New mouse model paves the way for the development of hep C vaccines
Posted: 2011-01-28 20:17
Researchers have created a new animal model for hepatitis C infection that could facilitate the development of new treatments for the disease.
Currently, the main therapeutic strategy for treating hepatitis C virus (HCV) infections involves the administration of a cytokine to modulate the immune system. However, this approach is difficult for patients to tolerate, often leading to excessive fatigue, nausea and anemia, among other ailments. New antiviral medications are on the horizon, but even these are not expected to help around 30% of people infected.
One critical roadblock to developing better treatment options is a lack of suitable mouse models. At present, researchers searching for new HCV therapies rely on chimpanzees, which are susceptible to HCV infection. This sensitivity could be because these primates also have cell surface proteins similar to those found in humans that are thought to facilitate viral infection.
Now, Charles Rice, a virologist at Rockefeller University in New York, and his colleagues have engineered mice susceptible to HCV infection by introducing two human protein receptors that facilitate virus entry into the liver. In a series of unpublished experiments presented on Monday at the New York Academy of Sciences, the Rockefeller team showed that vaccinated mice had lower rates of HCV infection compared to non-vaccinated controls. According to study lead author Alexander Ploss, another Rockefeller virologist, these mice can now be used to develop HCV vaccines and to search for new drugs to prevent re-infection in people who receive liver transplants as a result of HCV-triggered disease.
This study follows the introduction of another humanized mouse model — published online earlier this month from a team that included Rice and Ploss— that recapitulates liver disease characteristic of people suffering from chronic HCV infection.
For more on the quest to develop mouse models of HCV infection, check out our 'community corner' discussion on the topic.
Image: GrahamColm, Wikimedia
Two Supplements May Strengthen Hep C Antiviral Treatment
Although many have heard of the supplements SAMe and betaine, their potential benefits to those on Hepatitis C treatment are not yet widely known.
by Nicole Cutler, L.Ac.
For the estimated four to five million American adults with chronic Hepatitis C, attempts to conquer the virus can be challenging. This illness' current antiviral treatment, pegylated interferon and ribavirin, is only about 50 percent effective in those infected with the most common strain of Hepatitis C in North America. Thus, investigators are constantly seeking ways to boost the success of these medicines. Building on previous knowledge about S-adenosyl-L-methionine (SAMe) and betaine, researchers from Switzerland have found two potential, seemingly non-toxic contenders for supporting Hepatitis C antiviral therapy.
Those unable to rid themselves of all Hepatitis C genetic material are burdened by the prospect of chronic liver disease progressing, a process that could eventually lead to liver cirrhosis, liver failure or liver cancer. Until better treatment options actualize, people in this situation typically seek experimental, innovative or alternative solutions to preserve their health. There are several ways health professionals attempt to help those who are not responsive to Hepatitis C treatment, such as:
· Developing more potent drugs that have a higher success rate for eliminating the Hepatitis C virus.· Guiding infected individuals toward herbal supplements and lifestyle choices that strengthen liver cells to better protect them from the virus.
· Adding certain substances to pegylated interferon and ribavirin that enhance their success rate.
While true progress against Hepatitis C is likely to involve all three of these approaches, the research from Switzerland focuses on the latter - enhancing pegylated interferon and ribavirin.
About the ResearchA research team from Basel, Switzerland identified viral interference with interferon signal transduction as an important factor explaining the mediocre success of Hepatitis C treatment. Because prior experiments with SAMe and betaine have shown these substances can increase interferon signal strength, the researchers investigated if adding SAMe and betaine to Hepatitis C treatment would increase its efficacy.
As published in a November 2010 edition of the journal PLoS ONE, the researchers tested this concept in Hepatitis C patients who had previously failed antiviral therapy. For their trial, the participants were treated with pegylated interferon, ribavirin, SAMe and betaine.
Compared with their first attempt at antiviral treatment consisting of just pegylated interferon and ribavirin, study participants fared better in their second therapy attempt that included SAMe and betaine. This improvement was measured by a higher percentage of participants achieving an early virological response - undetectable viral load 12 weeks after starting treatment.
The researchers concluded that adding SAMe and betaine to pegylated interferon/ribavirin therapy improves early virological response in chronic Hepatitis C. Based on the fact that the inability to detect Hepatitis C genetic material after 12 weeks increases the chances of treatment success, some clinicians are recognizing the potential therapeutic application of SAMe and betaine.
About SAMe and BetaineBoth considered to be natural substances, SAMe and betaine are nutrients known as methyl donors. Other methyl donors include folic acid and vitamins B6 and B12. These substances carry and donate methyl molecules in the body to help make chemical processes work. Donation of methyl molecules is involved in proper liver function and cellular reproduction.
SAMe is a synthetic form of a compound formed naturally in the body from the essential amino acid methionine and adenosine triphosphate (ATP), the energy-producing compound found in all cells in the body. Besides studies supporting SAMe's use for relieving the pain of osteoarthritis and helping depression, trials examining this supplement also suggest that it may help to normalize liver enzyme levels.
Betaine can be obtained in the diet from beets, broccoli, grains, shellfish and spinach. Besides studies supporting betaine's use for heart disease and homocystinuria, there is also evidence that betaine may help protect against fatty deposits in the liver.
The research from Switzerland on these two supplements is encouraging, but there is far more evidence needed to accept SAMe and betaine as worthy and valuable additions to Hepatitis C treatment medications. Although not yet open to participant recruitment, one related follow-up study is being conducted at the University of Nebraska. This pilot study will examine betaine's addition to Hepatitis C antiviral therapy in those who have either not responded to previous treatment or who have relapsed. More information on this study can be found at http://www.clinicaltrials.gov/
As the quest to help people conquer the Hepatitis C virus intensifies, expect to see more research into substances that aid pegylated interferon/ribavirin efficacy. SAMe and betaine are two such contenders, and the Hepatitis C community will be keeping a close eye on future developments involving these nutrients..
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Study finds little decline in hepatitis C infections among injection drug users
Research suggests improvements in prevention and treatment efforts needed
[EMBARGOED FOR JAN. 31, 2011]
A recent 20-year study of injection drug users (IDUs) in Baltimore found a significant decline in new cases of HIV infection but only a slight decline in new cases of hepatitis C virus (HCV) infection. The findings suggest that efforts to curb blood-borne transmission of these viral infections have had success but must be expanded against the highly transmissible HCV. Researchers from Johns Hopkins School of Public Health and other centers, led by Shruti H. Mehta, PhD, MPH, report the findings in the March 1 issue of The Journal of Infectious Diseases, now available online. (Please see below for a link to the embargoed study online.)
Previous data had suggested that HIV incidence among IDUs has declined. This trend is often attributed in part to harm reduction measures, including needle exchange programs and substance abuse treatment. However, these measures have not been as successful in lowering the rates of HCV incidence and prevalence. For example, HCV infection is nearly 10 times more transmissible by sharing needles than is HIV infection. Sharing a needle even once can be enough to transmit HCV.
The investigators found that new cases of HIV infection declined dramatically across four different time periods during the past 20 years, from 5.5 per 100 person-years (PY) in 1988-'89, to two per 100 PY in 1994-'95, and to zero cases in 1998 and 2005-'08. While researchers also observed reductions in new cases of HCV infection, these were not nearly as substantial: from 22 per 100 PY in 1988-'89, to 17.2 per 100 PY in 1994-'95, to 17.9 in 1998, and to 7.8 per 100 PY in 2005-'08. Overall, cases appeared to decline only among younger IDUs, who had started injecting drugs recently.
According to researchers, these data suggest that "current prevention efforts delay but do not prevent HCV at the population level and will need to be further intensified to reduce risk of HCV infection to the level of HIV." Efforts on both the prevention and the treatment fronts to reduce the reservoir of HCV-infected IDUs will have to be expanded, the investigators concluded.
In an accompanying editorial, Jason Grebeley, PhD, and Gregory J. Dore, MB BS, MPH, PhD, of the University of New South Wales in Australia, agreed that higher prevalence of HCV infection and greater transmission risk following an injection with a contaminated syringe as compared to HIV have hampered harm reduction measures. They also noted that current implementation of harm reduction measures in most settings is inadequate. Rates of equipment sharing remain high, and access to opioid substitution therapy and other drug treatment programs is limited.
The editorial authors also pointed out the impact that an HCV vaccine could have on new cases of HCV infection. Though a highly efficacious vaccine has not yet been discovered, efforts to do so are crucial. They suggested that even though the window for preventing HCV may be small, improvements in HCV prevention are feasible.
###
Fast Facts:
1) Among the community of injection drug users (IDUs) in Baltimore, HIV incidence declined dramatically over 20 years, while new cases of hepatitis C virus (HCV) infection declined only slightly.
2) HIV incidence decreased from 5.5 per 100 person-years (PY) in 1988-'89, to two per 100 PY in 1994-'95, and to zero in 1998 and 2005-'08. The declines in HCV infection were not nearly as substantial: from 22 per 100 PY in 1988-'89, to 17.2 per 100 PY in 1994-'95, to 17.9 in 1998, and to 7.8 per 100 PY in 2005-'08.
3) Prevention and treatment efforts must be expanded to reduce the number of HCV infections among IDUs.
NOTE: The study and the accompanying editorial are available online. They are embargoed until 12:01 a.m. EST on Monday, Jan. 31, 2011:
"Changes in Blood-borne Infection Risk Among Injection Drug Users" http://www.oxfordjournals.org/our_journals/jid/jiq112.pdf
"Prevention of Hepatitis C Virus in Injecting Drug Users: A Narrow Window of Opportunity" http://www.oxfordjournals.org/our_journals/jid/jiq111.pdf
Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Arlington, Va., IDSA is a professional society representing more than 9,000 physicians and scientists who specialize in infectious diseases. For more information, visit
http://www.idsociety.org/.
Elastography for Hepatic Fibrosis Severity in Chronic Hepatitis B or CMaria-Vasiliki
Papageorgioua, George V. Papatheodoridisa, Spilios Manolakopoulosa, Emmanuel Tsochatzisa, Hariklia Kranidiotia, Georgia Kafirib, Athanasios I. Archimandritisaa2nd Department of Internal Medicine, Medical School of Athens University, andbDepartment of Pathology, ‘Hippokration’ General Hospital of Athens, Athens, Greece
Abstract
Aims: To assess the value of transient elastography for predicting significant fibrosis or cirrhosis in chronic hepatitis B or C (CHB or CHC) patients.
Methods: 75 patients (CHB: 45, CHC: 32) were included. All underwent elastography and liver biopsy concurrently. Biopsies were evaluated using Ishak’s classification. Fibrosis was mild, moderate or severe/cirrhosis when scores were 0–1 (n = 30), 2–3 (n = 20), 4–6 (n = 25), respectively.
Results: Median liver stiffness values were higher in patients with severe fibrosis or cirrhosis than in those with moderate or mild fibrosis (14.8 vs. 6.4 vs. 5.3 kPa, p < 0.001). The diagnostic accuracy of elastography for severe fibrosis and cirrhosis was excellent [area under the receiver operating characteristic (AUROC) curve 0.938 vs. 0.948], but it was not optimal for mild fibrosis (AUROC 0.78). Values of 7.5, 9.0 and 12 kPa had a sensitivity and specificity for severe fibrosis/cirrhosis of 96, 84 and 60%, and 76, 90 and 94%, respectively.
The median stiffness value in cirrhotic patients (score 5–6) was 16.6 kPa (7.7–48). No differences in accuracy of elastography between CHB or CHC patients were found. Cutoff was 12.5 kPa for cirrhosis; 10/75 patients (13%) were misclassified. Conclusion: Transient elastography has an excellent diagnostic accuracy for severe fibrosis and cirrhosis in CHB and CHC, but the cutoffs need further evaluation. Copyright © 2011 S. Karger AG, Basel
Also See; Liver Biopsy and Noninvasive Tests For Fibrosis
Trapero-Marugán M, Mendoza J, Chaparro M, González-Moreno L, Moreno-Monteagudo JA, Borque MJ, Moreno-Otero R
Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin.
[JOURNAL ARTICLE]World J Gastroenterol 2011 Jan 28; 17(4):493-498.
AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy.
METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually.
RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors.
CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.
More from this journal
World journal of gastroenterology : WJG [World J Gastroenterol]
Aoki YH, Ohkoshi S, Yamagiwa S, Yano M, Takahashi H, Waguri N, Igarashi K, Sugitani SI, Takahashi T, Ishikawa T, Kamimura T, Wakabayashi H, Watanabe T, Matsuda Y, Nomoto M, Aoyagi Y
Characterization of elevated alanine aminotransferase levels during pegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C.
Abnormal ALT values during treatment were observed in 23.0% of patients
[JOURNAL ARTICLE]Hepatol Res 2011 Feb; 41(2):118-125.
Aim: Elevation of alanine aminotransferase (ALT) levels during pegylated-interferon (peg-IFN) plus ribavirin therapy in patients with chronic hepatitis C [CHC] is a problem that cannot be disregarded. The aim of this study is to assess the frequency and to characterize clinical parameters of this phenomenon.
Methods: Two hundred and thirty-five (235) CHC patients with genotype 1b receiving peg-IFN α-2b plus ribavirin therapy were analyzed. Clinical parameters that may be associated with abnormal ALT values during treatment and therapy outcomes were evaluated statistically. One hundred and sixteen (116) patients treated with peg-IFN α-2a plus ribavirin were also included for partial analysis.
Results: Abnormal ALT values during treatment were observed in 23.0% of patients. It was observed in 14.5% of those with sustained virological response (SVR) and 17.8% of those with relapse, in whom viral clearance was observed during therapy. Multivariate logistic regression analysis revealed that pretreatment ALT values, therapy outcome, and body mass index (BMI) were significant factors related to abnormal ALT values during treatment. Abnormal ALT values during treatment became normal in SVR patients at 6 months after the completion of treatment, but not in NR (non-response) patients.
Mean ALT values were significantly higher at some time points during treatment in patients treated with α-2a when compared to those treated with α-2b.
Conclusion: Abnormal ALT values during peg-IFN plus ribavirin treatment are observed relatively frequently, even in patients without detectable HCV RNA. Direct or indirect involvement of drugs is considered as one possible cause.
More from this journal
Hepatology research : the official journal of the Japan Society of Hepatology [Hepatol Res]
HIV
HIV Causes Rapid Aging In Key Infection-Fighting Cells, Research Suggests
29 January 2011In the early years of the AIDS epidemic, being infected with the virus that causes the disease was considered a virtual death sentence. But with the development of antiretroviral therapy, many with HIV are now living much longer...
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HIV/AIDS Awareness
(NAPSI)—Black Americans continue to be disproportionately affected by HIV/AIDS, according to the U.S. Centers for Disease Control and Prevention (CDC). In fact, in their lifetime, one in 16 black men and one in 32 black women will be infected with HIV. This National Black HIV/AIDS Awareness Day, as the nation approaches the 30th year of the HIV epidemic, we are faced with the stark reminder that HIV prevalence in blacks is almost eight times that of whites.
“These alarming statistics remind us that all communities—particularly communities of color—need new biomedical tools, including a vaccine to prevent further spread of the virus,” says S. Wakefield, director of external relations at the HIV Vaccine Trials Network. “It is also essential that we identify culturally appropriate approaches to engage all individuals in using proven HIV prevention tools and in the search for new ones. This is critical as we continue to search for ways to overcome the health inequities currently impacting black communities. A commitment to engaging those most affected is the only way we can truly make a significant difference in HIV research.”
CDC data show that more people are living with HIV in the United States than ever before, and while there is no cure for HIV/AIDS, advances in treatment can help the majority of those who are infected live longer, fuller lives. But treatment is costly and remains out of reach for many people in the United States. The best hope in the fight against AIDS is to find a preventive HIV vaccine, and recent studies are bringing us closer than ever before to that discovery.
Scientists are gaining new insights into how vaccines, microbicides and other HIV prevention strategies may work. These studies would not have been possible without the support and participation of volunteers of all races and ethnicities, including African Americans. However, more volunteers are still needed to find a safe and effective vaccine that prevents HIV infection for everyone.
Because community involvement and education are essential to the success of HIV vaccine research, initiatives are under way across the country to help people understand why HIV vaccine research is relevant to them and how they can support these efforts.
About HIV Vaccine Research
• HIV/AIDS is the third-leading cause of death for black men and women aged 35 to 44.
• Historically, vaccines have been the most powerful weapon against infectious diseases such as polio, measles and hepatitis B.
• The HIV vaccine candidates being studied in humans do not contain the actual HIV virus, so they cannot cause anyone to become infected with HIV.
To learn more about HIV vaccine research in the United States,
visit http://www.bethegenera/ tion.nih.gov.
Access To Medicines: Johnson & Johnson/Tibotec AIDS Drug Licenses Exclude Too Many Patients
31 January 2011Licenses just agreed between three generic manufacturers and pharmaceutical company Tibotec, owned by Johnson & Johnson, will keep a promising new AIDS medicine out of the hands of many patients across the developing world...
[read article]
Tibotec Signs Multiple Agreements With Generic Manufacturers To Provide Access To New HIV Treatment
30 January 2011Tibotec Pharmaceuticals announced that it has granted multiple non-exclusive licenses to generic manufacturers including Hetero Drugs Limited, Matrix Laboratories Limited (a Mylan company) of India and Aspen Pharmacare of...
[read article]
HIV Causes Rapid Aging In Key Infection-Fighting Cells, Research Suggests
29 January 2011In the early years of the AIDS epidemic, being infected with the virus that causes the disease was considered a virtual death sentence. But with the development of antiretroviral therapy, many with HIV are now living much longer...
[read article]
Liver Cancer
Microsulis Medical Limited Receives Health Canada Approval of the Accu2i Percutaneous Microwave Tissue Ablation Device
Microsulis Medical Limited, the leading company in microwave technology for medical devices, today announced that it has received approval from Health Canada for the Acculis Accu2i percutaneous microwave tissue ablation (pMTA) system for the coagulation of soft tissue during surgical procedures. The system has already been in use in Europe and the United States treating liver and lung tumors via a small 1.8 mm needle puncture of the skin. This groundbreaking treatment allows physicians to apply precise microwave energy to remove unwanted tissue masses whilst avoiding the risks associated with longer, more invasive surgical interventions.
The Accu2i pMTA system is now cleared in Europe, the United States, and Canada and it delivers 2.45 GHz of power to ablate tumors of the liver and lung. The design consists of a 1.8 mm diameter closed water cooled needle that allows physicians to ablate up to five centimeter lesions in minutes. The system is unique in that it uses specialized patented microwave antenna designs that achieve the very high levels of microwave energy deposition into tissue needed to quickly and effectively coagulate unwanted areas of soft tissue.
“The Health Canada approval builds on the momentum we experienced in 2010 with the CE mark and FDA clearance of the Accu2i pMTA system,” said Stuart McIntyre, CEO of Microsulis Medical Limited. “We are pleased to have received this approval from Health Canada for the pMTA system so physicians can begin to offer this game changing treatment options for patients in Canada with liver or lung tumors.”
For more information about the Acculis Accu2i pMTA system, visit http://www.acculis.com/.
Read more: http://www.financialpost.com/
Provectus Pharmaceuticals, Inc. (OTC-BB: PVCT),
a development-stage oncology and dermatology biopharmaceutical company, has completed patient accrual and treatment of all subjects in its Phase 1 clinical trial of PV-10 for liver cancer.
Dr. Craig Dees, PhD, CEO of Provectus said, “Preliminary results for PV-10 as a treatment for liver cancer are very encouraging as they show the treatment was generally well-tolerated, with substantial evidence of efficacy. We believe PV-10’s ability to selectively target and destroy cancer cells without harming surrounding healthy tissue make it a potentially attractive therapy for cancers of the liver, which can be very serious and difficult to treat if they cannot be fully removed through surgery.”The Phase 1 study of PV-10 for liver cancer involved six subjects with cancer metastatic to the liver or with recurrent liver cancer. The primary objective of the open-label study is to determine the safety and tolerability of a single intralesional injection of PV-10 in patients with cancer of the liver.
Additional objectives include assessing the distribution and retention of PV-10 in the injected lesion, tumor response and viability, and plasma pharmacokinetics of PV-10 following intralesional injection. In each of two dose cohorts there were three subjects. Dose escalation occurred following assessment of safety and tolerability in the first cohort. Dr. Paul Goldfarb, M.D., of Sharp Memorial Hospital in San Diego, is the Principal Investigator for the study.Malignant lesions in the liver arising from primary hepatocellular carcinoma (HCC) or metastases from a wide range of cancers represent an ongoing treatment challenge for oncologists. HCC is one of the most common malignancies worldwide, and its incidence is rapidly increasing in the United States.
The liver is a common site of metastases from solid tumors, particularly those arising in the gastrointestinal tract. Other tumors, such as lung and breast cancer and melanoma, also readily spread to the liver.
New book urges use of antidepressants to treat, prevent cancer
"Killing Cancer" by Dr. Julian Lieb reviews medical research in an effort to demonstrate that antidepressants have anticancer properties
BURLINGTON, Vt. (MMD Newswire) January 31, 2011 -- In "Killing Cancer", Dr. Julian Lieb cites clinical and laboratory studies with hopes of illuminating the anticancer properties of antidepressants.
"Antidepressants kill cancer cells, inhibit their proliferation, protect nonmalignant cells from damage by ionizing radiation and chemotherapy toxicity, restore sensitivity to multidrug resistant cells and target the mitochondria of cancer cells while sparing those of healthy ones," explains Lieb. Lieb believes antidepressants are capable of arresting cancer even in advanced stages and occasionally eradicating it.
"Killing Cancer" presents a list of 60 published reports which reveal that antidepressants are potentially effective for the treatment of malignancies, including those that often resist treatment, such as cancer of the lungs, kidneys and liver; malignant gliomas of the brain; and inflammatory breast cancer. Lieb points out that the use of relatively inexpensive antidepressants could make cancer treatment available to low-income and disadvantaged segments of the population as well.
"Great advances seldom emanate from ivory tower medical schools or government health agencies," Lieb says. "They are often made by outsiders that draw together observations whose relationship to each other had never been suspected."
"Killing Cancer" is available for sale online at Amazon.com and other channels.
About the AuthorDr. Julian Lieb is a former Yale School of Medicine psychiatry professor and director of the Dana Psychiatric Clinic at Yale-New Haven Hospital. The author or co-author of 48 published articles and 11 books, Lieb is a recognized expert on the immunostimulating and antimicrobial properties of lithium and antidepressants and the anticancer properties of antidepressants. He has worked closely with pioneers in prostaglandin research, and has been invited to address international cancer conferences in Greece, Germany and India.
MEDIA CONTACT:Dr. Julian Lieb E-mail: julian@doctorlieb.com Phone: (802) 658-4909
Source
Transplants
Digital image analysis of liver collagen predicts clinical outcome of recurrent hepatitis C Virus 1 year after liver transplantation†
Pinelopi Manousou1,Amar P. Dhillon2,†, Graziela Isgro1, Vincenza Calvaruso1,3,
T.V. Luong2, Emmanuel Tsochatzis1, E. Xirouchakis1, G. Kalambokis1, Timothy J. Cross1,
N. Rolando1,James O'Beirne1, David Patch1, . Thornburn1, drew K. Burroughs1,*,‡
Article first published online: 28 JAN 2011
DOI: 10.1002/lt.22209
Abstract
Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation.
Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow-up of 76 months were evaluated.
At 1 year, median CPA was 4.6% (0.2%-36%) and Ishak stage was 0-2 in 101 patients, 3-4 in 23 patients, and 5-6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15-138).
Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037-1.317).
Area under the ROC curve was 0.97 (95%CI, 0.94-0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained.
When both cutoffs of CPA more then 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1-year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG. Liver Transpl 17:178–188, 2011. © 2011 AASLD.
Source
HIV, Hepatocellular Carcinoma And Liver Transplantation
Main Category: HIV / AIDSAlso
Included In: Liver Disease / Hepatitis;
Transplants / Organ Donations; Cancer / Oncology
French researchers determined that infection with human immunodeficiency virus (HIV) impaired results of transplant surgery for liver cancer, with more HIV infected patients dropping off the transplantation wait list.
The team found that overall survival and recurrence-free survival was not impacted following liver transplantation in patients with controlled HIV disease. Details of this single center study - the largest to date - are published in the February issue of Hepatology, a peer-reviewed journal of the American Association for the Study of Liver Diseases (AASLD). More than 40 million individuals are infected with HIV; of these roughly two to four million and four to five million are also carriers of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. With the introduction of highly active antiretroviral therapy (HAART) in 1996 the survival of patients with HIV infection has improved dramatically and now end-stage liver disease has become the principal cause of death among HIV- positive patients co-infected HBV or HCV. Prior studies have shown that 25% of liver-related mortality in HIV-positive patients is attributable to hepatocellular carcinoma (HCC), or liver cancer.
"Liver transplantation is the optimum treatment for HCC and can also be considered for controlled HIV-positive patients with liver cancer," said René Adam, MD, PhD, from Hospital Paul Brousse in France and lead author of the current study. "Our study showed that HIV infection impaired the results of liver transplantation on an intent-to-treat basis but exerted no significant impact on overall survival and recurrence-free survival following transplantation." The research team analyzed data from 21 HIV-infected and 65 HIV-negative patients with HCC who were listed for liver transplantation between 2003 and 2008. All HIV-positive patients were treated with HAART and had not experience any AIDS event or opportunistic infections prior to being place on the wait list. Researchers observed a trend towards a higher drop-out among HIV-positive wait listed patients (23%) compared to patients without HIV (10%).
Patients with HIV who dropped out had significantly higher alpha-fetoprotein (AFP) levels at the time of listing than those who received a transplant - 98 μg/L versus 12 μg/L, respectively. A similar difference in AFP levels was not found in HIV-negative patients -18 μg/L in those who dropped out versus 13 μg/L for those who underwent liver transplantation. Only one HIV-positive patient who did not have increased AFP levels while on the wait list dropped out due to progression from controlled HIV to AIDS. Medical evidence indicates a major predictive factor for HCC recurrence post-transplantation is an increase in patient's AFP level of more than 15 μg/L per month while on the waiting list. "Our study confirmed the importance of this preoperative factor (AFP levels), as all HIV-positive patients who dropped out displayed a rise in AFP levels," Dr. Adam concluded.
"There is clearly a critical need for more effective neoadjuvant therapy in HIV-positive patients with HCC, however there are no objective arguments to contraindicate liver transplantation in this group if strict criteria are used for selection and patients are closely monitored until surgery." Article: "Liver transplantation for Hepatocellular Carcinoma: The Impact of HIV Infection." Eric Vibert, Jean-Charles Duclos-Vallée, Maria-Rosa Guigna, Emir Hoti, Chady Salloum, Catherine Guettier, Denis Castaing, Didier Samuel, René Adam. Hepatology; Published Online: January 3, 2010 (DOI: 10.1002/hep.24062); Print Issue Date:
February 2011. Source: Dawn PetersWiley-Blackwel
Healthy You
Winning The Battle With Fibromyalgia
After 27 years of service, decorated U.S. Army Brigadier General Becky Halstead (Retired), the first female West Point graduate in U.S. history to command at the strategic level in Iraq and Afghanistan, decided to retire after being diagnosed with fibromyalgia - a medically unexplained syndrome affecting the muscles and connective tissues. Currently, the disease affects as many as 12 million Americans and has been reported two times as prevalent in deployed veterans (Annals of Internal Medicine, June 7, 2005, Vol. 142 No.11).
"Agonizing pain, debilitating fatigue, joint stiffness and sleep deprivation-you name it and I felt it," says Halstead. "There I was in Iraq, responsible for over 20,000 military men and women, and I privately struggled to physically keep myself going."
Initially, Halstead was prescribed every drug imaginable, though the pills only masked the pain and resulted in a spiral of reactions affecting her psychological and physical health. It wasn't until a close friend suggested chiropractic that she was able to find relief and return to a normal, nearly pain-free life. She discovered that the comprehensive treatment of chiropractic care improves joint motion, reducing and in some cases eliminating the pains and symptoms associated with fibromyalgia - such as fatigue, sleep deprivation and depression.
"Chiropractic treatment helped improve my whole outlook on dealing with this chronic ailment," she says. "The spinal adjustments along with the postural and nutritional advice I received helped to treat the fibromyalgia and allowed me to have many days with minimal pain -- and most days without any medications. The care of a doctor of chiropractic was life changing for me."
Today, Halstead is a spokesperson for the Foundation for Chiropractic Progress, a not-for-profit organization dedicated to raising public awareness of the benefits associated with chiropractic care. Brig. General Halstead has made it her personal mission to educate others suffering with fibromyalgia - and to consider consulting with doctor of chiropractic, as she did.
"Chiropractic care is a viable option that can positively impact overall wellness and health," she concludes.
Source: Foundation for Chiropractic Progress http://www.medicalnewstoday.com/
Daily Electronic Assessments Help Fibromyalgia Patients Cope
28 January 2011Hand-held PDA devices for recording daily symptoms are helping fibromyalgia patients and their doctors better understand links between pain, emotional distress and fatigue in this complex pain disorder, according to research...
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UNMC Study Links Chronic Hives, Vitamin D Deficiency
A University of Nebraska Medical Center research study has determined that patients with chronic hives may benefit by supplementing their diet with vitamin D. The study also suggests that health providers consider screening their patients with chronic hives for vitamin D deficiencies. Jill Poole, M.D., assistant professor in the UNMC Department of Internal Medicine, was the principal investigator on the study recently published in the Journal of Allergy and Clinical Immunology. "Chronic hives can be quite frustrating for patients as treatment options are limited.
They can make you feel miserable," said Dr. Poole, an allergist. "Vitamin D may be one part of the answer to this troublesome disease. Given the health benefits, there's no harm in taking vitamin D if you don't overdo it. It's easy, inexpensive and can be taken daily at 1,000 to 2,000 international units (IUs)." Chronic hives typically occur at least three times a week and last longer than six weeks. They appear as red, itchy welts and can lead to difficulty in breathing. In the small study, researchers compared 25 patients with chronic hives to 25 patients with nasal allergies. Researchers found patients with hives had significantly reduced levels of vitamin D, with nearly half of them considered to be vitamin D deficient. Dr. Poole said more studies are warranted to determine if vitamin D supplementation could improve health outcomes in patients with mild to severe hives.
Vitamin D deficiencies also are associated with osteoporosis, autoimmune diseases, cancer, cardiovascular disease, hypertension and even death. In a type of eczema, vitamin D has been found to help relieve symptoms. Through world-class research and patient care, UNMC generates breakthroughs that make life better for people throughout Nebraska and beyond. Its education programs train more health professionals than any other institution in the state. Source: University of Nebraska Medical Center
Lightly Steamed Broccoli Has Powerful Anticancer Enzyme Myrosinase
30 January 2011Broccoli can significantly reduce your risk of developing cancers if you don't destroy the enzyme myrosinase - you can only do this effectively by steaming the vegetable lightly...
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In Memory
Breaking News: Charles Nolan dies aged 53
Sadly, American designer, Charles Nolan, passed away on Sunday in his Manhatten apartment, at the tender age of 53.Vogue UK reports the designer’s life was unfortunately taken by liver cancer- leaving his partner, Andrew Tobias and large family behind.
Throughout his extensive career, Nolan designed for labels such as Anne Klein, Ellen Tracy, Blassport, Tahari, Christian Dior and Bill Haire- bringing a touch of preppy sportswear chic to the American fashion scene.
He later established his own eponymous label in 2003- followed shortly by an exclusive collection for Saks Fifth Avenue in 2004- WWD reports he was one of the first overseas designer’s to include a wide varying range in his prices, as well as introducing gifts, home goods and furniture to his list of talents.
His multitude of artistic skills will surely be missed in, and out of, the fashion world- our condolences go out to his friends and family.
New On The Blog;
Treating Hepatitis C In 2011; The Bible Of Links
Its time to roll out the "Bible of Links" for all those people who may be getting ready to contemplate treatment. If all goes well the two new HCV drugs, telaprevir and boceprevir should be ready for market by the end of this year. This blog has made an attempt to breakdown the data in order for you to ready yourself for that first treatment consultation.
New At HCV Advocate
http://www.hcvadvocate.org/ and http://www.hbvadvocate.org/:
Hear Gene’s Story about his struggles with hepatitis C and his need for a liver transplant.
Check out our drug pipeline which has been updated to include the latest information.
Many of our fact sheets have also been revised or updated.
Last but not least—find out the results from the survey about the top news stories of 2010 for HBV and HCV.
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