Public release date: 17-Nov-2010
Contact: Marsha Austin
maustin@healthgrades.com
720-963-3848
HealthGrades
210 hospitals evaluated on HealthGrades.com
GOLDEN, Colo. (November 17, 2010) – HealthGrades, the nation's leading independent ratings organization, today made available to organ transplant patients a list of those hospitals with the best track record for survival and chances of receiving a donor organ. HealthGrades annual evaluation of the nation's top-performing hospitals in organ transplantation includes clinical quality data, based on patient outcomes, for each of the 210 adult acute care hospitals that perform transplants. This information is available, free to the public, at HealthGrades.com and is intended to help patients in need of kidney, lung, heart or liver transplants.
"More than 108,000 patients are on a waiting list for an organ transplant in the U.S and it is imperative that patients have a resource to compare patient outcomes and other criteria at programs across the country," said HealthGrades' Rick May, MD. "HealthGrades' hospital ratings are based on objective patient outcomes, empowering patients to choose a program that gives them the best chance at survival."
The following data is displayed on HealthGrades.com and was calculated by the Scientific Registry of Transplant Recipients (SRTR) for all adult acute care hospitals in the U.S. with transplant programs:
• One and three-year risk-adjusted patient survival;
• One and three-year risk-adjusted graft survival;
• The rate at which waitlisted patients receive transplants; and
• Waitlist mortality.
Hospitals with transplant programs received HealthGrades Transplant Excellence Awards if they had a statistically significantly higher three-year survival rate. Award recipients were also required to have waitlist mortality that was either not significantly different than expected or was significantly lower than expected based on SRTR calculations. Of the 210 hospitals evaluated, 20 hospitals received this award.
The recipients are as follows*:
HealthGrades Kidney Transplant Excellence Award recognized 11 recipients out of 199 hospitals evaluated:
• Sutter General Hospital
• UC Davis Medical Center
• Yale - New Haven Hospital
• Tampa General Hospital
• MCG Health Medical Center
• Clarian Methodist Hospital
• Ochsner Clinic Foundation
• Boston Medical Center Corporation
• New York - Presbyterian/Weill Cornell
• Allegheny General Hospital
• University of Washington Medical Center
HealthGrades Lung Transplant Excellence Award recognized 3 recipients out of 53 hospitals evaluated:
• Shands Hospital at the University of Florida
• Tampa General Hospital
• University of Minnesota Medical Center – Riverside
HealthGrades Heart Transplant Excellence Award recognized 2 recipients out of 98 hospitals evaluated:
• Newark Beth Israel Medical Center
• Temple University Hospital
HealthGrades Liver Transplant Excellence Award recognized 4 recipients out of 95 hospitals evaluated:
• California Pacific Medical Center - Pacific
• UCSF Medical Center
• Cleveland Clinic
• Saint Lukes Episcopal Hospital
###
The ratings of individual hospitals, as well as the full methodology of the analysis, can be found at http://www.healthgrades.com/. For additional information about each of these transplant programs, or about the methods used for computing the measures above, please visit the SRTR website at http://www.ustransplant.org/. The SRTR is not in any way involved in determining award status.
HealthGrades
Health Grades, Inc. is the leading independent healthcare ratings organization, providing quality ratings, profiles and cost information on the nation's hospitals, physicians, nursing homes and prescription drugs. Millions of patients and many of the nation's largest hospitals, health plans and employers rely on HealthGrades' quality ratings, advisory services and decision-support resources. The HealthGrades Network of websites, including HealthGrades.com and WrongDiagnosis.com, is a top-ten health property according to comScore and is the Internet's leading destination for patients choosing providers. More information on how HealthGrades guides Americans to their best health can be found at http://www.healthgrades.com/.
*The HealthGrades Transplant Excellence Award list is © Copyright 2010 by Health Grades, Inc. and may not be used for marketing by hospitals or reproduced in whole or in part in any manner without its express written permission.
November 17, 2010
Doctor Charged With Tipping Hedge Fund Gets Bail
November 17, 2010, 1:32 PM EST
By Don Jeffrey and Patricia Hurtado
(Updates with comment from prosecutor in fifth paragraph.)
Nov. 17 (Bloomberg) -- A Human Genome Sciences Inc. consultant accused of tipping off hedge fund FrontPoint Partners LLC about the results of trials involving the hepatitis-C drug Albuferon was granted $3 million bail by a judge in New York.
Dr. Yves Benhamou, 50, of France, was charged Nov. 2 by prosecutors in the office of Manhattan U.S. Attorney Preet Bharara with insider-trading and conspiracy.
U.S. Magistrate Judge Frank Maas set bail at $3 million, secured by $1 million in cash or property in the U.S. He said Benhamou will be subjected to “home incarceration” in the New York area and monitored electronically.
“All conditions must be met before his release,” Maas said.
“We’re gratified that the court set conditions of bail that we hope will permit Dr. Benhamou to resume his communications with his patients,” said David Zornow, Benhamou’s lawyer, after the bail hearing ended.
Assistant U.S. Attorney Pablo Quinones opposed home incarceration, telling the magistrate “he has the means to flee. He has a country that is a safe haven.” France does not extradite its citizens to other countries.
Suspect Cried
Benhamou, of Neuilly-sur-Seine, France, lowered his head and cried after the bail was set. He waved to his brother and sister as he was led out of the courtroom. His siblings declined to comment.
Zornow told the magistrate Benhamou would probably rent an apartment in the New York area. He could confer with his patients in France by e-mail and telephone.
“It would be truly tragic to have this man sitting in a prison when he could be communicating with, helping his patients,” Zornow told the magistrate.
Maas said he had considered bail of as much as $5 million.
Benhamou, whose expertise is hepatitis and liver diseases, was arrested in Boston while attending a conference after a two- count criminal complaint was filed against him in federal court in Manhattan. He waived his rights to a hearing in Boston and agreed to have a detention hearing in New York.
Benhamou was charged with one count of conspiracy to commit securities fraud and one count of securities fraud. He faces as long as 20 years in prison if convicted.
Cooperation
The hedge fund, FrontPoint, which is being spun off from Morgan Stanley, said on Nov. 2 it is “cooperating fully” with federal authorities. Dr. Chip Skowron, a co-portfolio manager of the Greenwich, Connecticut-based firm’s health-care funds, was placed on leave pending the outcome of the probe, the firm said.
FrontPoint held 3.3 million shares of Human Genome at the end of the fourth quarter of 2007, valued at $34.3 million, according to data compiled by Bloomberg News. It held none at the end of the following quarter. Human Genome fell 44 percent on Jan. 23, 2008, after saying it would change the dosing of its experimental hepatitis-C drug Albuferon in patient tests.
Before joining FrontPoint, Skowron was an analyst at hedge funds Millennium Partners LLC in New York and SAC Capital Advisors LLC in Stamford, Connecticut, according to FrontPoint’s marketing documents.
Benhamou acted as a paid consultant to at least six hedge funds while working as an adviser to Human Genome, a developer of gene-based drugs, and serving on its steering committee for Albuferon trials, prosecutors and the U.S. Securities and Exchange Commission alleged in a parallel lawsuit.
Human Genome said after his arrest that Benhamou is no longer a consultant and the company had cooperated with the SEC.
Benhamou repeatedly shared nonpublic information he gleaned from working for Rockville, Maryland-based Human Genome with his co-conspirator at the fund, helping it avoid $30 million in losses, prosecutors alleged in court papers.
The case is U.S. v. Benhamou, 10-MAG-2424, U.S. District Court, Southern District of New York (Manhattan). The SEC case is SEC v. Benhamou, 10-CV-8266, U.S. District Court, Southern District of New York (Manhattan).
--Editors: Fred Strasser, Charles Carter
To contact the reporters on this story: Patricia Hurtado in New York at pathurtado@bloomberg.net; To contact the reporter on this story: Don Jeffrey in New York at djeffrey1@bloomberg.net.
To contact the editor responsible for this story: David E. Rovella at drovella@bloomberg.net.
Source
Also See: Hepatologist Arrested for Insider Trading
By Don Jeffrey and Patricia Hurtado
(Updates with comment from prosecutor in fifth paragraph.)
Nov. 17 (Bloomberg) -- A Human Genome Sciences Inc. consultant accused of tipping off hedge fund FrontPoint Partners LLC about the results of trials involving the hepatitis-C drug Albuferon was granted $3 million bail by a judge in New York.
Dr. Yves Benhamou, 50, of France, was charged Nov. 2 by prosecutors in the office of Manhattan U.S. Attorney Preet Bharara with insider-trading and conspiracy.
U.S. Magistrate Judge Frank Maas set bail at $3 million, secured by $1 million in cash or property in the U.S. He said Benhamou will be subjected to “home incarceration” in the New York area and monitored electronically.
“All conditions must be met before his release,” Maas said.
“We’re gratified that the court set conditions of bail that we hope will permit Dr. Benhamou to resume his communications with his patients,” said David Zornow, Benhamou’s lawyer, after the bail hearing ended.
Assistant U.S. Attorney Pablo Quinones opposed home incarceration, telling the magistrate “he has the means to flee. He has a country that is a safe haven.” France does not extradite its citizens to other countries.
Suspect Cried
Benhamou, of Neuilly-sur-Seine, France, lowered his head and cried after the bail was set. He waved to his brother and sister as he was led out of the courtroom. His siblings declined to comment.
Zornow told the magistrate Benhamou would probably rent an apartment in the New York area. He could confer with his patients in France by e-mail and telephone.
“It would be truly tragic to have this man sitting in a prison when he could be communicating with, helping his patients,” Zornow told the magistrate.
Maas said he had considered bail of as much as $5 million.
Benhamou, whose expertise is hepatitis and liver diseases, was arrested in Boston while attending a conference after a two- count criminal complaint was filed against him in federal court in Manhattan. He waived his rights to a hearing in Boston and agreed to have a detention hearing in New York.
Benhamou was charged with one count of conspiracy to commit securities fraud and one count of securities fraud. He faces as long as 20 years in prison if convicted.
Cooperation
The hedge fund, FrontPoint, which is being spun off from Morgan Stanley, said on Nov. 2 it is “cooperating fully” with federal authorities. Dr. Chip Skowron, a co-portfolio manager of the Greenwich, Connecticut-based firm’s health-care funds, was placed on leave pending the outcome of the probe, the firm said.
FrontPoint held 3.3 million shares of Human Genome at the end of the fourth quarter of 2007, valued at $34.3 million, according to data compiled by Bloomberg News. It held none at the end of the following quarter. Human Genome fell 44 percent on Jan. 23, 2008, after saying it would change the dosing of its experimental hepatitis-C drug Albuferon in patient tests.
Before joining FrontPoint, Skowron was an analyst at hedge funds Millennium Partners LLC in New York and SAC Capital Advisors LLC in Stamford, Connecticut, according to FrontPoint’s marketing documents.
Benhamou acted as a paid consultant to at least six hedge funds while working as an adviser to Human Genome, a developer of gene-based drugs, and serving on its steering committee for Albuferon trials, prosecutors and the U.S. Securities and Exchange Commission alleged in a parallel lawsuit.
Human Genome said after his arrest that Benhamou is no longer a consultant and the company had cooperated with the SEC.
Benhamou repeatedly shared nonpublic information he gleaned from working for Rockville, Maryland-based Human Genome with his co-conspirator at the fund, helping it avoid $30 million in losses, prosecutors alleged in court papers.
The case is U.S. v. Benhamou, 10-MAG-2424, U.S. District Court, Southern District of New York (Manhattan). The SEC case is SEC v. Benhamou, 10-CV-8266, U.S. District Court, Southern District of New York (Manhattan).
--Editors: Fred Strasser, Charles Carter
To contact the reporters on this story: Patricia Hurtado in New York at pathurtado@bloomberg.net; To contact the reporter on this story: Don Jeffrey in New York at djeffrey1@bloomberg.net.
To contact the editor responsible for this story: David E. Rovella at drovella@bloomberg.net.
Source
Also See: Hepatologist Arrested for Insider Trading
Hepatitis C: is immunity on the horizon?
November 17th, 2010 (PhysOrg.com) -- More than 250,000 Canadians are infected with the highly infectious, chronic liver disease Hepatitis C, which is caused by the Hepatitis C Virus (HCV). The virus continues to spread in a variety of ways such as needle sharing, unsanitary tattooing, pedicures and manicures, and unprotected sex.
Unlike Hepatitis A and B, there is no vaccine for this unique strain and existing treatments are not always effective. Progress is, however, being made and new information will be shared on Nov. 19 at the Fifth Annual Immunology Montreal Symposium hosted by McGill University. The gathering of international experts will focus on recent advances made in the field of immunology regarding HCV infection.
WHAT: Fifth Annual Immunology Montreal Symposium
“Immunity to Hepatitis C Virus: Recent Advances”
WHEN: Nov. 19, 8:30 a.m.- 3 p.m.
WHERE: McGill University, New Residence Hall, 3625 Parc Ave.
Scheduled speakers include Stanley M. Lemon, a world-renowned expert on HCV replication and innate antiviral responses, from the University of North Carolina at Chapel Hill; Matthias Götte, an associate professor of biochemical virology at McGill and a recognized expert in HCV drug resistance; Daniel Lamarre, a professor at the Institute for Research in Immunology and Cancer at Université de Montréal, and a specialist of innate responses against HCV; Naglaa Shoukry, Director of the viral hepatitis research group of the CHUM Research Centre of Université de Montréal, and a specialist on T-cell responses against HCV in the acute phase of the infection; Arash Grakoui of the Emory Vaccine Center in Atlanta, Georgia; and Paul Klenerman, professor of immunology at the University of Oxford in the U.K., and one of the world’s leading HCV immunologists.
Immunology Montreal is a collaborative venture between McGill University, Université de Montréal and INRS-Institut Armand-Frappier. Its primary objective is to help educate students at all levels (with the focus on high school through university), as well as the general population, about immunology while forging ties between the educational institutions in the greater Montreal area.
Following presentations there will be an opportunity for students, trainees, researchers or the media to meet the speakers for additional information.
Provided by McGill University
Source
Unlike Hepatitis A and B, there is no vaccine for this unique strain and existing treatments are not always effective. Progress is, however, being made and new information will be shared on Nov. 19 at the Fifth Annual Immunology Montreal Symposium hosted by McGill University. The gathering of international experts will focus on recent advances made in the field of immunology regarding HCV infection.
WHAT: Fifth Annual Immunology Montreal Symposium
“Immunity to Hepatitis C Virus: Recent Advances”
WHEN: Nov. 19, 8:30 a.m.- 3 p.m.
WHERE: McGill University, New Residence Hall, 3625 Parc Ave.
Scheduled speakers include Stanley M. Lemon, a world-renowned expert on HCV replication and innate antiviral responses, from the University of North Carolina at Chapel Hill; Matthias Götte, an associate professor of biochemical virology at McGill and a recognized expert in HCV drug resistance; Daniel Lamarre, a professor at the Institute for Research in Immunology and Cancer at Université de Montréal, and a specialist of innate responses against HCV; Naglaa Shoukry, Director of the viral hepatitis research group of the CHUM Research Centre of Université de Montréal, and a specialist on T-cell responses against HCV in the acute phase of the infection; Arash Grakoui of the Emory Vaccine Center in Atlanta, Georgia; and Paul Klenerman, professor of immunology at the University of Oxford in the U.K., and one of the world’s leading HCV immunologists.
Immunology Montreal is a collaborative venture between McGill University, Université de Montréal and INRS-Institut Armand-Frappier. Its primary objective is to help educate students at all levels (with the focus on high school through university), as well as the general population, about immunology while forging ties between the educational institutions in the greater Montreal area.
Following presentations there will be an opportunity for students, trainees, researchers or the media to meet the speakers for additional information.
Provided by McGill University
Source
Bristol-Myers Squibb Enhances Co-pay Assistance Program for Entecavir (Baraclude) for Hepatitis B
SUMMARY: Bristol-Myers Squibb this summer expanded its co-pay benefit program for individuals receiving or wishing to use entecavir (Baraclude) who have private insurance policies with out-of-pocket costs. The enhanced program will save eligible patients up to $200 per month for 4 years. Eligible participants may request a Co-Pay Benefit Card from their healthcare providers.
Below is an email advisory from Bristol-Myers Squibb describing the expanded program.
Baraclude (Entecavir) Co-pay Benefit Program Enhancements
Bristol-Myers Squibb enhanced its Baraclude (entecavir) Co-pay Benefit Program beginning on July 1, 2010, for eligible new and existing patients who have out-of-pocket costs through their commercial insurance coverage. We recognize that, especially in this economic environment, out-of-pocket costs for medicine may be prohibitive even for patients who have prescription drug benefits. This program reflects Bristol-Myers Squibb's ongoing commitment to helping patients who need our medicines to access them.
The Baraclude Co-pay Benefit Program will allow eligible patients to save up to $200 of co-pay costs monthly, for the next four years, through December, 2014. Bristol-Myers Squibb will now cover the first $200 of a patient's monthly co-pay or co-insurance costs; the patient will be responsible for any amount over $200. This means that 94.5% of eligible chronic hepatitis B patients with commercial insurance can have a co-pay of $0 per month over the next four years. Restrictions apply to certain patients, including those who reside in Massachusetts and those with prescription benefits funded through Medicare, Medicaid and other federal/state programs.
To access this benefit, eligible patients need to obtain a Co-pay Benefit Card to take to the pharmacy each time they fill their prescription for Baraclude. Benefit cards are available through their healthcare provider. Eligible patients who are currently utilizing our Co-pay Benefit Program for Baraclude do not need to obtain new benefit cards. These patients will begin receiving these new benefits, subject to the new program end date, upon their next use of their Co-pay Benefit Card.
The Co-pay Benefit Card currently is not valid in Massachusetts or for prescriptions purchased under Medicaid, Medicare, or federal or state programs (including state prescription drug programs, or private indemnity or HMO insurance plans, which reimburse patients for the entire cost of the prescription drugs).
This Co-pay Benefit Program is for eligible commercially insured patients only. For patients with chronic hepatitis B who are uninsured or underinsured, Bristol-Myers Squibb offers other programs to support access to medicines. Bristol-Myers Squibb provides our medicines free of charge to those who qualify through our Access Virology Patient Assistance Program and also participates in the pharmaceutical industry's Together Rx Access Program.
Bristol-Myers Squibb is a global biopharmaceutical company committed to discovering, developing and delivering innovative medicines that help patients prevail over serious diseases.
11/16/10
Source
Bristol-Myers Squibb. Baraclude (entecavir) Co-pay Benefit Program enhancements. Email advisory. November 12, 2010.
Source
Below is an email advisory from Bristol-Myers Squibb describing the expanded program.
Baraclude (Entecavir) Co-pay Benefit Program Enhancements
Bristol-Myers Squibb enhanced its Baraclude (entecavir) Co-pay Benefit Program beginning on July 1, 2010, for eligible new and existing patients who have out-of-pocket costs through their commercial insurance coverage. We recognize that, especially in this economic environment, out-of-pocket costs for medicine may be prohibitive even for patients who have prescription drug benefits. This program reflects Bristol-Myers Squibb's ongoing commitment to helping patients who need our medicines to access them.
The Baraclude Co-pay Benefit Program will allow eligible patients to save up to $200 of co-pay costs monthly, for the next four years, through December, 2014. Bristol-Myers Squibb will now cover the first $200 of a patient's monthly co-pay or co-insurance costs; the patient will be responsible for any amount over $200. This means that 94.5% of eligible chronic hepatitis B patients with commercial insurance can have a co-pay of $0 per month over the next four years. Restrictions apply to certain patients, including those who reside in Massachusetts and those with prescription benefits funded through Medicare, Medicaid and other federal/state programs.
To access this benefit, eligible patients need to obtain a Co-pay Benefit Card to take to the pharmacy each time they fill their prescription for Baraclude. Benefit cards are available through their healthcare provider. Eligible patients who are currently utilizing our Co-pay Benefit Program for Baraclude do not need to obtain new benefit cards. These patients will begin receiving these new benefits, subject to the new program end date, upon their next use of their Co-pay Benefit Card.
The Co-pay Benefit Card currently is not valid in Massachusetts or for prescriptions purchased under Medicaid, Medicare, or federal or state programs (including state prescription drug programs, or private indemnity or HMO insurance plans, which reimburse patients for the entire cost of the prescription drugs).
This Co-pay Benefit Program is for eligible commercially insured patients only. For patients with chronic hepatitis B who are uninsured or underinsured, Bristol-Myers Squibb offers other programs to support access to medicines. Bristol-Myers Squibb provides our medicines free of charge to those who qualify through our Access Virology Patient Assistance Program and also participates in the pharmaceutical industry's Together Rx Access Program.
Bristol-Myers Squibb is a global biopharmaceutical company committed to discovering, developing and delivering innovative medicines that help patients prevail over serious diseases.
11/16/10
Source
Bristol-Myers Squibb. Baraclude (entecavir) Co-pay Benefit Program enhancements. Email advisory. November 12, 2010.
Source
AASLD: Direct-acting Drug Combos Suppress HCV without Interferon, but Resistance Remains a Concern
SUMMARY: Combinations of directing-acting oral drugs are effective against hepatitis C virus (HCV) and may enable patients to avoid interferon and its side effects -- or at least shorten the length of standard treatment -- according to studies presented at the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) in Boston. Researchers reported that 3 HCV protease/polymerase combinations -- Bristol-Myers Squibb's BMS-650032 + BMS-790052, Gilead's GS-9256 + GS-9190, and Boerhinger Ingelheim's BI 201335 + BI 207127 -- showed potent early anti-HCV activity, but more than 2 drugs will likely be needed to hold off resistance. Ribavirin without pegylated interferon may fulfill this role.
By Liz Highleyman
Current standard therapy for genotype 1 chronic hepatitis C consists of pegylated interferon plus ribavirin for 48 weeks. Interferon-based therapy can cause difficult side effects, however, and only about half of people with this hard-to-treat genotype achieve a cure.
The first oral drugs that directly target steps of the viral lifecycle -- such as HCV protease and polymerase inhibitors -- are in the final stages of development. Most studies to date have looked at these agents used alone in regimens with pegylated interferon/ribavirin, but new research shows that dual or triple combinations may allow selected patients to achieve sustained response without interferon.
BMS-650032 + BMS-790052
At a late breaker session, Anna Lok from the University of Michigan at Ann Arbor and colleagues presented data on Bristol-Myers Squibb's combination regimen consisting of the HCV NS3 protease inhibitor BMS-650032 and the NS4A inhibitor BMS-790052. NS4A is a non-structural protein adjacent to the NS5B polymerase; its function is not fully understood, but it appears to play a crucial role in HCV replication.
In the Phase 2a Study AI447011, genotype 1 (mostly 1a) chronic hepatitis C patients who were null responders to previous interferon-based therapy (< 2 log decline in HCV RNA) were randomly assigned to received 600 mg twice-daily BMS-650032 plus 60 mg once-daily BMS-790052, either alone (Group A) or in combination with 180 mcg/week pegylated interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-adjusted ribavirin (Group B) for 24 weeks.
After 2 weeks of therapy, participants in both the 2-drug and 4-drug groups saw median HCV RNA viral load decreases of about -5 log. At week 4, about two-thirds of patients in both groups (64% vs 60%, respectively) experienced rapid virological response (RVR), or undetectable viral load (< 10 IU/mL).
After this point, however, the 4-drug combo with interferon began to show an advantage. In an intent-to-treat analysis, 45% of patients (5 out of 11) in the 2-drug oral-only group achieved complete early virological response (EVR) or undetectable HCV RNA at 12 weeks, compared with 90% (9 out of 10) in the 4-drug group.
Just over half of people (55%) receiving only the oral drugs experienced virological breakthrough, while everyone taking the 4-drug combo maintained viral suppression through week 12. Viral breakthrough occurred exclusively in people with genotype 1a; the 2 participants with genotype 1b in the 2-drug group maintained viral suppression. Breakthrough occurred as early as week 3 and as late as week 12. Genotyping identified drug-resistance mutations in the NS3 protease and NS5A regions. Patients who experienced viral breakthrough in Group A added pegylated interferon/ribavirin, and most then achieved undetectable viral load.
BMS-650032 and BMS-790052 were generally well-tolerated. The most common side effect was diarrhea, usually mild-to-moderate, affecting about 70% of patients in both groups. Nausea was more common in the 4-drug group, but otherwise side effects were statistically similar in the 2 arms. There were no serious adverse events, treatment discontinuations due to adverse events, or deaths in either group during the study period.
These findings indicate that these 2 oral drugs alone are not potent enough to maintain long-term viral suppression for genotype 1a patients, likely due to development of drug resistance. But the BMS-650032/BMS-790052 combination increased the likelihood of response to standard therapy at 12 weeks, and may ultimately allow for shorter interferon-based treatment.
GS-9256 + GS-9190
At the same session, Stefan Zeuzem from J.W. Goethe University Hospital in Frankfurt and colleagues presented data from a study of Gilead Sciences' NS3 protease inhibitor GS-9256 and NS5B polymerase inhibitor GS-9190, now named tegobuvir. Study 196-0112 is a Phase 2a trial looking at treatment-naive genotype 1 patients -- an easier-to-treat population than the null responders in the Bristol-Myers Squibb study described above.
In this novel study design, 16 patients were randomly assigned to receive dual therapy with the 2 direct-acting agents alone (75 mg GS-9256 and 40 mg GS-9190, both twice-daily), 15 received triple therapy with these drugs plus 1000-1200 mg/day weight-adjusted ribavirin, and 15 were to be treated with quadruple therapy using the same 3 drugs plus 180 mcg/week pegylated interferon alfa-2a for up to 28 days. Participants with suboptimal response or viral breakthrough in the 2-drug or 3-drug arms added standard therapy.
Median maximum HCV viral load declines at day 28 were -4.1 log in the 2-drug group and -5.1 log in the 3-drug group, indicating that ribavirin enhanced the antiviral activity of GS-9256 plus GS-9190, even without interferon. Here too, some participants experienced virological breakthrough. Further analysis showed that most patients who did so had HCV isolates with NS3 plus NS5B resistance mutations.
At the time of analysis, all 14 participants who had taken the 4-drug regimen of GS-9256/GS-9190 plus standard therapy for 28 days achieved RVR (HCV RNA < 25 IU/mL) without viral breakthrough. With 4-drug therapy the median maximum viral load decline was -5.7 log.
Again, treatment was generally well-tolerated. Most adverse events were mild-to-moderate and resolved with ongoing therapy. The most common side effects in each of the 3 arms were headache, diarrhea, and nausea. Some patients taking the 3-drug combination also experienced fatigue and insomnia, and some taking the 4-drug regimen experienced flu-like symptoms. Nearly one-third of patients in all arms saw an increase in indirect bilirubin levels, which typically resolved with continued dosing and did not lead to treatment discontinuation.
This study also showed that the combination of direct-acting agents had potent antiviral activity, but worked better with the addition of ribavirin and even more so with interferon. These findings suggest some patients may be able to use HCV protease and polymerase inhibitors with ribavirin in interferon-sparing regimens.
BI 201335 + BI 207127
Finally, Zeuzem also presented the latest data on Boehringer Ingelheim's direct-acting dual combination, the NS3/4A protease inhibitor BI 201335 plus the NS5B polymerase inhibitor BI 207127, also used with ribavirin.
In this Phase 1b trial, 32 treatment-naive patients with genotype 1 chronic hepatitis C were randomly assigned to receive either 400 or 600 mg 3-times-daily BI 207127, plus 120 mg once-daily BI 201335, plus 1000-1200 mg/day weight-adjusted ribavirin for 28 days. At that point all switched to BI 201335 plus pegylated interferon/ribavirin.
All participants experienced a "rapid and sharp" decline in HCV viral load during the first 2 days of treatment, followed by a slower second-phase decline in all but 2 patients. At 28 days, 11 of 15 patients (73%) in the 400 mg BI 201335 dose arm and all 17 (100%) in the 600 mg arm achieved HCV RNA suppression < 25 IU/mL.
Two hard-to-treat patients with genotype 1a and high baseline viral load in the lower BI 201335 dose arm experienced virological breakthrough (0.7 and > 1 log increase). At the higher BI 201335 dose level, there was no difference in response between patients with genotype 1a and 1b, but in the 400 mg dose arm genotype 1a patients had a lower response rate.
Once again, BI 201335/BI 207127 plus ribavirin was generally well-tolerated. The most common adverse events were mild-to-moderate gastrointestinal symptoms including diarrhea and nausea, as well as skin rash, and photosensitivity. There were no severe adverse events or treatment discontinuations during the 28-day study period. Unconjugated bilirubin levels also increased in this study.
Investigators concluded that interferon-sparing treatment with BI 201335, BI 207127, and ribavirin demonstrated strong early antiviral activity against HCV genotype 1 with good safety and tolerability.
Overview
Taken together, these studies indicate that combinations of direct-acting agents have potent activity against HCV, but require additional drugs to maintain viral suppression long enough to achieve sustained virological response, or continued undetectable HCV viral load 24 weeks after completion of therapy.
Addition of ribavirin alone -- creating an all-oral, interferon-sparing regimen -- may be a viable option for some patients. Harder-to-treat individuals, including those with genotype 1a, may also require pegylated interferon, but the direct-acting drugs will shorten total treatment time.
In addition to the combinations described here, Vertex Pharmaceuticals recently announced that it will modify an ongoing Phase 2 trial evaluating the HCV protease inhibitor telaprevir plus the polymerase inhibitor VX-222 so that some participants will also receive ribavirin (without pegylated interferon).
Investigator affiliations:
Abstract LB-8: Research & Development, Bristol-Myers Squibb, Hopewell, NJ, Princeton, NJ, and Wallingford, CT; University of Michigan, Ann Arbor, MI; Alamo Medical Research, San Antonio, TX; The Research Institute, Springfield, MA; University of Colorado-Denver, Aurora, CO; Liver Institute at Methodist, Dallas, TX; Carolinas Center for Liver Disease, Statesville, NC; Metropolitan Research, Fairfax, VA
Abstract LB-1: J.W. Goethe University Hospital, Frankfurt, Germany; ifi-Studien und Projekte GmbH an der Asklepios Klinik St, Georg Haus K, Hamburg, Germany; Institute of Liver Studies, London, UK; Medizinische Hochschule Hannover, Hannover, Germany; Hospital Beaujon, Clichy, France; Barts and London NHS Trust, London, UK; Hôspital Saint-Louis, Paris, France; Universitatsklinikum Würzburg, Würzburg, Germany; Hôspital Erasme, Bruxelles, Belgium; CHU de Grenoble - Hospital Michallon, La Tronche, France; Gilead Sciences, Foster City, CA.
Abstract LB-7: J.W. Goethe University Hospital, Frankfurt, Germany; Hôpital Beaujon, Paris, France; Austin Hospital, Heidelberg, VIC, Australia; Hôpital Albert Michallon, Grenoble, France; Hôpital Saint-Eloi, Montpellier, France; University Hospital of Zurich, Zurich, Switzerland; Auckland City Hospital, Auckland, New Zealand; Johannes Gutenberg University Mainz, Mainz, Germany; University Hospital Hamburg-Eppendorf, Hamburg, Germany; Hôpital Cochin, Paris, France; Hôpital Pitié-Salpêtrière, Paris, France; Hôpital de Brabois, Nancy, France; Alfred Hospital, Melbourne, VIC, Australia; Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany; Hôpital Hotel-Dieu , Lyon, France; University Hospital Basel, Basel, Switzerland; Boehringer Ingelheim, Ridgefield, CT; Boehringer Ingelheim (Canada) Ltd, Laval, QC, Canada; Boehringer-Ingelheim GmbH, Biberach, Germany.
11/16/10
References
A Lok, D Gardiner, E Lawitz, and others. Combination Therapy With BMS-790052 and BMS-650032 Alone or With PegylatedInterferon and Ribavirin (pegIFN/RBV) Results in Undetectable HCV RNA Through 12 Weeks of Therapy in HCV Genotype 1 Null Responders. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract LB-8.
M Bifano, H Sevinsky, BR Bedford, and others. Co-administration of BMS-790052 and BMS-650032 does not result in a clinically meaningful pharmacokinetic interaction in healthy subjects. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 827.
S Zeuzem, P Buggisch, K Agarwal, and others. Dual, Triple, and Quadruple Combination Treatment with a Protease Inhibitor (GS-9256) and a Polymerase Inhibitor (GS-9190) alone and in Combination with Ribavirin (RBV) or PegIFN/RBV for up to 28 days in Treatment Naïve, Genotype 1 HCV Subjects. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract LB-1.
S Zeuzem, T Asselah, PW Angus, and others. Strong antiviral activity and safety of IFN-sparing treatment with the protease inhibitor BI 201335, the HCV polymerase inhibitor BI 207127 and ribavirin in patients with chronic hepatitis C. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract LB-7.
Other Sources
Bristol-Myers Squibb. Bristol-Myers Squibb Posts New Data on Combination of Investigational Compounds BMS-790052 and BMS-650032 for the Treatment of Chronic Hepatitis C. Press release. November 1, 2010; Pipeline Asset Update for BMS-790052 (NS5A inhibitor) and BMS-650032 (NS3 inhibitor) (undated).
Gilead Sciences. Gilead's Investigational Hepatitis C Compounds GS 9190 and GS 9256 in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study. Press release. October 30, 2010.
Boehringer Ingelheim. Boehringer Ingelheim's oral hepatitis C protease inhibitor and polymerase inhibitor combination shows rapid viral response without use of pegylated interferon. Press release. October 30, 2010.
Vertex Pharmaceuticals. Vertex Announces Plans to Enroll Additional Treatment Arm in Ongoing Phase 2 Combination Study of Telaprevir and VX-222 for the Treatment of People with Hepatitis C. Press release. November 10, 2010.
Source
By Liz Highleyman
Current standard therapy for genotype 1 chronic hepatitis C consists of pegylated interferon plus ribavirin for 48 weeks. Interferon-based therapy can cause difficult side effects, however, and only about half of people with this hard-to-treat genotype achieve a cure.
The first oral drugs that directly target steps of the viral lifecycle -- such as HCV protease and polymerase inhibitors -- are in the final stages of development. Most studies to date have looked at these agents used alone in regimens with pegylated interferon/ribavirin, but new research shows that dual or triple combinations may allow selected patients to achieve sustained response without interferon.
BMS-650032 + BMS-790052
At a late breaker session, Anna Lok from the University of Michigan at Ann Arbor and colleagues presented data on Bristol-Myers Squibb's combination regimen consisting of the HCV NS3 protease inhibitor BMS-650032 and the NS4A inhibitor BMS-790052. NS4A is a non-structural protein adjacent to the NS5B polymerase; its function is not fully understood, but it appears to play a crucial role in HCV replication.
In the Phase 2a Study AI447011, genotype 1 (mostly 1a) chronic hepatitis C patients who were null responders to previous interferon-based therapy (< 2 log decline in HCV RNA) were randomly assigned to received 600 mg twice-daily BMS-650032 plus 60 mg once-daily BMS-790052, either alone (Group A) or in combination with 180 mcg/week pegylated interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-adjusted ribavirin (Group B) for 24 weeks.
After 2 weeks of therapy, participants in both the 2-drug and 4-drug groups saw median HCV RNA viral load decreases of about -5 log. At week 4, about two-thirds of patients in both groups (64% vs 60%, respectively) experienced rapid virological response (RVR), or undetectable viral load (< 10 IU/mL).
After this point, however, the 4-drug combo with interferon began to show an advantage. In an intent-to-treat analysis, 45% of patients (5 out of 11) in the 2-drug oral-only group achieved complete early virological response (EVR) or undetectable HCV RNA at 12 weeks, compared with 90% (9 out of 10) in the 4-drug group.
Just over half of people (55%) receiving only the oral drugs experienced virological breakthrough, while everyone taking the 4-drug combo maintained viral suppression through week 12. Viral breakthrough occurred exclusively in people with genotype 1a; the 2 participants with genotype 1b in the 2-drug group maintained viral suppression. Breakthrough occurred as early as week 3 and as late as week 12. Genotyping identified drug-resistance mutations in the NS3 protease and NS5A regions. Patients who experienced viral breakthrough in Group A added pegylated interferon/ribavirin, and most then achieved undetectable viral load.
BMS-650032 and BMS-790052 were generally well-tolerated. The most common side effect was diarrhea, usually mild-to-moderate, affecting about 70% of patients in both groups. Nausea was more common in the 4-drug group, but otherwise side effects were statistically similar in the 2 arms. There were no serious adverse events, treatment discontinuations due to adverse events, or deaths in either group during the study period.
These findings indicate that these 2 oral drugs alone are not potent enough to maintain long-term viral suppression for genotype 1a patients, likely due to development of drug resistance. But the BMS-650032/BMS-790052 combination increased the likelihood of response to standard therapy at 12 weeks, and may ultimately allow for shorter interferon-based treatment.
GS-9256 + GS-9190
At the same session, Stefan Zeuzem from J.W. Goethe University Hospital in Frankfurt and colleagues presented data from a study of Gilead Sciences' NS3 protease inhibitor GS-9256 and NS5B polymerase inhibitor GS-9190, now named tegobuvir. Study 196-0112 is a Phase 2a trial looking at treatment-naive genotype 1 patients -- an easier-to-treat population than the null responders in the Bristol-Myers Squibb study described above.
In this novel study design, 16 patients were randomly assigned to receive dual therapy with the 2 direct-acting agents alone (75 mg GS-9256 and 40 mg GS-9190, both twice-daily), 15 received triple therapy with these drugs plus 1000-1200 mg/day weight-adjusted ribavirin, and 15 were to be treated with quadruple therapy using the same 3 drugs plus 180 mcg/week pegylated interferon alfa-2a for up to 28 days. Participants with suboptimal response or viral breakthrough in the 2-drug or 3-drug arms added standard therapy.
Median maximum HCV viral load declines at day 28 were -4.1 log in the 2-drug group and -5.1 log in the 3-drug group, indicating that ribavirin enhanced the antiviral activity of GS-9256 plus GS-9190, even without interferon. Here too, some participants experienced virological breakthrough. Further analysis showed that most patients who did so had HCV isolates with NS3 plus NS5B resistance mutations.
At the time of analysis, all 14 participants who had taken the 4-drug regimen of GS-9256/GS-9190 plus standard therapy for 28 days achieved RVR (HCV RNA < 25 IU/mL) without viral breakthrough. With 4-drug therapy the median maximum viral load decline was -5.7 log.
Again, treatment was generally well-tolerated. Most adverse events were mild-to-moderate and resolved with ongoing therapy. The most common side effects in each of the 3 arms were headache, diarrhea, and nausea. Some patients taking the 3-drug combination also experienced fatigue and insomnia, and some taking the 4-drug regimen experienced flu-like symptoms. Nearly one-third of patients in all arms saw an increase in indirect bilirubin levels, which typically resolved with continued dosing and did not lead to treatment discontinuation.
This study also showed that the combination of direct-acting agents had potent antiviral activity, but worked better with the addition of ribavirin and even more so with interferon. These findings suggest some patients may be able to use HCV protease and polymerase inhibitors with ribavirin in interferon-sparing regimens.
BI 201335 + BI 207127
Finally, Zeuzem also presented the latest data on Boehringer Ingelheim's direct-acting dual combination, the NS3/4A protease inhibitor BI 201335 plus the NS5B polymerase inhibitor BI 207127, also used with ribavirin.
In this Phase 1b trial, 32 treatment-naive patients with genotype 1 chronic hepatitis C were randomly assigned to receive either 400 or 600 mg 3-times-daily BI 207127, plus 120 mg once-daily BI 201335, plus 1000-1200 mg/day weight-adjusted ribavirin for 28 days. At that point all switched to BI 201335 plus pegylated interferon/ribavirin.
All participants experienced a "rapid and sharp" decline in HCV viral load during the first 2 days of treatment, followed by a slower second-phase decline in all but 2 patients. At 28 days, 11 of 15 patients (73%) in the 400 mg BI 201335 dose arm and all 17 (100%) in the 600 mg arm achieved HCV RNA suppression < 25 IU/mL.
Two hard-to-treat patients with genotype 1a and high baseline viral load in the lower BI 201335 dose arm experienced virological breakthrough (0.7 and > 1 log increase). At the higher BI 201335 dose level, there was no difference in response between patients with genotype 1a and 1b, but in the 400 mg dose arm genotype 1a patients had a lower response rate.
Once again, BI 201335/BI 207127 plus ribavirin was generally well-tolerated. The most common adverse events were mild-to-moderate gastrointestinal symptoms including diarrhea and nausea, as well as skin rash, and photosensitivity. There were no severe adverse events or treatment discontinuations during the 28-day study period. Unconjugated bilirubin levels also increased in this study.
Investigators concluded that interferon-sparing treatment with BI 201335, BI 207127, and ribavirin demonstrated strong early antiviral activity against HCV genotype 1 with good safety and tolerability.
Overview
Taken together, these studies indicate that combinations of direct-acting agents have potent activity against HCV, but require additional drugs to maintain viral suppression long enough to achieve sustained virological response, or continued undetectable HCV viral load 24 weeks after completion of therapy.
Addition of ribavirin alone -- creating an all-oral, interferon-sparing regimen -- may be a viable option for some patients. Harder-to-treat individuals, including those with genotype 1a, may also require pegylated interferon, but the direct-acting drugs will shorten total treatment time.
In addition to the combinations described here, Vertex Pharmaceuticals recently announced that it will modify an ongoing Phase 2 trial evaluating the HCV protease inhibitor telaprevir plus the polymerase inhibitor VX-222 so that some participants will also receive ribavirin (without pegylated interferon).
Investigator affiliations:
Abstract LB-8: Research & Development, Bristol-Myers Squibb, Hopewell, NJ, Princeton, NJ, and Wallingford, CT; University of Michigan, Ann Arbor, MI; Alamo Medical Research, San Antonio, TX; The Research Institute, Springfield, MA; University of Colorado-Denver, Aurora, CO; Liver Institute at Methodist, Dallas, TX; Carolinas Center for Liver Disease, Statesville, NC; Metropolitan Research, Fairfax, VA
Abstract LB-1: J.W. Goethe University Hospital, Frankfurt, Germany; ifi-Studien und Projekte GmbH an der Asklepios Klinik St, Georg Haus K, Hamburg, Germany; Institute of Liver Studies, London, UK; Medizinische Hochschule Hannover, Hannover, Germany; Hospital Beaujon, Clichy, France; Barts and London NHS Trust, London, UK; Hôspital Saint-Louis, Paris, France; Universitatsklinikum Würzburg, Würzburg, Germany; Hôspital Erasme, Bruxelles, Belgium; CHU de Grenoble - Hospital Michallon, La Tronche, France; Gilead Sciences, Foster City, CA.
Abstract LB-7: J.W. Goethe University Hospital, Frankfurt, Germany; Hôpital Beaujon, Paris, France; Austin Hospital, Heidelberg, VIC, Australia; Hôpital Albert Michallon, Grenoble, France; Hôpital Saint-Eloi, Montpellier, France; University Hospital of Zurich, Zurich, Switzerland; Auckland City Hospital, Auckland, New Zealand; Johannes Gutenberg University Mainz, Mainz, Germany; University Hospital Hamburg-Eppendorf, Hamburg, Germany; Hôpital Cochin, Paris, France; Hôpital Pitié-Salpêtrière, Paris, France; Hôpital de Brabois, Nancy, France; Alfred Hospital, Melbourne, VIC, Australia; Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany; Hôpital Hotel-Dieu , Lyon, France; University Hospital Basel, Basel, Switzerland; Boehringer Ingelheim, Ridgefield, CT; Boehringer Ingelheim (Canada) Ltd, Laval, QC, Canada; Boehringer-Ingelheim GmbH, Biberach, Germany.
11/16/10
References
A Lok, D Gardiner, E Lawitz, and others. Combination Therapy With BMS-790052 and BMS-650032 Alone or With PegylatedInterferon and Ribavirin (pegIFN/RBV) Results in Undetectable HCV RNA Through 12 Weeks of Therapy in HCV Genotype 1 Null Responders. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract LB-8.
M Bifano, H Sevinsky, BR Bedford, and others. Co-administration of BMS-790052 and BMS-650032 does not result in a clinically meaningful pharmacokinetic interaction in healthy subjects. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 827.
S Zeuzem, P Buggisch, K Agarwal, and others. Dual, Triple, and Quadruple Combination Treatment with a Protease Inhibitor (GS-9256) and a Polymerase Inhibitor (GS-9190) alone and in Combination with Ribavirin (RBV) or PegIFN/RBV for up to 28 days in Treatment Naïve, Genotype 1 HCV Subjects. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract LB-1.
S Zeuzem, T Asselah, PW Angus, and others. Strong antiviral activity and safety of IFN-sparing treatment with the protease inhibitor BI 201335, the HCV polymerase inhibitor BI 207127 and ribavirin in patients with chronic hepatitis C. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract LB-7.
Other Sources
Bristol-Myers Squibb. Bristol-Myers Squibb Posts New Data on Combination of Investigational Compounds BMS-790052 and BMS-650032 for the Treatment of Chronic Hepatitis C. Press release. November 1, 2010; Pipeline Asset Update for BMS-790052 (NS5A inhibitor) and BMS-650032 (NS3 inhibitor) (undated).
Gilead Sciences. Gilead's Investigational Hepatitis C Compounds GS 9190 and GS 9256 in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study. Press release. October 30, 2010.
Boehringer Ingelheim. Boehringer Ingelheim's oral hepatitis C protease inhibitor and polymerase inhibitor combination shows rapid viral response without use of pegylated interferon. Press release. October 30, 2010.
Vertex Pharmaceuticals. Vertex Announces Plans to Enroll Additional Treatment Arm in Ongoing Phase 2 Combination Study of Telaprevir and VX-222 for the Treatment of People with Hepatitis C. Press release. November 10, 2010.
Source
The efficacy and safety of pegylated interferon plus ribavirin combination therapy in chronic hepatitis c patients with hepatocellular carcinoma post curative therapies - A multicenter prospective trial
J Hepatol. 2010 Sep 7. [Epub ahead of print]
Huang JF, Yu ML, Huang CF, Chiu CF, Dai CY, Huang CI, Yeh ML, Yang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, Wang LY, Chuang WL.
Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
BACKGROUND & AIMS: Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, compared to cirrhotic patients.
METHODS: This prospective, multicenter, case-control study recruited 82 consecutive CHC patients with HCC after curative management and 87 sex/age-matched cirrhotic patients. All patients received pegIFN-alpha-2a and weight-based RBV according to current treatment recommendations. The primary outcome measurement was sustained virological response (SVR, seronegative of hepatitis C virus RNA throughout the 6-month post-treatment follow-up period).
RESULTS: The SVR rate was significantly lower in the HCC group compared to the cirrhosis group (48.8% vs 64.4%, p=0.04). However, the significantly lower rate of SVR in the HCC group was observed among genotype-1 patients (33.3% vs 60.7%, p=0.005) but not among genotype-2/3 patients (70.6% vs 71.0%, p=0.88). In patients who achieved 80/80/80 adherence, there was no significant difference of SVR rate between groups (50.7% vs 64.2%, p=0.12) Multivariate logistic regression analysis demonstrated that rapid virological response (viral clearance during the first 4weeks of treatment, odds ratio=22.1, p<0.001) and adherence (odds ratio=3.1, p=0.05) were predictive factors associated with SVR, whilst previous occurrence of HCC was not associated with SVR (Odds ratio=0.4, p=0.09). The incidence of severe adverse events did not differ between the two groups.
CONCLUSIONS: The study proved the feasibility of pegIFN/RBV therapy with current treatment guidelines in CHC patients after successful eradication of HCC, with careful monitoring.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21056500 [PubMed - as supplied by publisher]
Source
Huang JF, Yu ML, Huang CF, Chiu CF, Dai CY, Huang CI, Yeh ML, Yang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, Wang LY, Chuang WL.
Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
BACKGROUND & AIMS: Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, compared to cirrhotic patients.
METHODS: This prospective, multicenter, case-control study recruited 82 consecutive CHC patients with HCC after curative management and 87 sex/age-matched cirrhotic patients. All patients received pegIFN-alpha-2a and weight-based RBV according to current treatment recommendations. The primary outcome measurement was sustained virological response (SVR, seronegative of hepatitis C virus RNA throughout the 6-month post-treatment follow-up period).
RESULTS: The SVR rate was significantly lower in the HCC group compared to the cirrhosis group (48.8% vs 64.4%, p=0.04). However, the significantly lower rate of SVR in the HCC group was observed among genotype-1 patients (33.3% vs 60.7%, p=0.005) but not among genotype-2/3 patients (70.6% vs 71.0%, p=0.88). In patients who achieved 80/80/80 adherence, there was no significant difference of SVR rate between groups (50.7% vs 64.2%, p=0.12) Multivariate logistic regression analysis demonstrated that rapid virological response (viral clearance during the first 4weeks of treatment, odds ratio=22.1, p<0.001) and adherence (odds ratio=3.1, p=0.05) were predictive factors associated with SVR, whilst previous occurrence of HCC was not associated with SVR (Odds ratio=0.4, p=0.09). The incidence of severe adverse events did not differ between the two groups.
CONCLUSIONS: The study proved the feasibility of pegIFN/RBV therapy with current treatment guidelines in CHC patients after successful eradication of HCC, with careful monitoring.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21056500 [PubMed - as supplied by publisher]
Source
FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC(3) program
J Hepatol. 2010 Sep 15. [Epub ahead of print]
Poynard T, Munteanu M, Colombo M, Bruix J, Schiff E, Terg R, Flamm S, Moreno-Otero R, Carrilho F, Schmidt W, Berg T, McGarrity T, Heathcote EJ, Gonçales F, Diago M, Craxi A, Silva M, Boparai N, Griffel L, Burroughs M, Brass C, Albrecht J.
APHP-UPMC Liver Center, Paris, France.
Abstract
BACKGROUND & AIMS: EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients.
METHODS: Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy.
RESULTS: Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3 and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p⩽0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p⩽0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5).
CONCLUSIONS: FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21056496 [PubMed - as supplied by publisher]
Source
Poynard T, Munteanu M, Colombo M, Bruix J, Schiff E, Terg R, Flamm S, Moreno-Otero R, Carrilho F, Schmidt W, Berg T, McGarrity T, Heathcote EJ, Gonçales F, Diago M, Craxi A, Silva M, Boparai N, Griffel L, Burroughs M, Brass C, Albrecht J.
APHP-UPMC Liver Center, Paris, France.
Abstract
BACKGROUND & AIMS: EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients.
METHODS: Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy.
RESULTS: Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3 and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p⩽0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p⩽0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5).
CONCLUSIONS: FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21056496 [PubMed - as supplied by publisher]
Source
Budget cuts stop Phoenix man from getting new liver
By Michelle Ye Hee Lee, The Arizona Republic
PHOENIX — A liver-disease patient missed his opportunity for an organ transplant Tuesday, becoming the most dire example yet of an Arizonan denied life-saving medical care because of budget cuts to the state's health-care system for the poor.
Francisco Felix, 32, of Laveen, Ariz., was in the hospital ready to receive a liver that was donated to him late Monday night. But the liver went to another recipient Tuesday morning because he couldn't find $200,000 overnight to pay for the liver transplant, one of seven kinds of transplant surgery the state stopped covering Oct. 1.
Felix was the first liver-transplant patient known to be affected but is not likely to be the last.
Of the about 100 Arizonans enrolled in the Arizona Health Care Cost Containment System who are awaiting transplants no longer covered, 60 of them are candidates like Felix with liver disease related to hepatitis C. Transplant is their only cure.
Last month, Goodyear, Ariz., leukemia patient Mark Price became a poster child for the impact of the budget cuts after his doctor found donors who matched his bone marrow a day after Price lost coverage. Price's story gained attention nationally and an anonymous donor later covered all costs for his surgery.
Because bone marrow comes from living donors, the donated marrow was able to be used at a late date.
It's a different story for liver-transplant patients.
The chances of finding a liver donor are slim because these transplants usually are livers from deceased donors and the demand far exceeds the supply.
If a donor is found, the surgery must take place in less than a day.
Patients who lost transplant coverage have been allowed to stay on the waiting list, but when a match is found they are faced with a ticking clock to come up with up to half a million dollars to pay for the procedure.
Francisco's story
Monday night, Felix's wife received a call from a family friend whose wife was nearing death and wanted to donate her liver to Felix. Their organs matched, and doctors prepared Felix for a surgery set for 10 a.m. Tuesday.
Banner Good Samaritan Medical Center gave Felix until that time to come up with the money for his surgery.
Despite efforts to reach out to the media and the public, the family could not raise the money. Felix was discharged from the hospital and his liver went to the next patient on the waiting list.
"It was his day today. If we had the money, someone to pay for it, he would have received the liver," said Flor, Francisco's wife. "How can people make this decision? How does one person have the right to decide who's going to live and who's not?"
At least 23 low-income patients at Banner Good Samaritan are waiting for transplants, hospital spokesman Bill Byron said.
Byron said patients must meet three criteria before receiving transplants: They must be healthy enough for a transplant procedure, they must have a network of people who can support them after surgery and they must be able to afford the surgery.
Patients who can't afford the surgery after finding a match are placed on a hold list until they can pay for it.
Flor Felix has applied to the National Transplant Assistance Fund so that the family can raise money for her husband's surgery. Byron said doctors believe Francisco will be healthy enough to receive a transplant if another match comes along within the next year or two.
According to United Network for Organ Sharing, a national nonprofit that is contracted with the federal government to manage the U.S. organ-transplant system, the average wait time for a liver is 796 days. Francisco has been on the waiting list since April and only got this chance so quickly because the family friend wanted to donate to him.
Budget cuts
Arizona legislators earlier this year decided to stop paying for certain transplants based on analyses by the Arizona Health Care Cost Containment System.
Certain kinds of pancreas, lung and bone-marrow transplants are among those no longer covered.
The state agency stopped covering liver transplants for hepatitis C because of the procedure's low long-term success rate.
According to the agency, studies showed that when a patient with hepatitis C receives a liver transplant, the virus can infect the new liver within 24 hours. The virus returning is the No. 1 cause of the new liver failing, according to the analysis.
But according to the national transplant organization, transplant is the best treatment option for patients with end-stage liver failure.
Following the public reports of Price's transplant story last month, state lawmakers asked Gov. Jan Brewer to reconsider the cuts. Tuesday, a group of Democrats asked again.
But Brewer's spokesman, Paul Senseman, said the governor would not consider a special legislative session unless someone proposes a way for the state to make up for the $1 billion gap in the agency's budget.
Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study)
Link to publisher abstract
Bibliographic details: Degos F, Perez P, Roche B, Mahmousi A, Asselineau J, Voitot H, Bedossa P. (2010) Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study). Journal of Hepatology 53(6) 1013-1021
Background & Aims: The diagnostic accuracy of non-invasive liver fibrosis tests that may replace liver biopsy in patients with chronic hepatitis remains controversial.
We assessed and compared the accuracy of FibroScan® and that of the main biomarkers used for predicting cirrhosis and significant fibrosis (METAVIR F2) in patients with chronic viral hepatitis.
Methods: A multicenter prospective cross-sectional diagnostic accuracy study was conducted in the Hepatology departments of 23 French university hospitals. Index tests and reference standard (METAVIR fibrosis score on liver biopsy) were measured on the same day and interpreted blindly. Consecutive patients with chronic viral hepatitis (hepatitis B or C virus, including possible Human Immunodeficiency Virus co-infection) requiring liver biopsy were recruited in the study.
Results: The analysis was first conducted on the total population (1839 patients), and after excluding 532 protocol deviations, on 1307 patients (non-compliant FibroScan® examinations). The overall accuracy of FibroScan® was high (AUROC 0.89 and 0.90, respectively) and significantly higher than that of biomarkers in predicting cirrhosis (AUROC 0.77–0.86). All non-invasive methods had a moderate accuracy in predicting significant fibrosis (AUROC 0.72–0.78). Based on multilevel likelihood ratios, non-invasive tests provided a relevant gain in the likelihood of diagnosis in 0–60% of patients (cirrhosis) and 9–30% of patients (significant fibrosis).
Conclusions: The diagnostic accuracy of non-invasive tests was high for cirrhosis, but poor for significant fibrosis. A clinically relevant gain in the likelihood of diagnosis was achieved in a low proportion of patients. Although the diagnosis of cirrhosis may rely on non-invasive tests, liver biopsy is warranted to diagnose intermediate stages of fibrosis.
The Journal of Hepatology is the official journal of the European Association for the Study of the Liver. The Journal of Hepatology publishes papers, reviews, case reports and correspondance. It covers clinical and basic research in the field of hepatology
Access: The full text of this editorial is available freely from the journal website.
Publication Date: 01 Dec 2010
Publication Type: News
Publisher: Elsevier Ireland Ltd
Source
Bibliographic details: Degos F, Perez P, Roche B, Mahmousi A, Asselineau J, Voitot H, Bedossa P. (2010) Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study). Journal of Hepatology 53(6) 1013-1021
Background & Aims: The diagnostic accuracy of non-invasive liver fibrosis tests that may replace liver biopsy in patients with chronic hepatitis remains controversial.
We assessed and compared the accuracy of FibroScan® and that of the main biomarkers used for predicting cirrhosis and significant fibrosis (METAVIR F2) in patients with chronic viral hepatitis.
Methods: A multicenter prospective cross-sectional diagnostic accuracy study was conducted in the Hepatology departments of 23 French university hospitals. Index tests and reference standard (METAVIR fibrosis score on liver biopsy) were measured on the same day and interpreted blindly. Consecutive patients with chronic viral hepatitis (hepatitis B or C virus, including possible Human Immunodeficiency Virus co-infection) requiring liver biopsy were recruited in the study.
Results: The analysis was first conducted on the total population (1839 patients), and after excluding 532 protocol deviations, on 1307 patients (non-compliant FibroScan® examinations). The overall accuracy of FibroScan® was high (AUROC 0.89 and 0.90, respectively) and significantly higher than that of biomarkers in predicting cirrhosis (AUROC 0.77–0.86). All non-invasive methods had a moderate accuracy in predicting significant fibrosis (AUROC 0.72–0.78). Based on multilevel likelihood ratios, non-invasive tests provided a relevant gain in the likelihood of diagnosis in 0–60% of patients (cirrhosis) and 9–30% of patients (significant fibrosis).
Conclusions: The diagnostic accuracy of non-invasive tests was high for cirrhosis, but poor for significant fibrosis. A clinically relevant gain in the likelihood of diagnosis was achieved in a low proportion of patients. Although the diagnosis of cirrhosis may rely on non-invasive tests, liver biopsy is warranted to diagnose intermediate stages of fibrosis.
The Journal of Hepatology is the official journal of the European Association for the Study of the Liver. The Journal of Hepatology publishes papers, reviews, case reports and correspondance. It covers clinical and basic research in the field of hepatology
Access: The full text of this editorial is available freely from the journal website.
Publication Date: 01 Dec 2010
Publication Type: News
Publisher: Elsevier Ireland Ltd
Source
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