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Does antiviral therapy prevent hepatocellular carcinoma?
Kwon H, Lok AS; Antiviral Therapy 16 (6), 787-95 (2011)
Source: Antiviral Ther
Chronic infection with HBV or HCV can lead to the development of hepatocellular carcinoma (HCC). The major risk factors for HBV-related HCC are persistent presence of hepatitis B e antigen (HBeAg) and/or high serum HBV DNA levels, and cirrhosis.
The major risk factor for HCV-related HCC is cirrhosis. One randomized double blind controlled trial of lamivudine in patients with HBeAg and/or high serum HBV DNA levels showed that antiviral therapy prevented disease progression and reduced the incidence of HCC.
A beneficial effect of antiviral therapy on the risk of HCC has also been shown in cohort studies and meta-analyses, particularly among responders. Several randomized controlled trials of interferon in patients with HCV-related cirrhosis showed that treated patients had a lower incidence of HCC.
A greater effect was observed in patients who achieved sustained virological response, while the benefit in non-responders is unclear. Antiviral therapies for hepatitis B and hepatitis C can prevent but not completely eliminate HCC.
Improvement in identification of infected persons, accessibility of care and affordability of treatment is needed for antiviral therapy to have a major impact on the global incidence of HCC.
Ribavirin priming improves the virological response to antiviral treatment in transplanted patients with recurrent hepatitis C: a pilot study
Merli M, Giannelli V, Gentili F, Giusto M, Simmaco M, Lionetto L, Corradini SG, Biliotti E, Attili AF, Rossi M, Taliani G; Antiviral Therapy 16 (6), 879-85 (2011)
INTRODUCTION
Patients with hepatitis C recurrence after liver transplantation represent a clinical challenge. Antiviral treatment in transplant patients has usually poor tolerability and limited efficacy, with a mean sustained virological response (SVR) of 30%. Our pilot study was aimed at evaluating whether 8-week ribavirin pre-treatment could increase either adherence or antiviral effect of a 48-week combination therapy.
METHODS
Ribavirin pre-treatment (8 weeks) was started with 600 mg daily and increased to 10.4 mg/kg/day. After pre-treatment, 1.5 μg/kg/week pegylated interferon-α2b was added for 48 additional weeks of combination therapy. Blood count, liver function tests and plasma HCV-RNA were examined monthly. Ribavirin plasma concentrations were determined by HPLC.
RESULTS
Thirteen patients (mean age 53 ±2 years, 11 males) were treated: eight were HCV genotype 1/4; five were genotype 2/3. The median baseline HCV RNA level was 6.5 log (10) (range 5.84-7.42 log (10) ). During ribavirin pre-treatment the median HCV RNA levels decreased significantly (5.7 log (10) ; P=0.023). During combination therapy 6/13 (46%) patients exhibited a rapid virological response (RVR) and 10/13 (77%) patients a complete early virological response, two were non-responders. A decline of 0.5 log (10) HCV RNA during pre-treatment predicted RVR. SVR occurred in six patients (46%): four were genotype 2/3. Stable ribavirin dose reduction was required in only two patients (15%) in whom transient interferon reduction was also required.
CONCLUSION
This proof-of-concept study indicates that ribavirin pre-treatment increased the tolerability of the antiviral treatment, and improved its efficacy in liver transplant patients. Moreover, the degree of HCV RNA decline during pre-treatment allowed one to predict on-treatment response.
Analysis of the Complete Open Reading Frame of Genotype 2b Hepatitis C Virus in Association with the Response to Peginterferon and Ribavirin Therapy
Patients infected with genotype 2b hepatitis C virus (HCV) generally can achieve favorable responses to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV). However, a proportion of patients show poorer responses and the correlation between viral sequence variation and treatment outcome remains unclear.The pretreatment complete open reading frame (ORF) sequences of genotype 2b HCV determined by direct sequencing were investigated for correlation with the final outcome in a total of 60 patients...Full Text
Related; RSS From PLoS ONE Blog
From Expert Review of Anti-Infective Therapy
Management of Viral Infections in Solid Organ Transplant Recipients
Raymund R Razonable
Authors and Disclosures
Posted: 09/16/2011; Expert Rev Anti Infect Ther. 2011;9(6):685-700. © 2011 Expert Reviews Ltd.
Introduction Only
Click Here For Full Text
Viruses are major pathogens that cause morbidity and mortality after solid organ transplantation (SOT). Some of these infections generally follow a stereotypical temporal pattern. The first month after SOT represents the period when herpes simplex virus (HSV)-seropositive transplant recipients are at highest risk of HSV-1 and HSV-2 infection.[1] Other viruses that present during this time are often donor derived, such as the rare transmission of West Nile virus, rabies virus and lymphocytic choriomeningitis virus.[2–4] The classic 'opportunistic' viral pathogens typically occur during the second to the sixth months after SOT, when impairment in cell-mediated immunity is most intense; primary or reactivated cytomegalovirus (CMV) disease is most common during this period.[5–9] During the 'late period,' which begins more than 6 months after SOT, Varicella zoster virus (VZV) may reactivate to cause mono- or multidermatomal zoster or disseminated disease. Liver recipients with chronic viral hepatitis B and C may have an accelerated course that progresses to allograft failure.[10–14]
Late-onset CMV disease, with either classic or atypical presentation, may also occur.[15–21] Adenoviruses and community-acquired respiratory viruses such as respiratory syncytial virus (RSV), influenza virus and parainfluenza virus occur anytime after SOT, but with the risk of severe illness and outcome during the first 3 months.[22,23]
Epstein–Barr virus infection may occur anytime after SOT to cause post-transplant lymphoproliferative disorders (PTLDs).[9,24] In endemic regions, human herpesvirus 8 (HHV-8) reactivation may lead to the development of Kaposi's sarcoma (KS). In this article, the current management of virus infections after SOT are discussed, with particular focus on herpes, hepatitis, polyoma and RNA viruses causing respiratory diseases... Continue Reading..
Ask the Doctor: What is Hepatitis and HIV co-infection?
Hepatitis is a viral infection that attacks liver cells. There are three main types of hepatitis: A, B and C. Hepatitis A is a liver infection caused by a virus that does not produce long-term or chronic liver problems... Continue Reading..
T cells making brain chemicals may lead to better treatments for inflammation, autoimmune diseases
MANHASSET, NY -- Scientists have identified a surprising new role for a new type of T cell in the immune system: some of them can be activated by nerves to make a neurotransmitter (acetylcholine) that blocks inflammation. The discovery of these T cells is novel and suggests that it may be possible to treat inflammation and autoimmune diseases by targeting the nerves and the T cells. The study was published this week in Science.
"The discovery that 2 percent of T cells can make acetylcholine under the control of nerves gives a new insight into how the nervous system regulates immunity," said Kevin J. Tracey, MD, president and chief executive officer of The Feinstein Institute for Medical Research, and principal investigator of the study. "The arrival of electrical signals from nerves activates these specialized T cells to produce the acetylcholine necessary to block inflammation, and protect against damage. It is possible to transfer these cells to cross-protect mice from inflammation, and to control these T cells by electrically stimulating the nerves directly."
The present study followed years of work from Dr. Tracey's lab that identified the role of the vagus nerve, named for its wandering course from the base of the brain to the liver, spleen and other organs, in blocking inflammation. Applying electrodes to stimulate the vagus nerve blocked the release of tumor necrosis factor (TNF) and other cytokines that underlie the tissue damage in arthritis, inflammatory bowel disease and other syndromes. Stimulating this nerve pathway led to increased production of acetylcholine, a neurotransmitter that binds to the alpha 7 nicotinic acetylcholine receptor. Activating this receptor on macrophages blocked the release of immune molecules (the cytokines,) suggesting a novel strategy for developing anti-inflammatory agents.
But these results raised an important question because the nerve fibers in spleen release norepinephrine, another neurotransmitter, but not acetylcholine. The search for the cells that produce acetylcholine led these investigators to use "nude" mice, devoid of T cells. Then they examined the spleen cells that make acetylcholine and that led them to a subset of T cells. Transferring these acetylcholine producing T-cells into nude mice restored the vagus nerve circuit that blocked inflammation.
"Our results point to a population of acetylcholine-synthesizing memory T cells in spleen that is integral to the function of the inflammatory reflex, the nerve circuit that regulates inflammation and immunity," said Dr. Tracey. "It is as if these T cells occupy a nerve-like function in this important circuit."
It should be possible to target these T cells and to modulate this neural circuitry to develop therapeutic modalities for inflammatory and autoimmune diseases. In the future, it may be possible to isolate these T cells and exploit their anti-inflammatory activity. In the meantime, there is a more direct route to use this discovery for therapy. Rheumatoid arthritis patients in Europe are being studied in clinical trials where vagus nerve stimulators are implanted and turned on to stimulate this circuit and suppress inflammation.
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About The Feinstein Institute for Medical Research Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in Parkinson's disease, Alzheimer's disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. For more information: http://www.feinsteininstitute.org/
This video covers Hepatitis A after exposure
*Remember that chronic liver disease puts you at risk for serious complications if you get infected with the hepatitis A virus.
Dr. Ron Warner answers viewers questions about Hepatitis A
Ron Warner, Ph.D., is an Infectious Disease Specialist and Professor at the Texas Tech Health Sciences Center. He has provided this information to our viewers in addition to the questions he answered in our segment on NewsChannel 11 at Ten.
-Karin McCay
Media
37 students stabbed with needle in Puerto Rico
By Danica Coto, Associated Press
SAN JUAN, Puerto Rico — A 14-year-old girl went on a playground rampage with a hypodermic needle, stabbing 37 classmates, Puerto Rican officials said Thursday."She would stab one, run, stab another, run, like it was some sort of joke," Education Secretary Jesus Rivera Sanchez said about Tuesday's lunchtime attack on 12- to 14-year-olds at the Jose de Choudens middle school in the southern coastal town of Arroyo.Health Department spokeswoman Margarita Casalduc said it was unclear if the syringe contained anything and further tests were needed to determine if it was contaminated.But the victims, accompanied by their shaken parents, gathered at a convention center to be tested for HIV and hepatitis C and to be given preventive medications.Sanchez said counselors also were helping the victims and their parents.
Social workers were interviewing the alleged attacker to try to determine a motive, Justice Department spokesman Fidel Rodriguez said. He said no charges had yet been filed, but officials said she had been suspended from school.Rivera said the girl first told investigators she found the syringe, but later said she stole an unused one while visiting a relative at a hospital and had planned to pierce her ear with it. He said it was not clear why she decided to attack her classmates.A woman who answered the phone at the school said the director, Gloria Ramos, was not available for comment.
Pharmaceutical
Teva bets $7.5M on hep C program at upstart Cocrystal
As the generic drug giant pushes to capitalize on more novel therapies, Teva Pharmaceutical ($TEVA) has invested an initial $7.5 million in Bothell, WA-based developer Cocrystal Discovery to advance its work on new drugs targeting the hepatitis C virus. If it likes what it sees, Teva has the option to pump more money into the upstart, which is focused on small-molecule antiviral drugs.
Hep C has attracted lots of pharma investment due to the white-hot market opportunity for developing oral drugs that home in on viral replication enzymes. Upping its bet on the hep C game after Vertex ($VRTX) and Merck ($MRK) hit the market this year with protease inhibitors against the liver-wrecking virus, Teva has gained an option for exclusive development rights to Cocrystal's drug. The generic drugmaker also has the option to back Cocrystal's development of antiviral drugs for other diseases. The start-up now has programs in influenza and the common cold... Continue Reading...
Will the UN backtrack on accessible medicine?
The US and Europe are pushing the UN to flout the Doha Declaration, which improves poorer countries' access to drugs.
The term "compulsory license" is used to describe cases in which governments or courts set aside the exclusive rights of a patent, and allow others to use inventions, normally in return for a royalty payment to the patent owner. In such cases, the patent is no longer an absolute monopoly to use the invention, but does ensure that patent owners are paid when the inventions are used by third parties.
The use of compulsory licenses are as old as the patent system itself (a 1474 Venetian statute and an English law passed in 1623 both sanctioned compulsory licenses), and are used in a wide range of cases. While maintaining an active trade policy to prevent developing countries from using compulsory licenses for patents on medicines, at home the United States has used compulsory licenses to expand access to patented inventions to treat cancer, diagnose the Hepatitis C virus, manufacture contact lenses, and treat aortic valve heart disease.
Health Insurance
Helping the uninsured sign up for health insurance
As you may have heard, a new nonprofit group launched yesterday to help get Americans – specifically those who, beginning in 2014, will be eligible for coverage under the Affordable Care Act – signed up for insurance. Enroll America, a coalition of 42 companies and organizations, is planning a state-by-state publicity campaign and will launch an effort to help state leaders “put in place procedures to simplify enrollment.” (Its website also offers resources for people currently looking for coverage.) Over at Wonkblog, Sarah Kliff tells readers they should keep an eye on the group:
Enroll America is taking on a challenging issue on in a big way. The majority of uninsured Americans don’t think the health reform law will help them, the most recent Kaiser Family Foundation report found.As the Hill’s Sam Baker smartly pointed out, polling data seems to show Americans forgetting what the reform law does as we move further away from its passage. “Our biggest hurdle is most people don’t even know this is coming,” says Rachel Klein, director of Enroll America. How much a multi-million campaign can change that will be a key factor to watch in the health law’s success... Continue Reading...
FYI
Tempest In A Lunch Box: Arsenic Traces In Apple Juice
A lot of parents might be worried about what's in their kids' sippy cups if they caught a recent report by TV talk show host Dr. Mehmet Oz about high levels of arsenic in popular brands of apple juice.
But the Food and Drug Administration and medical experts are attacking Oz's report, saying it's inaccurate and needlessly panics parents.
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