine Thursday recognized the biosensor as one of the 100 most technologically significant new products of the year, the Journal said.
Kenner Boy, 12 Dies from Bacterial Infection
http://www.examiner.com
Karen Gros
John Lopez, age 12 died from a rare form of bacteria, Vibrio Vulnificus, that he contracted while walking in the water at the beach.
The Lopez family were on a vacation to attend a car show and also took a walk along the beach. John became sick shortly after the walk on the beach and was seriously ill 24 hours later. The boy passed away early Saturday morning.
John Lopez had a compromised immune system because he already had Hepatitis C. Anyone with pre-existing conditions is more susceptible to an infection with Vibrio Vulnificus, which enters the body though a cut or broken skin.
John's mother confirmed that he had a sore on one of his feet. This was most likely how the virus entered his body.
Vibrio Vulnificus infections can cause heart failure, the loss of one or more limbs and even death.
According to the Centers for Disease Control and Prevention, Vibrio Vulnificus is defined as "a bacterium that is a rare cause of illness in the United States . The illness is very different from cholera, which is caused by different bacteria, called Vibrio cholerae. V. Vulnificus's infections do not spread directly from one person to another and are a serious health threat predominantly to persons with underlying illness, such as liver disease, or a compromised immune system. The organism is a natural inhabitant of warm coastal waters. Infection can occur after a wound is exposed to warm coastal waters where the V. vulnificus organism is growing. Infection may also be acquired by eating raw or undercooked seafood from those waters."
The CDC receives reports of over 400 Vibrio illnesses each year. Only about 90 each year are due to V. vulnificus. Most of the V. vulnificus illnesses occur during warm-weather months.
July 12, 2010
Medivir Announces Phase 2b 24-week Interim Results of TMC435 in Treatment-naïve Patients Chronically Infected with Genotype-1 Hepatitis C Virus
http://www.financialpost.com
Potent and consistent antiviral efficacy was demonstrated at 24-week end-of-treatment and in interim SVR4 and SVR12 results. There were no clinically relevant differences between TMC435 treatment groups and placebo for adverse events.
Medivir (STO:MVIRB) announced today 24-week end-of-treatment interim results from the 5-arm phase 2b response guided PILLAR study in 386 treatment-naïve patients with hepatitis C virus (HCV) genotype-1 (TMC435-C205).
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals, dosed as one pill once daily (q.d.) to treat hepatitis C virus infections (HCV).
In the PILLAR study, 75mg or 150mg TMC435 was given for either 12 weeks or 24 weeks in combination with 24 weeks of ribavirin and pegIFNalpha-2A, the current standard of care (SOC). Patients stopped all treatment at week 24 when HCV RNA levels at week 4 were < 25 log10 IU/mL detectable or undetectable and HCV RNA levels at week 12, week 16 and week 20 were < 25 log10 IU/mL undetectable. Patients who did not meet the above response-guided criteria continued with SOC until week 48. The results showed that in the TMC435 treatment groups 83% of patients were able to stop all therapy at Week 24.
Potent and consistent antiviral efficacy was demonstrated at 24-week end-of-treatment and in interim SVR4 and SVR12 rates with no major differences between TMC435 doses or length of triple therapy. 92% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels at week 4 and 92% at week 12 after cessation of treatment, i.e. SVR4 and SVR12. SVR4 and SVR12 data were available for 82% and 42% of the TMC435-treated patients respectively who had stopped all therapy before or at Week 24 and had completed the follow-up visits. Both the viral breakthrough rate (4.9%) and relapse rate (1.6%) were low in the TMC435 treatment groups.
TMC435 was generally safe and well tolerated with no relevant differences in adverse events (AEs) between placebo and TMC435 treatment groups. Most AEs were mild to moderate in severity and the discontinuation rate due to AEs was low and not different from placebo.
When looking at particular adverse events of interest, the incidence of rash, pruritis, GI side effects and anemia were similar in TMC435 groups and placebo and were generally mild to moderate in nature. Use of erythropoetin-stimulating agents (ESAs) was not allowed during the trial.
In laboratory parameters, there were no clinically relevant differences between any TMC435 groups and placebo except for mild bilirubin elevations. Significant decreases in transaminases (ALT and AST) were observed in all treatment groups.
Further safety and efficacy data will be presented at future scientific meetings later in 2010.
"We are extremely encouraged and excited by the efficacy and safety demonstrating that TMC435 is truly a second-generation HCV protease inhibitor," stated Bertil Samuelsson, CSO of Medivir. "We also are looking forward to the top-line data coming up from the phase 2b trial C206 (ASPIRE) in treatment-experienced patients later this year as well as start of phase 3 clinical trials in treatment-naïve patients early next year.”
| Frequency of Undetectable* HCV RNA Levels During and After Treatment |
| Treatment week |
|
TMC12PR24 |
|
TMC24PR24 |
|
TMC12PR24 |
|
TMC24PR24 |
|
SoC |
|
|
75mg q.d. |
|
75mg q.d. |
|
150mg q.d. |
|
150mg q.d. |
|
|
| N (%) |
|
N=78 |
|
N=75 |
|
N=77 |
|
N=79 |
|
N=77 |
| |
|
|
|
|
|
|
|
|
|
|
| Week-24, EoT*** |
|
67/73 (92%) |
|
65/67 (97%) |
|
68/74 (92%) |
|
73/78 (94%) |
|
4/18 (22%)** |
| Follow-up at Week-4 and Week-12 after EoT |
| SVR4 |
|
59/65 (91%) |
|
56/60 (93%) |
|
57/61 (93%) |
|
63/68 (93%) |
|
NA**** |
| SVR12 |
|
32/33 (97%) |
|
27/29 (93%) |
|
32/36 (89%) |
|
29/32 (91%) |
|
NA |
* < 25 log10 IU/mL undetectable
** End of treatment
***EoT: End of Treatment
**** Patients in the control arm continue SoC till Week 48 and SVR data are not available
q.d.: once daily, PR: pegIFNalpha-2A and ribavirin, SVR4: undetectable HCV RNA at EoT & undetectable HCV RNA 4 weeks after planned EoT, SVR12: undetectable HCV RNA at EoT & undetectable HCV RNA 12 weeks after planned EoT
About TMC435 clinical trial programs
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections (HCV).
TMC435 is currently being developed in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. Safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2010.
TMC435-C205 is a global phase 2b study in 386 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C215 is a Japan phase 2b study in 92 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C206 is a global phase 2b study in 463 genotype-1 treatment-experienced patients. It is a once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
Invitation to a Press Conference
Medivir will host a teleconference today at 15:00 (Central European summer time) focusing on the phase 2b 24-week interim results.
To participate in the teleconference, please call +46 8 619 75 30 using the participant code 195272#.
For more information on Medivir, please see the company website: www.medivir.se (http://www.medivir.se)
This information was brought to you by Cision http://www.cisionwire.com
Radiology: Perfusion CT May Aid in Liver Disease Staging
http://www.healthimaging.com/
Perfusion CT may help discriminate between minimal and intermediate stages of fibrosis in patients with chronic liver disease, according to a study in the July issue of Radiology.
Maxime Ronot, MD, from the unit for training and research in medicine at Université Paris in Paris, and colleagues sought to prospectively assess the utility of perfusion CT for differentiating minimal from intermediate fibrosis in treatment-naïve patients with chronic hepatitis C virus infection.
For the study, 52 patients with treatment-naïve HCV infection underwent perfusion CT and percutaneous liver biopsy on the same day. The researchers measured portal vein, arterial and total liver perfusion, mean transit time and distribution volumes for the right and left liver lobes. Liver samples were scored for fibrosis, and fibrosis area was determined. They then tested the differences in quantitative perfusion parameters between patients with minimal fibrosis (score of F1) and those with intermediate fibrosis (score of F2 or F3).
In patients with intermediate fibrosis (F2 and F3) compared with those with minimal fibrosis (F1), the portal venous perfusion (87 mL vs. 138 mL) and total liver perfusion (107 mL vs. 169 mL) were significantly decreased, and the mean transit time was significantly increased (16 seconds vs. 13 seconds), according to Ronot and colleagues.
At multivariate analysis, the researchers wrote that only the mean transit time was an independent factor. Receiver operating characteristic curve analysis showed that a mean transit time threshold of 13.4 seconds allowed discrimination between minimal and intermediate fibrosis with a sensitivity of 71 percent and a specificity of 65 percent.
Based on the study, the investigators found that perfusion changes occur early during fibrosis in chronic hepatitis C virus infection and can be detected with perfusion CT.
Ronot and colleagues did not find any correlations between fibrosis stage and immunohistochemical markers or between perfusion parameters and immunohistochemical markers. The researchers said they “expected to at least find a relationship between the stage of fibrosis and vascular changes.”
“Perfusion CT may help to discriminate minimal from intermediate fibrosis,” the authors wrote. “Mean transit time appears to be the most promising perfusion parameter for differentiating between fibrosis stages, although the large amount of overlap in the measured parameters limits the clinical utility of this test at present.”
July 13, 2010
56 Kids Get HIV, Hepatitis after Blood Transfusion
http://timesofindia.indiatimes.com
JODHPUR: At least 56 children suffering from thalassaemia tested positive for HIV, hepatitis B and hepatitis C after receiving blood transfusion at government-run Umaid hospital in Jodhpur. They are among the 130 thalassaemic children registered with Jodhpur’s Marwar Thalassaemic Society, said a source.
Terming it as a case of negligence, Union health minister Ghulam Nabi Azad said that the state government was responsible in the case. “It is a case of negligence. It is the responsibility of the state government to take proper precautions,” Azad said in Srinagar.
In the last one-and-a-half years, at least eight thalassaemic children in the city were found to be HIV positive while 46 others were infected by hepatitis B virus prompting a probe by the state government.
In December 2008, five children tested positive for HIV and 29 for hepatitis C virus. In May 2010, three more children were found HIV positive and 17 suffered from hepatitis C. According to the Thalassaemic Society, if all the children who received blood transfusion are tested, the numbers may go up.
Recently, members met the principal of S N Medical College and the divisional commissioner and demanded nucleic acid test at Umaid Hospital blood bank to prevent infection during transfusion.
Medical college principal R K Aseri said a proposal for nucleic acid test — which is a more advanced blood test — has been sent to Rajasthan government which is now studying the expenses involved. The college has also formed a three-member committee to probe if there are any flaws in the blood bank's testing methods.
The Society also demanded special consideration for families below poverty line and adequate staff and resources at Umaid Hospital's thalassaemia ward. Society secretary Vipin Gupta said, “We want the blood banks to have better technology.''
Currently, ELISA test has a longer window period, disabling it to detect any antibody at early stage in the donated blood. Window period is the time taken for seroconversion after exposure to the HIV virus.
VA Hospital Problems to Be Subject of House Panel Hearing Tuesday in St. Louis
http://www.bnd.com
AP
ST. LOUIS -- The House Committee on Veterans' Affairs is meeting Tuesday in St. Louis in the fallout of the report that lapses in sterilization of dental equipment at the city's VA hospital potentially exposed 1,802 veterans to hepatitis B, hepatitis C and HIV.
The hearing is scheduled for 1 p.m. CDT at the Eagleton U.S. Courthouse. It will also include members of Congress from Missouri and Illinois.
Several witnesses are scheduled to testify, including veterans, a former dental employee of the St. Louis VA Medical Center and top officials from the VA.
The VA sent letters two weeks ago to those who had dental procedures at the center from Feb. 1, 2009, through March 11, 2010. VA officials say the risk of exposure is extremely low.
Donor Kidneys from Hepatitis C Patients Needlessly Denied to Patients with That Infection
http://www.hopkinsmedicine.org
--Johns Hopkins study shows hepatitis C-positive organs pointlessly discarded
More than half of donor kidneys in the United State infected with hepatitis C are thrown away, despite the need among hepatitis C patients who may die waiting for an infection-free organ, Johns Hopkins research suggests.
In a study of national data published online in the American Journal of Transplantation, the researchers say that while outcomes are slightly worse when hepatitis C-positive patients receive hepatitis C-positive organs, the advantages of more timely transplants may outweigh the risk of waiting — perhaps more than year — for a hepatitis C-negative kidney.
Patients with hepatitis C-positive make up about 12 percent of the population with kidney failure, and those patients have an increased risk of death on dialysis compared with those without the virus, the study says.
“Nationwide, kidneys from infected donors are inappropriately thrown out and denied to patients in need,” says transplant surgeon Dorry L. Segev, M.D., Ph.D., an associate professor of surgery at the Johns Hopkins University School of Medicine and the study’s leader. “Many transplant centers don’t use these kidneys at all, effectively consigning hepatitis C-positive patients to an average unnecessary wait of a year longer for an uninfected organ.”
That, he says, “means an extra year on dialysis, in which the risk of death is 10 to 15 percent.”
The use of hepatitis C-positive kidneys has been controversial in the past, owing in part to a 1 percent difference in one-year survival for patients who receive the infected kidneys and a 2 percent difference in three-year survival. Segev says this difference “is easily made up for by getting off dialysis sooner.”
Hepatitis C-positive kidneys rarely go to hepatitis C-negative patients because the organ would infect the recipient with the chronic liver disease.
In looking at data from more than 93,000 deceased kidney donors between 1995 and 2009, Segev and his colleagues found that hepatitis C-positive kidneys were two and a half times more likely to be discarded than hepatitis C-negative kidneys. Since 1995, more than 3,500 hepatitis C-positive kidneys were thrown away.
“That’s a lot of kidneys we could have transplanted into people who need them,” Segev says.
Meanwhile, he adds, some 4,800 hepatitis C patients got hepatitis C-negative kidneys. “Using hepatitis C-positive kidneys in people who are infected with the virus could help those with hepatitis C and also expand the organ supply for everyone.”
One-third of the nation’s transplant centers, according to the study, did not use any hepatitis C-positive kidneys for their hepatitis C patients, while 13 percent transplanted more than half of their hepatitis C patients with hepatitis C-positive kidneys.
At The Johns Hopkins Hospital, where doctors specialize in patients with hepatitis C and kidney failure, a patient with hepatitis C could likely be successfully transplanted with a hepatitis C-positive kidney within several months of being put on the waiting list, Segev says. Recipients of hepatitis C-positive kidneys waited, on average, 395 days less than those recipients who waited for hepatitis C-negative kidneys at the same transplant center, the study shows.
Other Johns Hopkins researchers on the study include Lauren M. Kucirka, Sc.M.; Andrew L. Singer, M.D., Ph.D.; R. Loris Ros, Sc.M.; Robert A. Montgomery, M.D., Ph.D.; and Nabil N. Dagher, M.D.
For more information:
http://www.hopkinsmedicine.org/transplant
/About/Segev.html
http://www.hopkinsmedicine.org/transplant/
Hopkins Medicine Today http://www.hopkinsmedicine.org/mediaII/index.html is the online news site that links you to the latest news, features, videos and podcasts from around Johns Hopkins Medicine.
Antivirals Are Poorly Tolerated, Largely Ineffective against HCV after Liver Transplantation
http://www.medscape.com
Lara C. Pullen, PhD
July 13, 2010 (Hong Kong, China) — Results from a new study suggest that antiviral therapy should be used more judiciously in patients with hepatitis C virus (HCV) infection who have undergone liver transplantation.
Specifically, these patients should not be started on antiviral therapy in the first postoperative year unless there is clear evidence of histologic recurrence of HCV infection, investigator Michael Charlton, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, told attendees here at the International Liver Transplantation Society 16th Annual International Congress.
The most common indication for liver transplantation in North America is HCV-related end-stage liver disease. Most of these transplant recipients go on to experience virological recurrence, which is a major cause of morbidity and mortality. Cirrhosis is diagnosed in 20% to 40% of patients in the 5 years after transplantation, Dr. Charlton noted during an interview with Medscape Medical News.
"I think the study highlights the difficulties we face in treating HCV infection in liver transplant recipients with our current tools — peginterferon and ribavirin. Most patients don't tolerate treatment and most of those who do tolerate treatment don't respond to it."
In the PHOENIX study, the Mayo Clinic team looked at the safety, tolerability, and safety of prophylactic peginterferon alfa-2a plus ribavirin therapy after liver transplantation in 115 patients randomized to treatment (55 patients) or observation (60 patients) 10 to 26 weeks after transplantation. The mean age in the prophylaxis group was 51.0 years (range, 35 to 68 years) and in the observation group was 53.5 years (range, 38 to 66 years). Patients in the prophylaxis group received peginterferon alfa-2a (135 µg/week for 4 weeks followed by 180 µg/week for 44 weeks) and ribavirin (initially dosed at 400 mg/day and escalated to 1200 mg/day).
Dr. Charlton reported sustained virologic response in 22% of the patients in the prophylaxis group and 21% of those in the observation group, who were treated if histologic recurrence was demonstrated.
When analyzed at 120 weeks on an intent-to-treat basis, the frequency of histologically confirmed HCV recurrence was similar in both groups (P = .725).
Prophylactic antiviral therapy had no effect on patient or graft survival. Antiviral therapy was poorly tolerated, and only 55.6% of the prophylaxis group and 28.6% of the observation group were able to tolerate more than 80% of the intended antiviral dosing.
Dr. Charlton added: "I hope the results will provoke new studies of strategies to improve the tolerability and efficacy of posttransplant antiviral therapy. The near-term advents of IL28b testing and the addition of protease inhibitors are eagerly awaited."
Brian B. Borg, MD, MHSc, from the Ochsner Multi-Organ Transplant Institute in New Orleans, Louisiana, added that after liver transplantation, "patients are on multiple immune suppressive regimens, especially in the early posttransplant period, and are prone to other comorbidities making them less optimal candidates for treatment. The treatment response is not as good as in pretransplant patients and adherence to current combination therapy is poor because of side effects and potential complications." Dr. Borg is not affiliated with the study, but spoke with Medscape Medical News about the implications of the research.
Other transplantation centers have found alternative strategies for dealing with this problem. Luca Cicalese, MD, from the Texas Transplant Center at the University of Texas Medical Branch in Galveston, told Medscape Medical News that "at the Texas Transplant Center, we start treatment for hepatitis C after liver transplant only when there is evidence of active infection. We are also using a particular immunosuppressive protocol (to reduce the risk of rejection) that is particularly designed to reduce the risk of recurrence of hepatitis C posttransplant in our patients, which has drastically reduced such occurrence." Dr. Cicalese was not involved with the study.
Dr. Charlton's study was funded entirely by Roche/Genentech, the makers of peginterferon alfa-2a and ribavirin. Dr. Borg and Dr. Cicalese have disclosed no relevant financial relationships.
International Liver Transplantation Society (ILTS) 16th Annual International Congress: Abstract 0-162. Presented June 19, 2010.
FDA Approves Infergen Combo Therapy for Retreating HCV
http://www.medscape.com
Yael Waknine
Bacterial RTIs: Consider the importance of broad-spectrum coverage See coverage in community-acquired pneumonia (CAP) Read more
July 12, 2010 — The US Food and Drug Administration (FDA) has approved an expanded indication for interferon alfacon-1 subcutaneous injection (Infergen; Three Rivers Pharmaceuticals, LLC), in combination with ribavirin, for retreatment of chronic hepatitis C (HCV) viral infection.
The action was based on data from the United States–based Daily-Dose Consensus Interferon and Ribavirin: Efficacy of Combined Therapy clinical trial of nonresponders to prior pegylated interferon plus ribavirin therapy who were randomly assigned to receive active treatment or placebo for up to 48 weeks.
Results showed that 9% of patients receiving 15 μg interferon alfacon-1/ribavirin achieved a sustained virologic response, defined as undetectable HCV RNA levels at 24 weeks posttherapy (vs placebo, 0%).
The retreatment strategy was especially effective for interferon-sensitive patients with lower baseline fibrosis scores. According to a company news release, up to 38% of noncirrhotic patients who were sensitive to pegylated interferon/ribavirin and who did not modify their interferon alfacon-1/ribavirin dosages achieved a sustained virologic response. Cirrhotic patients were less likely to benefit from treatment unless they displayed previous interferon sensitivity or a minimum 1 log10 drop in HCV RNA on prior therapy.
"Approximately 50 percent of patients with chronic hepatitis C do not respond to their initial course of therapy," stated Bruce Bacon, MD, in the company news release. "The FDA's recognition of this expanded label allows patients failing therapy a safe and efficacious retreatment strategy. The results from this study legitimize how we properly treat these patients helping them to achieve [a sustained virologic response]." Dr. Bacon was the lead investigator for the registration trial.
Adverse events most commonly reported with 15 μg interferon alfacon-1/ribavirin included fatigue, nausea, influenza-like symptoms, headache, arthralgia, myalgia, neutropenia, leukopenia, insomnia, and depression. Dose modifications were required in 52% of patients, primarily because of neutropenia/leukopenia, thrombocytopenia, and fatigue/weakness.
Interferon alfacon-1 previously was approved as monotherapy for chronic HCV in adults with compensated liver disease.
Presidio Pharmaceuticals, Inc. Successfully Completes Phase 1a Clinical Trial of PPI-461, a Potent, New Hepatitis C Virus (HCV) Inhibitor
http://finance.yahoo.com
SAN FRANCISCO--(BUSINESS WIRE)--Presidio Pharmaceuticals, Inc. announced today the successful completion of a Phase 1a clinical trial of PPI-461, its lead HCV NS5A inhibitor, in healthy subjects. This first-in-human trial evaluated four single doses of PPI-461, followed by a five-day, once-a-day treatment regimen with PPI-461 at the highest tested dose.
The randomized, double-blind, placebo-controlled trial was completed with 40 healthy subjects in the United Kingdom. The trial results indicated that PPI-461 was well-tolerated in all dose regimens. There were no serious adverse events, and all subjects completed the trial successfully. Among PPI-461 recipients there were only transient adverse events, none of which were attributed to study drug by the investigator, and there were no significant changes in safety-related clinical laboratory assessments.
Pharmacokinetic (PK) analyses showed substantial blood levels of PPI-461 were rapidly and consistently achieved and were dose proportional. PPI-461 plasma concentrations were orders of magnitude above those shown to suppress viral replication in vitro and were maintained at predicted effective concentrations for more than 24 hours. In the five-day, multi-dose regimen, steady-state PK was readily achieved, supportive of once-daily dosing.
“These first clinical data of PPI-461 indicate excellent tolerance in healthy subjects with all tested dosing regimens. The PK profile is very encouraging, suggesting that plasma concentrations of PPI-461 can be obtained with a relatively low dose, once-daily (QD) regimen that may provide a continuous antiviral effect,” said Nathaniel Brown, M.D., Chief Medical Officer.
Presidio Pharmaceuticals, Inc. plans to initiate a Phase 1b proof-of-concept trial in patients with HCV in Q4 2010 and expects to have early results regarding the clinical efficacy of PPI-461 near year-end.
About PPI-461
PPI-461 is a novel, proprietary NS5A inhibitor against hepatitis C virus (HCV), exhibiting highly potent and selective activity against all genotypes in HCV replicon assays.
Inhibitors of the HCV NS5A protein represent an exciting, highly potent class that is distinct from other classes of HCV antivirals that target the viral protease or replicase. With poor response and tolerance issues associated with the current standard of care treatment—pegylated-IFN and ribavirin—there is clear need for more potent and better tolerated inhibitors that can be orally administered in future combination therapies.
About Presidio
Presidio Pharmaceuticals, Inc. is a San Francisco-based specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics for novel and validated targets. For more information, please visit our website at: www.presidiopharma.com.
Indiana Blood Center, Roche Form New Partnership
http://www.insideindianabusiness.com
(INDIANAPOLIS - July 13, 2010) Indiana Blood Center announced today it is switching to an automated testing platform from Roche Diagnostics for its donor testing lab, a move that will represent testing for nearly 375,000 samples each year when the conversion is complete. Representatives of the two Indiana life sciences organizations will celebrate the new partnership at a ribbon cutting event at Indiana Blood Center on July 14.
“Roche is gaining a reputation as being on the forefront of technology and innovation in the blood industry,” said Mike Parejko, executive vice president and chief operating officer at Indiana Blood Center. “Our goal was to select the platform that fit our needs today and that had the promise of meeting our needs into the future. The fact that Roche is core to Indiana’s life sciences community made the prospect of working together on this and other projects even more intriguing.”
The new technology from Roche, the cobas TaqScreen MPX test for use on the cobas s 201 system, is the most comprehensive system to screen donated blood for HIV, hepatitis b and hepatitis c viruses. Designed to reduce test time, the automated platform allows samples to be started as they are received rather than being submitted in batches, which the previous system required. A shorter turnaround time could translate to quicker release of donated blood into the inventory of products for transfusion.
Efficiencies for the not-for-profit Indiana Blood Center and the more than 60 hospitals it serves are imperative. The comprehensive testing capabilities of the cobas s 201 system are expected to enable Indiana Blood Center to consolidate its testing operations and eventually eliminate the need for one of its current labs. Staffing one all-inclusive donor testing lab allows for cross training and creates a single pool of employees with the high-tech skills needed to run the lab. The lab that will no longer be needed for donor screening will be emptied and used for research, potentially with Roche Diagnostics or other partners.
On July 1, Indiana Blood Center began using the cobas s 201 system to screen organ donors as part of a new contract with the Indiana Organ Procurement Organization (IOPO). The technology was a significant factor in IOPO’s decision because the turnaround time and the elimination of the need to send organ samples out-of-state offer significant benefits in the time-sensitive practice of organ transplantation.
Screening with the cobas s 201 system for donated blood components from Indiana Blood Center and the 11 other independent blood centers that contract with Indiana Blood Center for the donor testing will begin May 1, 2011.
Indiana Blood Center is a vital link in Indiana's health care infrastructure, supplying more than 550 units of blood to more than 60 Indiana hospitals every day. The not-for-profit community service organization was founded in 1952 to provide a continuous, safe and adequate supply of blood products and testing services first to the people in our own communities, then wherever our blood products and testing services are needed. For more information, call 800-632-4722 or visit www.indianablood.org.
Source: Indiana Blood Center
FDA Adds Information on Severe Liver Injury to Leflunomide's Boxed Warning
http://www.aafp.org/
Agency Acts in Wake of Dozens of Case Reports, 14 Deaths
The FDA has identified 49 cases of severe liver injury -- 14 of which proved fatal -- in patients taking the rheumatoid arthritis drug leflunomide, which is marketed as Arava. The agency said in a July 13 safety announcement that it has responded by adding information about severe liver injury to the boxed warning of the product's package label.
FDA Advisory
The FDA previously had required a boxed warning stating that the medication was contraindicated in pregnant women or women of childbearing potential who were not using reliable contraception.
The following information about liver injury was added to the boxed warning:
- patients with elevated liver enzymes (i.e., alanine transaminase, or ALT, levels greater than two times the upper limit of normal) and those with pre-existing liver disease should not receive leflunomide;
- liver enzymes should be monitored at least monthly for three months after starting leflunomide and at least quarterly thereafter;
- if ALT levels rise to greater than two times the upper limit of normal while a patient is on leflunomide, the medication should be stopped, a cholestyramine washout should be performed to speed removal of the drug from the body, and follow-up liver function tests should be conducted at least weekly until the ALT value is within normal range; and
- caution should be used in patients who are taking other drugs that can cause liver injury.
The FDA's review of adverse events reported from August 2002 to May 2009 indicate that 46 of the 49 patients who had severe liver injury were taking other medications that have been associated with liver injury, including methotrexate, which is marketed as Rheumatrex and Trexall; tumor necrosis factor blockers; hydroxychloroquine, which is marketed as Plaquenil; acetaminophen; nonsteroidal anti-inflammatory drugs; and statins.
In addition, 14 patients had pre-existing liver disease, such as acute or chronic infection with hepatitis B or hepatitis C virus, and/or a history of alcohol abuse.
Although many patients were taking other drugs or had pre-existing liver disease, the FDA concluded that the use of leflunomide was associated with the development of severe liver injury in the affected patients.
The agency advised physicians that only patients for whom the anticipated therapeutic benefit is expected to outweigh the risk of severe liver injury should be considered for leflunomide treatment.
Patients who experience signs or symptoms of severe liver injury -- itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools -- should contact their physicians right away, according to the FDA.
Side effects associated with leflunomide use should be reported to the FDA's MedWatch program.
July 15, 2010
Missouri: VA Technician Says She Warned of Sterilization Problems
http://www.thebody.com
A former technician at the St. Louis Veterans Affairs Medical Center said she warned supervisors of sterilization errors more than a year before the VA was forced to notify vets of possible exposure to hepatitis B, hepatitis C, and HIV.
"If people were taking their jobs seriously, not passing the buck and pointing the finger, none of this would have happened," medical supply technician Earlene Johnson said at a congressional hearing Tuesday in St. Louis.
The lapses involved prewashing dental equipment without detergent prior to sterilization, VA Undersecretary for Health Robert Petzel said.
In March 2010, the St. Louis VA concluded that its dental clinic sterilization processes between February 1, 2009, and March 11, 2010, were inadequate. Two weeks ago, the VA sent letters to 1,812 veterans urging them to be tested for viruses including hepatitis B, hepatitis C, and HIV.
While these viruses have been found in some of the 950 vets tested so far, it is not known if exposure at the VA is the source, said Dr. George Arana of the Veterans Health Administration.
Sterilization procedures have been revised, and no one who received services since March 11 is at risk, Petzel said.
Johnson said she first alerted officials at the VA of problems in March 2009. She believes her complaints resulted in her subsequent termination, and she is seeking to be reinstated.
The VA took heat at the hearing for the gap between confirmation of the exposure in March of this year and notification almost four months later.
"We did not respond quickly enough," Petzel said.
Back to top
Back to News Review
|
