Medical Microbiology and Immunology
DOI: 10.1007/s00430-010-0172-zOnline First™
Original Investigation
Stefan Reuter, Mark Oette, Frank Clemens Wilhelm, Bastian Beggel, Rolf Kaiser, Melanie Balduin, Finja Schweitzer, Jens Verheyen, Ortwin Adams and Thomas Lengauer, et al.
Abstract
In HIV-infected treatment-naïve patients, we analyzed risk factors for either chronic hepatitis B (HBV) infection, occult HBV infection (OHBV) or a positive hepatitis C (HCV) serostatus. A total of 918 patients of the RESINA-cohort in Germany were included in this study. Before initiating antiretroviral therapy, clinical parameters were collected and blood samples were analyzed for antibodies against HIV, HBV and HCV, HBs antigen and viral nucleic acids for HIV and HBV. Present or past HBV infection (i.e. HBsAg and/or anti-HBc) was found in 43.4% of patients. HBsAg was detected in 4.5% (41/918) and HBV DNA in 6.1% (34/554), resulting in OHBV infection in 2.9% (16/554) of patients. OHBV infection could not be ruled out by the presence of anti-HBs (50.1%) or the absence of all HBV seromarkers (25%). A HCV-positive serostatus was associated with the IVDU transmission route, non-African ethnicity, elevated liver parameters (ASL or GGT) and low HIV viral load. Replicative HBV infection and HCV-positive serostatus both correlated with HIV resistance mutations (P = 0.001 and P = 0.028). HBV and HCV infection are frequent co-infections in HIV treatment-naive patients. These co-infections influence viral evolution, clinical parameters and serological markers. Consequently, HIV patients should routinely be tested for HBV and HCV infection before initiating HIV treatment. OHBV infection constituted almost half of all HBV infections with detectable HBV DNA. Due to a lack of risk factors indicating OHBV infection, HBV diagnosis should not only include serological markers but also the detection of HBV DNA.
Keywords HBV - HCV - Co-infection - Resistance mutations - Occult infection
S. Reuter and M. Oette contributed equally to this work.
This study is conducted for the RESINA study group.
Source
October 2, 2010
NS5B RNA Dependent RNA Polymerase Inhibitors: The Promising Approach to Treat Hepatitis C Virus Infections
Curr Med Chem. 2010 Sep 22. [Epub ahead of print]
Deore RR, Chern JW.
1343, School of Pharmacy, College of Medicine, National Taiwan University, No.1, Section 1, Jen-Ai Road, Taipei, 100, Taiwan. jwchern@ntu.edu.tw.
Abstract
Hepatitis C virus (HCV), a causative agent for non-A and non-B hepatitis, has infected approximately 3% of world's population. The current treatment option of ribavirin in combination with pegylated interferon possesses lower sustained virological response rates, and has serious disadvantages. Unfortunately, no prophylactic vaccine has been approved yet. Therefore, there is an unmet clinical need for more effective and safe anti-HCV drugs. HCV NS5B RNA dependent RNA polymerase is currently pursued as the most popular target to develop safe anti-HCV agents, as it is not expressed in uninfected cells. More than 25 pharmaceutical companies and some research groups have developed ≈50 structurally diverse scaffolds to inhibit NS5B. Here we provide comprehensive account of the drug development process of these scaffolds. NS5B polymerase inhibitors have been broadly classified in nucleoside and non nucleoside inhibitors and are sub classified according to their mechanism of action and structural diversities. With some additional considerations about the inhibitor bound NS5B enzyme X-ray crystal structure information and pharmacological aspects of the inhibitors, this review summarizes the lead identification, structure activity relationship (SAR) studies leading to the most potent NS5B inhibitors with subgenomic replicon activity.
PMID: 20858218 [PubMed - as supplied by publisher]
Source
Deore RR, Chern JW.
1343, School of Pharmacy, College of Medicine, National Taiwan University, No.1, Section 1, Jen-Ai Road, Taipei, 100, Taiwan. jwchern@ntu.edu.tw.
Abstract
Hepatitis C virus (HCV), a causative agent for non-A and non-B hepatitis, has infected approximately 3% of world's population. The current treatment option of ribavirin in combination with pegylated interferon possesses lower sustained virological response rates, and has serious disadvantages. Unfortunately, no prophylactic vaccine has been approved yet. Therefore, there is an unmet clinical need for more effective and safe anti-HCV drugs. HCV NS5B RNA dependent RNA polymerase is currently pursued as the most popular target to develop safe anti-HCV agents, as it is not expressed in uninfected cells. More than 25 pharmaceutical companies and some research groups have developed ≈50 structurally diverse scaffolds to inhibit NS5B. Here we provide comprehensive account of the drug development process of these scaffolds. NS5B polymerase inhibitors have been broadly classified in nucleoside and non nucleoside inhibitors and are sub classified according to their mechanism of action and structural diversities. With some additional considerations about the inhibitor bound NS5B enzyme X-ray crystal structure information and pharmacological aspects of the inhibitors, this review summarizes the lead identification, structure activity relationship (SAR) studies leading to the most potent NS5B inhibitors with subgenomic replicon activity.
PMID: 20858218 [PubMed - as supplied by publisher]
Source
Use of Hepatitis C–Infected Deceased Donors in Liver Transplantation
Current Hepatitis Reports
Volume 9, Number 4, 253-259, DOI: 10.1007/s11901-010-0057-z
Richard S. Mangus
Abstract
The use of hepatitis C–infected (HCV+) liver donors for HCV+ transplant recipients was previously controversial, but mounting evidence now supports this practice. HCV-related cirrhosis accounts for 45% of the liver transplants in the United States; however, these transplant recipients have worse transplant outcomes when compared to non–HCV infected (HCV-) recipients. The optimal utility of the donor graft is therefore decreased with transplantation of HCV+ recipients because the largest percentage of organs are transplanted into patients with inferior survival outcomes. Increased use of HCV+ livers, which can only be transplanted into HCV+ recipients, provides additional transplant liver allografts directly targeted to the recipient population at greatest need. As HCV+ recipients are transplanted with previously unusable organs, more HCV- donor livers are available for the HCV- recipient population, thereby increasing the utility of HCV- grafts. Therefore, increased use of HCV+ donors results in increased utility of all available liver allografts and a shorter waitlist time to transplant, because the total number of available organs is increased. This review discusses the use of HCV+ donor livers in transplantation, including donor organ evaluation, hepatitis C in liver transplantation, a review of the available literature, and the future direction of HCV+ donors in transplantation.
Keywords Liver transplant - Hepatitis C - Extended criteria donor (ECD) - Transplant outcomes
Source
Volume 9, Number 4, 253-259, DOI: 10.1007/s11901-010-0057-z
Richard S. Mangus
Abstract
The use of hepatitis C–infected (HCV+) liver donors for HCV+ transplant recipients was previously controversial, but mounting evidence now supports this practice. HCV-related cirrhosis accounts for 45% of the liver transplants in the United States; however, these transplant recipients have worse transplant outcomes when compared to non–HCV infected (HCV-) recipients. The optimal utility of the donor graft is therefore decreased with transplantation of HCV+ recipients because the largest percentage of organs are transplanted into patients with inferior survival outcomes. Increased use of HCV+ livers, which can only be transplanted into HCV+ recipients, provides additional transplant liver allografts directly targeted to the recipient population at greatest need. As HCV+ recipients are transplanted with previously unusable organs, more HCV- donor livers are available for the HCV- recipient population, thereby increasing the utility of HCV- grafts. Therefore, increased use of HCV+ donors results in increased utility of all available liver allografts and a shorter waitlist time to transplant, because the total number of available organs is increased. This review discusses the use of HCV+ donor livers in transplantation, including donor organ evaluation, hepatitis C in liver transplantation, a review of the available literature, and the future direction of HCV+ donors in transplantation.
Keywords Liver transplant - Hepatitis C - Extended criteria donor (ECD) - Transplant outcomes
Source
ZymoGenetics and Bristol-Myers Squibb to Present PEG-Interferon Lambda Phase 2a Interim Clinical Trial Results at AASLD 2010
SEATTLE & PRINCETON, N.J.--(BUSINESS WIRE)--Oct 1, 2010 - ZymoGenetics, Inc. (NASDAQ: ZGEN) and Bristol-Myers Squibb Company (NYSE: BMY) announced that interim results from Phase 2a of the EMERGE clinical trial of PEG-Interferon lambda administered with ribavirin in treatment-naïve hepatitis C virus patients, will be presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting in Boston, October 29 – November 2, 2010. PEG-Interferon lambda abstracts, including clinical, pharmacokinetic and viral kinetic data along with in vitro data in combination with direct-acting antiviral agents, were published today and are available on the AASLD website at http://www.aasld.org/.
AASLD 2010 PEG-Interferon lambda Poster Presentations
Title: Pegylated Interferon Lambda (PEG-IFN-λ) Phase 2 Dose-Ranging, Active-Controlled Study in Combination with Ribavirin (RBV) for Treatment-Naïve HCV Patients (Genotypes 1, 2, 3, or 4): Safety, Viral Response, and Impact of IL-28B Host Genotype through Week 12
Abstract: 821
Presenter: A.J. Muir
Date: Sunday, October 31, 2010
Time: 8:00 AM – 5:30 PM
Title: Pharmacokinetics of PEG-Interferon lambda (PEG-IFN-λ) Following Fixed Dosing in Treatment-Naïve Hepatitis C Subjects (Single Dose Interim Data from a Dose-Ranging Phase 2A Study)
Abstract: 830
Presenter: K.A. Byrnes-Blake
Date: Sunday, October 31, 2010
Time: 8:00 AM – 5:30 PM
Title: The Effect of Treatment Group, HCV Genotype, and IL28B Genotype on Early HCV Viral Kinetics in a Phase 2A Study of PEG-Interferon lambda (PEG-IFN-λ) in Hepatitis C Patients
Abstract: 831
Presenter: J.A. Freeman
Date: Sunday, October 31, 2010
Time: 8:00 AM – 5:30 PM
Title: In vitro activity of the combination of pegylated interferon lambda (PEG-IFN-λ) with direct-acting antivirals in the HCV replicon model
Abstract: 1854
Presenter: F. McPhee
Date: Tuesday, November 2, 2010
Time: 7:00 AM - 12:00 PM
About PEG-Interferon lambda
PEG-Interferon lambda (IL-29) is a novel and first in class interferon in development for hepatitis C. The native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than type I interferons, such as interferon alpha. Because this receptor is present on fewer cell types within the human body, it is hypothesized that PEG-Interferon lambda may be able to demonstrate an improved safety and tolerability profile compared to alpha interferons.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com/ or follow us on Twitter at http://twitter.com/bmsnews.
About ZymoGenetics
ZymoGenetics is a biopharmaceutical company focused on the development and commercialization of therapeutic proteins for the treatment of human diseases. The company developed and is marketing RECOTHROM® Thrombin, topical (Recombinant) in the United States. ZymoGenetics has two product candidates in Phase 2 clinical development: PEG-Interferon lambda, being studied in collaboration with Bristol-Myers Squibb for treatment of hepatitis C virus infection, and IL-21, being tested as a potential treatment for metastatic melanoma. In addition, ZymoGenetics has an anti-IL-31 monoclonal antibody in preclinical development, which it expects to test initially as a treatment for atopic dermatitis. Several of the product candidates previously identified through ZymoGenetics' discovery research efforts have been licensed to and are being developed by third parties, including Merck Serono and Novo Nordisk. ZymoGenetics is eligible to receive milestone payments and royalties related to these assets. For further information, visit http://www.zymogenetics.com/.
Bristol-Myers Squibb Forward-Looking Statements
This press release contains "forward-looking statements" relating to the acquisition of ZymoGenetics by Bristol-Myers Squibb. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the acquisition will be completed, or if it is completed, that it will close within the anticipated time period. Forward-looking statements in the press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2009, its Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Except for the historical information presented herein, matters discussed herein may constitute forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words “future”; “anticipate”; “potential”; “believe”; or similar statements are forward-looking statements. Risks and uncertainties include uncertainties as to the timing of the tender offer and merger; uncertainties as to how many of the ZymoGenetics shareholders will tender their shares in the offer; the risk that competing offers will be made; the possibility that various closing conditions for the transaction may not be satisfied or waived, including that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the transaction; the effects of disruption from the transaction making it more difficult to maintain relationships with employees, licensees, other business partners or governmental entities; as well as risks detailed from time to time in ZymoGenetics' public disclosure filings with the SEC, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2009, subsequent quarterly filings on Form 10-Q and the Solicitation/Recommendation Statement filed in connection with the tender offer. The information contained in this release is as of September 28, 2010.
This press release is neither an offer to purchase nor a solicitation of an offer to sell shares of ZymoGenetics. Bristol-Myers Squibb Company and Zeus Acquisition Corporation have filed a tender offer statement with the SEC, and have mailed an offer to purchase, forms of letter or transmittal and related documents to ZymoGenetics shareholders. ZymoGenetics has filed with the SEC, and has mailed to ZymoGenetics shareholders a solicitation/recommendation statement on Schedule 14D-9. These documents contain important information about the tender offer and stockholders of ZymoGenetics are urged to read them carefully when they become available.
These documents will be available at no charge at the SEC's website at http://www.sec.gov/. The tender offer statement and the related materials may be obtained for free by directing a request by mail to Georgeson Inc., 199 Water Street, 26th Floor, New York, New York 10038 or by calling toll-free (800) 491-3096. In addition, a copy of the offer to purchase, letter or transmittal and certain other related tender offer documents (once they become available) may also be obtained free of charge from Bristol-Myers Squibb by directing a request to: Public Affairs, Telephone No.: (609) 252-6579; E-Mail: jennifer.mauer@bms.com.
ZymoGenetics Forward-Looking Statement
This press release contains forward-looking statements, including statements related to conducting and analyzing the results of clinical trials. Phrases such as “look forward” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon ZymoGenetics' current expectations and involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to ZymoGenetics' ability to design and conduct clinical trials, the possibility that clinical trial results may vary between different arms of a clinical trial and the difficulty of using prior clinical trial results to predict future outcomes, as well as those other risks detailed in ZymoGenetics' filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2009 and periodic reports on Form 10-Q and current reports on Form 8-K. Do not place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and, except where required by law, ZymoGenetics undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.
PEGASYS® (Peginterferon alfa-2a) is a registered trademark of Hoffmann-La Roche
Contact: Bristol-Myers Squibb
Media
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors
John Elicker, 609-252-4611
john.elicker@bms.com
or
ZymoGenetics
Media and Investors
Susan W. Specht, 206-442-6592
spechts@zymogenetics.com
Source
AASLD 2010 PEG-Interferon lambda Poster Presentations
Title: Pegylated Interferon Lambda (PEG-IFN-λ) Phase 2 Dose-Ranging, Active-Controlled Study in Combination with Ribavirin (RBV) for Treatment-Naïve HCV Patients (Genotypes 1, 2, 3, or 4): Safety, Viral Response, and Impact of IL-28B Host Genotype through Week 12
Abstract: 821
Presenter: A.J. Muir
Date: Sunday, October 31, 2010
Time: 8:00 AM – 5:30 PM
Title: Pharmacokinetics of PEG-Interferon lambda (PEG-IFN-λ) Following Fixed Dosing in Treatment-Naïve Hepatitis C Subjects (Single Dose Interim Data from a Dose-Ranging Phase 2A Study)
Abstract: 830
Presenter: K.A. Byrnes-Blake
Date: Sunday, October 31, 2010
Time: 8:00 AM – 5:30 PM
Title: The Effect of Treatment Group, HCV Genotype, and IL28B Genotype on Early HCV Viral Kinetics in a Phase 2A Study of PEG-Interferon lambda (PEG-IFN-λ) in Hepatitis C Patients
Abstract: 831
Presenter: J.A. Freeman
Date: Sunday, October 31, 2010
Time: 8:00 AM – 5:30 PM
Title: In vitro activity of the combination of pegylated interferon lambda (PEG-IFN-λ) with direct-acting antivirals in the HCV replicon model
Abstract: 1854
Presenter: F. McPhee
Date: Tuesday, November 2, 2010
Time: 7:00 AM - 12:00 PM
About PEG-Interferon lambda
PEG-Interferon lambda (IL-29) is a novel and first in class interferon in development for hepatitis C. The native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than type I interferons, such as interferon alpha. Because this receptor is present on fewer cell types within the human body, it is hypothesized that PEG-Interferon lambda may be able to demonstrate an improved safety and tolerability profile compared to alpha interferons.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com/ or follow us on Twitter at http://twitter.com/bmsnews.
About ZymoGenetics
ZymoGenetics is a biopharmaceutical company focused on the development and commercialization of therapeutic proteins for the treatment of human diseases. The company developed and is marketing RECOTHROM® Thrombin, topical (Recombinant) in the United States. ZymoGenetics has two product candidates in Phase 2 clinical development: PEG-Interferon lambda, being studied in collaboration with Bristol-Myers Squibb for treatment of hepatitis C virus infection, and IL-21, being tested as a potential treatment for metastatic melanoma. In addition, ZymoGenetics has an anti-IL-31 monoclonal antibody in preclinical development, which it expects to test initially as a treatment for atopic dermatitis. Several of the product candidates previously identified through ZymoGenetics' discovery research efforts have been licensed to and are being developed by third parties, including Merck Serono and Novo Nordisk. ZymoGenetics is eligible to receive milestone payments and royalties related to these assets. For further information, visit http://www.zymogenetics.com/.
Bristol-Myers Squibb Forward-Looking Statements
This press release contains "forward-looking statements" relating to the acquisition of ZymoGenetics by Bristol-Myers Squibb. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the acquisition will be completed, or if it is completed, that it will close within the anticipated time period. Forward-looking statements in the press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2009, its Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Except for the historical information presented herein, matters discussed herein may constitute forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words “future”; “anticipate”; “potential”; “believe”; or similar statements are forward-looking statements. Risks and uncertainties include uncertainties as to the timing of the tender offer and merger; uncertainties as to how many of the ZymoGenetics shareholders will tender their shares in the offer; the risk that competing offers will be made; the possibility that various closing conditions for the transaction may not be satisfied or waived, including that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the transaction; the effects of disruption from the transaction making it more difficult to maintain relationships with employees, licensees, other business partners or governmental entities; as well as risks detailed from time to time in ZymoGenetics' public disclosure filings with the SEC, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2009, subsequent quarterly filings on Form 10-Q and the Solicitation/Recommendation Statement filed in connection with the tender offer. The information contained in this release is as of September 28, 2010.
This press release is neither an offer to purchase nor a solicitation of an offer to sell shares of ZymoGenetics. Bristol-Myers Squibb Company and Zeus Acquisition Corporation have filed a tender offer statement with the SEC, and have mailed an offer to purchase, forms of letter or transmittal and related documents to ZymoGenetics shareholders. ZymoGenetics has filed with the SEC, and has mailed to ZymoGenetics shareholders a solicitation/recommendation statement on Schedule 14D-9. These documents contain important information about the tender offer and stockholders of ZymoGenetics are urged to read them carefully when they become available.
These documents will be available at no charge at the SEC's website at http://www.sec.gov/. The tender offer statement and the related materials may be obtained for free by directing a request by mail to Georgeson Inc., 199 Water Street, 26th Floor, New York, New York 10038 or by calling toll-free (800) 491-3096. In addition, a copy of the offer to purchase, letter or transmittal and certain other related tender offer documents (once they become available) may also be obtained free of charge from Bristol-Myers Squibb by directing a request to: Public Affairs, Telephone No.: (609) 252-6579; E-Mail: jennifer.mauer@bms.com.
ZymoGenetics Forward-Looking Statement
This press release contains forward-looking statements, including statements related to conducting and analyzing the results of clinical trials. Phrases such as “look forward” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon ZymoGenetics' current expectations and involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to ZymoGenetics' ability to design and conduct clinical trials, the possibility that clinical trial results may vary between different arms of a clinical trial and the difficulty of using prior clinical trial results to predict future outcomes, as well as those other risks detailed in ZymoGenetics' filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2009 and periodic reports on Form 10-Q and current reports on Form 8-K. Do not place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and, except where required by law, ZymoGenetics undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.
PEGASYS® (Peginterferon alfa-2a) is a registered trademark of Hoffmann-La Roche
Contact: Bristol-Myers Squibb
Media
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors
John Elicker, 609-252-4611
john.elicker@bms.com
or
ZymoGenetics
Media and Investors
Susan W. Specht, 206-442-6592
spechts@zymogenetics.com
Source
Get The Facts About Hepatitis C Viral Load
Hepatitis-Central.com
20 April 2010, 9:57 am
Those with Hepatitis C are often occupied with whether or not they have a high viral load. Despite the tendency to associate a high viral load with worsening illness, experts agree that the results of this test have little bearing on Hepatitis C disease progression.
by Nicole Cutler, L.Ac.
Upon being diagnosed with Hepatitis C, the myriad of subsequent tests can seem like a flurry of being poked and prodded. As one of the primary markers physicians use to assess this illness, viral load’s significance can be misleading. One of the most common misconceptions among Hepatitis C patients is that a higher viral load indicates a greater severity of their disease. This causes many people to incorrectly conclude that if their viral load is high they are in much more serious trouble than if it was low. However, the primary purpose of viral load testing is to determine someone’s candidacy, progress and success for Hepatitis C antiviral treatment.
Hepatitis C is a viral infection of the liver. However, the virus does make its way outside of the liver. This is why Hepatitis C can be measured in the bloodstream. A viral load test determines how many viral particles are floating around in the blood. These particles contain RNA, copies of Hepatitis C’s genetic material. There are three types of tests used to evaluate viral load:
1. PCR (Polymerase Chain Reaction) - PCR tests measure Hepatitis C RNA in the blood to tell if there is an active infection. This test can measure small amounts of the virus (5-10 IU/mL).
2. bDNA (Branched-chain DNA) - The bDNA test only measures medium to high viral loads above 50 IU/mL. This means that if a person has a viral load below 50 IU/mL, a bDNA test may not be able to detect the virus.
3. TMA (Transcription-mediated amplification) – The TMA test also measures Hepatitis C RNA in a blood sample. The TMA test can measure very small amounts of the virus (as few as 5-10 IU/mL).
Results of these viral load tests can be translated in two ways – either in the number of copies of the virus per milliliter or by International Units per milliliter (IU/mL). Physicians often differ in their opinion about what constitutes a high or a low viral load measurement. While these ranges may not be completely agreed on, the following measurements generally denote a high or low Hepatitis C viral load:
When expressed in terms of copies per mL:
· Low = fewer than 2 million copies
· High = greater than 2 million copies
When expressed in terms of International Units per mL:
· Low = fewer than 800,000 IU/mL
· High = greater than 800,000 IU/mL
Viral load does not appear to correlate with a person’s wellness. In fact, a person with a viral load below 200,000 (in terms of copies/mL) may not be able to get out of bed because of their Hepatitis C infection – while someone with a viral load of 10 million (in terms of copies/mL) could feel fine. When it comes to determining liver disease severity, a liver biopsy – or similarly equivalent method – is the only way for a physician to accurately determine his or her patient’s health. This is because a liver biopsy – not viral load – physically examines liver tissue to see how much damage actually exists.
Although Hepatitis C viral load is not a measure of liver disease severity, it is an important marker for several other reasons:
1. A viral load test can determine if the Hepatitis C virus is still present in the body, or if it has been cleared.
2. The chance of a pregnant woman passing the virus on to her child is very low – unless she has a high viral load. An expectant mother with a high viral load has a slightly greater chance of passing the virus to her baby.
3. Numerous studies have shown that people with lower Hepatitis C viral loads respond better to interferon therapy than those with higher viral loads. This information may help physicians determine who is a good candidate for interferon therapy.
4. For those on interferon treatment, viral load testing helps physicians determine if the treatment is working and how long a person should take it.
When a physician evaluates your viral load to see if you are responding to interferon treatment, they look at this number in terms of logarithims:
· A 1-log change is a 10-fold difference.
· Significant changes in viral load are a 2-log difference or a 100-fold change. Differentiating between a 1- and 2-log change can be deceiving.
· A viral load of 800,000 that drops down to 400,000 might appear to be a big drop but it’s only changed by a factor of two – which is just a fraction of a 1-log change.
· However, a change from 800,000 to 8,000 would be significant – as that is a 100-fold change.
· In general, if a person’s viral load has dropped 2 logs or more after 12 weeks of antiviral treatment, there is a greater chance that his or her treatment will be successful.
Besides viral load’s use for monitoring during treatment, it is also used to evaluate the success of Hepatitis C treatment. Viral load is measured to see if the person achieved a sustained virilogic response (SVR). Achieving SVR means that six months after antiviral treatment was completed, viral load tests found no detectable Hepatitis C virus in the blood.
Hepatitis C viral load will normally fluctuate throughout the course of anyone’s illness. In and of itself, viral load is not a reason for concern. It may sound like a good measure of how someone is faring with Hepatitis C. But outside of this test’s use to determine if someone is a candidate for treatment, to monitor treatment or to see if treatment was successful, Hepatitis C viral load reveals very little about the degree of a person’s liver disease.
References:
http://www.ehow.com/how_4448469_understand-hepatitis-c-viral-load.html, How to Understand Hepatitis C Viral Load, Richard Ferri, Retrieved December 3, 2009, eHow, Inc., 2009.
http://www.hcvadvocate.org/hepatitis/Basics/Viralload_09.pdf, HCV Viral Load Tests, Alan Franciscus, Retrieved December 3, 2009, The Hepatitis C Support Project, 2009.
Source
20 April 2010, 9:57 am
Those with Hepatitis C are often occupied with whether or not they have a high viral load. Despite the tendency to associate a high viral load with worsening illness, experts agree that the results of this test have little bearing on Hepatitis C disease progression.
by Nicole Cutler, L.Ac.
Upon being diagnosed with Hepatitis C, the myriad of subsequent tests can seem like a flurry of being poked and prodded. As one of the primary markers physicians use to assess this illness, viral load’s significance can be misleading. One of the most common misconceptions among Hepatitis C patients is that a higher viral load indicates a greater severity of their disease. This causes many people to incorrectly conclude that if their viral load is high they are in much more serious trouble than if it was low. However, the primary purpose of viral load testing is to determine someone’s candidacy, progress and success for Hepatitis C antiviral treatment.
Hepatitis C is a viral infection of the liver. However, the virus does make its way outside of the liver. This is why Hepatitis C can be measured in the bloodstream. A viral load test determines how many viral particles are floating around in the blood. These particles contain RNA, copies of Hepatitis C’s genetic material. There are three types of tests used to evaluate viral load:
1. PCR (Polymerase Chain Reaction) - PCR tests measure Hepatitis C RNA in the blood to tell if there is an active infection. This test can measure small amounts of the virus (5-10 IU/mL).
2. bDNA (Branched-chain DNA) - The bDNA test only measures medium to high viral loads above 50 IU/mL. This means that if a person has a viral load below 50 IU/mL, a bDNA test may not be able to detect the virus.
3. TMA (Transcription-mediated amplification) – The TMA test also measures Hepatitis C RNA in a blood sample. The TMA test can measure very small amounts of the virus (as few as 5-10 IU/mL).
Results of these viral load tests can be translated in two ways – either in the number of copies of the virus per milliliter or by International Units per milliliter (IU/mL). Physicians often differ in their opinion about what constitutes a high or a low viral load measurement. While these ranges may not be completely agreed on, the following measurements generally denote a high or low Hepatitis C viral load:
When expressed in terms of copies per mL:
· Low = fewer than 2 million copies
· High = greater than 2 million copies
When expressed in terms of International Units per mL:
· Low = fewer than 800,000 IU/mL
· High = greater than 800,000 IU/mL
Viral load does not appear to correlate with a person’s wellness. In fact, a person with a viral load below 200,000 (in terms of copies/mL) may not be able to get out of bed because of their Hepatitis C infection – while someone with a viral load of 10 million (in terms of copies/mL) could feel fine. When it comes to determining liver disease severity, a liver biopsy – or similarly equivalent method – is the only way for a physician to accurately determine his or her patient’s health. This is because a liver biopsy – not viral load – physically examines liver tissue to see how much damage actually exists.
Although Hepatitis C viral load is not a measure of liver disease severity, it is an important marker for several other reasons:
1. A viral load test can determine if the Hepatitis C virus is still present in the body, or if it has been cleared.
2. The chance of a pregnant woman passing the virus on to her child is very low – unless she has a high viral load. An expectant mother with a high viral load has a slightly greater chance of passing the virus to her baby.
3. Numerous studies have shown that people with lower Hepatitis C viral loads respond better to interferon therapy than those with higher viral loads. This information may help physicians determine who is a good candidate for interferon therapy.
4. For those on interferon treatment, viral load testing helps physicians determine if the treatment is working and how long a person should take it.
When a physician evaluates your viral load to see if you are responding to interferon treatment, they look at this number in terms of logarithims:
· A 1-log change is a 10-fold difference.
· Significant changes in viral load are a 2-log difference or a 100-fold change. Differentiating between a 1- and 2-log change can be deceiving.
· A viral load of 800,000 that drops down to 400,000 might appear to be a big drop but it’s only changed by a factor of two – which is just a fraction of a 1-log change.
· However, a change from 800,000 to 8,000 would be significant – as that is a 100-fold change.
· In general, if a person’s viral load has dropped 2 logs or more after 12 weeks of antiviral treatment, there is a greater chance that his or her treatment will be successful.
Besides viral load’s use for monitoring during treatment, it is also used to evaluate the success of Hepatitis C treatment. Viral load is measured to see if the person achieved a sustained virilogic response (SVR). Achieving SVR means that six months after antiviral treatment was completed, viral load tests found no detectable Hepatitis C virus in the blood.
Hepatitis C viral load will normally fluctuate throughout the course of anyone’s illness. In and of itself, viral load is not a reason for concern. It may sound like a good measure of how someone is faring with Hepatitis C. But outside of this test’s use to determine if someone is a candidate for treatment, to monitor treatment or to see if treatment was successful, Hepatitis C viral load reveals very little about the degree of a person’s liver disease.
References:
http://www.ehow.com/how_4448469_understand-hepatitis-c-viral-load.html, How to Understand Hepatitis C Viral Load, Richard Ferri, Retrieved December 3, 2009, eHow, Inc., 2009.
http://www.hcvadvocate.org/hepatitis/Basics/Viralload_09.pdf, HCV Viral Load Tests, Alan Franciscus, Retrieved December 3, 2009, The Hepatitis C Support Project, 2009.
Source
The Importance of Laboratory Test Results in Hepatitis C Infection
David Bernstein, MD, FACP, FACG
Director of Hepatology
North Shore University Hospital
Associate Professor of Medicine
SUNY-Downstate School of Medicine
Most people with hepatitis C feel well and have no specific findings on physical examination that would lead a health care provider to suspect liver disease. Even the vast majority of people with liver disease that has advanced to cirrhosis have a normal physical examination. Therefore, the evaluation and treatment of liver disease, in particular hepatitis C, places a large emphasis on laboratory tests results to diagnose, stage and predict and evaluate response to therapy.
The liver has several general functions and it is often called both the body’s manufacturing center and its filtering plant. Blood tests used to evaluate the liver can be divided into those representing liver cell damage, cholestasis or liver function. The serum aminotransaminases, alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT) are part of most automated blood chemistry panels. Elevation of these enzymes is caused by damage to the hepatocyte or liver cell. The degree of elevation may be important in acute disease but is unimportant in chronic disease. The most common causes of elevated aminotransaminases are fatty liver, viral hepatitis, medication induced hepatitis, autoimmune hepatitis and alcoholic liver disease. The tests are a reflection of cell damage and death but are not liver function tests. Although many patients and physicians refer to these tests as “liver function tests”, this term is incorrect and they do not reflect the liver’s ability to either synthesize or metabolize various chemicals. Therefore, an abnormality in these tests does not mean that the liver is not functioning. In fact, the vast majority of patients with elevated aminotransaminases, regardless of degree, have normal liver function.
Cholestatic liver disease is any condition leading to the obstruction of bile ducts in either the liver or biliary tree. Elevation of the enzymes alkaline phosphatase and gamma-glutamyl transpeptidase are indicative of this type of disease. Conditions that commonly lead to the elevation of these enzymes include primary biliary cirrhosis, primary sclerosing cholangitis and gallstone disease.
Bilirubin is the final breakdown product of heme, the majority of which comes from hemoglobin. Bilirubin can be elevated in many liver-related and non-liver- related conditions and it may be elevated in conditions which lead to liver cell damage and cholestasis. The level of serum bilirubin is not a sensitive indicator of liver function and it may not accurately reflect the degree of liver damage.
Albumin and blood clotting factors are proteins made in the liver. Blood tests such as the serum albumin and prothrombin time are measures of these proteins. As these tests evaluate the functional integrity of the liver, they can be correctly called “liver function tests”. Abnormalities of these tests are of concern and are indicative of extensive liver damage.
The most common laboratory abnormality seen in chronic hepatitis C infection is an isolated, elevated alanine aminotransferase (ALT) although as many as 60% of hepatitis C infected patients will have a normal ALT level. The level of serum ALT elevation does not correlate with histological disease and may be normal in any stage of chronic hepatitis C. Therefore, patients with minimal ALT elevations should be evaluated for the presence of chronic hepatitis. In advanced disease, an increase in alkaline phosphatase and total bilirubin as well as thrombocytopenia (low platelets) may be seen.
In the patient with risk factors for hepatitis C or an abnormal ALT, the most practical method of diagnosing HCV infection is by obtaining a second generation enzyme linked immunosorbent assay (EIA) antibody to hepatitis C (anti-HCV). False-positive results may occur at a rate of 10-20% and are usually seen in the presence of autoimmune disease, hypergammaglobulinemia and low-risk blood donors. False negative results may occur in immunosuppressed patients, including people infected with the human immunodeficiency virus. In early infection, anti-HCV testing may be negative, as antibodies may not develop until 4-6 weeks after exposure. Unfortunately, a positive hepatitis C antibody does not distinguish acute from chronic disease or active from past infection nor is it a sign of immunity or protection. Therefore, a positive EIA anti-HCV test is a marker that hepatitis C may be present and it must be followed by confirmatory viral load testing.
The recombinant immunoblot assay (RIBA) is another type of antibody test with limited utility. As with EIA antibody tests, it does not distinguish between acute or chronic disease or between past and active infection. Therefore, it adds little to the care of a patient with a positive hepatitis C antibody by the EIA method and known risk factors except extra expense. The NIH consensus conference on hepatitis C has recommended that it be used as a confirmatory test in patients without known risk factors who test positive for the EIA anti-HCV to eliminate the possibility of a false positive EIA. RIBA testing is not influenced by the presence of autoimmune disease or hypergammaglobulinemia. In clinical practice, this test has little if any utility and, except for rare exceptions, it should not be obtained.
Confirmatory tests for the presence of hepatitis C infection are those tests that determine the presence of hepatitis C viral particles (HCV-RNA) in the blood. A positive HCV-RNA in the serum confirms the diagnosis of active hepatitis C. This type of viral testing may be either qualitative or quantitative. Qualitative testing is more sensitive and specific than quantitative testing and results are reported as either positive or negative. Quantitative testing reports on the actual measured amount of viral particles in the serum and the viral levels are usually expressed as thousands or millions of international units. Of note, quantitative viral testing may be falsely negative if viral levels are below the lower limit of detection of the assay being used. Therefore, qualitative HCV-RNA testing is used for diagnosis while quantitative testing should be reserved for use during treatment. It is important to note that the level of virus does not correlate with prognosis, underlying liver histology or how ill a person feels. Therefore, a patient with a viral level of 3,000,000 international units does not have a worse prognosis nor is the person any sicker than someone with a viral count of 200,000 international units. Small fluctuations in HCV-RNA level are equally unimportant. A patient whose viral level has decreased from five to one million international units has shown no significant change in viral level and should not be rejoicing. The converse is also true and an elevation from one to five million international units should not lead a patient to be upset. It is important to understand the relative lack of importance of viral level in the untreated hepatitis C patient. Misconceptions about viral levels often lead to tremendous angst among patients who insist on comparing numbers in the waiting room, are upset by the initial level of viremia or feel falsely relieved or upset with small changes in HCV-RNA viral load. Recently, however, it has been suggested that in the population co-infected with hepatitis C and HIV, a higher hepatitis C viral load is associated with a more rapid progression to advanced disease. As regards viral level and its significance, the co-infected patient appears to behave differently than the HCV mono-infected person. Quantitative viral load testing should not be repeated yearly or more often as it adds little to the care of the untreated patient other than increased expense and anxiety. These tests, however, should be followed serially in someone undergoing anti-viral therapy, as the goal of therapy is the loss of detectable serum HCV-RNA.
Several other liver tests are frequently obtained in patients with hepatitis C. The serum alpha-fetoprotein is a marker of liver cancer but it may be mildly elevated in patients with chronic hepatitis C in the absence of liver cancer. If it is elevated, this test should be followed closely. Autoimmune markers may be present in as many as 25% patients with hepatitis C without the presence of autoimmune disease. These markers include an anti-nuclear antibody, smooth muscle antibody, anti-mitochondrial antibody or anti-thyroid antibodies. The presence of these antibodies does not appear to influence disease progression. Patients in whom autoimmune disease is suspected should be adequately evaluated before the presence of autoantibodies is attributed to HCV infection.
The adequate interpretation of laboratory test results is very important to understand the evaluation of hepatitis C infection. Unfortunately, in the majority of cases, these blood tests are unable to accurately predict current disease stage or possible disease progression. Therefore, despite all these advanced tests, the performance of a liver biopsy cannot be emphasized enough as this is the best test to accurately stage the disease and predict disease progression.
Source
Director of Hepatology
North Shore University Hospital
Associate Professor of Medicine
SUNY-Downstate School of Medicine
Most people with hepatitis C feel well and have no specific findings on physical examination that would lead a health care provider to suspect liver disease. Even the vast majority of people with liver disease that has advanced to cirrhosis have a normal physical examination. Therefore, the evaluation and treatment of liver disease, in particular hepatitis C, places a large emphasis on laboratory tests results to diagnose, stage and predict and evaluate response to therapy.
The liver has several general functions and it is often called both the body’s manufacturing center and its filtering plant. Blood tests used to evaluate the liver can be divided into those representing liver cell damage, cholestasis or liver function. The serum aminotransaminases, alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT) are part of most automated blood chemistry panels. Elevation of these enzymes is caused by damage to the hepatocyte or liver cell. The degree of elevation may be important in acute disease but is unimportant in chronic disease. The most common causes of elevated aminotransaminases are fatty liver, viral hepatitis, medication induced hepatitis, autoimmune hepatitis and alcoholic liver disease. The tests are a reflection of cell damage and death but are not liver function tests. Although many patients and physicians refer to these tests as “liver function tests”, this term is incorrect and they do not reflect the liver’s ability to either synthesize or metabolize various chemicals. Therefore, an abnormality in these tests does not mean that the liver is not functioning. In fact, the vast majority of patients with elevated aminotransaminases, regardless of degree, have normal liver function.
Cholestatic liver disease is any condition leading to the obstruction of bile ducts in either the liver or biliary tree. Elevation of the enzymes alkaline phosphatase and gamma-glutamyl transpeptidase are indicative of this type of disease. Conditions that commonly lead to the elevation of these enzymes include primary biliary cirrhosis, primary sclerosing cholangitis and gallstone disease.
Bilirubin is the final breakdown product of heme, the majority of which comes from hemoglobin. Bilirubin can be elevated in many liver-related and non-liver- related conditions and it may be elevated in conditions which lead to liver cell damage and cholestasis. The level of serum bilirubin is not a sensitive indicator of liver function and it may not accurately reflect the degree of liver damage.
Albumin and blood clotting factors are proteins made in the liver. Blood tests such as the serum albumin and prothrombin time are measures of these proteins. As these tests evaluate the functional integrity of the liver, they can be correctly called “liver function tests”. Abnormalities of these tests are of concern and are indicative of extensive liver damage.
The most common laboratory abnormality seen in chronic hepatitis C infection is an isolated, elevated alanine aminotransferase (ALT) although as many as 60% of hepatitis C infected patients will have a normal ALT level. The level of serum ALT elevation does not correlate with histological disease and may be normal in any stage of chronic hepatitis C. Therefore, patients with minimal ALT elevations should be evaluated for the presence of chronic hepatitis. In advanced disease, an increase in alkaline phosphatase and total bilirubin as well as thrombocytopenia (low platelets) may be seen.
In the patient with risk factors for hepatitis C or an abnormal ALT, the most practical method of diagnosing HCV infection is by obtaining a second generation enzyme linked immunosorbent assay (EIA) antibody to hepatitis C (anti-HCV). False-positive results may occur at a rate of 10-20% and are usually seen in the presence of autoimmune disease, hypergammaglobulinemia and low-risk blood donors. False negative results may occur in immunosuppressed patients, including people infected with the human immunodeficiency virus. In early infection, anti-HCV testing may be negative, as antibodies may not develop until 4-6 weeks after exposure. Unfortunately, a positive hepatitis C antibody does not distinguish acute from chronic disease or active from past infection nor is it a sign of immunity or protection. Therefore, a positive EIA anti-HCV test is a marker that hepatitis C may be present and it must be followed by confirmatory viral load testing.
The recombinant immunoblot assay (RIBA) is another type of antibody test with limited utility. As with EIA antibody tests, it does not distinguish between acute or chronic disease or between past and active infection. Therefore, it adds little to the care of a patient with a positive hepatitis C antibody by the EIA method and known risk factors except extra expense. The NIH consensus conference on hepatitis C has recommended that it be used as a confirmatory test in patients without known risk factors who test positive for the EIA anti-HCV to eliminate the possibility of a false positive EIA. RIBA testing is not influenced by the presence of autoimmune disease or hypergammaglobulinemia. In clinical practice, this test has little if any utility and, except for rare exceptions, it should not be obtained.
Confirmatory tests for the presence of hepatitis C infection are those tests that determine the presence of hepatitis C viral particles (HCV-RNA) in the blood. A positive HCV-RNA in the serum confirms the diagnosis of active hepatitis C. This type of viral testing may be either qualitative or quantitative. Qualitative testing is more sensitive and specific than quantitative testing and results are reported as either positive or negative. Quantitative testing reports on the actual measured amount of viral particles in the serum and the viral levels are usually expressed as thousands or millions of international units. Of note, quantitative viral testing may be falsely negative if viral levels are below the lower limit of detection of the assay being used. Therefore, qualitative HCV-RNA testing is used for diagnosis while quantitative testing should be reserved for use during treatment. It is important to note that the level of virus does not correlate with prognosis, underlying liver histology or how ill a person feels. Therefore, a patient with a viral level of 3,000,000 international units does not have a worse prognosis nor is the person any sicker than someone with a viral count of 200,000 international units. Small fluctuations in HCV-RNA level are equally unimportant. A patient whose viral level has decreased from five to one million international units has shown no significant change in viral level and should not be rejoicing. The converse is also true and an elevation from one to five million international units should not lead a patient to be upset. It is important to understand the relative lack of importance of viral level in the untreated hepatitis C patient. Misconceptions about viral levels often lead to tremendous angst among patients who insist on comparing numbers in the waiting room, are upset by the initial level of viremia or feel falsely relieved or upset with small changes in HCV-RNA viral load. Recently, however, it has been suggested that in the population co-infected with hepatitis C and HIV, a higher hepatitis C viral load is associated with a more rapid progression to advanced disease. As regards viral level and its significance, the co-infected patient appears to behave differently than the HCV mono-infected person. Quantitative viral load testing should not be repeated yearly or more often as it adds little to the care of the untreated patient other than increased expense and anxiety. These tests, however, should be followed serially in someone undergoing anti-viral therapy, as the goal of therapy is the loss of detectable serum HCV-RNA.
Several other liver tests are frequently obtained in patients with hepatitis C. The serum alpha-fetoprotein is a marker of liver cancer but it may be mildly elevated in patients with chronic hepatitis C in the absence of liver cancer. If it is elevated, this test should be followed closely. Autoimmune markers may be present in as many as 25% patients with hepatitis C without the presence of autoimmune disease. These markers include an anti-nuclear antibody, smooth muscle antibody, anti-mitochondrial antibody or anti-thyroid antibodies. The presence of these antibodies does not appear to influence disease progression. Patients in whom autoimmune disease is suspected should be adequately evaluated before the presence of autoantibodies is attributed to HCV infection.
The adequate interpretation of laboratory test results is very important to understand the evaluation of hepatitis C infection. Unfortunately, in the majority of cases, these blood tests are unable to accurately predict current disease stage or possible disease progression. Therefore, despite all these advanced tests, the performance of a liver biopsy cannot be emphasized enough as this is the best test to accurately stage the disease and predict disease progression.
Source
Understanding the functions of your liver
THE liver is the largest internal organ of the body. this vital organ is crucial to the smooth functioning of the human body.
It metabolises most of the nutrients that are absorbed by the intestine and detoxifies the blood by removing medications, alcohol and potentially harmful chemicals from the bloodstream – processing them chemically so that they can be expelled from the body by the digestive or urinary systems.
The liver also produces clotting factors and other proteins, stores certain vitamins, minerals (including iron) and sugars, regulates fat stores, and controls the production and excretion of cholesterol.
It is an amazing organ that can regenerate its cells within a few weeks. in fact, the liver can tolerate a fair amount of “abuse” and will only show signs of injury when the hurt is very advanced.
Liver disorders include hepatitis and cirrhosis. Hepatitis is inflammation of the liver and cirrhosis is scarring of the liver. these two conditions may progress to liver cancer if they are not monitored or treated properly.
Cirrhosis of the liver happens when your liver has a complication of many diseases. Anatomically, your liver will have a lot of scar tissue manifested in nodules and fibrous tissue that is hard.
When this happens, it could be due to the following factors:
1. That your liver is damaged by chronic liver disease.
2. That there is a lot of damaged liver tissue, leading to inflammation and subsequent repair and replacement by fibrous or scar tissue.
3. That there is regeneration of liver tissue from the cells that are still remaining, but it doesn’t go quite normally, leading to regenerative nodules.
If it were only the structure of the liver that is affected, cirrhosis would just be an ugly feature on an ultrasound. unfortunately, this is not a common occurance. usually, your liver functions are also affected and that’s when the problem starts.
As the largest internal organ of the body, the liver performs the following essential functions:
1. it controls the levels of fats, amino acids and glucose in your blood. Stores glycogen (glucose in another form), iron, vitamins and other essential nutrients.
2. it manufactures bile and aids in your digestive process, especially in the breakdown of fats.
3. it detoxifies your blood by clearing it of toxic wastes, breaking them down and getting rid of them either through your faeces or releasing them into your blood in smaller particles to be further cleared by your kidneys.
4. Manufactures and regulates various hormones, enzymes and clotting factors.
5. Fights infections, especially through macrophages.
Cirrhosis of the liver occurs because the liver anatomy is so scarred that it interferes with the liver cells’ functions, and thus renders the liver to be unable to perform many of its functions well.
The trouble with cirrhosis is that it has no clear symptoms or very few which are nondescript, like tiredness or fatigue. So you will not know that you have it till liver failure creeps up on you by which time may be a small too late.
Some symptoms associated with cirrhosis are fatigue, weakness, loss of appetite, itching, and sometimes jaundice if there is accumulation of bilirubin in your blood. Your clotting factors may also be affected and you can have simple bruising of your skin.
Often when cirrhosis becomes severe, you will develop complications. these complications can be a lot more clear in their symptoms and usually are the first physical sign that something is wrong.
1) You begin to retain water, leading to a condition called ascites, where there is excessive water in your peritoneal cavity (cavity within your abdomen). there is also a lot of water accumulated in your ankles and feet, manifested by swelling. the ascites is a magnet for bacteria to grow, and you may have an infection.
2) You can also have bleeding from oesophageal veins. in cirrhosis, the scar tissue blocks the flow of blood from the intestines to the heart, resulting in the distension of the portal vein. (This is the vein that is very important in the digestive process.) the back pressure leads to distension of your veins in the lower part of your oesophagus. these veins can bleed, leading to you vomiting blood (haematemesis). this can be life-threatening.
3) this pressure can also cause your spleen to distend and become so swollen that it sometimes becomes a hard mass in your abdomen. this gigantic spleen traps your blood cells and causes you to have anaemia and prolonged bleeding.
4) Because your liver cannot detoxify your body, this can lead to toxic substances in your blood. this goes to your brain and causes sleepiness during the day, irritability, confusion, loss of concentration, and finally coma and death.
5) Cirrhosis greatly increases the risk of you getting liver cancer
Causes of liver cirrhosis include excessive alcohol consumption that leads to hurt of your liver cells, resulting in a fatty liver (something which is heightened by obesity); chronic viral hepatitis (B,C); genetic liver disorders; and possibly anything that can hurt your liver can lead to cirrhosis.
Avoid excessive alcohol consumption, and make sure you have your hepatitis jabs, especially if you intend to travel to anyplace where hepatitis is viral . Lose any excess weight, and ensure you go for frequent check-ups
As the saying goes, prevention is better than cure and here are some measures you can take to preserve your liver health:
Poor nutrition rarely causes liver disease but excellent nutrition in the form of a balanced diet will enable the liver to perform its many various functions efficiently, resulting in better overall health. it can also help liver cells damaged by hepatitis viruses to regenerate, forming new liver cells.
But, whilst it is important to take vitamins and minerals, please note that an excess of Vitamin A is toxic to the liver and should be taken in moderation.
2. Limit intake of calories.
Excess calories in the form of carbohydrates can add to liver dysfunction and can cause fat deposits in the liver, contributing to fatty liver.
No more than 30% of a person’s total calories should come from fat because of the danger to the cardiovascular system. in order to estimate your daily calorie needs, you will need a minimum of 15 calories a day for each pound you weigh
3. Hold the alcohol
Liquor, beer and wine are hard for the liver to metabolise. the daily recommended alcohol intake is three units/drinks for men and two units/drinks for women.
As a general guide, one unit of alcohol translates to half a pint of ordinary strength beer, a small measure (25ml) of spirits or a standard measure (50ml) of fortified wine such as sherry or port.
Having three drinks or more per day should be avoided, as it may lead to alcoholic hepatitis and cirrhosis. People with liver disease should never drink alcohol at all. the same goes for individuals who are taking medication ? mixing alcohol with painkillers or other types of medications can be perilous to your liver.
In particular, the mixture of alcohol and acetaminophen (an ingredient in pain killers and cough medication) can cause sudden, severe hepatitis and even fatal liver failure. If you are not sure which medications to take in combination, please consult your doctor.
4. Beware “nutritional therapies”
Herbal treatments and alternative liver medicines should undergo rigorous scientific study before they can be recommended.
“Natural” or diet treatments and herbal remedies can be quite perilous. Plants of the Crotalaria, Senecio and Heliotopium families, as well as chaparral, mistletoe, skullcap, germander, comfrey, margosa oil, mate tea, Gordolobo yerba tea, pennyroyal, and Jin Blu Huan are all toxic to the liver.
Several scientific studies suggest that substances in milk thistle may protect the liver from harmful substances such as acetaminophen, which can cause liver hurt. it is also believed that milk thistle has antioxidant and anti-inflammatory properties, and it may help the liver repair itself by growing new cells.
5. stop smoking and stay away from toxic fumes and liquids.
Fumes from paint thinners, bug sprays, and other aerosol sprays are picked up by the tiny blood vessels in your lungs and carried to your liver where they are detoxified and discharged in your bile.
The amount and concentration of those chemicals should be controlled to prevent liver hurt. make certain you have excellent ventilation, use a mask, cover your skin, and wash off any chemicals you get on your skin with soap and water as soon as possible.
Hands should be washed with soap and water following bowel movements and before food preparation and consumption. this will help prevent the spread of hepatitis A.
Avoid sex with multiple partners or wear protection where unavoidable. Hepatitis B and C are transmitted through blood and body fluids. So use condoms and avoid sharing your personal items such as toothbrush, razor or manicure sets, especially if your partner may be suffering from a liver disease.
Vaccination for hepatitis A and B is available. an immunisation programme for hepatitis B has been in place for all children and adults since 1989 to prevent hepatitis B infection. it is essential to vaccinate newborns for hepatitis B as infections in this group will result in 90% chronic infection. there is no vaccination available for hepatitis C.
Chronic liver infection can lead to cirrhosis, where there are areas of scarring and liver cell regeneration within the liver.
Cirrhosis can lead to liver cancer, which is often diagnosed too late as few symptoms appear until it has reached an advanced stage. Signs and symptoms of liver cancer include right upper abdominal pain, jaundice (yellowing of the skin), abdominal swelling, weight loss, fatigue, simple bruising or bleeding.
Apart from surgery, for which most liver cancer patients are ineligible due to the advanced stages of the disease at time of diagnosis, there is currently an oral treatment that has been found to be effective in targeting the liver cancer cells specifically and can be used in patients who are unsuitable for surgery.
Sorafenib is an oral treatment available for the treatment of advanced liver cancer.
Keeping the liver healthy is essential to keeping your entire being healthy, so take excellent care of your liver, so that it can take care of you.
Source
It metabolises most of the nutrients that are absorbed by the intestine and detoxifies the blood by removing medications, alcohol and potentially harmful chemicals from the bloodstream – processing them chemically so that they can be expelled from the body by the digestive or urinary systems.
The liver also produces clotting factors and other proteins, stores certain vitamins, minerals (including iron) and sugars, regulates fat stores, and controls the production and excretion of cholesterol.
It is an amazing organ that can regenerate its cells within a few weeks. in fact, the liver can tolerate a fair amount of “abuse” and will only show signs of injury when the hurt is very advanced.
Liver disorders include hepatitis and cirrhosis. Hepatitis is inflammation of the liver and cirrhosis is scarring of the liver. these two conditions may progress to liver cancer if they are not monitored or treated properly.
Cirrhosis of the liver happens when your liver has a complication of many diseases. Anatomically, your liver will have a lot of scar tissue manifested in nodules and fibrous tissue that is hard.
When this happens, it could be due to the following factors:
1. That your liver is damaged by chronic liver disease.
2. That there is a lot of damaged liver tissue, leading to inflammation and subsequent repair and replacement by fibrous or scar tissue.
3. That there is regeneration of liver tissue from the cells that are still remaining, but it doesn’t go quite normally, leading to regenerative nodules.
If it were only the structure of the liver that is affected, cirrhosis would just be an ugly feature on an ultrasound. unfortunately, this is not a common occurance. usually, your liver functions are also affected and that’s when the problem starts.
As the largest internal organ of the body, the liver performs the following essential functions:
1. it controls the levels of fats, amino acids and glucose in your blood. Stores glycogen (glucose in another form), iron, vitamins and other essential nutrients.
2. it manufactures bile and aids in your digestive process, especially in the breakdown of fats.
3. it detoxifies your blood by clearing it of toxic wastes, breaking them down and getting rid of them either through your faeces or releasing them into your blood in smaller particles to be further cleared by your kidneys.
4. Manufactures and regulates various hormones, enzymes and clotting factors.
5. Fights infections, especially through macrophages.
Cirrhosis of the liver occurs because the liver anatomy is so scarred that it interferes with the liver cells’ functions, and thus renders the liver to be unable to perform many of its functions well.
The trouble with cirrhosis is that it has no clear symptoms or very few which are nondescript, like tiredness or fatigue. So you will not know that you have it till liver failure creeps up on you by which time may be a small too late.
Some symptoms associated with cirrhosis are fatigue, weakness, loss of appetite, itching, and sometimes jaundice if there is accumulation of bilirubin in your blood. Your clotting factors may also be affected and you can have simple bruising of your skin.
Often when cirrhosis becomes severe, you will develop complications. these complications can be a lot more clear in their symptoms and usually are the first physical sign that something is wrong.
1) You begin to retain water, leading to a condition called ascites, where there is excessive water in your peritoneal cavity (cavity within your abdomen). there is also a lot of water accumulated in your ankles and feet, manifested by swelling. the ascites is a magnet for bacteria to grow, and you may have an infection.
2) You can also have bleeding from oesophageal veins. in cirrhosis, the scar tissue blocks the flow of blood from the intestines to the heart, resulting in the distension of the portal vein. (This is the vein that is very important in the digestive process.) the back pressure leads to distension of your veins in the lower part of your oesophagus. these veins can bleed, leading to you vomiting blood (haematemesis). this can be life-threatening.
3) this pressure can also cause your spleen to distend and become so swollen that it sometimes becomes a hard mass in your abdomen. this gigantic spleen traps your blood cells and causes you to have anaemia and prolonged bleeding.
4) Because your liver cannot detoxify your body, this can lead to toxic substances in your blood. this goes to your brain and causes sleepiness during the day, irritability, confusion, loss of concentration, and finally coma and death.
5) Cirrhosis greatly increases the risk of you getting liver cancer
Causes of liver cirrhosis include excessive alcohol consumption that leads to hurt of your liver cells, resulting in a fatty liver (something which is heightened by obesity); chronic viral hepatitis (B,C); genetic liver disorders; and possibly anything that can hurt your liver can lead to cirrhosis.
Avoid excessive alcohol consumption, and make sure you have your hepatitis jabs, especially if you intend to travel to anyplace where hepatitis is viral . Lose any excess weight, and ensure you go for frequent check-ups
As the saying goes, prevention is better than cure and here are some measures you can take to preserve your liver health:
Poor nutrition rarely causes liver disease but excellent nutrition in the form of a balanced diet will enable the liver to perform its many various functions efficiently, resulting in better overall health. it can also help liver cells damaged by hepatitis viruses to regenerate, forming new liver cells.
But, whilst it is important to take vitamins and minerals, please note that an excess of Vitamin A is toxic to the liver and should be taken in moderation.
2. Limit intake of calories.
Excess calories in the form of carbohydrates can add to liver dysfunction and can cause fat deposits in the liver, contributing to fatty liver.
No more than 30% of a person’s total calories should come from fat because of the danger to the cardiovascular system. in order to estimate your daily calorie needs, you will need a minimum of 15 calories a day for each pound you weigh
3. Hold the alcohol
Liquor, beer and wine are hard for the liver to metabolise. the daily recommended alcohol intake is three units/drinks for men and two units/drinks for women.
As a general guide, one unit of alcohol translates to half a pint of ordinary strength beer, a small measure (25ml) of spirits or a standard measure (50ml) of fortified wine such as sherry or port.
Having three drinks or more per day should be avoided, as it may lead to alcoholic hepatitis and cirrhosis. People with liver disease should never drink alcohol at all. the same goes for individuals who are taking medication ? mixing alcohol with painkillers or other types of medications can be perilous to your liver.
In particular, the mixture of alcohol and acetaminophen (an ingredient in pain killers and cough medication) can cause sudden, severe hepatitis and even fatal liver failure. If you are not sure which medications to take in combination, please consult your doctor.
4. Beware “nutritional therapies”
Herbal treatments and alternative liver medicines should undergo rigorous scientific study before they can be recommended.
“Natural” or diet treatments and herbal remedies can be quite perilous. Plants of the Crotalaria, Senecio and Heliotopium families, as well as chaparral, mistletoe, skullcap, germander, comfrey, margosa oil, mate tea, Gordolobo yerba tea, pennyroyal, and Jin Blu Huan are all toxic to the liver.
Several scientific studies suggest that substances in milk thistle may protect the liver from harmful substances such as acetaminophen, which can cause liver hurt. it is also believed that milk thistle has antioxidant and anti-inflammatory properties, and it may help the liver repair itself by growing new cells.
5. stop smoking and stay away from toxic fumes and liquids.
Fumes from paint thinners, bug sprays, and other aerosol sprays are picked up by the tiny blood vessels in your lungs and carried to your liver where they are detoxified and discharged in your bile.
The amount and concentration of those chemicals should be controlled to prevent liver hurt. make certain you have excellent ventilation, use a mask, cover your skin, and wash off any chemicals you get on your skin with soap and water as soon as possible.
Hands should be washed with soap and water following bowel movements and before food preparation and consumption. this will help prevent the spread of hepatitis A.
Avoid sex with multiple partners or wear protection where unavoidable. Hepatitis B and C are transmitted through blood and body fluids. So use condoms and avoid sharing your personal items such as toothbrush, razor or manicure sets, especially if your partner may be suffering from a liver disease.
Vaccination for hepatitis A and B is available. an immunisation programme for hepatitis B has been in place for all children and adults since 1989 to prevent hepatitis B infection. it is essential to vaccinate newborns for hepatitis B as infections in this group will result in 90% chronic infection. there is no vaccination available for hepatitis C.
Chronic liver infection can lead to cirrhosis, where there are areas of scarring and liver cell regeneration within the liver.
Cirrhosis can lead to liver cancer, which is often diagnosed too late as few symptoms appear until it has reached an advanced stage. Signs and symptoms of liver cancer include right upper abdominal pain, jaundice (yellowing of the skin), abdominal swelling, weight loss, fatigue, simple bruising or bleeding.
Apart from surgery, for which most liver cancer patients are ineligible due to the advanced stages of the disease at time of diagnosis, there is currently an oral treatment that has been found to be effective in targeting the liver cancer cells specifically and can be used in patients who are unsuitable for surgery.
Sorafenib is an oral treatment available for the treatment of advanced liver cancer.
Keeping the liver healthy is essential to keeping your entire being healthy, so take excellent care of your liver, so that it can take care of you.
Source
Terlipressin treatment for gastrointestinal bleeding reduces serum sodium
Public release date: 22-Sep-2010
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Hyponatremia may lead to neurological complications
A new study published in the October issue of the journal Hepatology found that patients with severe portal-hypertensive bleeding who are treated with terlipressin may experience an acute reduction of sodium in their blood. This reduction in serum sodium, known as hyponatremia, can cause adverse reactions such as neurological complications, and is rapidly reversible upon terlipressin withdrawal. Researchers suggest that serum sodium should be closely monitored in these patients and caution that use of solutions with high sodium content to treat this condition may cause a too rapid recovery of sodium leading to adverse events.
Cirrhosis and portal vein thrombosis are two of the primary causes of severe portal hypertension—an increase in blood pressure of the (portal) vein between digestive organs and the liver. This increase in pressure contributes to the development of varices, or large veins, that can weaken over time and lead to gastrointestinal bleeding. Terlipressin is commonly used to treat acute variceal bleeding, however its effect on serum sodium is largely unknown and the focus of the current retrospective study, led by Pere Ginès, MD, from the Hospital Clínic in Barcelona, Spain.
The study included 58 consecutive patients treated with terlipressin for gastrointestinal bleeding due to portal-hypertension. Median age of participants was 54 years, with 77% of the cohort being male and 22% female. Initially patients were treated with somatostatin, but switched to terlipressin due to uncontrolled bleeding or rebleeding in 57% and 43% of cases, respectively.
Researchers noted a significant reduction in serum sodium concentration during terlipressin treatment (from 134.9 at baseline to 130.5 mEq/L at day 5 of treatment). A reduction of sodium in the blood was found in 67% of patients with 31% having a moderate decrease (5-10 mEq/L) and 36% experiencing a marked decrease in serum sodium (greater than 10mEq/L). Only 19 patients were determined to have no change in serum sodium levels.
Further results indicate that patients with a low model for end-stage liver disease (MELD) score and normal or near-normal baseline serum sodium had the highest risk of hyponatremia. "The reduction in serum sodium concentration, common in terlipressin therapy, develops rapidly after onset of treatment, said Dr. Ginès. "In some patients hyponatremia can be severe, leading to neurological complications which usually resolve upon withdrawl from treatment."
The research team found that 3 of the 21 patients who had a marked reduction in serum sodium developed neurological manifestations. Two of the patients with neurological complications improved after withdrawal of therapy and administration of hypertonic saline. One patient who developed a progressive impairment in neurological status leading to coma, did not improve after terlipressin withdrawal and treatment with hypertonic saline, and later died due to multiorgan failure.
"In patients with high risk of reduction in serum sodium levels (low MELD scores and normal or near-normal baseline serum sodium concentration), serum sodium concentration should be monitored closely during treatment and terlipressin stopped if hyponatremia develops. Hypotonic fluids should probably be avoided to prevent a further reduction in serum sodium concentration," concluded Dr. Ginès. "Physicians should be aware of our findings in order to prevent the possible neurological complications related to acute hyponatremia or rapid recovery of serum sodium levels."
###
Article: "Hyponatremia in Patients Treated with Terlipressin for Severe Gastrointestinal Bleeding due to Portal Hypertension." Elsa Solà, Sabela Lens, Mónica Guevara, Marta Martín-Llahí, Claudia Fagundes, Gustavo Pereira, Marco Pavesi, Javier Fernández, Juan González-Abraldes, Angels Escorsell, Antoni Mas, Jaume Bosch, Vicente Arroyo, and Pere Ginès. Hepatology; Published Online: August 5, 2010 (DOI: 10.1002/hep.23893); Print Issue Date: October 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23893/abstract
These studies are published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities
Source
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Hyponatremia may lead to neurological complications
A new study published in the October issue of the journal Hepatology found that patients with severe portal-hypertensive bleeding who are treated with terlipressin may experience an acute reduction of sodium in their blood. This reduction in serum sodium, known as hyponatremia, can cause adverse reactions such as neurological complications, and is rapidly reversible upon terlipressin withdrawal. Researchers suggest that serum sodium should be closely monitored in these patients and caution that use of solutions with high sodium content to treat this condition may cause a too rapid recovery of sodium leading to adverse events.
Cirrhosis and portal vein thrombosis are two of the primary causes of severe portal hypertension—an increase in blood pressure of the (portal) vein between digestive organs and the liver. This increase in pressure contributes to the development of varices, or large veins, that can weaken over time and lead to gastrointestinal bleeding. Terlipressin is commonly used to treat acute variceal bleeding, however its effect on serum sodium is largely unknown and the focus of the current retrospective study, led by Pere Ginès, MD, from the Hospital Clínic in Barcelona, Spain.
The study included 58 consecutive patients treated with terlipressin for gastrointestinal bleeding due to portal-hypertension. Median age of participants was 54 years, with 77% of the cohort being male and 22% female. Initially patients were treated with somatostatin, but switched to terlipressin due to uncontrolled bleeding or rebleeding in 57% and 43% of cases, respectively.
Researchers noted a significant reduction in serum sodium concentration during terlipressin treatment (from 134.9 at baseline to 130.5 mEq/L at day 5 of treatment). A reduction of sodium in the blood was found in 67% of patients with 31% having a moderate decrease (5-10 mEq/L) and 36% experiencing a marked decrease in serum sodium (greater than 10mEq/L). Only 19 patients were determined to have no change in serum sodium levels.
Further results indicate that patients with a low model for end-stage liver disease (MELD) score and normal or near-normal baseline serum sodium had the highest risk of hyponatremia. "The reduction in serum sodium concentration, common in terlipressin therapy, develops rapidly after onset of treatment, said Dr. Ginès. "In some patients hyponatremia can be severe, leading to neurological complications which usually resolve upon withdrawl from treatment."
The research team found that 3 of the 21 patients who had a marked reduction in serum sodium developed neurological manifestations. Two of the patients with neurological complications improved after withdrawal of therapy and administration of hypertonic saline. One patient who developed a progressive impairment in neurological status leading to coma, did not improve after terlipressin withdrawal and treatment with hypertonic saline, and later died due to multiorgan failure.
"In patients with high risk of reduction in serum sodium levels (low MELD scores and normal or near-normal baseline serum sodium concentration), serum sodium concentration should be monitored closely during treatment and terlipressin stopped if hyponatremia develops. Hypotonic fluids should probably be avoided to prevent a further reduction in serum sodium concentration," concluded Dr. Ginès. "Physicians should be aware of our findings in order to prevent the possible neurological complications related to acute hyponatremia or rapid recovery of serum sodium levels."
###
Article: "Hyponatremia in Patients Treated with Terlipressin for Severe Gastrointestinal Bleeding due to Portal Hypertension." Elsa Solà, Sabela Lens, Mónica Guevara, Marta Martín-Llahí, Claudia Fagundes, Gustavo Pereira, Marco Pavesi, Javier Fernández, Juan González-Abraldes, Angels Escorsell, Antoni Mas, Jaume Bosch, Vicente Arroyo, and Pere Ginès. Hepatology; Published Online: August 5, 2010 (DOI: 10.1002/hep.23893); Print Issue Date: October 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23893/abstract
These studies are published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities
Source
Merck Announces Pivotal Phase III Data for Boceprevir will be Presented at the American Association for the Study of Liver Diseases 2010 Annual Meeting
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Oct 1, 2010 - Merck today announced that final results from two pivotal Phase III studies of boceprevir, its investigational oral hepatitis C protease inhibitor, will be presented in oral plenary sessions at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which is taking place from Oct. 29 through Nov. 2 in Boston. Results for boceprevir in response-guided therapy strategies, which evaluated treatment durations shorter than current standard therapy, will be presented during the meeting. In total, more than 20 oral and poster presentations of clinical studies highlighting Merck medicines and investigational therapies for chronic hepatitis C virus (HCV) infection will be presented.
Boceprevir, in combination with PEGINTRON® (peginterferon alfa-2b) and REBETOL® (ribavirin, USP) (Peg/riba), is being studied for the treatment of patients with HCV genotype 1 infection who were previously treated (treatment-failure; HCV RESPOND-2) and in patients who are new to treatment (treatment-naïve; HCV SPRINT-2).
As previously reported, Merck plans to submit a New Drug Application (NDA) for boceprevir to the U.S. Food and Drug Administration (FDA) on a rolling basis, and expects to complete regulatory submissions in the U.S. and E.U. in 2010.
The AASLD presentations of the boceprevir Phase III data will include sustained virologic response (SVR)1 rates by patient sub-groups, including treatment-naïve patients (African-American/Black and non-African-American/Black), patients who experienced prior relapse, prior non-responders, and patients with a poor response to interferon, defined as having achieved less than a 1 log decrease in viral load (HCV-RNA) after a 4-week Peg/riba lead-in period.
The HCV RESPOND-2 and HCV SPRINT-2 studies each evaluated two treatment strategies with boceprevir to assess the ability to improve SVR and potentially shorten overall treatment duration compared to Peg/riba alone:
• Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which treatment-naïve patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and
• 48 weeks of treatment (4-week Peg/riba lead-in followed by the addition of boceprevir for 44 weeks).
In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of REBETOL (600-1,400 mg/day), followed by the addition of boceprevir (800 mg three times a day).
The abstracts were published today and can be accessed on the AASLD website. For program information, please visit http://www.aasld.org/.
Boceprevir Oral Presentations
HCV SPRINT-2 Final Results (Late-Breaking Oral Session)
Boceprevir (BOC) Combined with Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1: SPRINT-2 Final Results; F. Poordad et al. Abstract LB-4. Monday, Nov. 1, 5:30 – 5:45 PM, Location: Hynes Auditorium
HCV RESPOND-2 Final Results (Viral Hepatitis Plenary Session)
HCV RESPOND-2 Final Results: High Sustained Virologic Response Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin when Re-Treated with Boceprevir Plus PEGINTRON (Peginterferon alfa-2b)/Ribavirin; B. R. Bacon et al. Abstract 216. Tuesday, Nov. 2, 9:15 – 9:30 AM, Location: Hynes Auditorium
Boceprevir Poster Presentations
HCV SPRINT-2 (Late-Breaking Poster Session)
Response-Guided Therapy (RGT) with Boceprevir (BOC) + Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1 Was Similar to a 48-Wk Fixed-Duration Regimen with BOC + P/R in SPRINT-2; J. Bronowicki et al. Abstract LB-15. Monday, Nov. 1, 8:00 AM – 5:00 PM, Location: Hynes Exhibit Hall C
HCV SPRINT-1 Phase II Data
Hemoglobin Decline During Lead-In Phase as an Early Predictor of Anemia After the Addition of Boceprevir: A Retrospective Analysis of HCV SPRINT-1; F. Poordad et al. Abstract 933. Sunday, Oct. 31, 8:00 AM – 5:30 PM, Location: Hynes Exhibit Hall C
Frequencies of Resistance-Associated Amino Acid Variants Following Combination Treatment with Boceprevir Plus PEGINTRON (PegInterferon Alfa-2b)/Ribavirin in Patients With Chronic Hepatitis C (CHC), Genotype 1 (G1); J. M. Vierling et al. Abstract 801. Sunday, Oct. 31, 8:00 AM – 5:30 PM, Location: Hynes Exhibit Hall C
Other Key Merck Data
High Correlation Between Week 4 and Week 12 as the Definition for Null Response to Peginterferon alfa (PEG) plus Ribavirin (R) Therapy: Results from the IDEAL Trial; F. Poordad et al. Abstract 797. Sunday, Oct. 31, 8:00 AM – 5:30 PM, Location: Hynes Exhibit Hall C
Merck's global commitment to advancing hepatitis therapy
Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. Extensive research efforts are underway to develop differentiated oral therapies that bring innovation to viral hepatitis care.
About PEGINTRON
PEGINTRON is indicated for use in combination with REBETOL (ribavirin) for the treatment of chronic hepatitis C in patients three years of age and older with compensated liver disease.
The following points should be considered when initiating therapy with PEGINTRON in combination with REBETOL: (1) These indications are based on achieving undetectable
HCV-RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose. (2) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety and efficacy data are available for treatment of longer than one year.
PEGINTRON is also indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.
The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with REBETOL is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, REBETOL. Combination therapy provides substantially better response rates than monotherapy.
Contraindications
PEGINTRON is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to interferon alpha or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. PEGINTRON/REBETOL combination therapy is additionally contraindicated in women who are pregnant or may become pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL per min.
Pregnancy
REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for six months after completion of therapy. If this drug is used during pregnancy, or if a patient becomes pregnant, the patient should be apprised of the potential hazard to a fetus. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for six months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.
Patients with the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
• Hemolytic anemia with ribavirin
• Neuropsychiatric events
• History of significant or unstable cardiac disease
• Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication
• New or worsening ophthalmologic disorders
• Ischemic and hemorrhagic cerebrovascular events
• Severe decreases in neutrophil or platelet counts
• History of autoimmune disorders
• Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis
• Pulmonary infiltrates or pulmonary function impairment
• Child-Pugh score greater than 6 (Class B and C)
• Increased creatinine levels in patients with renal insufficiency
• Serious, acute hypersensitivity reactions and cutaneous eruptions
• Dental/periodontal disorders reported with combination therapy
• Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides greater than 1000 mg/dL)
• Weight loss and growth inhibition reported with combination therapy in pediatric patients.
Life-threatening or fatal neuropsychiatric events, including suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior, sometimes directed towards others, have occurred in patients with and without a previous psychiatric disorder during PEGINTRON treatment and follow-up.
Adverse events
Serious adverse reactions have occurred in approximately 12 percent of subjects in clinical trials. The most common serious events occurring in subjects treated with PEGINTRON and REBETOL were depression and suicidal ideation, each occurring at a frequency of less than 1 percent. The most common fatal events occurring in subjects treated with PEGINTRON and REBETOL were cardiac arrest, suicidal ideation, and suicide attempt, all occurring in less than 1 percent of subjects.
The incidence of serious adverse reactions was comparable between PEGINTRON monotherapy (about 12 percent) and PEGINTRON/REBETOL combination therapy weight-based (12 percent) or flat-dose (17 percent). In many but not all cases, adverse reactions resolved after dose reduction or discontinuation of therapy. Some patients experienced ongoing or new serious adverse reactions during the 6-month follow-up period. In a study with PEGINTRON/REBETOL (weight-based) combination therapy in adult patients, anemia with weight-based dosing occurred at an increased rate (29 percent vs. 19 percent); however, the majority of these cases were mild and responded to dose reductions. The incidence of serious adverse reactions reported for the weight-based REBETOL group was 12 percent. There were 31 deaths in clinical trials which occurred during treatment or during follow-up. Of the deaths, 19 were patients on either PEGINTRON or PEGINTRON/REBETOL combination therapy and three occurred during the follow-up period but had been on PEGINTRON/REBETOL combination therapy.
Additional serious adverse reactions seen in clinical trials at a frequency of equal to or less than 1 percent included psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, angina, pericardial effusion, retinal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombocytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis, aggravated psoriasis, urticaria, injection site necrosis, vasculitis, and phototoxicity.
Greater than 96 percent of all subjects in clinical trials experienced one or more adverse events. Most common adverse reactions (greater than 40 percent) in adult patients receiving either PEGINTRON or PEGINTRON/REBETOL are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability.
The adverse reaction profile was similar between weight-based and flat-dose PEGINTRON/REBETOL therapies. Weight-based PEGINTRON/REBETOL dosing resulted in increased rates of anemia. Most common adverse reactions with PEGINTRON/REBETOL (weight-based) therapy were psychiatric, which occurred among 68-69 percent of patients and included depression, irritability, and insomnia, each reported by approximately 30-40 percent of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2 percent of all patients during treatment or during follow-up after treatment cessation. Other common reactions included injection site reactions, fatigue/ asthenia, headache, rigors, fever, nausea, myalgia, anxiety/emotional lability/irritability. The severity of some of these systemic symptoms tends to decrease as treatment continues.
Subjects receiving PEGINTRON/REBETOL as re-treatment after failing a previous interferon combination regimen reported adverse reactions similar to previous treatment-naïve patients receiving this regimen.
In general, the adverse reaction profile in the pediatric population was similar to that observed in adults. Most common adverse reactions (greater than 25 percent) in pediatric patients receiving PEGINTRON/REBETOL are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, abdominal pain, and vomiting.
Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit http://www.merck.com/.
Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2009 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (http://www.sec.gov/).
Please see attached Prescribing Information and Medication Guide including Boxed Warning for PEGINTRON and REBETOL. The full Prescribing Information and Medication Guide is also available at http://www.spfiles.com/pipeg-intron.pdf .
PEGINTRON® and REBETOL® are registered trademarks of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA
Source
Boceprevir, in combination with PEGINTRON® (peginterferon alfa-2b) and REBETOL® (ribavirin, USP) (Peg/riba), is being studied for the treatment of patients with HCV genotype 1 infection who were previously treated (treatment-failure; HCV RESPOND-2) and in patients who are new to treatment (treatment-naïve; HCV SPRINT-2).
As previously reported, Merck plans to submit a New Drug Application (NDA) for boceprevir to the U.S. Food and Drug Administration (FDA) on a rolling basis, and expects to complete regulatory submissions in the U.S. and E.U. in 2010.
The AASLD presentations of the boceprevir Phase III data will include sustained virologic response (SVR)1 rates by patient sub-groups, including treatment-naïve patients (African-American/Black and non-African-American/Black), patients who experienced prior relapse, prior non-responders, and patients with a poor response to interferon, defined as having achieved less than a 1 log decrease in viral load (HCV-RNA) after a 4-week Peg/riba lead-in period.
The HCV RESPOND-2 and HCV SPRINT-2 studies each evaluated two treatment strategies with boceprevir to assess the ability to improve SVR and potentially shorten overall treatment duration compared to Peg/riba alone:
• Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which treatment-naïve patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and
• 48 weeks of treatment (4-week Peg/riba lead-in followed by the addition of boceprevir for 44 weeks).
In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of REBETOL (600-1,400 mg/day), followed by the addition of boceprevir (800 mg three times a day).
The abstracts were published today and can be accessed on the AASLD website. For program information, please visit http://www.aasld.org/.
Boceprevir Oral Presentations
HCV SPRINT-2 Final Results (Late-Breaking Oral Session)
Boceprevir (BOC) Combined with Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1: SPRINT-2 Final Results; F. Poordad et al. Abstract LB-4. Monday, Nov. 1, 5:30 – 5:45 PM, Location: Hynes Auditorium
HCV RESPOND-2 Final Results (Viral Hepatitis Plenary Session)
HCV RESPOND-2 Final Results: High Sustained Virologic Response Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin when Re-Treated with Boceprevir Plus PEGINTRON (Peginterferon alfa-2b)/Ribavirin; B. R. Bacon et al. Abstract 216. Tuesday, Nov. 2, 9:15 – 9:30 AM, Location: Hynes Auditorium
Boceprevir Poster Presentations
HCV SPRINT-2 (Late-Breaking Poster Session)
Response-Guided Therapy (RGT) with Boceprevir (BOC) + Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1 Was Similar to a 48-Wk Fixed-Duration Regimen with BOC + P/R in SPRINT-2; J. Bronowicki et al. Abstract LB-15. Monday, Nov. 1, 8:00 AM – 5:00 PM, Location: Hynes Exhibit Hall C
HCV SPRINT-1 Phase II Data
Hemoglobin Decline During Lead-In Phase as an Early Predictor of Anemia After the Addition of Boceprevir: A Retrospective Analysis of HCV SPRINT-1; F. Poordad et al. Abstract 933. Sunday, Oct. 31, 8:00 AM – 5:30 PM, Location: Hynes Exhibit Hall C
Frequencies of Resistance-Associated Amino Acid Variants Following Combination Treatment with Boceprevir Plus PEGINTRON (PegInterferon Alfa-2b)/Ribavirin in Patients With Chronic Hepatitis C (CHC), Genotype 1 (G1); J. M. Vierling et al. Abstract 801. Sunday, Oct. 31, 8:00 AM – 5:30 PM, Location: Hynes Exhibit Hall C
Other Key Merck Data
High Correlation Between Week 4 and Week 12 as the Definition for Null Response to Peginterferon alfa (PEG) plus Ribavirin (R) Therapy: Results from the IDEAL Trial; F. Poordad et al. Abstract 797. Sunday, Oct. 31, 8:00 AM – 5:30 PM, Location: Hynes Exhibit Hall C
Merck's global commitment to advancing hepatitis therapy
Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. Extensive research efforts are underway to develop differentiated oral therapies that bring innovation to viral hepatitis care.
About PEGINTRON
PEGINTRON is indicated for use in combination with REBETOL (ribavirin) for the treatment of chronic hepatitis C in patients three years of age and older with compensated liver disease.
The following points should be considered when initiating therapy with PEGINTRON in combination with REBETOL: (1) These indications are based on achieving undetectable
HCV-RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose. (2) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety and efficacy data are available for treatment of longer than one year.
PEGINTRON is also indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.
The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with REBETOL is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, REBETOL. Combination therapy provides substantially better response rates than monotherapy.
Contraindications
PEGINTRON is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to interferon alpha or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. PEGINTRON/REBETOL combination therapy is additionally contraindicated in women who are pregnant or may become pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL per min.
Pregnancy
REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for six months after completion of therapy. If this drug is used during pregnancy, or if a patient becomes pregnant, the patient should be apprised of the potential hazard to a fetus. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for six months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.
Patients with the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
• Hemolytic anemia with ribavirin
• Neuropsychiatric events
• History of significant or unstable cardiac disease
• Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication
• New or worsening ophthalmologic disorders
• Ischemic and hemorrhagic cerebrovascular events
• Severe decreases in neutrophil or platelet counts
• History of autoimmune disorders
• Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis
• Pulmonary infiltrates or pulmonary function impairment
• Child-Pugh score greater than 6 (Class B and C)
• Increased creatinine levels in patients with renal insufficiency
• Serious, acute hypersensitivity reactions and cutaneous eruptions
• Dental/periodontal disorders reported with combination therapy
• Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides greater than 1000 mg/dL)
• Weight loss and growth inhibition reported with combination therapy in pediatric patients.
Life-threatening or fatal neuropsychiatric events, including suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior, sometimes directed towards others, have occurred in patients with and without a previous psychiatric disorder during PEGINTRON treatment and follow-up.
Adverse events
Serious adverse reactions have occurred in approximately 12 percent of subjects in clinical trials. The most common serious events occurring in subjects treated with PEGINTRON and REBETOL were depression and suicidal ideation, each occurring at a frequency of less than 1 percent. The most common fatal events occurring in subjects treated with PEGINTRON and REBETOL were cardiac arrest, suicidal ideation, and suicide attempt, all occurring in less than 1 percent of subjects.
The incidence of serious adverse reactions was comparable between PEGINTRON monotherapy (about 12 percent) and PEGINTRON/REBETOL combination therapy weight-based (12 percent) or flat-dose (17 percent). In many but not all cases, adverse reactions resolved after dose reduction or discontinuation of therapy. Some patients experienced ongoing or new serious adverse reactions during the 6-month follow-up period. In a study with PEGINTRON/REBETOL (weight-based) combination therapy in adult patients, anemia with weight-based dosing occurred at an increased rate (29 percent vs. 19 percent); however, the majority of these cases were mild and responded to dose reductions. The incidence of serious adverse reactions reported for the weight-based REBETOL group was 12 percent. There were 31 deaths in clinical trials which occurred during treatment or during follow-up. Of the deaths, 19 were patients on either PEGINTRON or PEGINTRON/REBETOL combination therapy and three occurred during the follow-up period but had been on PEGINTRON/REBETOL combination therapy.
Additional serious adverse reactions seen in clinical trials at a frequency of equal to or less than 1 percent included psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, angina, pericardial effusion, retinal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombocytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis, aggravated psoriasis, urticaria, injection site necrosis, vasculitis, and phototoxicity.
Greater than 96 percent of all subjects in clinical trials experienced one or more adverse events. Most common adverse reactions (greater than 40 percent) in adult patients receiving either PEGINTRON or PEGINTRON/REBETOL are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability.
The adverse reaction profile was similar between weight-based and flat-dose PEGINTRON/REBETOL therapies. Weight-based PEGINTRON/REBETOL dosing resulted in increased rates of anemia. Most common adverse reactions with PEGINTRON/REBETOL (weight-based) therapy were psychiatric, which occurred among 68-69 percent of patients and included depression, irritability, and insomnia, each reported by approximately 30-40 percent of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2 percent of all patients during treatment or during follow-up after treatment cessation. Other common reactions included injection site reactions, fatigue/ asthenia, headache, rigors, fever, nausea, myalgia, anxiety/emotional lability/irritability. The severity of some of these systemic symptoms tends to decrease as treatment continues.
Subjects receiving PEGINTRON/REBETOL as re-treatment after failing a previous interferon combination regimen reported adverse reactions similar to previous treatment-naïve patients receiving this regimen.
In general, the adverse reaction profile in the pediatric population was similar to that observed in adults. Most common adverse reactions (greater than 25 percent) in pediatric patients receiving PEGINTRON/REBETOL are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, abdominal pain, and vomiting.
Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit http://www.merck.com/.
Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2009 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (http://www.sec.gov/).
Please see attached Prescribing Information and Medication Guide including Boxed Warning for PEGINTRON and REBETOL. The full Prescribing Information and Medication Guide is also available at http://www.spfiles.com/pipeg-intron.pdf .
PEGINTRON® and REBETOL® are registered trademarks of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA
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